Textbook of Oral Medicine Oral Diagnosis and Oral Radiology

Textbook of

Oral Medicine, Oral Diagnosis and Oral Radiology

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Textbook of

Oral Medicine, Oral Diagnosis and Oral Radiology Second Edition

Editors Ravikiran Ongole BDS, MDS Professor Department of Oral Medicine and Radiology Manipal College of Dental Sciences, Manipal University Mangalore, India

Praveen BN BDS, MDS Professor and Head Department of Oral Medicine and Radiology KLE Society’s Institute of Dental Sciences Bengaluru, India

ELSEVIER A division of Reed Elsevier India Private Limited

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Textbook of Oral Medicine, Oral Diagnosis and Oral Radiology, 2/e Ongole and Praveen ELSEVIER A division of Reed Elsevier India Private Limited Mosby, Saunders, Churchill Livingstone, Butterworth Heinemann and Hanley & Belfus are the Health Science imprints of Elsevier. © 2013 Elsevier First Edition 2010 Second Edition 2013 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher. ISBN: 978-81-312-3091-6 Medical knowledge is constantly changing. As new information becomes available, changes in treatment, procedures, equipment and the use of drugs become necessary. The authors, editors, contributors and the publisher have, as far as it is possible, taken care to ensure that the information given in this text is accurate and up-to-date. However, readers are strongly advised to confirm that information, especially with regard to drug dose/usage, complies with current legislation and standards of practice. Please consult full prescribing information before issuing prescriptions for any product mentioned in the publication. Published by Elsevier, A division of Reed Elsevier India Private Limited. Registered Office: 305, Rohit House, 3, Tolstoy Marg, New Delhi – 110 001. Corporate Office: 14th Floor, Building No. 10B, DLF Cyber City, Phase-II, Gurgaon, Haryana – 122 002. Publishing Manager: Ritu Sharma Sr. Commissioning Editor: Nimisha Goswami Managing Editor: Anand K Jha Copy–Editor: Saroj K Sahoo Publishing–Operations Manager: Sunil Kumar Production Manager: NC Pant Typeset by Olympus Premedia Pvt. Ltd. (formerly Olympus Infotech Pvt. Ltd.), Chennai, India. www.olympus.co.in Printed and bound at

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Dedicated to My Wife, Parents and Brother —Ravikiran Ongole My Parents, Wife and Daughter (Aadya) —Praveen BN

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Foreword I

The current academic scenario in our country has witnessed an abundance of postgraduate courses and postgraduate teachers. An offshoot of this has been the burgeoning demand for reliable sources of knowledge for undergraduates, postgraduates and the dental practitioners. The mushrooming number of textbooks is a welcome sign of enterprise and effort on the part of our teachers. However all are not of acceptable quality. One needs to separate the wheat from the chaff and restrict one’s interest to the textbooks with quality content. Once such gem is the Textbook of Oral Medicine, Oral Diagnosis and Oral Radiology brought out by Dr Ravikiran Ongole and Dr Praveen BN, committed academicians with a number of scientific publications and a previous textbook to their credit; they have succeeded in creating a tome of oral medicine and radiology. It is a matter of great pride to me personally since Dr Ravikiran is a faculty member and a gifted teacher in my institution. Their task has been a Herculean one since they have not only contributed their own knowledge to this book; they have also used the combined experience of other dental and medical professionals from diverse fields. I am happy that the first edition of the book was received well and I am confident that the second edition of the book with an additional section on dental radiology would help in imparting further knowledge to students in the field of Oral Medicine and Radiology. A brief overview of the book reveals the amount of effort put in by the editors and their contributors. I wish them all the best in their endeavor to spread knowledge in Oral Diagnosis and Radiology and whole heartedly recommend this book to all those who seek the same. Prof (Dr) V Surendra Shetty Pro Vice Chancellor Manipal University, Mangalore

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Foreword II

Dentistry has always been an evolving science and every effort is to be made to keep up pace with the advancement. This textbook has received wide recognition for its contribution to the practice of dentistry. I would like to congratulate the editors in their continuing effort to present the second edition with attention to detail, written principally for a student in an attempt to penetrate some depth towards newer research. The edition has maintained its firm commitment in assuring a thorough and complete text. The ‘examination of a case’ confronts every clinician. I think this book gives a well-reasoned explanation of fundamental aspects, emphasized on clinical scenario with illustrations, which are of value to a practicing dentist. Launching a subsequent edition of a warmly received text is more of a challenge. I whole heartedly congratulate their feat for their truly admirable skills and the contributors for this splendid work of knowledge. Prof (Dr) Srivatsa G Principal KLE Society’s Institute of Dental Sciences Bengaluru

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List of Contributors

Carol M Stewart MS, DDS, MS Professor, Oral Medicine Department of Oral and Maxillofacial Surgery and Diagnostic Sciences University of Florida College of Dentistry Gainesville, Florida, USA Madhu K Nair BDS, DMD, MS, Lic Odont (Sweden), PhD Associate Professor Oral and Maxillofacial Radiology Department of Oral and Maxillofacial Surgery and Diagnostic Sciences University of Florida College of Dentistry Associate Professor, Radiology UF College of Medicine Gainesville, Florida, USA Syed Vaseemuddin BDS, MDS Formerly Assistant Professor Department of Oral Medicine and Radiology KLE Society’s Institute of Dental Sciences Bengaluru, India Francisco Lopez Sanchez DDS, MDS Professor Periodontics and Oral Pathology UMSNH College of Dentistry Professor, Endodontic surgery, Endo-periodontology and Ortho-periodontolgy CUEPI Morelia Michoacan, México

Sadhana Shenoy S BDS, MDS Reader Dept of Oral Pathology Oxford Dental College Bengaluru, India Karen Boaz BDS, MDS Professor and Head Department of Oral Pathology Manipal College of Dental Sciences, Manipal University Mangalore, India Ajit Auluck MDS, PhD Clinician Scientist BC Cancer Agency Simon Fraser University Canada Manuel Thomas BDS, MDS Associate Professor Department of Conservative Dentistry Manipal College of Dental Sciences Mangalore, India Ajay G Nayak BDS, MDS Reader Department of Oral Medicine and Radiology Mahatma Gandhi Vidyamandir’s Karmaveer Bhausaheb Hiray Dental College and Hospital Nashik, India

Sara Carolina Rodriguez Peña DDS, MDS Orthodontist, Military College of Dentistry UNITEC, México

Joanna Baptist BDS, MDS Assistant Professor Department of Oral and Maxillofacial Surgery Manipal College of Dental Sciences Manipal University, Mangalore, India

Nandita Shenoy BDS, MDS Reader Department of Oral Medicine and Radiology Manipal College of Dental Sciences, Manipal University Mangalore, India

Thomas Zachariah BDS, MDS Reader Department of Oral and Maxillofacial Surgery Meenakshi Ammal Dental College and Hospital Chennai, India

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Ashok I Lingappa BDS, MDS Professor and Head Department of Oral Medicine and Radiology Bapuji Dental College and Hospital Davangere, India Nagamani Narayana DMD, MS Assistant Professor Department of Oral Biology College of Dentistry University of Nebraska Medical Center Lincoln, USA Keerthilatha M Pai BDS, MDS Associate Dean, Professor and Head Department of Oral Medicine and Radiology Manipal College of Dental Sciences Manipal, India Braz Campos Durso DDS, MSD Professor of Oral Diagnostic and Orofacial Pain Department School of Dental Medicine Porto Velho, RO Brazil K Srinivas BDS, MDS Professor Department of Oral Medicine and Radiology AECS Maruti College of Dental Sciences and Research Centre Bengaluru, India Sarita Dimri MD Formely Assistant Professor Department of Dermatology Kasturba Medical College and Hospital Mangalore, India Shibu Thomas BDS, MDS Reader Department of Oral Medicine and Radiology Indira Gandhi Institute of Dental Sciences Nellikuzhi, Kothamangalam Kerala, India Indraneel Bhattacharyya DDS, MSD Assistant Professor Oral and Maxillofacial Pathology Department of Oral and Maxillofacial Surgery and Diagnostic Sciences University of Florida College of Dentistry Gainesville, Florida, USA

James C Pettigrew DMD Associate Professor Oral and Maxillofacial Radiology Department of Oral and Maxillofacial Surgery and Diagnostic Sciences University of Florida College of Dentistry Associate Professor, Radiology, UF College of Medicine Gainesville, Florida, USA Seunghee Cha DDS, PhD Assistant Professor Department of Oral and Maxillofacial Surgery and Diagnostic Sciences University of Florida College of Dentistry Gainesville, Florida, USA Joseph Katz DMD Professor Department of Oral and Maxillofacial Surgery and Diagnostic Sciences University of Florida College of Dentistry Gainesville, Florida, USA Sunanda C BDS, MDS Professor Department of Oral Medicine and Radiology Dr Syamala Reddy Dental College and Hospital Bengaluru, India NVS Sekhar Reddy BDS, MDS Professor Department of Oral and Maxillofacial Surgery Dr Syamala Reddy Dental College and Hospital Bengaluru, India Mala Kamboj BDS, MDS Associate Professor Department of Oral Pathology and Microbiology Career Institute of Dental Sciences and Hospital Lucknow, India SV Kumaraswamy BDS, MDS Formerly Professor and Head Department of Oral and Maxillofacial Surgery VS Dental College and Hospital Bengaluru, India Jeevan Prakash V BDS, MDS Professor and Head Department of Oral and Maxillofacial Surgery Jodhpur Dental College and General Hospital Jodhpur, Rajasthan, India Vivekananda Pai BDS, MDS Professor and Head Department of Conservative Dentistry Manipal College of Dental Sciences, Manipal University Mangalore, India

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Jeeth Rai BDS, MDS Assistant Professor Department of Periodontology KLE Society’s Institute of Dental Sciences Bengaluru, India

Veena KM BDS, MDS Professor Department of Oral Medicine and Radiology Yenepoya Dental College and Hospital Mangalore, India

Sumati Nagappa Baddannavar BDS, MDS Reader Department of Oral Medicine and Radiology KLE Society’s Institute of Dental Sciences Bengaluru, India

Manish Juneja BDS, MDS, DNB Associate Professor Department of Oral Pathology and Microbiology PDM Dental College and Research Institute Haryana, India

Syeda Arshiya Ara BDS, MDS Professor Department of Oral Medicine and Radiology Al-badar Rural Gulbarga Dental College and Hospital Gulbarga, India

Balaji Rao B BDS, MDS Formerly Principal, Professor Emeritus Department of Oral Medicine and Radiology KLE Society’s Institute of Dental Sciences Bengaluru, India

Ceena Denny E BDS, MDS Associate Professor Department of Oral Medicine and Radiology Manipal College of Dental Sciences, Manipal University Mangalore, India

Sumanth KN BDS, MDS Department of Oral Diagnosis, Oral Medicine and Oral Pathology Faculty of Dentistry, Melaka Manipal Medical College Melaka, Malaysia

Gajendra Veeraraghavan BDS, MDS, MFDS RCPS Reader Department of Oral Medicine and Radiology Sree Mookambika Institute of Dental Sciences Kulasekharam, Tamil Nadu, India

Adel Kauzman DMD, MSc, FRCD(c) Associate Professor, Department of Stomatology Faculty of Dentistry Université de Montréal, Quebec, Canada

Seema Patil BDS, MDS Reader, Department of Oral Medicine and Radiology DAPM RV Dental College Bengaluru, India Vishwananth R BDS, MDS Professor and Head Department of Oral Medicine and Radiology Indira Gandhi Institute of Dental Sciences Puducherry, India Sarat Gummadapu BDS, MDS, MFDS RCPSG Associate Professor Department of Oral Medicine and Radiology Drs Sudha and Nageswara Rao Siddhartha Institute of Dental Sciences Krishna (Dt), Andhra Pradesh, India Srikant N BDS, MDS Associate Professor Department of Oral Pathology and Microbiology Manipal College of Dental Sciences, Manipal University Mangalore, India

Iona Leong BDS, MSc, FRCD(c) Department of Oral Pathology and Oral Medicine Faculty of Dentistry University of Toronto, Ontario, Canada Head, Department of Dentistry Division of Oral Pathology and Oral Medicine Mount Sinai Hospital Nagaraj A BDS, MDS Reader Department of Oral Pathology KLE Society’s Institute of Dental Sciences Bengaluru, India Shubha Sairam BDS, MDS Assistant Professor Department of Oral Medicine and Radiology KLE Society’s Institute of Dental Sciences Bengaluru, India Ashith B Acharya BDS, GDFO Associate Professor and Head of Forensic Odontology SDM College of Dental Sciences and Hospital Dharwad, India

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Foluso J Owotade BChD, FWACS Associate Professor and Head Department of Oral and Maxillofacial Surgery and Oral Pathology College of Health Sciences Obafemi Awolowo University Ile-Ife, Nigeria Eyitope O Ogunbodede BSc, BChD, MPH, DDPH, RCS Head of the Department of Preventive Dentistry Faculty of Dentistry, Obafemi Awolowo University Ile-Ife, Nigeria Ranganath D Rattehalli MBBS, MRCPsych, M Med Sc, CCT(UK), DPM, PG Diploma (Cli Psy)

Consultant Psychiatrist, Leeds Partnerships NHS Trust, Seacroft Hospital, Leeds, UK Sandip Deshpande MBBS, MD, DPM, MRCPsych, CCT (UK), PG Diploma (Sex and Reln. therapy)

Consultant Psychiatrist, Sexual and Relationship therapist Manipal Northside Hospital, Bengaluru Ex-consultant, NHS, Leeds, UK Raghavendra Kini BDS, MDS Professor Department of Oral Medicine and Radiology AJ Institute of Dental Sciences Mangalore, India Anshul Mehra BDS, MDS Reader Babu Banrasi Das College of Dental Sciences Faizabad Road, Lucknow Uttar Pradesh, India Thomas George BDS, MDS Faculty of Dentistry University of Malaya, Kuala Lumpur, Malaysia Shubhasini AR BDS, MDS Reader, Department of Oral Medicine and Radiology, KLE Society’s Institute of Dental Sciences, Bengaluru, India Bhanushree R BDS, MDS Lecturer, Department of Oral Medicine and Radiology, KLE Society’s Institute of Dental Sciences, Bengaluru, India Kıvanç Kamburoğlu DDS, MSc, PhD Associate Professor Department of Dentomaxillofacial Radiology Faculty of Dentistry, Ankara University, Ankara, Turkey

Gail F Williamson RDH, MS Faculty Fellow of Faculty Advancement Initiatives Professor of Dental Diagnostic Sciences Oral Pathology, Medicine and Radiology Indiana University School of Dentistry Indianapolis, USA Muralidhar Mupparapu D MD Director, Oral and Maxillofacial Radiology University of Pennsylvania School of Dental Medicine Philadelphia, USA Suman Jai Sanghar BDS, MDS Professor Department of Oral Medicine and Radiology KSR Institute of Dental Sciences and Research Tiruchengode, Tamil Nadu, India Jai Sanghar N BDS, MDS Professor and Head Department of Oral Medicine and Radiology Rajah Muthiah Dental College and Hospital Annamalai University, Chidambaram Tamil Nadu, India Medha Babshet BDS, MDS Assistant Professor Department of Oral Medicine and Radiology Hasanamba Dental College and Hospital Hassan, Karnataka, India Rinky Nyachhyon BDS, MDS Assistant Professor Department of Oral Medicine and Radiology, Peoples Dental College and Hospital Kathmandu, Nepal Apeksha Mainali BDS, MDS Assistant Professor Department of Oral Medicine and Radiology Kantipur Dental College kathmandu, Nepal Praveen BN BDS, MDS Professor and Head Department of Oral Medicine and Radiology KLE Society’s Institute of Dental Sciences Bengaluru, India Ravikiran Ongole BDS, MDS Professor Department of Oral Medicine and Radiology Manipal College of Dental Sciences Mangalore, India

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Preface to the Second Edition

The first edition of the book was published two years ago. Since then we have received very encouraging feedback from students and faculty alike. It was also heartening to note that this book was included by various health universities in their recommended list of textbooks for undergraduate and postgraduate students. We also received suggestions for including a section on dental radiology with a special request to include chapters on implant imaging and cone beam computed tomography. Taking these views into consideration, we included a section on radiology that covers varied topics from radiation physics to specialized imaging techniques. The oral medicine section has also been updated with the latest concepts in the diagnosis and medical management of various orofacial disorders. We wish this comprehensive Textbook of Oral Medicine, Oral Diagnosis and Oral Radiology gains wider popularity amongst the student community and the faculty and continues to cater to the needs of students pursuing the specialty of Oral Medicine and Radiology. Ravikiran Ongole Praveen BN

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Preface to the First Edition

Oral Medicine in India is still in its nascent stages of growth. Consequently, there is not much literature that is easily available to the student community. While there are many excellent textbooks available outside the Indian shores, in the editors’ opinion, there is not much emphasis on diseases that tend to occur in the Indian subcontinent. Further, content prescribed by the Dental Council of India, which is very useful to undergraduate and postgraduate students of dentistry, is rarely available. Many popular textbooks that are available to students of dentistry in India are either exam-oriented (not sufficient background material; not suitable for reference beyond a particular examination) or focus only on oral medicine or on oral radiology. Our goal was two-fold: publish content that would appeal to undergraduate students because the content corresponded to DCI curriculum; to postgraduate students and practitioners to serve as reference for diseases that seem to occur very frequently in India. We have tried our best to combine oral medicine, diagnosis and radiological aspects of various orofacial diseases and oral manifestations of systemic disorders. Chapters such as maxillofacial trauma, Lab investigations, Mental illness and Syndromes of the head and neck have been specially written for postgraduate students. We have tried our best to provide up to date references. Another unique feature of this book is the contributions made from more than 60 authors from various dental colleges all over India and from countries such as USA, England, Canada, Mexico, Brazil and Nigeria. We have made a conscious effort to tap into the expertise of authors from various fields of medicine such as plastic surgery, dermatology and psychiatry and from various dental specialties apart from oral medicine such as oral pathology, oral surgery, conservative dentistry, orthodontics, prosthodontics and periodontics. We sincerely hope that this textbook will stimulate minds and satiate the intellectual appetite of the students of oral medicine, diagnosis and radiology. Ravikiran Ongole Praveen BN

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Acknowledgments

The editors would whole heartedly like to acknowledge contributions from various individuals, especially the authors to this book. We would like to acknowledge the encouragement, guidance and support rendered by Dr V Surendra Shetty, Pro Vice Chancellor, Manipal University, Dr Dilip G. Nayak, Dean, Manipal College of Dental Sciences, Manipal University, Mangalore and Dr Srivatsa G, Principal, KLE Society’s Institute of Dental Sciences, Bengaluru. We would also like to thank them for graciously permitting us to use photographs from the department archives. We would like to thank the teaching faculty of the Departments of Oral Medicine and Radiology, MCODS (Mangalore) and KLE Society’s Institute of Dental Sciences (Bengaluru) for their help and suggestions provided during the preparation of this book. Our heartfelt thanks to Dr Saranya B, Dr Richa Gaba, Dr Bijina, Dr Sumsum P Sunny, Dr Sushma CN and Dr Pramila Mendonca who helped us at every step during the preparation of the book. Our sincere sense of gratitude go out to Mr Mark Dirlam, Supervisor and Graphic Artist and Mr Timothy Centers, Photographer, Department of Illustrations, Indiana University School of Dentistry, Indianapolis, Indiana, USA and Dr Jaideep Shekhar for helping us in preparing illustrations for the book. We are extremely indebted to Dr John O’ Keefe, Editor, Journal of the Canadian Dental Association, Dr Foluso Owotade and Dr Carol Stewart for their words of strength and encouragement and for lending us photographs. We appreciate the support and constant encouragement received from the ever enthusiastic publishing team of Elsevier India, especially Ms Ritu Sharma, Ms Nimisha Goswami and Mr Anand K Jha. Our sincere appreciation and gratitude to our patients, some of who were terminally ill, for enduring pain and discomfort in the hope of relief and cure. We hope that this textbook will in some small way alleviate their sufferings. Above all our deepest gratitude to our families for their affection, unconditional support and encouragement. We sincerely apologize to individuals whose names have been inadvertently not mentioned.

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Contents

Dedication Foreword I Foreword II List of Contributors Preface to the Second Edition Preface to the First Edition Acknowledgments

v vii ix xi xv xvii xix

Part I—Oral Medicine and Oral Diagnosis SECTION I

INTRODUCTION AND APPROACH TO DIAGNOSIS

Chapter 1

History and Scope of Oral Medicine and Oral Radiology

5

History of Oral Medicine • Oral and Maxillofacial Radiology • Oral Medicine and Radiology in India

SECTION II

ORAL AND MAXILLOFACIAL DISTURBANCES

Chapter 2

Developmental Disturbances

11

Fordyce’s Granules (Fordyce’s Spots/Disease) • Lingual Tonsils • Leukoedema • Retrocuspid Papillae • Prominent Palatal Rugae • Circumvallate Papillae or Vallate Papillae • Parotid Papilla • Racial Pigmentation/Physiological Pigmentation • Mandibular and Maxillary Tori • Developmental Disorders Affecting Tongue • Developmental Disorders Affecting the Lip • Developmental Disorders Affecting Buccal Mucosa and Gingiva • Developmental Disturbances of the Jaws • Developmental Disturbances Affecting Teeth Chapter 3

Orofacial Pigmentation Disorders

61

Pigmented Lesions of Oral Mucosa • Pigmentation of Teeth • Dental Fluorosis Chapter 4

Bacterial, Viral and Fungal Infections

82

Scarlet Fever • Diphtheria • Tularemia (Rabbit Fever, Deer-fly Fever, Francis’ Disease, Tick-Borne Disease, Ohara’s Disease) • Erysipelas • Impetigo • Melioidosis • Tetanus • Actinomycosis • Noma (Cancrum Oris, Gangrenous or Necrotizing Stomatitis) • Botryomycosis (Bacterial Pseudomycosis) • Rhinoscleroma (Respiratory Scleroma) • Cat-scratch Disease • Infectious Mononucleosis (Monoglandular Fever, Kissing Disease) • Acute Lymphonodular Pharyngitis • Measles (Rubeola) • German Measles (Rubella) • HIV and AIDS • Acquired Immune Deficiency Syndrome • Sinusitis • Histoplasmosis • Blastomycosis (Gilchrist Disease) • Mucormycosis (Zygomycosis, Phycomycosis) • Aspergillosis • Cryptococcosis (European Blastomycosis, Torulosis, Busse-Buschke Disease) Chapter 5

Orofacial Pain

111

Pain Physiology • Classification of Orofacial Pain • Clinical Assessment of Pain • Pain from Orodental Structures • Barodontalgia • Paranasal Sinus-related Pain • Myofascial Pain • Neuralgias • Atypical Odontalgia • Atypical Facial Pain • Burning Mouth Syndrome

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Contents

SECTION III MUCOCUTANEOUS DISORDERS Chapter 6

Red and White Lesions

133

Description of Red and White Lesions • Etiologic Classification of Red and White Lesions • White Lesions of the Oral Cavity • Red Lesions of the Oral Cavity • Red Lesions of the Tongue Chapter 7

Vesiculobullous Disorders

174

Classification of Vesiculobullous Lesions • Predominantly Vesicular Lesions • Herpes Simplex Virus (HSV) Infections • Herpetic Whitlow and Herpes Gladiatorum • Recurrent Herpes Infections • Varicella Zoster Infections • Hand, Foot and Mouth Disease • Herpangina • Dermatitis Herpetiformis • Predominantly Bullous Lesions • Bullous Lichen Planus • Erythema Multiforme • Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis (Lyell’s Syndrome) • Bullous Impetigo • Epidermolysis Bullosa Chapter 8

Oral Ulcerative Diseases

196

Classification of Oral Ulcers • Traumatic Ulcers • Primary Herpetic Gingivostomatitis • Recurrent Herpes Infection • Varicella Zoster Infection • Acute Necrotizing Ulcerative Gingivitis (Trench Mouth, Vincent’s Disease, Vincent’s Gingivostomatitis) • Tuberculosis • Syphilis • Deep Fungal Infections • Drug-induced Oral Ulcers • Erythema Multiforme • Blood Disorders Causing Oral Ulcers • Immunologic Disorders • Dermatological Disorders • Pemphigoid • Gastrointestinal Disorders Associated with Oral Ulcers • Neoplastic Ulcers • Ulcers of Unknown Etiology • Syndromes Associated with Oral Ulcers • Diagnostic Protocol Chapter 9

Dermatological Diseases

218

Lichen Planus • Epidermolysis Bullosa • Psoriasis • Ectodermal Dysplasia • Ehlers–Danlos Syndrome • Pachyonychia Congenita • Dyskeratosis Congenita • Pityriasis Rosea • Xeroderma Pigmentosum • Acanthosis Nigricans • Goltz–Gorlin Syndrome • Acrodermatitis Enteropathica • Hailey–Hailey Disease (Familial Benign Chronic Pemphigus) • Darier’s Disease (Keratosis Follicularis) • Reiter’s Syndrome • Incontinentia Pigmenti (Bloch–Sulzberger Syndrome) • Kawasaki Disease (Mucocutaneous Lymph Node Syndrome) • Tuberous Sclerosis Complex (Epiloia, Bourneville’s Disease) • Graft-versus-Host Disease

SECTION IV DISEASES OF SPECIFIC STRUCTURES Chapter 10

Temporomandibular Disorders

239

Components of Temporomandibular Joint • Clinical Evaluation of Temporomandibular Joint • Clinical Evaluation of Muscles of Mastication and Accessory/Cervical Muscles • Disorders Associated with Deviation/Alteration in the Form of Articular Surfaces • Articular Disk Defects • Inflammatory Joint Disorders • Degenerative Joint Diseases • TMJ Ankylosis • Masticatory Muscle Disorders • Congenital, Developmental and Acquired Disorders of the TMJ • Neoplasms Affecting the TMJ • Condylar Fractures Chapter 11

Diseases of Salivary Glands

265

Developmental Disturbances • Saliva, Xerostomia, Hyposalivation and Sialorrhea • Inflammatory Conditions of Salivary Glands • Viral-induced Salivary Gland Pathology • Non-inflammatory Conditions of Salivary Glands • Salivary Gland Tumors • Benign Tumors • Malignant Tumors

SECTION V

CYSTS AND TUMORS OF OROFACIAL REGION

Chapter 12

Cysts of Orofacial Region

303

Classification of Cysts of Orofacial Region • Theories of Cyst Expansion • Odontogenic Cysts • Odontogenic Keratocyst • Gingival Cysts of Adults • Calcifying Epithelial Odontogenic Cyst (Gorlin Cyst) • Glandular Odontogenic Cyst • Nonodontogenic Cysts • Nasolabial Cyst • Mid-palatal Raphe Cyst of Infants • Cysts of Maxillary Antrum and Salivary Glands • Inflammatory Cysts • Pseudocysts • Cysts of Soft Tissues of Mouth, Face and Neck • Nasopharyngeal Cysts • Thyroglossal Duct Cysts • Lymphoepithelial Cysts (Branchial Cleft Cysts) • Cystic Hygroma • Dermoid, Epidermoid and Teratoid Cysts • Parasitic Cysts Chapter 13

Tumors of Orofacial Region

331

Benign Odontogenic Tumors • Odontogenic Carcinomas • Odontogenic Sarcomas • Epithelial Malignant Tumors • Connective Tissue Malignant Tumors xxii

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Contents

Chapter 14

Oral Cancer

380

Incidence of Cancer of Head and Neck • Etiology and Risk Factors for Oral and Maxillofacial Cancer • Tobacco • Alcohol • Systemic Health • Molecular Basis of Cancer • Clinical Signs of Cancer • Clinical Examination of a Patient with Suspected Malignancy • TNM Staging • Nodal Metastasis • Diagnosis of Oral Cancer

SECTION VI TEETH AND PERIODONTIUM Chapter 15

Dental Caries, Pulp and Periapical Lesions

405

Definition and Etiology • Contributory Factors in Dental Caries • Classification of Dental Caries • Microbiology of Dental Caries • Fascial Space Infection • Ludwig’s Angina • Osteomyelitis Chapter 16

Gingival and Periodontal Diseases

440

Classification System in Periodontal Disease • Gingival Diseases • Host–Microbial Interaction • Periodontal Diseases • Syndromes • Sex Hormones • Stress and Psychosomatic Factors • Nutritional Factors • Radiographic Evaluation of Periodontal Diseases Chapter 17

Regressive Alterations of Teeth

458

Classification of Regressive Alterations Affecting Teeth • Tooth Surface Loss • Attrition • Abrasion • Erosion (Corrosion) • Abfraction • Classification of Tooth Wear • Resorption of Teeth

SECTION VII Chapter 18

SYSTEM REVIEW Systemic Disorders and their Clinical Implications

473

Symptoms Suggestive of Cardiovascular Disease • Common Cardiovascular Disorders and their Dental Considerations • Ischemic or Coronary Heart Disease • Myocardial Infarction • Congenital Heart Disease • Rheumatic Fever • Infective (Bacterial) Endocarditis • Heart Failure • Red Blood Cell Disorders • Polycythemia • Anemia • Thalassemia • White Blood Cell Disorders • Qualitative Disorders • Non-neoplastic Disorders • Neoplastic Disorders • Bleeding Disorders • Vascular Disorders (Vessel Wall) • Platelet Disorders • Thrombocytopathic Disorders • Thrombocytopenic Disorders • Disorders of Coagulation • Inherited Coagulation Disorders • Acquired Coagulation Disorders • Upper Respiratory Tract Infections • Lower Respiratory Tract Infections • Granulomatous Diseases • Malignant Disorders • Other Respiratory Diseases Renal Diseases • Gastroesophageal Reflux Disease • Inflammatory Bowel Disease • Ulcerative Colitis • Crohn’s Disease • Hiatal Hernia • Peptic Ulcer Disease • Eating Disorders • Liver Diseases • Bell’s Palsy • Epilepsy • Parkinsonism • Multiple Sclerosis • Muscular Dystrophy • Oromandibular Dystonia • Myasthenia Gravis • Growth Hormone • Thyroid Gland • Parathyroid Glands • Hypothalamus–Pituitary–Adrenal Axis • Pregnancy • Saliva and Monitoring of Hormone Levels • Interesting Interface between ‘Dentistry’ and ‘Psychiatry’ • Management of Psychiatric Disorders Chapter 19

Bone Diseases and Fibro-osseous Lesions

568

Fibro-osseous Lesions • Bone Diseases Chapter 20

Autoimmune Disorders

590

Concepts of Immunity and Autoimmunity • Pemphigus • Epidermolysis Bullosa Acquisita • Systemic Lupus Erythematosus • Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy • Diabetes Mellitus Type I (IDDM) • Systemic Sclerosis • Myasthenia Gravis Chapter 21

Granulomatous Diseases

605

Tuberculosis • Leprosy (Hansen’s Disease) • Syphilis • Deep Fungal Infections • Foreign Body Granulomas • Wegener’s Granulomatosis • Sarcoidosis • Orofacial Granulomatosis • Crohn’s Disease (Regional Ileitis, Regional Enteritis) Chapter 22

Sexually Transmitted Diseases

625

Fellatio Syndrome • Traumatic Lesions of Lingual Frenum • Syphilis or Lues • Human Immunodeficiency Virus Infection • Intraoral Molluscum Contagiosum • Condyloma Acuminatum • Oropharyngeal Gonorrhea • Oropharyngeal Chlamydial Infection • Oropharyngeal Trichomonal Infection Chapter 23

Nutritional and Metabolic Disorders

633

Nutritional Requirements of Indians • Carbohydrates • Proteins • Lipids • Vitamins • Metabolic Disorders • Lipid Reticuloendothelioses xxiii

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Contents

SECTION VIII Chapter 24

FORENSIC DENTISTRY

Clinical and Radiological Perspective

653

Introduction, History and Relevance • Dental Identification • Challenges in Postmortem Examination • Postmortem Alterations to the Teeth and Oral Tissues • Social Profiling • Identifying the Edentulous • Craniofacial Identification • Facial Approximation • Age Estimation Methods • Bite Mark Procedures • Lip Print Investigation

Part II—Oral Radiology SECTION IX BASICS OF RADIOLOGY Chapter 25

Basics of Radiation Physics

685

Pioneers in Dental Radiology • Fundamentals of Radiation Physics • Intraoral X-Ray Units • Interaction of X-Rays with Matter Chapter 26

Radiation Biology

697

Effects on Living Systems • Molecular and Cellular Radiobiology • Deterministic and Stochastic Effects • Sources of Radiation • Dose and Risk in Radiography • Radiation Detection and Measurement • Film Exposure and Processing

SECTION X

RADIOGRAPHIC METHODOLOGY

Chapter 27

Radiographic Films and Accessories

719

Intraoral Films • Extraoral Films Chapter 28

Radiographic Techniques

724

Conventional Imaging • Intraoral Radiography • Extraoral Radiography • Posteroanterior Projection • Standard Occipitomental view • 30ⴗ Occipitomental • Parietoacanthial View (Waters’ View) • Parietoacanthial View (Open Mouth Waters’ View) • Modified Parietoacanthial Projection (Modified Waters’ View) • Acanthoparietal Projection (Reverse Waters’ Method) • Submentovertex View (Base or Full Axial Projection, Schuller Method) • Lateral View • Lateral Cephalometry • AP Axial Projection (Townes’ Method) • Reverse Townes’ View • Lateral Oblique View • TMJ Radiography • Transcranial View • Transpharyngeal View (Parma Projection, Macqueen-Dell Technique) • Transorbital View • Lesser Known/Forgotten Extraoral Radiographic Techniques • Panoramic Radiology • Specialized Imaging • Computed Tomography • Dentomaxillofacial Cone-Beam Computed Tomography • Magnetic Resonance Imaging • Nuclear Medicine • Ultrasonography • Sialography • Arthrography • Thermography (Thermal Imaging or Infrared Imaging)

SECTION XI PROCESSING OF RADIOGRAPHS AND RADIOGRAPHIC INTERPRETATION Chapter 29

Latent Image Formation

801

Formation of Latent Image Chapter 30

Processing of Radiographic Films

803

Manual Processing of Films • Automatic Processing Chapter 31

Radiographic Faults

812

Errors in Film Storage and Handling • Errors in Film Placement and Projection Technique • Errors in Exposure Parameters and Processing Technique • Artifacts

SECTION XII Chapter 32

RADIOGRAPHIC LANDMARKS Intraoral Radiographic Anatomical Landmarks

825

Landmarks Common to both the Maxillary and Mandibular Radiographs • Landmarks Unique to the Maxillary Intraoral Periapical Radiograph • Landmarks Unique to the Mandibular Intraoral Periapical Radiograph Chapter 33

Extraoral Radiographic Landmarks

837

Chapter 34

Site Selection, Evaluation and Imaging for Dental Implants

842

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Contents

SECTION XIII

APPENDICES

Appendix 1

Terminologies

861

Appendix 2

Summary of Radiographic Pathology

867

Appendix 3

Characteristics of Ideal Radiograph

871

Appendix 4

Indications for Intraoral Radiography

872

Appendix 5

Patient Position for Extraoral Radiography

873

References

879

Index

885

Contents on Website (http://www.manthan.info) I. A B C of Drugs Used in Dentistry

e1

II. Syndromes of the Head and Neck

e23

III. Laboratory Diagnostic Procedures

e78

IV. Halitosis

e147

V. Occupational Hazards in Dentistry

e154

References

e236

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PART

I

Oral Medicine and Oral Diagnosis

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SECTION

I

Introduction and Approach to Diagnosis

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CHAPTER

Carol Stewart, Madhu K Nair, Syed Vaseemuddin, Ravikiran Ongole

➧ History of Oral Medicine

➧

Mission Training and Scope of Practice Future ➧

1

Oral Medicine and Radiology in India Course and Curriculum of Oral Medicine and Radiology Undergraduate Student Competencies as per Dental Council of India Regulations Scope of Oral Medicine and Radiology in India

Oral and Maxillofacial Radiology

HISTORY OF ORAL MEDICINE Carol Stewart In the British literature, Sir Jonathan Hutchinson (1828– 1900), a surgeon at the London Hospital, is regarded as the Father of Oral Medicine. He described dental manifestations of congenital syphilis, intraoral pigmentation and perioral pigmentation associated with intestinal polyposis, later described by Peutz and Jegher. Much of the early description of oral mucosal diseases was found in dermatology textbooks, as documented in the works of Dr Erasmus Wilson. Sir William Osler recognized the importance of the oral cavity and believed that the tongue and oral mucosa acted as mirrors reflecting the state of health of a patient. He studied medicine at McGill University and in 1884, moved to Philadelphia and became the Chair of Clinical Medicine at the University of Pennsylvania. Ultimately, he became the Chief of Staff at Johns Hopkins University and Hospital. The early influence of Dr Kurt Thoma is internationally recognized as well. Dr Thoma was a Swiss-born oral surgeon who produced significant textbooks in the 1920s and 1930s on oral surgery and oral pathology. His work promoted these disciplines, oral diagnosis, oral medicine and oral pathology, to have greater prominence in dental schools. The study of oral medicine in the United States has a unique history among medical/dental specialties. In the United States, the roots of considering oral medicine as a distinct area of study began with Dr William Gies of Columbia University. Dr Gies, a professor of biological chemistry, became interested in dental research. In 1926, the Carnegie Foundation sponsored Dr Gies’ work entitled

‘Report on Dental Education in the United States and Canada’. He believed that dental students’ education should be more similar to that of medical students. He stressed the importance of biomedical sciences and research in the dental school curriculum. His report suggested that oral medicine be included in a dental curriculum. Another pioneer of great intellect and vision was Dr Lester Burket, professor of Oral Medicine at Pennsylvania School of Dental Medicine. He also promoted the integration of medicine into dental education and the role of oral health in reflecting systemic health. He is considered by many as the Father of Oral Medicine and published one of the first definitive textbooks devoted to oral medicine in 1946. The American Academy of Oral Medicine (AAOM) was organized in 1945 as the American Academy of Dental Medicine, and its founder was Samuel Charles Miller, Professor and Chairman of the Department of Periodontics at New York University College of Dentistry. In 1966, the name was changed to the American Academy of Oral Medicine. The academy was founded to broaden understanding and knowledge of oral disease and to integrate dentistry with medicine to provide more complete patient care. The memberships include an internationally recognized group of professionals.

Mission The mission of the AAOM is stated in Box 1. The AAOM is the heart and pulse of oral medicine in the United States and is also internationally recognized through the excellent educational training programs and scientific symposia hosted, and the educational literature and treatment guidelines published for medically complex patients. 5

Section I – Introduction and Approach to Diagnosis

Box 1

Mission of the American Academy of Oral Medicine

• To foster excellence in education, research and patient care in the field of oral medicine • To promote the study and dissemination of knowledge regarding the medical aspects of dentistry while serving the best interests of the public • To promote the highest standard of care in the diagnosis and treatment of oral conditions that are not responsive to conventional dental, oral or maxillofacial surgical procedures • To provide an avenue of referral for dental practitioners who have patients with severe, life-threatening medical disorders or complex diagnostic problems involving the oral and maxillofacial region that require ongoing non-surgical management • To improve the quality of life in patients with medically-related oral disease • To foster increased understanding and cooperation between the medical and dental professions

and sexually transmitted diseases as well. Skills mastered include completion of a comprehensive physical evaluation and medical risk assessment, selection of appropriate diagnostic and laboratory procedures including blood studies, cytology, culture, biopsy techniques, and delivery of appropriate care and assessment of treatment outcomes. Critical to completing an oral medicine curriculum is the acquisition of skills necessary to communicate effectively with patients regarding the nature, rationale, advantages, disadvantages, risks and benefits of a recommended treatment. American Academy of Oral Medicine is a sponsor of the American Board of Oral Medicine, the body responsible for examining and certifying candidates who have received approved post doctoral training. The board examination is offered during September/October each year.

Future Healthy collaborations have been developed between AAOM and the European Academy of Oral Medicine (EAOM). EAOM was founded in 1998 based on representation from European countries including Austria, Croatia, Denmark, England, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Israel, Italy, Latvia, Netherlands, Norway, Portugal, Romania, Scotland, Serbia, Slovenia, Spain and Sweden.

Training and Scope of Practice As defined on the website of the AAOM, oral medicine is the specialty of dentistry concerned with the oral healthcare of medically complex patients and the diagnosis and non-surgical management of medically related disorders or conditions affecting the oral and maxillofacial regions. These conditions include oral mucosal diseases, oral manifestations of systemic conditions and oral sequelae of medical treatments. In addition, practitioners have special expertise in the management of neuropathic pain conditions involving the head and neck area and in pharmacotherapy and drug interactions. Currently, 10 certified 2-year programs are thriving throughout the United States and Canada. The curriculum consists of clinical sciences, biomedical sciences and clinical care interacting with all medical specialties. The material presented in the biomedical sciences provides the scientific basis needed to understand and carry out the diagnostic and therapeutic skills required by the clinical, academic and research aspects of oral medicine. A distinct curriculum in internal medicine allows the oral medicine specialist to gain unique expertise in the management of patients with endocrine, neuromuscular, hematopoietic, immune and autoimmune, mucocutaneous, cardiovascular, renal, respiratory, musculoskeletal, gastrointestinal 6

Future research will move further into genetics and proteomics to define etiopathogenesis of these complex diseases as well as find targeted treatment approaches. The potential for using saliva as a diagnostic tool is growing as well. As the life span of patients continues to lengthen due to polypharmacy, advancement in diagnostic technologies and treatment strategies, the demand for the oral medicine specialist, both as a primary provider and consultant, will grow exponentially. Medicine and dentistry are coming closer together as they gain an appreciation of what each can provide to enhance patient care. The quality of patient care will continue to improve in parallel with these synergistic interactions.

ORAL AND MAXILLOFACIAL RADIOLOGY Madhu K Nair Oral and Maxillofacial Radiology is the newest dental specialty recognized by the American Dental Association. The prospects of this discipline are excellent, especially in light of the increased use of advanced imaging techniques in dentistry. Two-dimensional imaging that was used in clinical dentistry is being replaced by newer image acquisition modalities that can generate information in 3D. Digital radiography is fast replacing film-based imaging, bringing with it numerous advantages. These include among others, the ability to reduce doses (in comparison with older generation films and the use of round collimation), faster image generation, the capability to post-process images based on the diagnostic task and also carry out specific image processing to enhance the signal-to-noise ratio, as well as the ability to archive, transmit and retrieve images using dedicated Picture Archiving and Communications System (PACS).

Chapter 1 – History and Scope of Oral Medicine and Oral Radiology

In addition, the introduction and increased use of advanced imaging modalities such as cone beam volumetric computed tomography (CBVCT) and MRI in dentistry has resulted in the need for these images to be interpreted by a board certified maxillofacial radiologists to rule out the presence of other incidental pathology, and patients referred for specialized techniques including contrast imaging or functional studies in selected cases. Integration of services with Neuroradiology/Head and Neck Imaging at hospitals is thus essential for ensuring optimal patient care. Most medical radiologists are not trained in the interpretation of oral and maxillofacial pathology, anatomic variations or anomalies and treatment modalities in dentistry to the extent a maxillofacial radiologist is. The maxillofacial radiologist understands the diagnostic needs of the dental patient both from a dental and general maxillofacial perspective and can cater to the needs of the dental community more efficiently based on a specific diagnostic task. Most specialty areas within dentistry including Oral and Maxillofacial Surgery, Orthodontics, Periodontics, Prosthodontics, Pedodontics, Endodontics, etc. use advanced imaging for a variety of diagnostic tasks and treatment planning, as also for follow-up evaluations. Some instances include trauma, facial and other developmental anomalies such as isolated clefts or defects, syndromes, obstructive sleep apnea, temporomandibular joint disorders, implant surgery, localization of impacted teeth and root canals, image-guided surgical applications, and orthodontic evaluation and treatment planning. When an advanced imaging study is done, it is expected that the entire volume of data is interpreted to prevent any incidental pathology from being missed. Some examples include life-threatening arteriovenous or lymphovenous malformations, malignancies, aggressive benign tumors, intracranial lesions and cystic lesions of jaws in patients imaged for dental purposes. The future of Oral and Maxillofacial Radiology is bright. Medical radiology went through the same phases of evolution in the 1990s as many hospitals transitioned to a filmless, paper-less environment and improved their workflow by incorporating digital imaging and PACS on an enterprisewide basis. Currently, radiology is one of the highly ranked and fiercely competitive residencies in medicine. The evolution of radiology informatics as a separate discipline within radiology indicates the significance of information technology resources and computer applications in the continued development and growth of radiology. Oral and maxillofacial radiology is headed down the same path. Medical radiology textbooks acknowledge the fact that interpretation of oral and maxillofacial pathology on the need for maxillofacial radiologists in optimizing patient care. Currently, several post-doctoral and residency programs exist in the United States and Canada for dental students to specialize in the discipline (http://www.aaomr. org/adv_edu_prog.php). The American Board of Oral and Maxillofacial Radiology grants Diplomate status to residents

once they successfully challenge a very rigorous written and oral examination lasting several days, upon completion of an accredited oral and maxillofacial radiology residency/ graduate program (http://www.aaomr.org/abomr_contact. php). The Board comprises a Board of Directors elected by the Diplomates.

ORAL MEDICINE AND RADIOLOGY IN INDIA Syed Vaseemuddin, Ravikiran Ongole Oral Medicine was introduced in the curriculum and syllabus of the Bachelor of Dental Surgery (BDS) course in India about 37 years ago. The Government Dental College, Bangalore affiliated to Bangalore University was the first dental school in India to teach Oral Medicine. Dental radiology was only a minor subject being merged with subjects like Conservative Dentistry, Periodontia and Oral Surgery. However, its importance was appreciated in the late 1950s and Master of Dental Surgery (MDS) in radiology, a 2-year program, was introduced by Bombay University in 1959. However, oral medicine was still not included in the BDS curriculum. Under the expert guidance of WHO advisors, ‘Oral Medicine, Diagnosis and Radiology’ was introduced as a separate subject by Bangalore University in 1966. It was taught during the third and final year BDS course in Government Dental College, Bangalore. However, without qualified and trained teachers in this specialty, the training of BDS students remained inadequate. Government Dental College, Bangalore was the first institute to start MDS course with 2-year duration in ‘Oral Medicine, Diagnosis and Radiology’ in 1970. As a part of the training program the first orthopantomograph X-ray unit, the first in India was installed and commissioned in Government Dental College in 1970—a gift from the WHO. The subject was introduced in the southern universities in both BDS and MDS courses a few years later. Bombay University followed, changing the MDS course in Dental Radiology to MDS course in Oral Medicine, Diagnosis and Radiology in the 1970s. The growth and development of the subject oral medicine would have remained incomplete without an organization for the specialists to meet, discuss and propagate the acquired knowledge. Hence, the specialists mostly of Karnataka and a few from Andhra Pradesh and Tamil Nadu met on 20th June 1985 in Bangalore and unanimously resolved to form an organization called Indian Academy of Oral Medicine. Dr BK Venkataraman and Dr Ramachandra Reddy were the founder members of this academy. The society was registered under Karnataka Societies Registration Act of 1960 at Bangalore. During the fifth national conference in Chennai, the Academy was renamed as Indian Academy of Oral Medicine and Radiology. 7

Section I – Introduction and Approach to Diagnosis

The Indian Academy of Oral Medicine and Radiology, launched its official publication Journal of Indian Academy of Oral Medicine and Radiology in the year 1986. Presently, the Academy has 800 members.

Course and Curriculum of Oral Medicine and Radiology In India, the specialty of Oral Medicine, Diagnosis and Radiology is taught to undergraduate students in the third and final year of the BDS program. Following the BDS degree a student can pursue a 3-year program in the specialty that leads to an MDS degree in Oral Medicine, Diagnosis and Radiology. Admission to the MDS program is gained through competitive exams. The syllabus in Oral Medicine and Radiology is divided into Diagnosis, Diagnostic Methods, Oral Medicine and Oral Radiology.

Undergraduate Student Competencies as per Dental Council of India Regulations The student should be able to recognize various diseases affecting the oral and paraoral structures and identify precancerous and cancerous lesions of the oral cavity and refer the patient to the concerned specialist for necessary management. They should have adequate knowledge about common laboratory investigations and interpretations of their results. The student should have adequate knowledge about medical complications that can arise while treating systemically compromised patients and take prior precautions/ consent from the concerned medical specialist. He or she should have adequate knowledge about radiation health hazards, radiation safety and protection. Students should be competent to take intraoral radiographs and interpret the radiographic findings. They should gain adequate knowledge of various extraoral radiographic procedures, TMJ radiography and sialography. The student should be aware of the importance of intra- and extraoral radiographs in forensic identification and age estimation. They should be familiar with jurisprudence, ethics and understand the significance of dental records with respect to law.

8

Scope and Future of Oral Medicine and Radiology in India Oral Medicine and Radiology specialists in India are usually full-time academicians in teaching hospitals. Some of the specialists engage in specialty practice that includes diagnosing orofacial diseases, recognizing the oral manifestations of systemic diseases and assessing oral health of medically compromised patients and medically managing these patients. Oral medicine specialists can further pursue a PhD in the area of their interest as a part-time program or a full-time program. In spite of remarkable progress made by the subject of Oral Medicine and Radiology during the last two decades many teachers and clinicians feel that there is plenty of scope for improvement in teaching methodology and research. Presently across all dental schools in India, the Department of Oral Medicine and Radiology functions more like a source of patient referral to various dental specialties rather than a specialty in itself. Following the registration formalities, patients are sent to the Oral Medicine Department, wherein patients are interviewed, examined, diagnosed and referred to various specialties for the necessary treatment. The authors instead feel that the patients should be directed from the reception/registration counter to the necessary department based on the patient’s need. Those specialties in turn can refer patients for an expert opinion and further management of specific problems such as orofacial pain, temporomandibular disorders, oral precancers and cancers, salivary gland disorders, cysts and tumors of the head and neck and syndromes or patients with various underlying systemic illnesses that may require modifications in the treatment plan and maxillofacial imaging. Another area that needs a lot of improvement is oral and maxillofacial radiology. Although radiology is an integral part of the course and curriculum of both the undergraduate and postgraduate training in oral medicine and radiology, it is mainly confined to extensive training in conventional radiographic techniques. Though specialized imaging techniques such as computed tomography, magnetic resonance imaging, ultrasonography, sialography and arthrography are theoretically taught, the practical exposure to the technique and interpretation is far from adequate.

SECTION

II

Oral and Maxillofacial Disturbances

2 3 4 5

Developmental Disturbances Orofacial Pigmentation Disorders Bacterial, Viral and Fungal Infections Orofacial Pain

11 61 82 111

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Developmental Disturbances

CHAPTER

Sadhana Shenoy, Karen Boaz, Sara Carolina Rodriguez Peña, Francisco Lopez Sanchez, Ravikiran Ongole

NORMAL ANATOMIC VARIATIONS

Lingual Varices Lingual Thyroid

➧

Fordyce’s Granules

➧

Lingual Tonsils

➧

Fissured Tongue

➧

Leukoedema

➧

Retrocuspid Papillae

➧

Prominent Palatal Rugae

➧

Lingual Varices

➧

Circumvallate Papillae

➧

Parotid Papilla

➧

Physiological Pigmentation

Hard Tissue Disturbances (Jaws)

➧

Hairy Tongue

➧

➧

Exostoses/Tori

➧

➧

Developmental Disorders of the Jaws Agnathia, Micrognathia, Macrognathia Hemifacial Hyperplasia, Atrophy Condylar Aplasia, Hypoplasia, Hyperplasia Bifid/Trifid Condyle Coronoid Hyperplasia Exostoses, Tori

Developmental Disorders Affecting Tongue

Identification of normal anatomical structures forms the basis for diagnosis. The skill and knowledge to differentiate normal from abnormal plays a decisive role in effective management of the disease process. It is a known fact that normal anatomic structures can have various clinical presentations within the same species. However, one should realize that even the slightest of change in the appearance of the structure of organs and tissues makes the recognition of pathological conditions challenging. On the other hand, normal oral anatomic structures can induce cancerophobia in many individuals. These individuals have to be educated regarding the absolutely benign nature of these anatomical variations.

Developmental Disorders Affecting Buccal Mucosa and Gingiva Oral Melanotic Macule Fordyce’s Granules Fibromatosis Gingivae

Soft Tissue Disturbances Aglossia Microglossia/Hypoglossia Macroglossia Ankyloglossia Cleft Tongue Fissured Tongue Geographic Tongue

Developmental Disorders Affecting the Lip Paramedian Lip Pits/Commissural Pits Double Lip Cleft Lip and Palate

DEVELOPMENTAL DISTURBANCES ➧

2

➧

Developmental Disorders of the Teeth Disturbances Affecting Size of Teeth Disturbances Affecting Shape of the Teeth Disturbances Affecting Number of Teeth Disturbances Affecting Eruption of Teeth Disturbances Affecting Structure of Teeth

FORDYCE’S GRANULES (Fordyce’s Spots/Disease) Fordyce’s granules are named after an American dermatologist, John Addison Fordyce. This is an ectopic/heterotopic collection of sebaceous glands seen in more than 80% of the normal population. They are considered ectopic because sebaceous glands are typically appendages of the skin. When they are present in the oral mucosa they seldom have hair follicles. This condition is characterized by the presence of multiple discrete minute yellow colored ‘dots’, ‘spots’ or ‘granules’ involving various sites in the oral cavity such as 11

Section II – Oral and Maxillofacial Disturbances

Figure 1

Figure 2

Duct opening into epithelium

Sebaceous glands

Multiple yellowish ‘dots’ on the buccal mucosa suggestive of Fordyce’s granules. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

the buccal mucosa (opposite the molar teeth), lips, oral commissures, retromolar pad, faucial pillars and the palate (Figure 1). Some authors have described the appearance as ‘rice-like’, white or yellow white papules. The sebum produced by these sebaceous glands imparts the yellow color to these spots. Each of these granules can vary in size from 1 to 3 mm. The condition is asymptomatic and usually prominent in adults and generally persist throughout life. Histopathologically acinar lobules are seen below the surface epithelium. These acinar lobules usually communicate with the epithelial surface via a central duct (Figure 2). The ducts may show keratin plugging. The sebaceous cells are roughly polygonal in shape with a central nucleus. The cells contain copious amounts of foamy cytoplasm. Unless these granules are esthetically disturbing in an individual, no surgical intervention is recommended. Patient should be educated regarding the harmless and persistent nature of the condition. Ocampo-Candiani et al (2003) showed that CO2 superpulsed laser can be used as an effective treatment modality for patients who desire treatment for cosmetic reasons. Sebaceous gland adenoma may occur at times.

LINGUAL TONSILS Lingual tonsils are the lymphoid aggregates present in the oral cavity that are part of the Waldeyer’s ring. It can occur unilaterally or bilaterally on the posterolateral border of the base of the tongue. Lymphoid follicles of the lingual tonsil are irregular in shape and size and vary in number from 30 to 100. 12

The acinar lobules of the sebaceous glands below the epithelium with a central duct opening into the epithelium. Courtesy: Department of Oral Pathology, MCODS, Mangalore

Anatomically, the arterial supply to the lingual tonsils is via the lingual branches of the external carotid arteries. The venous drainage is through the lingual vein that finally empties into the internal jugular vein. The lingual tonsils are mainly innervated by the lingual branch of the glossopharyngeal nerve and to some extent from the superior laryngeal branch of the vagus nerve. Lymphatic vessels of the lingual tonsil drain into the superior deep cervical or jugular lymph nodes. The lingual tonsil is generally not evident on routine clinical examination. It may appear as solitary pink colored papule or nodule with a glossy yellowish-pink surface. However, it becomes clinically evident when inflamed and enlarged. Persistent inflammation of these tonsils has also been referred to as lingual tonsillitis. Lingual tonsillitis which is a painful condition characterized by the symptoms of sore throat and cough. The tonsils are erythematous and spongy or soft on palpation, mimicking lesions of erythroplakia or oral cancer. However, the bilateral presence of these nodules will help in differentiating it from carcinoma. Lingual tonsils do not require any active management. The patient should be reassured and told to report any change in size or presence of symptoms. Lingual tonsillitis can be managed with antibiotics. Extensive enlargement of the lymphoid aggregates can impede intubation. Histopathological evaluation is advised when the lymphoid aggregate enlarges rapidly in size or exhibits surface ulceration.

Chapter 2 – Developmental Disturbances

Figure 3 A

B

(A) Fissured tongue with central median groove. (B) Fissured tongue with multiple grooves in irregular fashion. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Fissured Tongue

Management

Fissured tongue has been described by various names in literature such as scrotal tongue or lingua scrotalis, lingua plicata, lingua fissurata, cerebriform tongue and furrowed tongue. The tongue in this relatively common malformation exhibits multiple grooves or furrows of 2–6 mm depth and varied pattern on the dorsal surface. Heredity, aging, chronic trauma and vitamin deficiency have been proposed as the causes for this condition. The exact etiology for this condition is still unknown. However, a polygenic mode of inheritance is suspected because it is seen clustering in families who are affected. Based on the geographic location and population studies, the prevalence of fissured tongue ranges from about 2% to 21%. Males are said to be slightly more predisposed to exhibiting this condition. The fissures are seen on the dorsal surface of the tongue sometimes extending to the lateral margins. The fissures can have various morphological patterns; a single prominent groove in the midline of the tongue, multiple horizontal groves radiating from the median groove and multiple grooves in an irregular fashion (Figure 3A, B). The tongue fissures can be seen in childhood. However, the fissures are usually prominent with advancing age. Fissured tongue is usually associated with other conditions such as geographic tongue (see Figure 21), Melkersson– Rosenthal syndrome and Down syndrome. The condition is generally asymptomatic. However, the deep fissures provide an excellent site for lodgment of food debris and candidal colonization. These patients may complain of burning sensation in the tongue.

Patients should be counseled regarding the benign nature of the condition. They should be motivated to follow optimum oral hygiene practices. They can be encouraged to use a soft bristled toothbrush to cleanse the grooves of food debris. In symptomatic patients, topical application of clotrimazole is recommended.

LEUKOEDEMA Leukoedema is a common alteration of the oral mucosa, which appears as a diffuse grayish white opalescent area on the oral mucosa. It is believed that the intercellular edema of the superficial epithelial cells and the parakeratinized epithelium produces the typical grayish white appearance in this condition. Axell et al (1981) studied the influence of tobacco habits and leukoedema among 20,333 individuals in Sweden. In his study 48.9% of the individuals exhibited leukoedema. Males were more commonly affected. Leukoedema was more commonly found in the second and third decades of life. The condition was significantly more prevalent in individuals with any form of tobacco habit (60%) and relatively less common in individuals without any tobacco habit (36.3%). Van Wyk (1985) studied the association between leukoedema and smoking. He examined 1996 high school students. He concluded that smoking does not cause leukoedema but may aggravate it. He also suggested that the etiology for leukoedema is multifactorial. 13


Clinical features Leukoedema presents as an asymptomatic, grayish white diffuse opalescent region on the buccal mucosa and occasionally extending into the vestibule, floor of the mouth and soft palate. The surface appears spongy and usually comprises folds or grooves. It has been shown that it is more common in blacks (almost 90%) compared to whites (Figure 4). Clinically, this condition can be differentiated from other white lesions occurring in the oral cavity by stretching the mucosa. Grayish white areas of leukoedema usually disappear at least partially on stretching. Some authors call this technique the ‘stretch test’. Histopathology and ultrastructural features Histopathological studies reveal increased epithelial thickness. Parakeratinized epithelium with broad and elongated rete pegs are typically seen. Intracellular edema within the spinous layer is a characteristic feature in leukoedema. The edematous/vacuolated cells are large with a pyknotic nuclei. Histopathologically it is believed to mimic lesions of white sponge nevus. Van Wyk and Ambrosio (1983) studied the ultrastructural and histochemical features of leukoedema in 12 individuals and compared it with normal buccal mucosa. They concluded that the ‘intracellular edema’ of the epithelial cells in leukoedema is due to vacuolation in the cytoplasm of cells. Toward the surface of the epithelium, the vacuolated cells collapsed into a compact layer of flattened cells. The outer cells of this layer abruptly swelled again to form the characteristic superficial layer of ‘ballooning’ cells of leukoedema.

Figure 4

Opalescent grayish white hue on the buccal mucosa characteristic of leukoedema. Courtesy: Dr Ajit Auluck

14

They proposed that the vacuolation in the cell cytoplasm represents a reversible form of cellular degeneration resulting from cell damage. They believed that the vacuolation was caused because of reduced mitochondrial function. The superficial ‘ballooning’ cells are degenerated cells. They stated that the presence of a compact layer of vacuolated cells, keratohyalin granules and keratohyalinlike structures in the superficial cells are features of an aborted form of keratinization. Treatment No active treatment is necessary as it is considered as a variation in the normal anatomy of the oral cavity. However, it is believed that the condition becomes less prominent with the cessation of tobacco habit.

RETROCUSPID PAPILLAE The retrocuspid papilla is a normal variation in anatomy characterized by the presence of pink colored, soft to firm, generally sessile papule or nodule (Figure 5), located on the gingiva on the lingual surface of the mandibular canines (cuspid). The size of the nodule may vary in size from 1 to 5 mm in diameter. It is very commonly seen in children and believed to regress with age. D’Aoust et al (1991) studied the distribution of retrocuspid papillae among three groups (Ecuador, Honduras and Nicaragua) of Latin American patients. He found that the retrocuspid papilla was most prevalent in children below the age of 5 years. He also found a significantly higher female

Figure 5

Retrocuspid papilla. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore


predilection in the Honduras group of Latin Americans and unilateral presentation was more common. Bilateral presence of retrocuspid papillae was seen in the Nicaragua group. Retrocuspid papilla was seen involving the attached gingiva more frequently than the free marginal gingiva. Brannon et al (2003) also showed that retrocuspid papillae are common in females and young children. In the 51 cases that were evaluated, bilateral retrocuspid papillae was more common. Histological features Buchner et al (1990), histopathologically analyzed 30 specimens of retrocuspid papillae. They showed that almost 80% of the specimens showed loosely arranged delicate fibrous connective tissue with stellate and multinucleated fibroblasts. They also showed that significant number of specimens exhibited elongated rete ridges and/or increased vascularity. These papillae do not require any form of treatment. The need for treatment may arise only during the fabrication of prosthetic appliances.

PROMINENT PALATAL RUGAE Palatal rugae have also been referred to as rugae palatinae and plicae palatinae transversae. The word ruga (plural: rugae) is a Latin word meaning ridge, wrinkle or fold. For descriptive purposes palatine rugae are anatomical ridges, folds or wrinkles in the anterior part of the palatal mucosa. The rugae are present on either side of the median palatal raphe behind the incisive papilla. Approximately four to seven rugae are seen on either side of the midpalatine raphe (Figure 6). Based on the shape of the rugae they have been categorized as curved, wavy, straight and circular. Individual studies have shown that males generally have slightly Figure 6

more number of palatine rugae and the left side of the palate shows slightly more number of rugae in both males and females. No bilateral symmetry is seen in the number of rugae. As age advances, the length of the rugae and the transverse palatal rugal region width increases. Luke (1988) studied the development of palatal rugae in mice. He showed that the rugae develop as localized regions of epithelial proliferation and thickening prior to the elevation of the palatal shelves. Later on, the fibroblasts and collagen fibers accumulate within the connective tissue beneath the thickened epithelium and then assume a characteristic orientation. The direction of the collagen fibers running across the base of the palatine rugae determines their orientation. In the human embryos the palatal rugae are usually prominent and present throughout the length of the palatal shelves at the time of their elevation. At about the 550 mm stage of the embryo there are about five to seven symmetrical ridges. The anterior ridges originate at the midpalatine raphe. Other ridges are seen laterally. However, toward the end of the intrauterine life, the posterior ridges almost disappear completely and the anterior ridges become compressed and prominent. It is believed that the role of rugae in humans is more or less vestigial. However, in animals palatine rugae help in suckling and feeding.

Classification of Palatine Rugae Based on Length Kapali et al (1997) in their study to evaluate the palatal rugae patterns in Australian Aborigines and Caucasians used the following clinical classification: 1. 2. 3.

Primary rugae: (A—5 to 10 mm; B—10 mm or more) Secondary rugae: 3 to 5 mm Fragmentary rugae: Less than 3 mm.

On histological examination palatine rugae are stratified squamous (predominantly parakeratinized) epithelium on a connective tissue base, which is similar to the adjacent palatal tissue. Palatal rugae pattern analysis has been employed successfully in positive human identification. Coslet et al (1980) reported that the palatal rugae returned back in several months after its surgical removal. Many studies have shown that although minor changes in the morphology of the rugae occur due to orthodontic tooth movement, extractions, aging and palatal expansion, these do not significantly alter the rugal morphology enough to hamper identification.

Lingual Varices Palatal rugae. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Lingual varices are characterized by the presence of tortuous dilated veins on the ventral surface of the tongue. It is estimated that approximately 10% of the patients in the 15


4th decade and above exhibit lingual varicosities and the extent of the varicosities increases with advancing age. Lingual varices have been referred to by various other names in literature such as phlebectasia linguae, caviar lesions and linguae varicosities.

Figure 7

Etiopathogenesis Various theories have been proposed to explain the occurrence of these varices. Ettinger et al (1974) showed that the incidence of varicosities increases with age. Koscard et al (1970) reported that the elastic support to capillaries significantly diminishes with advancing age. This reduction in the elastic support of the connective tissue supporting the blood vessels leads to dilation of capillaries and formation of varicosities. It is also suggested that these are due to abnormally dilated and tortuous veins (varices), as they are not protected by surrounding tissues against hydrostatic pressure. Eddy et al (1977) studied the role of vitamin C in 22 elderly vegetarians. He showed that vegetarians had high levels of ascorbic acid values in plasma (10.2 ⫾ 0.4 mg/l), compared to other elderly individuals. He concluded that there was a lower incidence of sublingual petechiae and varicosities in the vegetarian group.

Sublingual varices. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Clinical features In this condition multiple, bluish-purple papular blebs are seen on the ventral and lateral borders of the tongue and occasionally seen on the lips and buccal mucosa. Ventral surface of tongue reveals the presence of tortuous and dilated veins (Figure 7). Susmita et al (2006) reported a case with palatal varicosities. These are usually seen in the elderly and are not symptomatic unless the varices are thrombosed. Jassar et al (2000) reported a symptomatic case of sublingual varices in a patient with portal hypertension secondary to liver cirrhosis.

Figure 8

Histopathologic features Microscopically, dilated veins are seen with little smooth muscle and elastic tissue. Thrombosis may be seen as concentric zones of platelets and erythrocytes (lines of Zahn). Older thrombi show dystrophic calcification and/or phleboliths. Management Treatment is usually unnecessary. Surgical treatment is indicated for cosmetic purposes or when there is thrombosis.

CIRCUMVALLATE PAPILLAE OR VALLATE PAPILLAE The word vallate is derived from the Latin word vallatus, which means walled. Hence circumvallate papillae do not 16

Mushroom-shaped circumvallate papillae. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

project out onto the surface of the tongue. They are surrounded by a marginal groove. Each of the papillae are attached to the tongue via their slender bases. Roughly eight to 12 large (3–5 mm in diameter) mushroom shaped papillae are arranged all along the V-shaped sulcus terminalis that divides the tongue into the body and base (Figure 8). However, occasionally they tend to grow in size when inflamed.


Figure 9

Figure 10 Keratinized stratified squamous epithelium Nonkeratinized epithelium Circular trench Taste bud Von Ebner gland

Circumvallate papillae. The picture reveals keratinized stratified squamous epithelium, circular trough, taste bud on the lateral surface of the papilla and von Ebner gland. Courtesy: Department of Oral Pathology, MCODS, Mangalore

Histologically, the surface of the vallate papillae exhibits secondary papillae that are covered by stratified squamous epithelium. The epithelium lining the lateral surface of the papillae shows numerous taste buds (Figure 9). The minute ducts of the von Ebner’s glands pours its serous secretions into the base of the circular depression (trough). It is believed that the secretions of the von Ebner’s glands is the primary source of salivary lipase and it also cleanses the trough so that the taste buds can respond to various stimuli instantaneously. Sbarbati et al (1999) suggest that the concept of von Ebner’s gland described as ancillary to the taste buds (washing the trough around the vallate papillae or in perireceptorial events) should be discarded. In their laboratory studies they have found that the von Ebner’s gland and the vallate papillae form a single functional unit. They suggest this unit be termed ‘circumvallate papilla/von Ebner’s gland (CP/VEG) complex’. They believe that the CP/VEG complex represented an important enzyme- and pheromoneproducing system composed of a sensitive (taste buds) and an effectory (VEG) branch linked by feedback mechanisms of control. They hypothesize that the taste buds located in the distal portion of the VEG ductal system can be considered similar to the chemoreceptor cells located in other parts of the digestive apparatus such as pancreatic and bile ducts. Hence, they concluded that the CP/VEG complex represented a rare example of chemoreceptor-secretory organ. Though, circumvallate papillae are usually not readily evident on the surface of the tongue, some patients tend to panic when they notice these mushroom-shaped papillae while brushing their teeth. Patients need to be educated about their normal presence.

A small nodule on the buccal mucosa corresponding to the first and second molars characteristic of the parotid papilla. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

PAROTID PAPILLA Stensen’s duct of the parotid salivary gland opens into the oral cavity in the buccal mucosa opposite to the maxillary first and second molars. In many instances the orifice is hardly noticeable. However in some individuals a small, triangular raised pink to red color papule or nodule is readily visible. This flap of tissue covering the orifice of the Stensen’s duct is called parotid papilla (Figure 10). Parotid papillae are usually seen bilaterally. As a result of their anatomic location adjacent to the occlusal plane, the parotid papillae are common sites for formation of traumatic ulcers.

RACIAL PIGMENTATION/PHYSIOLOGICAL PIGMENTATION Pigmentation of the oral mucosa can occur due to a wide variety of endogenous and exogenous agents. Most of these are due to five basic pigments, namely, melanin, melanoid, oxyhemoglobin, reduced hemoglobin and carotene. Physiologic oral pigmentations are genetically determined. Various stimuli, such as trauma, hormonal changes, medication and radiation may result in an increased production of melanin. An age-related increase of oral melanocytes has also been observed. In dark-skinned people, oral pigmentation increases, but there is no difference in the number of melanocytes between fair-skinned and dark-skinned individuals. 17


Figure 11

Figure 12

Physiologic black colored pigmentation of the gingiva. Courtesy: Dr Ajit Auluck Physiologic black pigmentation of the dorsum of the tongue. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

The variation is related to the differences in the activity of melanocytes. Clinical features Physiologic pigmentation, which is common in African, Asian and Mediterranean populations is probably to the greater melanocyte activity. Oral physiological pigmentation is present in all races and seen equally in males and females. The pigmentation develops during the first decade of life but the patient may not be aware of it. The color depends on the amount of melanin produced and the site where it is deposited, which may vary from brown to black. It is clinically manifested as multifocal or diffuse melanin pigmentation. The attached gingiva is the most common intraoral site of such pigmentation (Figure 11), where it appears as a bilateral, well-demarcated, ribbon-like, dark brown band that usually spares the marginal gingiva. Other sites of involvement are the tongue (Figure 12), lips, buccal and labial mucosa and perioral skin. Pathophyisology The pigmentation of the skin depends on the natural pigment produced in the body called melanin. Melanin is formed by melanocytes, which are located at the stratum basale of the epidermis. Head and neck region is the first site of the body where melanocytes appear after approximately 10 weeks of gestation. These melanocytes produce melanin from tyrosine by the action of tyrosinase. The melanin that is formed is transported in the form of melanosomes to keratinocytes via the dendritic processes of the melanocytes. Melanosomes persist in dark complexioned individuals. However in fair skinned individuals the cells in the skin 18

breakdown the melanosomes and the melanin. Albinic individuals exhibit very minimal or no presence of melanin. Though all human beings have almost similar concentration of melanocytes, based on the race of the individual, melanin producing genes stimulate the production of melanin. Melanin is normally found in the skin, produced by melanocytes, its functions include absorption of ultraviolet light and scavenging of some cytotoxic compounds. There are typically three forms of melanin; namely, pheomelanin, eumelanin and neuromelanin. Eumelanin is found in abundant quantities. It is present in the skin and hair. It can produce colors ranging from black to gray and brown to yellow. Pheomelanin is abundantly found in women. It can produce colors ranging from pink to red. Neuromelanin is responsible for the pigmentation of four nuclei of the brain, namely, substantia nigra, locus ceruleus, median raphe nucleus of pons and dorsal motor nucleus of the vagus nerve. Management Physiological pigmentation is treated only when esthetics is the concern. Dermabrasion, use of chemical bleach, free gingival graft placement and cryosurgery are some of the surgical techniques to lighten the pigmentation.

Hairy Tongue This condition has also been referred to as black hairy tongue. Etiology is unknown, however certain predisposing factors include poor oral hygiene, frequent use of mouthwashes, smoking and alcohol consumption, radiation therapy


Figure 13

MANDIBULAR AND MAXILLARY TORI Exostoses Exostoses or hyperostoses are non-pathologic, benign bony growths projecting outward from the cortical plate. Though exostoses are developmental disturbances they are usually noticed only in adulthood and may enlarge with age. They are asymptomatic and self-limiting. It is estimated that the prevalence rate of tori is approximately 27 in every 1,000 individuals. Eskimos, American Indians and Asians and more specifically Koreans are said to have a higher incidence of tori. Etiopathogenesis

Yellowish-brown colored hairy tongue. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

for head and neck cancers, fungal infections, topical or systemic antibiotics and corticosteroids and debilitating systemic illness. Clinical features The condition is characterized by the hypertrophy of the filiform papillae on the dorsum, producing a hairy appearance. This condition results from inadequate desquamation or increased keratinization of the papillae. The filiform papillae are usually about 1 mm in length. However in hairy tongue these papillae may elongate to about 10 mm. Though the condition has historically been referred to as black hairy tongue, the color can vary from yellow to brown to black (Figure 13). The coloration depends on the chromogenic bacteria, consumption of beverages like tea and coffee and tobacco use. This condition is usually asymptomatic. However some individuals complain of altered taste sensation, halitosis and occasionally gagging sensation. Histologically hyperkeratosis of the filiform papillae is seen. Patients should be advised to avoid excessive consumption of beverages like tea and coffee. They should also be advised to discontinue the use of tobacco. They can be motivated to use a medium bristled brush over the dorsal surface of the tongue.

According to some authors, micro-damage and inflammation in periodontal tissue in genetically susceptible individuals causes exostoses. Abnormal loads during mastication have also been implicated in inducing exostoses. Buccal exostoses may result from lateral pressure of the adjacent teeth. Palatal tori may be a result of chronic periosteal ischemia due to nasal septum pressure. The torquing action of the arch of the mandible during mandibular movements is said to produce mandibular tori. Clinical classification Although a formal classification system does not exist, based on the clinical occurrence, exostoses may be categorized as those that are commonly seen and the rarer forms. Commonly occurring exostoses ❍ Palatal torus ❍ Mandibular torus Rarer forms of exostoses ❍ Buccal exostoses ❍ Palatal exostoses ❍ Subpontine exostoses

Torus/Tori The word torus is derived from Latin, which means a swelling or bulge. Although etiology is unknown, a hereditary basis is suspected. A torus located along the midline of the hard palate is called a palatal torus, or torus palatinus, and a torus in the lingual aspect of the mandible is called a mandibular torus, or torus mandibularis. Clinical classification of tori based on morphology Flat torus: Occurs as a slightly convex bony protuberance with a smooth surface for mandibular tori. However 19


Figure 14

Palatal torus. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 15

Bilateral mandibular tori. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

in the palatal region it extends symmetrically on either sides of the palate. Lobular torus: Occurs as a pedunculated or a sessile lobular mass on either the mandible or palate. It arises from a single base.

Figure 16

Nodular torus: These are seen as multiple bony protuberances each arising from individual bases. As they enlarge these may coalesce forming grooves between them. Spindle torus: Occurs along the length of the midpalatal raphe region for palatal tori. Elongated tori are evident bilaterally in the mandible.

Torus palatinus This condition exhibits exostoses in the midline of the hard palate. It may be inherited as an autosomal dominant trait. In individual studies the incidence of palatal tori among the population of United States has been reported as high as 20–35%. It is believed to be twice as prevalent in females as in males. The tori in the palatal vault may vary in size from a few centimeters to larger sized lesions and are usually lobulated and dome shaped with a smooth surface (Figure 14). These exostoses generally tend to enlarge with age. Histopathologically smaller lesions are composed of compact bone. However larger tori may exhibit a central core of cancellous bone covered by compact bone.

Buccal exostoses. Courtesy: Dr Evelyne Verweij

female predilection is reported. The mandibular tori usually occur in a symmetric fashion on the lingual surface of the mandible above the level of the mylohyoid ridge (Figure 15). The tori are usually located near the canine and premolar teeth. Occasionally the bilateral tori are so extensive that they meet at the midline. These tori are termed ‘kissing tori’.

Buccal exostoses Torus mandibularis Torus mandibularis is the term used to describe exostoses occurring on the lingual surface of the mandible. It is estimated that 7–10% of the population of United States exhibit torus mandibularis. However no specific male or 20

Buccal exostoses are benign, broad-based surface masses of the outer or facial aspect of the maxilla (Figure 16) and less commonly, the mandible (5.1:1). They begin to develop in early adulthood and may very slowly enlarge over the years.


Figure 17

Occlusal radiograph with palatal torus marked. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 18

Mandibular occlusal radiograph showing radiopaque masses extending from the lingual cortical plate, bilaterally. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Palatal Exostoses They appear as bilateral bony nodular protuberances arising on the palatal cortical plate usually corresponding to the maxillary tuberosities.

Reactive Subpontine Exostoses It has also been referred to as subpontic osseous hyperplasia. It is a reactive exostoses arising from the crest of the alveolar ridge beneath the pontic of a fixed partial denture presenting as nodule or protruberance of crestal bone. It was first reported in 1971 by Calman et al. It may have a genetic origin similar to other exostoses. However some authors believe that a chronic gingival irritation leads to the subpontic bone proliferation. Radiographic findings Exostoses and tori appear as well-defined radiopacities superimposed on the roots of the teeth. Palatal tori may not be appreciated in periapical radiographs. However occlusal radiographs may show a faint radiopaque shadow over the midpalatal region (Figure 17). Mandibular tori are readily visualized as radiopaque areas projecting from the lingual cortical plate on mandibular occlusal radiographs (Figure 18). Histopathologic features Exostoses show dense cortical plate with a laminated pattern. The laminar bone reveals scattered osteocytes. The minute bone marrow spaces may show presence of a fatty marrow or a loose fibrovascular stroma. Generally minimal osteoblastic activity is seen. However some lesions

show excessive periosteal activity. The bone may show large lacunae with pyknotic osteocytes, indicative of bone ischemia. Clinical considerations Exostoses may interfere with normal speech and other functions. Occasionally these bony overgrowths may predispose to gingival and periodontal diseases by way of forcing food toward the gingival margins during mastication. Large overgrowths may be covered by relatively thin mucosa that ulcerates even by routine activities such as mastication and brushing. They also interfere with the preparation and insertion of prosthetic appliances and film placement in intraoral radiography. Some authors have reported obstructive sleep apnea in these patients. Difficulty in endotracheal intubation was also reported in these patients. Tori may be used for harvesting bone for alveolar ridge augmentation and as source of autogenous cortical bone in periodontal surgery. Management and prognosis Bony exostosis generally will not require any form of treatment. The indications for treatment include functional disturbance (difficulty in mastication), inability to place the denture or repeated history of traumatic ulcerations. These bony outgrowths can be surgically contoured or removed. Brunsvold et al (1995) reported recurrence of mandibular tori after surgical removal. The author followed up one patient for 11 years and the other for 14 years. 21


SOFT TISSUE DISTURBANCES

Figure 19

DEVELOPMENTAL DISORDERS AFFECTING TONGUE Aglossia/Lingual Agenesis/Aglossia Congenita Failure in the embryogenesis of lateral lingual swellings during intrauterine life leads to this rare and highly fatal condition of absence of tongue. However literature review reveals reports of individuals living a relatively normal life. Khalil et al (1995) reported aglossia in a 30-year-old man. It may occur alone or in association with other deformities including micrognathia; microsomia; congenital absence of mandibular incisors; collapse of the mandibular arch; sagittal band between the floor of the mouth and the palate; and situs inversus (also called situs transversus—congenital condition where all major visceral organs such as the heart, stomach, spleen, liver, etc. are placed reversed or mirrored from their normal position). Functional thyroid disorder may develop because of the embryological association between development of tongue and thyroid gland. The absence of the lingual muscular stimulus generally affects the development of jaws and results in malocclusion of teeth. These individuals have impaired speech and difficulty in swallowing. Highasi et al (1996) reported conductive deafness, esophageal atresia, hypoplastic epiglottis and ptosis of the eyelid in an individual with aglossia.

Microglossia/Hypoglossia This rare developmental condition is characterized by an abnormally small tongue. It may occur as an isolated anomaly or, more commonly, as part of oromandibular limb hypogenesis syndrome (hypoglossia-hypodactylia syndrome) or in association with micrognathia, hypodontia, situs inversus, asplenia, absence of lower incisors, or enamel hypoplasia. Prognosis depends on nature and severity of the condition. Treatment is directed toward improvement of oral function with an understanding of the changes in the mechanisms of oral suction, mastication, swallowing, speech, as well as dental occlusion.

Macroglossia An abnormally enlarged tongue is one that protrudes beyond the teeth or the alveolar ridge in the resting position (Figure 19). Macroglossia can be broadly categorized as true macroglossia and pseudo macroglossia (Table 1). In true macroglossia enlarged tongue is associated with histological abnormalities. In pseudo macroglossia (relative macroglossia) the enlargement is apparent; though histology does not provide a pathologic explanation (e.g. Down’s syndrome). 22

Macroglossia. Courtesy: Dr Sumanth

Table 1

Classification of macroglossia

Pseudo macroglossia Tongue posture Habitual (tongue thrust) Poor neuromuscular control Edentulousness Maxillofacial skeletal deficiencies Shallow palatal vault Deficient maxilla and mandible Effects of surrounding structures Enlarged adenoids Cysts, tumors, space infections displacing the tongue True macroglossia Congenital causes Muscular hypertrophy Vascular malformations (hemangioma, lymphangioma) Down syndrome Beckwith–Wiedemann syndrome Mucopolysaccharidoses I and II Congenital hypothyroidism Behmel syndrome Transient neonatal diabetes mellitus Trisomy 22 Laband syndrome Lethal dwarfism of Blomstrand Skeletal dysplasia of Urbach Tollner syndrome Ganglioside storage disease type I Lipoid proteinosis Acquired causes Endocrinal disturbances Acquired hypothyroidism Acromegaly Pituitary gigantism Myxedema (Contd...)


Table 1

Continued

Infections Tuberculosis Actinomycosis Traumatic injuries Self-inflicted (self-harm, injury during epileptic seizure) Presurgical (intubation)/surgical trauma/postsurgical (anesthesia/ hemorrhage) Neoplasms Lymphangioma Hemangioma Carcinoma Sarcoma Solitary plasmacytoma Neurofibroma Granular cell tumor Nutritional and metabolic disorders Amyloidosis Scurvy Pellagra Autoimmune disorders Sarcoidosis Giant cell arteritis Miscellaneous Angioneurotic edema Modified from Richard D Thrasher III (2007)

Figure 20

Ankyloglossia. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

tip (Figure 20). Messner (2000) reported that the incidence of ankyloglossia ranged from 0.02% to 4.8% in newborns. Classification of ankyloglossia I. Based on anatomical appearance

Clinical features Clinical features include, crenated lateral border of tongue, open bite, mandibular prognathism and airway obstruction. There may be ulceration, secondary infection and necrosis. In infants it leads to lisping speech, noisy breathing, drooling and difficulty in eating. The tongue has a pebbly surface with multiple vesicle like blebs in lymphangioma; in hypothyroidism there is diffuse smooth enlargement; the tongue is multinodular in amyloidosis and neurofibromatosis, papillary appearance of the tongue is seen in MEN type II and tongue is fissured in Down’s syndrome. A unilateral enlargement of tongue is seen in hemihyperplasia. Management Macroglossia, unless causing a functional disturbance need not be corrected. It is treated with surgical techniques chosen in accordance with the functional results that one wants to achieve. It must be the most conservative technique to preserve the vascular nerve bundle. Speech therapy may be required in some cases. Tracheostomy is indicated in cases of airway obstruction.

Ankyloglossia/Tongue-tie Ankyloglossia or tongue-tie, is the result of a short, tight, thick, lingual frenulum causing tethering of the tongue

Type 1: Frenulum attaches to tip of tongue in front of alveolar ridge in low lip sulcus Type 2: Attaches 2–4 mm behind tongue tip and attaches on alveolar ridge Type 3: Attaches to mid-tongue and middle of floor of the mouth, usually tighter and less elastic. The tip of the tongue may appear ‘heart-shaped’ Type 4: Attaches against base of tongue, is shiny, and is very inelastic II. Classification of ankyloglossia based on distance of the insertion of the lingual frenum to the tip of the tongue This classification was suggested by Kotlow (2004) Normal: 16 mm Class I (Mild): 12–16 mm Class II (Moderate): 8–12 mm Class III (Severe): 4–8 mm Class IV (Complete): 0–4 mm Clinical significance Ankyloglossia may lead to difficulties in breast feeding, articulation problems, gingival recession, open bite and abnormal facial development. Frenotomy and frenuloplasty have been effective treatments for ankyloglossia. 23


Intraoral radiography may be difficult in some patients owing to the limited space available to position the film.

Cleft Tongue Cleft tongue or bifid tongue is caused due to lack of merging of lateral lingual swellings of tongue. Partial cleft is more common than the total cleft and is characterized by a deep groove in the midline of the dorsal surface. It is often found as one of the features of orofacial digital syndrome with thick fibrous bands in the lower anterior mucobuccal fold and clefting of hypoplastic mandibular alveolar process. Food and microorganisms may collect in the base of the cleft and cause irritation.

Fissured Tongue Described on page 13.

Geographic Tongue Geographic tongue has also been referred to as benign migratory glossitis, wandering rash of the tongue, annulus migrans, stomatitis areata migrans and erythema areata migrans. It is a common benign condition that is seen in almost 3% of the population. Geographic tongue is seen in males and females equally. However, few articles in literature describe a slightly higher female predilection (2:1). However, the tongue changes are more prominent in adults compared to children. Etiopathogenesis and predisposing factors The etiopathogenesis of the condition is still not understood. Histologically it is said to be an inflammatory condition associated with human leukocyte antigen (HLA)-DR5, HLA-DRW6, and HLA-Cw6. Eidelman et al (1976) reported that many of the parents and siblings of individuals with geographic tongue also presented with the condition. This substantiated the possibility of heredity being an etiological factor. Guimaraes et al (2007) in their investigations found that the polymorphism⫹3954 interleukin (IL)-1B is associated with an increased risk of developing geographic tongue. Redman et al (1966) and Bánóczy (1975) et al suggested that emotional stress was associated with the occurrence and severity of geographic tongue. There are many studies with regard to the association of geographic tongue and diabetes mellitus. Wysocky et al (1987) reported a four-fold increase in the presence of geographic tongue in diabetics. However, Guggenheimer et al (2000) reported no significant correlation between geographic tongue and insulin-dependent diabetes mellitus. Waltimo (1991) in his study on the severity of geographic tongue in a patient taking oral contraceptive pills 24

reported that the tongue changes were the severest on the 17th day of the menstrual cycle. Marks and Simon (1979) showed a definitive association between geographic tongue and atopy. Many authors postulate that psoriasis manifests orally as geographic tongue. Gonzaga (1996) in his investigations showed a significant association of Cw6 with both psoriasis and benign migratory glossitis. This antigen was found in 59.1% of the patients with psoriasis and 43.8% of the patients with benign migratory glossitis. Zargari (2006) in a study including 306 patients with psoriasis concluded that geographic tongue is more common in early onset psoriasis and may be an indicator of the severity of psoriasis. Yarom et al (2004) found a strong correlation between the occurrence of geographic tongue and fissured tongue. Clinical features Geographic tongue is commonly seen in the 2nd decade of life. The common sites of involvement are the tip of the tongue, lateral margins and dorsum of the tongue. However some lesions tend to extend to the ventral surface. The appearance of the lesion typically mimics geographic outlines on a map, hence the name geographic tongue (Figure 21). It appears as circinate irregular erythematous patches which represent the atrophic filiform papillae, bound by keratotic white bands or lines which represent the regenerating filiform papillae (Figure 22). These erythematous patches occur in multiple sites on the tongue. Very rarely a single site of involvement may be seen. In this condition the filiform papillae regenerate in the atrophic site in a few days and a new site begins to reveal atrophy. Patients typically report this as ‘migrating rash’. Many patients are unaware of the condition as it is generally asymptomatic. However, some report of inability to consume spicy food owing to burning sensation. Some authors believe that the association of fissured tongue with superimposed candidal infection causes the burning sensation. The condition is seldom painful. Though this condition is typically seen involving the tongue, it can occur on other sites in the oral mucosa. Some authors use terms such as ectopic geographic tongue, geographic stomatitis, erythema migrans, erythema areata migrans, and stomatitis areata to refer to such a finding. The common ectopic sites include the buccal mucosa, labial mucosa (Figure 23), gingiva, floor of mouth and less commonly the soft palate and uvula. Histopathologic features Biopsy specimens should ideally be obtained from a site which includes the keratotic serpiginous margin and the atrophic area. On histopathological examination hyperkeratosis, acanthosis and slender, elongated rete pegs are seen.


Figure 21

Figure 23

Geographic lip. Courtesy: Dr Foluso Owotade

Geographic tongue. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 22

Management All patients of geographic tongue need to be reassured of the harmless nature of the condition. In symptomatic patients palliative therapy with topical or systemic antihistaminics have proved beneficial due to their local anesthetic effect (Sigal et al, 1992). Presence of associated fissured tongue with superimposed candidal infection can be effectively managed with topical clotrimazole. Benzydamine hydrochloride mouthrinse can be used to manage burning sensation. Gibson et al (1990) in their study showed that zinc supplements proved effective for managing geographic tongue.

Lingual Varices Described on page 15.

Lingual Thyroid

Geographic tongue on the dorsum of the tongue. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Neutrophil infiltrations are seen in the thick layer of keratin and to a lesser degree in other portions of the epithelium. These infiltrations produce microabscess (Munro’s abscess) in the keratin and spinous layers.

Failure of the thyroid tissue to descend from its developmental origin at the foramen caecum to its normal pretracheal location leads to its presence in the tongue at the foramen caecum. Van Der Gaag et al (1985) postulated that maternal antithyroid immunoglobulins may arrest the descent of the thyroid in some individuals. Thyroid tissue may be deposited ectopically along this early thyroglossal tract. Apart from tongue, ectopic thyroid tissue has also been reported at other midline locations of the neck such as below the level of hyoid bone, larynx and trachea, mediastinum and esophagus. It is estimated that the incidence of lingual thyroid varies between 1:3,000 and 1:100,000 (Williams et al, 1989). The lingual thyroid is seen as a nodular mass in the midline about 2–3 cm in diameter with a smooth surface. It appears erythematous when highly vascular. Depending 25


Figure 24

Lingual pits on the dorsum surface of the tongue. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

on the size, it may produce symptoms of pain, feeling of fullness in the throat, dysphagia, dysphonia and dyspnea. The diagnostic test is thyroid scan with iodine isotopes or technetium-99m, CT scan or MRI helps in delineating the size and extent of the lesion. Biopsy is avoided as there is risk of hemorrhage and it could be the only thyroid tissue (in about 70% cases). Histopathologically it resembles normal thyroid tissue. If it has to be excised, it should be done after confirming the presence of a functioning thyroid in the normal position. If it is not so, then the excised tissue is transplanted in a muscle with adequate vascularity.

Tongue Pits The authors report a case of lingual pits on the dorsal surface of the tongue in a 24-year-old male (Figure 24). The patient was asymptomatic and reported that these pits were present since childhood. Review of literature shows no mention of this condition.

DEVELOPMENTAL DISORDERS AFFECTING THE LIP Paramedian Lip Pits (Congenital Lip Pits) These congenital invaginations of the lower lip arise from persistent lateral sulci on the embryonic mandibular arch. They are seen as bilateral (occasionally unilateral), symmetrical pits on the vermillion border on either side of the midline ranging from subtle depressions to prominent humps. This trait may be transmitted genetically to the offspring. 26

Figure 25

Commisural lip pit. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

These can extend to a depth of 1.5 cm. On squeezing they may express salivary secretions. These lip pits may be a part of Van der Woude syndrome or popliteal pterygium syndrome. Histopathologically, tracts lined by stratified squamous epithelium are seen; minor salivary glands may be seen communicating with the sinus. Surrounding connective tissue is often infiltrated by chronic inflammatory cells. Excision of these pits may be performed for cosmetic reasons.

Commissural Lip Pits These small mucosal invaginations occur at the corners of the mouth on the vermillion border (unilaterally or bilaterally), possibly due to failure of fusion of embryonal maxillary and mandibular processes (Figure 25). Though considered congenital, these often develop later in life— prevalence in children (0.2–0.7%) being much lower than in adults (12–20%). Males are more often affected than females. An autosomal dominant pattern of transmission is noted in some families. In most cases, they are asymptomatic and are discovered on routine examination; they may express saliva on squeezing. The depth of these pits range from 1 mm to 4 mm. Associated preauricular pits may be seen in some. They are generally not associated with facial or palatal clefts. Histopathologically they are similar to paramedian lip pits. No treatment is necessary. However excision is indicated if there is excessive salivary secretion or secondary infection.

Double Lip Here a mucosal fold appears on the mucosal side of the lip, commonly the upper lip. The congenital form is due to


Table 2 Syndromes associated with cleft lip

Figure 26

Achondroplasia Beckwith–Wiedemann syndrome DiGeorge syndrome Fetal alcohol syndrome Goldenhar syndrome Gorlin syndrome Treacher Collins syndrome Van der Woude syndrome Waardenburg syndrome

Table 3 Syndromes associated with cleft palate Achondroplasia

Unilateral cleft lip extending into the floor of the nose. Courtesy: Dr Foluso Owotade

Beckwith–Wiedemann syndrome Cleidocranial dysplasia Crouzon syndrome (craniofacial dysostosis) Ehlers–Danlos syndrome Fetal alcohol syndrome

Figure 27

Gorlin syndrome (basal cell nevus syndrome) Marfan syndrome Pierre Robin syndrome Rubinstein–Taybi syndrome Treacher Collins syndrome (mandibulofacial dysostosis) Van der Woude syndrome

persistence of sulcus between the pars glabrosa and pars villosa of the lip. The acquired form may be due to trauma, repeated sucking on the lip or as part of Ascher’s syndrome (double lip, blepharochalasis and non-toxic thyroid enlargement). In most cases, it becomes visible only when the lip is tense or while smiling. Histopathologically normal structures are seen with a slight abundance of minor salivary glands. Excision is the treatment for esthetic reasons. Bilateral cleft lip. Courtesy: Department of Oral and Maxillofacial Surgery, MCODS, Mangalore

Cleft Lip and Cleft Palate Cleft lip results from failure of merging of epithelial groove between the medial and lateral nasal process by penetration of mesodermal cells. Cleft palate is the result of epithelial breakdown with in growth failure of mesodermal tissue and lack of lateral palatal segment fusion. Most cleft cases are polygenic but the 5% of cleft cases associated with syndromes are said to be monogenic (Tables 2 and 3). Environmental factors like nutritional deficiencies, stress, infections, alcohol, drugs, toxins and ischemia may cause clefts. Veau system of classification is generally used where the emphasis is on the extent to which the clefting is seen. Submucosal clefts are not included here.

Cleft lip ❍

Class I: Unilateral notching of vermillion border that does not extend into the lip ❍ Class II: Unilateral notching of the vermillion extending into the lip but not involving the floor of the nose ❍ Class III: Unilateral clefts of the vermillion border extending through the lip into the floor of the nose (Figure 26) ❍ Class IV: Any bilateral cleft of the lip exhibiting incomplete notching or a complete cleft (Figure 27). 27


Figure 28

Figure 29

Orthopantomograph showing cleft alveolus on the right maxillary lateral incisor region. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 30

Complete cleft palate in an adult. Courtesy: Dr Prakash Chhajlani

Cleft palate (Figure 28) ❍ ❍

Class I: Cleft limited to soft palate Class II: Defects of both hard and soft palate. They extend till the incisive foramen Cleft palate can either be complete or incomplete. Complete cleft includes cleft of soft and hard palate to the incisive foramen. Incomplete cleft involves the velum and a portion of the hard palate. ❍ Class III: These are complete unilateral clefts extending from the uvula to the incisive foramen in the midline and the alveolar process unilaterally (Figure 29). ❍ Class IV: Complete bilateral clefts involving the soft and hard palate and alveolar process on both sides of premaxilla leaving it free and often mobile. Rarely, a lateral cleft lip can be seen due to non-fusion of the maxillary and mandibular process (Figure 30). Cleft of soft palate including submucosal clefts are associated with eustachian tube dysfunction, recurrent otitis media and hearing deficits. Dental anomalies include congenitally missing lateral incisor, supernumerary teeth, delayed tooth formation, enamel hypoplasia, micro/macrodontia and fusion.

Prenatal Diagnosis of Clefts The facial structures of the fetus are best imaged after the 15th week in utero using ultrasound (Figure 31). Though 28

Lateral cleft lip. Courtesy: Dr Prakash Chhajlani

the fusion of the midline structures is complete by the 8th week, the position of the head is not readily accessible for adequate imaging. It is also believed that the head is relatively smaller compared to the size of the transducer in the first 15 weeks of gestation. Classification of clefts based on ultrasound imaging Type 1: Cleft lip Type 2: Unilateral cleft lip and palate Type 3: Bilateral cleft lip and palate Type 4: Midline clefts Type 5: Facial clefts associated with amniotic bands or limb-body wall complex. Treatment of clefts requires a multidisciplinary team including dental, medical and surgical specialists with assistance of allied health professionals in social services, child development and hearing and speech therapy. Cleft lip repair is done when the child weighs 10 pounds, has hemoglobin level of 10 mg/dl and older than 10 weeks. Cheiloplasty is required later in life. By 1 year, closure of soft palate with


Figure 31

Figure 32

In utero diagnosis of bilateral cleft lip at 30 weeks pregnancy using ultrasound. Courtesy: Dr Sudheer Gokhle, Ultrasonologist, Indore, India

pharyngeal flaps is recommended to promote normal speech development (Figure 32). Palatal obturators are used when there are feeding problems in cases of cleft palate (Figure 33).

Surgically closed cleft palate. Courtesy: Dr Prakash Chhajlani

Figure 33

DEVELOPMENTAL DISORDERS AFFECTING BUCCAL MUCOSA AND GINGIVA Oral Melanotic Macule Labial melanotic macule is an otherwise asymptomatic, usually solitary, small (generally ⬍ 5 mm), flat, brown to brownish-black lesion found on the vermillion border of the lower lip near the midline. It can occur at any age. Oral melanotic macules usually occur on the gingiva, buccal mucosa and soft palate. Histopathologically there is an increased amount of melanin in the basal cells with a dropout of melanin from these basal cells into the macrophages of connective tissue. This is called melanin incontinence. Unlike in actinic lentigo the rete ridges here are not elongated. Excision biopsy is done to rule out melanoma and other pigmented lesions. Excision of these macules may be undertaken for esthetic reasons.

Fordyce’s Granules (Fordyce’s Disease/Spots) Described on page 11.

Feeding palate for cleft lip and palate neonates. Courtesy: Dr Prakash Chhajlani

Fibromatosis Gingivae This is an autosomal dominant disorder affecting the gingiva of one or both arches and characterized by noninflamed, non-painful smooth or nodular diffuse overgrowth (Figure 34). The overgrowth may prevent eruption of teeth or may be seen covering a large portion of the 29


Figure 34

Figure 35

Diffuse non-inflammatory gingival enlargement in fibromatosis gingivae. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore Micrognathia

crown in erupted teeth. It may be associated with hypertrichosis, corneal dystrophy, craniofacial deformities, nail defects, deafness, epilepsy and mental retardation. Histopathologically dense non-inflamed collagenous connective tissue with the overlying epithelium showing elongated rete ridges are seen. Gingivectomy is the treatment of choice. Recurrences may be seen but can be prevented by extraction of teeth.

HARD TISSUE DISTURBANCES (JAWS) DEVELOPMENTAL DISTURBANCES OF THE JAWS These include complete absence or diminished or excessive development of the jaws. Abnormally small and large jaws are called micrognathia or macrognathia respectively. Apparent under-development or over-development due to skeletal malpositioning of the jaws (e.g. retrognathia or prognathia) is called pseudo-micrognathia or pseudomacrognathia. Disorders of development of facial skeleton may also affect the jaws. In hemifacial hyperplasia one side of the facial skeleton is abnormally large and in hemifacial atrophy, it is under-developed.

(e.g. missing premaxilla) or mandible (e.g. missing ramus). Partial absence of mandible is more common. When there is unilateral absence of mandibular ramus, the ear too may be deformed or absent.

Micrognathia Congenital micrognathia is usually seen in association with other congenital abnormalities like congenital heart disease and Pierre Robin syndrome. Occasionally, they may follow a hereditary pattern. Micrognathia of maxilla is usually due to deficiency in the premaxillary area. The middle third of face appears retracted. Associated maldevelopment of nasal and nasopharyngeal structures can predispose to mouth breathing. Mandibular micrognathia is commonly due to agenesis of the condyles. Normal growth of mandible depends on the development of condyles as well as muscle function. If there is ankylosis of the joint due to trauma, infection of mastoid, middle ear or the joint, it causes acquired micrognathia of mandible. Clinically, severe retrusion of chin, a steep mandibular angle, and a deficient chin button are observed (Figure 35). Table 4 lists few of the syndromes associated with micrognathia.

Macrognathia Agnathia Though the term agnathia refers to absence of jaws, usually there is incomplete development of either maxilla 30

Only the mandible, both maxilla and mandible or the entire skeleton may be abnormally large. Mandibular macrognathia may be due to increased height of ramus (Figure 36),


increased mandibular body length, increased gonial angle, anterior positioning of glenoid fossa or prominent chin button. Both the jaws are affected in Paget’s disease of bone, acromegaly, leontiasis ossea (a form of fibrous dysplasia). Pituitary gigantism leads to generalized increase in size of entire skeleton. In addition to treating the underlying cause, the length of the mandible may be reduced by ostectomy.

Hemifacial Hyperplasia Although this is known more commonly as hemifacial hypertrophy, there is actually hyperplasia of the tissues. Some degree of facial asymmetry is common. Hemifacial hyperplasia refers to significant unilateral enlargement of the face including eyes, ears, nose and intraoral tissues (Figure 37). It is often noted at birth and sometimes at puberty. The disproportionate growth continues until the patient’s overall growth ceases, resulting in permanent asymmetry.

Table 4

It may also be associated with malformation syndromes like Beckwith–Wiedemann syndrome, McCune–Albright’s syndrome and neurofibromatosis. Etiology and clinical features Etiologic factors suggested include vascular or lymphatic abnormalities, central nervous system disturbances, endocrine dysfunction, aberrant twinning mechanisms and chromosomal anomalies. Women are afflicted twice as many as men. In them, either side is equally affected, while in males, right side is more commonly affected. About 15–20% have enlargement of cerebrum and mental retardation. Malignancies of adrenal cortex, liver and kidney (e.g. Wilms’ tumor) are more common in them. On the affected side, the skin is thick and coarse, hair is thick and abundant and sebaceous and sweat gland secretions are excessive. Excessive pigmentation may also be evident. Lee et al (2001) described three cases with hemifacial hyperplasia of the muscles of facial expression with no other organ system involvement. They proposed to name this condition with unique characteristics as ‘hemifacial myohyperplasia’.

Syndromes associated with micrognathia

Cohen syndrome

Intraoral findings

DiGeorge syndrome

Malocclusion is common. Unilateral macroglossia with prominent papillae are characteristic.

Fetal alcohol syndrome Pierre Robin syndrome Potter syndrome

Radiographic features

Rubinstein–Taybi syndrome

The facial skull bones (mandible, maxilla, zygomatic, temporal and frontal) are enlarged on the affected side (Figure 38).

Treacher Collins syndrome

Figure 36 A

B

(A) Lateral cephalogram showing mandibular macrognathia. (B) Orthopantomograph showing increased ramal length and mandibular body in macrognathia

31


Figure 37 A

B

C

D

(A) A child with hemifacial hyperplasia affecting the right side. (B) Right side of the tongue showing enlargement. (C) PA view showing enlargement of the mandible and soft tissues on the right side. (D) Enlarged body and ramus of the mandible on the right side

Figure 38

The roots and crown of the teeth particularly the permanent teeth are often enlarged and may erupt prematurely. Primary teeth are shed prematurely on the affected side. The mandibular canal can appear enlarged. Management Functional and cosmetic improvements may be achieved through orthodontic tooth alignment and serial staged surgeries. Because enlargement is related to all tissue levels, perfect symmetry cannot be obtained.

Hemifacial Atrophy (Parry Romberg Syndrome, Romberg Syndrome) Photograph showing atrophic changes of the tissues in one side of the face. Courtesy: Department of Oral Medicine and Radiology, KLE Society’s Institute of Dental Sciences, Bangalore

32

This condition is characterized by atrophic changes of tissues on one side of the face including eyes, ears, nose and intraoral tissues. Trophic malfunction of the cervical sympathetic nervous system, viral or borrelia


infection, trauma, genetic factors, peripheral trigeminal neuritis, etc. have been speculated as the causes. Many investigators believe that it represents a localized form of scleroderma. It commonly affects females in the first two decades of life. The condition begins as a localized area of atrophy of skin and subcutaneous structures. This atrophy progresses at a variable rate and affects the dermatome of one or more branches of the trigeminal nerve. Osseous hypoplasia may occur when the condition begins during the first decade. The overlying skin often exhibits dark pigments (Figure 38). Some patients have a sharp line of demarcation resembling a large linear scar between normal and abnormal skin near the midline of the forehead known as coup de sabre (strike of the sword). Atrophy of upper lip may expose the maxillary teeth. Unilateral posterior open bite develops as a result of mandibular hypoplasia and delayed eruption of the teeth. Teeth on affected side may show deficient root development or root resorption. Atrophy progresses for several years and then becomes stable. Cosmetic surgery and orthodontic therapy may help in correcting deformity and malocclusion respectively.

injuries sustained during the growth and development of the mandible, therapeutic radiation and arthritis. This condition is managed using grafts followed by orthognathic surgery and orthodontic correction of malocclusion.

Condylar Hyperplasia Condylar hyperplasia refers to a unilateral enlargement of the mandibular condyle. Though the etiopathogenesis is still unclear, various causes have been proposed such as trauma, endocrinal disturbances and local deficiency of circulation. Clinical features

The complete failure of development of the mandibular condyle either unilaterally or bilaterally is referred to as condylar aplasia. It is estimated that the incidence of condylar aplasia is around 1 in 5,600 births. The developmental defect is rarely seen in isolation. It may usually be associated with hemifacial microsomia, Goldenhaar’s syndrome and Treacher Collins syndrome. Lesser known associations of condylar malformations and agenesis are with Proteus syndrome, Morquio syndrome and auriculocondylar syndrome. Santos et al (2007) reported a case of condylar aplasia without any syndrome association. In unilateral aplasia obvious facial asymmetry and shifting of the mandible to the affected side on mouth opening are common findings.

Condylar hyperplasia is usually encountered in the second and third decades of life. Patients generally complain of progressive facial asymmetry. On clinical examination unusually large condylar head can give arise to a clinically evident swelling in the temporomandibular joint region. The mandible is deflected to the normal side. Open bite on the affected side is a characteristic feature. The progressive facial asymmetry can be confirmed by comparing photographs of the patient from childhood through adolescence to adulthood. Orthopantomograph (OPG) is a good scout radiograph for comparing the relative increase in size of the condyle with respect to the unaffected side. Other radiographic views that could prove beneficial are the open and closed TMJ views, TMJ views (transcranial, transpharyngeal and transorbital), posteroanterior skull view, submentovertex base of skull view and computed tomography. Histopathologically the condition shows normal features after completion of the growth. However proliferation of the condylar cartilage is seen during the periods of active growth. The condition is generally self-limiting. However unusually large condyles causing functional and esthetic disturbances can be managed by surgical recontouring. In some cases condylectomy may be required.

Condylar Hypoplasia

Bifid/Trifid Condyle

Condylar hypoplasia results from congenital or developmental disturbances or due to acquired causes. In this condition the condyle usually retains its shape but appears smaller. Unilateral involvement of the condyles is more common than bilateral involvement. Most of these patients also present with a proportionately smaller ramus and body of the mandible. A prominent antigonial notch may be seen. The acquired causes that result in hypoplasia of the condyle include traumatic

Hrdlicka in 1941, was the first to describe bifid condyles in skull specimens. Schier in 1948 described bifid condyles in a living person based on radiographic findings. Artvinli et al (2003) and Cagirankaya et al (2005) reported trifid mandibular condyle. Most of the cases reported were involving individuals over 20 years of age. Males and females are equally affected. Literature reveals the left condyle being twice more affected than the right side.

Condylar Aplasia

33


Figure 39

34

Figure 40

Cropped orthopantomograph showing bifid condyle. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Cropped orthopantomograph showing trifid condyle. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

The etiology for the condition is unknown. Some authors believe that the condylar cartilage, during the early stages of its development, is divided by well-vascularized fibrous septa and the persistence of such a septum, within the growing cartilage might give rise to the bifid condyle. It is also believed that the rupture of the septal vessels secondary to trauma can give rise to the bifid condyle. Various other factors that have been implicated are exposure to teratogenic substances, endocrinal disturbances, infections, exposure to therapeutic radiation and nutritional deficiencies. It is believed that bifid mandibular condyle resulting from trauma will exhibit one glenoid fossa, whereas those of developmental origin exhibit separate glenoid fossa for each of the two parts of the bifid condyle. It is also postulated that the anteroposterior (sagittal) form of bifid condyle results from facial trauma during childhood, and the mediolateral form (coronal) with persistence of the fibrous septa at the condylar cartilage. Bifid or trifid condyles (Figures 39 and 40) are usually found incidentally on radiographic investigations. Though commonly an orthopantomograph can reveal the possibility of a bifid or trifid condyle the best imaging modality to visualize the condyle for this condition is coronal computed tomography. Moreover, a 3D reconstruction helps in accurately assessing the morphology of the condyles.

No treatment is required for this condition as it is asymptomatic.

Coronoid Hyperplasia Hyperplasia of the coronoid process is an uncommon developmental disturbance affecting the jaws. The hyperplasia of the coronoid process can either be unilateral or bilateral. This condition is characterized by a progressive limitation in mandibular movement, due to impingement of the elongated coronoid processes on the posterior surface of the zygomas. The shape of the coronoid process usually does not change, however it only increases in size. On clinical examination there is no apparent facial asymmetry or pain. It usually begins at puberty. Males are more commonly affected than females (5:1). Apart from genetic inheritance other causes for coronoid hyperplasia to occur have been proposed such as trauma, increased activity of the temporalis muscle and endocrinal stimulus. Waters’ view and orthopantomograph are usually sufficient to evaluate coronoid hyperplasia. It is believed that the projection of the tips of the coronoid processes at least 1 cm over the inferior rim of the zygomatic arch is pathognomonic of coronoid hyperplasia. The impingement


of the elongated coronoid process over the zygomas can be best appreciated by an axial CT image with the mouth open. Literature reveals reports of coronoid hyperplasia in syndromes such as trismus-pseudocamptodactyly syndrome (Yamashita et al, 1979) and nevoid basal cell carcinoma syndrome (Leonardi et al, 2001). The condition can be managed by surgically contouring the coronoid process or by coronoidectomy followed by a rigorous regimen of physiotherapy.

Figure 41

Exostoses/Tori Described on page 19.

DEVELOPMENTAL DISTURBANCES AFFECTING TEETH

Unusually elongated root in premolar. Courtesy: Department of Oral Pathology, MCODS, Mangalore

These include disorders of size, shape, number, structure and eruption of teeth. Figure 42

Developmental Disturbances Affecting Size of Teeth These include either decreased or increased size of the teeth. Localized microdontia is fairly common, especially that affecting maxillary lateral incisor (peg lateral) and the third molar. When only the roots are long/elongated, the condition is called rhizomegaly or radiculomegaly (Figure 41). Similarly, rhizomicry or root dwarfism is the term used to refer to teeth with short roots (Figure 42). Microdontia In this condition the teeth are smaller than usual (microdonts). Apparently small teeth due to abnormally large jaws (pseudomicrodontia) are not included here. Microdontia can either be localized or generalized (Figure 43). In generalized microdontia all the teeth are smaller than normal. It may be seen in pituitary dwarfism and Down syndrome (Figure 44A, B). Other conditions that are associated with microdontia are Axenfeld–Rieger syndrome (O’Dwyer et al, 2005), Fanconi anemia (Tekcicek et al, 2007), Bardet–Biedl syndrome (Drugowick et al, 2007) and oculodentodigital dysplasia (Vasconcellos et al, 2005). Remmers et al (2005) reported microdontia as a late effect of chemotherapy on dental development in a patient treated for neuroblastoma during the early years of life. Localized microdontia is a rather common condition. It affects most often the maxillary lateral incisor and third molar. The common form which affects maxillary lateral incisor is called peg lateral (Figure 45). Localized microdontia can be seen in hemihyperplasia.

Stunted root length in a maxillary central incisor. Courtesy: Department of Oral Pathology, MCODS, Mangalore

Macrodontia It refers to teeth that are larger than normal. However, the term macrodontia should not be applied to teeth that appear large due to fusion or gemination. Localized macrodontia is seen in hemihyperplasia. All the teeth are larger than normal in generalized macrodontia.

35


Figure 43

Figure 45

Microdontic tooth specimen. Courtesy: Department of Oral Pathology, MCODS, Mangalore Peg-shaped maxillary lateral incisor. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 44 A

et al, 2006), Ekman–Westborg and Julin syndrome (Nemes et al, 2006), Cockayne’s syndrome (Arenas–Sordo Mde et al, 2006), Dubowitz syndrome (Chan et al, 2005) and Schinzel– Giedion syndrome (Cooke et al, 2002).

Developmental Disturbances Affecting the Shape of the Teeth (Gemination, Fusion and Concrescence)

B

Generalized microdontia. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

It is associated with pituitary gigantism but is extremely rare. Various other syndromes are associated with either generalized or partial macrodontia such as Berardinelli–Seip syndrome (Solanki et al, 2008), KBG syndrome (Brancati 36

Gemination and fusion have been referred to by various names in literature such as double teeth, double formations, joined teeth, fused teeth and dental twinning. In gemination, a single tooth bud divides and results in the formation of teeth with a bifid crown and a common root and root canal. The crown may be clearly bifid or there may just be a groove (Figures 46 and 47). It is seen commonly in the maxillary anterior regions. Aquilo et al (1999) classified gemination into four types based on the morphology. Type I: Bifid crown with a single root Crown is larger than normal with a notch on the incisal edge and a bifid pulp chamber. The root and pulp chamber are of normal size. Type II: Large crown with a large root Crown is larger than normal and has no groove or notch. The pulp chamber is single and large. The root is wider than normal and has one large root canal. Type III: Two fused crowns with a single root There are two crowns with a vertical groove. The cervical portion of both crowns may be joined. The pulp chamber may be separate. The root is conical shaped and larger than normal. Type IV: Two fused crowns with two fused roots


Figure 46

Gemination of the lower anterior tooth exhibiting a subtle groove on the incisal edge. Courtesy: Department of Oral Medicine and Radiology, KLE Society’s Institute of Dental Sciences, Bangalore

Figure 48

Fusion of the central and lateral mandibular incisors. Courtesy: Department of Oral Medicine and Radiology, KLE Society’s Institute of Dental Sciences, Bangalore

Figure 49

Figure 47

Fusion of the crown and roots. Courtesy: Department of Oral Pathology, MCODS, Mangalore

Intraoral periapical radiograph showing a bifid crown with a common root and root canal. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

There are two crowns with a vertical groove. The cervical portion of both crowns is joined along with the pulp chambers. Fusion occurs when there is union of two tooth buds with the confluence of dentin, resulting in single tooth

with separate or fused root canals (Figures 48–50). Fusion may occur between normal tooth and a supernumerary tooth like mesiodens or distomolar. The most reliable method of distinguishing between gemination and fusion is by counting the number of teeth in the arch. In gemination, the count of teeth remains normal, whereas in fusion the tooth count will reveal a missing tooth. Concrescence is the union of two adjacent teeth by cementum alone without confluence of underlying dentin (Figures 51 and 52). The common teeth that may show concrescence are the maxillary molars, especially third molar and a supernumerary tooth. 37


Figure 50

Tooth specimen showing fusion of the roots. Courtesy: Department of Oral Pathology, MCODS, Mangalore

Figure 52

Radiograph showing concrescence. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 51 this may have to be resolved by radiography. Some authors have reported abnormal patterns in concrescence such as concrescence between an impacted third molar and an erupted second molar (Romito, 2004), concrescence between a third molar and a supernumerary fourth molar in the mandible (Gunduz et al, 2006) and concrescence of the crown of an impacted tooth and the roots of the erupted tooth as a result of the deposition of acellular cementum on the crown (Sugiyama et al, 2007). Presence of geminated and fused teeth in deciduous dentition can cause crowding, abnormal spacing, delayed or ectopic eruption of underlying permanent teeth. Extraction may be necessary to prevent an abnormality in eruption. If the permanent teeth are affected, treatment of choice is determined by patient’s needs. Surgical division followed by endodontic treatment may be done. Selective shaping is done with/without placement of full crowns. In some cases, surgical removal of tooth with prosthetic replacement is done. Concrescence (fusion of the teeth via the cementum). Courtesy: Department of Oral Pathology, MCODS, Mangalore

Unlike fusion and gemination, concrescence may be post inflammatory too (e.g. trauma, crowding with resorption of interdental bone, caries, etc.). In these conditions, there is discrepancy in the number of teeth and roots, and 38

Dilaceration It refers to a sharp bend or curve anywhere along the length of the tooth, most commonly at the root (Figures 53–55). Literature review reveals interesting names that have been used to describe dilaceration such as ‘scorpion tooth’ (Moreau, 1985) and ‘hand of a traffic policeman’ (Stewart, 1978).


Figure 53

Figure 55

Intraoral periapical radiograph reveals dilacerated root of the mandibular third molar. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Dilacerated roots of a molar. Courtesy: Department of Oral Pathology, MCODS, Mangalore

Figure 54

Dilacerated root of a premolar. Courtesy: Department of Oral Pathology, MCODS, Mangalore

Factors which affect the normal development of the tooth, including trauma, cyst, tumor, etc., can cause this condition. Dilaceration most commonly affects the anteriors and the teeth may be non-vital. Dilaceration of deciduous

teeth can cause delayed eruption of permanent teeth, and may require extraction. Malcic et al (2006) assessed the prevalence of dilaceration in Caucasian patients. Nine hundred and fifty-three periapical intraoral radiographs and 488 panoramic radiographs were evaluated. The results of the study showed that dilacerations were found more commonly in the maxilla and posterior teeth were the highest affected. The prevalence of the root dilacerations were mandibular third molars (24.1%), maxillary first molars (15.3%), maxillary second molars (11.4%) and maxillary third molars (8.1%). Hamasha et al (2002) studied the prevalence of dilaceration in Jordanian adults. 4,655 teeth from 814 dental records were evaluated. The results of the study showed that the mandibular third molar teeth were the most commonly affected teeth followed by the mandibular first molars. The maxillary anterior teeth and mandibular incisors were least affected. Almost two-thirds of the dilacerations were in the mandible and approximately 5% were in anterior teeth. Radiographically when the roots are dilacerated toward the buccal or lingual directions, a round opaque area with a dark shadow in its central region, cast by the apical foramen along with the root canal surrounded by a radiolucent halo formed by the periodontal ligament space is typically seen. This finding has been termed ‘bull’s eye’ appearance. Extraction may be difficult and result in root fracture on removal. Perforation of roots is a complication associated with root canal treatment of the dilacerated teeth.

Talon Cusp Mitchell in 1892 first described talon cusp as a prominent accessory cusp on the lingual surface of a maxillary incisor. 39


Figure 56

Intraoral photograph showing talon cusp in relation to the maxillary right lateral incisor. Courtesy: Department of Oral Medicine and Radiology. MCODS, Mangalore

Talon cusp was later defined by Gorlin and Goldman as a very high accessory cusp, which may meet the incisal edge of the tooth to give rise to a T- or a Y-shaped configuration. The name talon was used because this dental anomaly resembled the claw of an eagle (Figure 56). Talon cusp predominantly affects the permanent dentition. However there are reports of involvement of the deciduous dentition. Almost 90% of the talon cusps occur in the maxilla. The teeth commonly affected are the lateral incisors, central incisors and rarely the canines. Some authors have reported the presence of labial or facial talon cusps and very few reports mention the presence of facial and lingual talon cusp occurring on the same tooth. Males and females are equally affected. Etiopathogenesis A polygenetic component along with various external influences is proposed to be the cause for the formation of the talon cusp. It is believed that the compression of the lateral incisor tooth germ between the central incisors and canine during the morphodifferentiation stage will either produce infolding of the dental lamina (dens invaginatus) or an outfolding (dens evaginatus/talon cusp). Clinical classification of talon cusp Hattab et al classified talon cusps as Type 1 talon, Type 2 semi talon and Type 3 trace talon. However this classification did not take into consideration the presence of the talon cusp on the facial aspect of the tooth. Later on this classification was modified by Stephen-Ying et al, as major, minor and trace talon. Type 1 (major talon): A morphologically well-delineated additional cusp that prominently projects from the facial 40

or palatal/lingual surface of an anterior tooth and extends at least half the distance from the cementoenamel junction to the incisal edge. Type 2 (minor talon): A morphologically well-defined additional cusp that projects from the facial or palatal/ lingual surface of an anterior tooth and extends more than one fourth, but less than half the distance from the cementoenamel junction to the incisal edge. Type 3 (trace talon): Enlarged or prominent cingula and their variations, which occupy less than one-fourth the distance from the cementoenamel junction to the incisal edge. Talon cusp can either occur as an isolated dental anomaly or found in association with other developmental disturbances like supernumerary teeth, microdont and macrodonts. Literature reveals the association of talon cusp with Mohr syndrome (oral-facial-digital syndrome, type II), incontinenta pigmentii achromians (Bloch– Sulzberger syndrome), Rubinstein–Taybi syndrome, Ellis– van Creveld syndrome, Sturge–Weber syndrome and Alagille’s syndrome. Radiographically, the talon cusp is seen as a radiopaque structure, in which the enamel, dentin and occasionally the pulp can be seen. Typically the cusp resembles a V-shaped structure superimposed over the normal image of the crown. The common problems associated with talon cusps are increased susceptibility to caries, occlusal interferences and esthetic concerns. Other associated problems are speech disturbances, tongue irritation, accidental cuspal fracture and periodontal problems due to excessive occlusal forces. This accessory cusp can be removed via periodic selective grinding, such that adequate time is allowed for deposition of tertiary dentin and pulpal recession.

Dens Invaginatus Dens invaginatus has also been referred to as dens in dente and gestant odontome. Dens invaginatus is an enamel-lined surface invagination of the crown or root. Based on the site the condition may be subdivided into coronal and radicular forms. Cementum-lined invaginations of the root are considered variations in the root morphology and are not a type of invaginatus. The coronal form is formed by the infolding of the enamel organ into the dental papilla. The radicular form of dens invaginatus is produced because of the invagination of the Hertwig’s epithelial root sheath. The invagination can be of varying lengths. It may be restricted to the coronal portion or it may extend into the root. When it extends into the root, it may or may not communicate with the pulp. If the invagination is too extensive it gives the appearance of a tooth within a tooth (dens in dente) (Figure 57). Some of the invaginations can get


Figure 57

Figure 58 Coronal dens in dente

Type I

Type II

Type III

The three stages of dens in dente based on Oehlers classification. Type I dens invaginatus, Type II dens invaginatus, Type III dens invaginatus. Courtesy: Dr Ravikiran Ongole

Intraoral radiograph showing dens in dente appearance. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

dilated, with dystrophic enamel at the base and these are referred to as dilated odontomas. Such teeth usually show abnormal crowns. Others may perforate the root and cause inflammatory lesions in spite of the vital pulp. Oehlers in 1957 classified coronal dens invaginatus into three types, depending on the depth of invagination (Figure 58). Type I: Invagination ends in a blind sac, limited to the dental crown. Type II: Invagination extends to the cementoenamel junction, also ending in a blind sac. Type III: Invagination extends to the interior of the root, providing an opening to the periodontium, sometimes presenting another foramen in the apical region of the tooth. The maxillary teeth are more commonly affected. Dens invaginatus most commonly affects the maxillary lateral incisor followed by the central incisors, premolars, canines and the molars. Radiographically dens invaginatus is evident as a looplike or pear-shaped defect lined by a radiopaque line with density equal to that of enamel, resembling a tooth within a tooth. In severe forms of invagination, the crown is malformed and an open apex is present. The point of invagination is caries prone and as a preventive measure, restoration is recommended. If the tooth is carious and the invagination is close to the pulp then indirect pulp capping is done. However pulpally involved invagination is best managed by endodontic treatment.

Dens Evaginatus Dens evaginatus has also been referred to as occlusal enamel pearl, Leong’s premolar, tuberculated cusp, accessory tubercle, occlusal tuberculated premolar and evaginatus odontomas. Dens evaginatus is a rare developmental anomaly characterized by the presence of an accessory cusp or enamel pearl on the occlusal surface of the premolars occurring between the cusps. The tubercle consists of enamel, dentin and pulp. The condition occurs as a result of proliferation and evagination of an area of the inner enamel epithelium and the underlying dental papilla into the enamel organ during early stages of tooth development. It is believed that the prevalence of this condition ranges between 1 and 4%. It occurs most commonly in the Mongoloids, Chinese, Thai and Caucasians. The premolars are most commonly affected followed by the molars, canines and incisors. The mandibular teeth are five times more frequently affected than the maxillary teeth. Presence of the occlusal tubercle can lead to occlusal disharmony, attrition and tendency to fracture thereby resulting in pulpal exposure. The involved tooth can turn non-vital. Some authors have reported fascial space infections and osteomyelitis. Grinding of the accessory cusp along with indirect pulp capping is recommended. Non-vital teeth are best treated endodontically. Shovel-shaped incisors Shovel-shaped incisors may be seen in association with dens evaginatus. Marginal ridges of the incisors are prominent 41


and lingual surface is hollowed resulting in a shovel shape. At the cingulum a deep pit or fissure or in some cases dens invaginatus may be seen. These are caries-prone and hence should be restored soon after eruption.

Figure 59

Taurodontism Taurodontism originated from the Greek words ‘tauros’ meaning bull and ‘odontos’ meaning tooth. Like the name suggests the tooth resembles the tooth of a bull. The term taurodontism was first used by Keith in 1913. He defined taurodontism as ‘a tendency for the body of the tooth to enlarge at the expense of the roots. According to Witkop ‘taurodont teeth have pulp chambers in which the bifurcation or trifurcation is displaced apically, so that the chamber has a greater apico-occlusal height than in cynodont teeth and lacks a constriction at the level of the cementoenamel junction. The distance from the bifurcation or trifurcation of the roots to the cementoenamel junction is greater than the occlusal-cervical distance’. In this condition the body of the tooth (usually the molars) is enlarged and rectangular in shape at the expense of the roots. The teeth thus resemble bull’s teeth. The pulp chamber is large, with a greater apico-occlusal height. It also lacks the constriction at the cervix. Shaw in 1928 classified the affected tooth into three subtypes based on the degree of apical displacement of the pulpal floor, namely hypotaurodontism, mesotaurodontism and hypertaurodontism (Figure 59). Taurodontism is more frequently seen in permanent dentition compared to deciduous dentition (Figure 60). The first molar is the most frequently affected followed by the second and the third molar (Figure 61). Premolars may also be affected (Figure 62). Taurodontism may be associated with multiple syndromes. A few of the syndrome associated with this condition have been listed in Table 5. The condition needs no specific dental management. However there is difficulty in locating, instrumenting and obturating pulp canals during endodontic treatment.

A

B

C

Shaw’s classification of the subtypes of taurodontism. (A) Normal tooth. (B) Mild taurodontism (hypotaurodont). (C) Moderate taurodontism (mesotaurodont). (D) Severe taurodontism (hypertaurodont). Courtesy: Dr Ravikiran Ongole

Figure 60

Orthopantomograph showing taurodontism in deciduous dentition. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 61

Ectopic Enamel It is a term used to describe the enamel present in unusual locations like the root. Enamel pearls and cervical enamel extensions are two types of ectopic enamel seen (Figure 63).

Enamel Pearl (Enameloma) It is an ectopic mass of enamel which can occur anywhere on the roots of teeth but is usually found at the furcation area of roots. Maxillary molars are more frequently affected than the mandibular molars. Premolars and incisors are rarely affected. These radiopaque droplets may also contain 42

D

Intraoral periapical radiograph showing taurodontic maxillary permanent first molar. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore


Figure 62

Figure 63

A

B

C

Types of ectopic enamel. (A) Normal cervical enamel. (B) Extension of cervical enamel. (C) Enamel pearl in the furcation area. Courtesy: Dr Ravikiran Ongole Intraoral periapical radiograph showing taurodontic mandibular permanent second premolar. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 64

Table 5 Taurodontism and syndrome association Aarskog syndrome (Dayal et al, 1990) Amelogenesis imperfecta, severe form (Pavlic et al, 2007) Amelo onycho hypohidrotic syndrome (Herrerias et al, 1987) Chondroectodermal dysplasia/Ellis–van Creveld syndrome (Hunter et al, 1998) Down syndrome (Moraes et al, 2007) Goltz–Gorlin syndrome (McNamara et al, 1996) Hypophosphatemic vitamin D rickets (Goodman et al, 1998) Hypohidrotic ectodermal dysplasia (Glavina et al, 2001) Klinefelter’s syndrome (Schulman et al, 2005) Lowe syndrome (Tsai et al, 1997) Microcephalic dwarfism (Sauk Jr, 1973) Seckel syndrome (Seymen et al, 2002)

Intraoral periapical radiograph showing radiopaque enamel pearl in the furcation area of the mandibular first molar. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Smith–Magenis syndrome (Tomona et al, 2006) Tricho-dento-osseous syndrome (Wright et al, 2008) Trisomy 18 (Ribiero et al, 2006) von Gierke’s disease/glycogen storage disease type IA (Avsar, 2007)

The complications associated with the presence of the ectopic enamel in deciduous teeth are delayed exfoliation of the primary tooth and deviation in the eruption path of the succedaneous tooth.

Wolf–Hirschhorn syndrome (Johnston et al, 2006) XXXXY syndrome (Hata et al, 2006)

small amounts of dentin and pulp (Figure 64). Removal of the lesion may lead root caries, external resorption and pulpitis, as the pearl may contain vital pulp tissue. Hence they are not generally treated; maintenance of good oral hygiene is recommended. Literature review shows reports of enamel pearls occurring in the furcation area of deciduous teeth.

Cervical Enamel Extensions (Cervical Enamel Projections) In this condition, enamel extends from the CEJ toward the bifurcation of molars forming a triangular extension on the buccal surface. Localized loss of periodontal attachment may be seen with furcation involvement. This may lead to formation of buccal bifurcation cyst. Flattening or removing the enamel in combination with an excisional 43


new attachment procedure and furcation plasty is done to achieve a durable attachment.

Supernumerary Roots/Accessory Roots This is characterized by an increase in the number of roots, commonly in the third molars, mandibular canines and premolars (Figure 65). These supernumerary roots may occur due to the disturbances of the Hertwig’s epithelial root sheath during root formation. During extraction it is important to make sure that all the roots are removed. This condition may also pose problems during endodontic procedures.

surface of the crown of the mandibular molar. The protostylid is usually seen on the first or third permanent molars or in deciduous lower second molars. It is seen in almost 40% of the population. The appearance can vary from a simple pit in the buccal groove to a furrow or a prominent cusp (Figure 69). The Uto-Aztecan upper premolar is known to occur only in native Americans, with its highest frequency in Arizona. It occurs in the permanent upper first premolar. In this trait the buccal cusp may bulge out to the buccal aspect with a marked fossa in its distal shoulder (Figure 70).

Figure 66

Supernumerary Cusps/Accessory Cusps The common accessory cusps that are seen are talon cusp, dens evaginatus, cusp of Carabelli and protostylid of lower molars. Other rare alterations in morphology are the 6th cusp, 7th cusp, Uto-Aztecan upper premolar, deflecting wrinkle and sinodonty. These alterations in tooth morphology are race specific. Occasionally the accessory cusps can be located on non-specific sites on the tooth surface (Figures 66 and 67). The cusp of Carabelli was first described in 1841 by Georg Carabelli, who was a court dentist to the Austrian Emperor Franz. It was also referred to as Carabelli’s tubercle and tuberculus anomalus of Georg Carabelli. This accessory cusp is located on the palatal aspect of the mesiopalatal cusp of the maxillary molar. Though this trait is commonly seen on the first molar it may also be seen involving the second and the third molar. Permanent and deciduous dentitions may exhibit this trait (Figure 68). Protostylid was first described and extensively studied by Dahlberg (1945). Protostylid is a feature on the mesiobuccal

Accessory cusp on the lingual surface of the mandibular molar. Courtesy: Department of Oral Pathology, MCODS, Mangalore

Figure 67 Figure 65

Tooth specimen showing six roots in a mandibular molar. Courtesy: Department of Oral Pathology, MCODS, Mangalore

44

Accessory cusps in relation to the buccal aspect of the maxillary first molar. Courtesy: Department of Oral Medicine and Radiology, KLE Society’s Institute of Dental Sciences, Bangalore


Developmental Disturbances in Number of Teeth This includes total absence of teeth (anodontia), reduced number of teeth (hypodontia and oligodontia), and increased number of teeth (hyperdontia/supernumerary teeth). Hypodontia and oligodontia Hypodontia is lack of development of one or more teeth. Oligodontia refers to lack of development of six or more teeth. Anodontia is rare and most cases occur in the presence of ectodermal dysplasia. Damage to dental lamina before tooth formation can result in hypodontia. Causes of hypodontia include genetic (autosomal dominant, recessive or sex-linked patterns), trauma, endocrine disturbances, infection, radiation and chemotherapeutic medications. Hypodontia may also occur in hereditary syndromes such as Crouzon syndrome, Down’s syndrome, ectodermal dysplasia, Hurler syndrome and Turner syndrome (Figure 71). Hypodontia is more common in females. It usually affects permanent third molars, second premolars and lateral incisors in that order. Associated microdontia may be

observed. Hypodontia may cause abnormal spacing of teeth, delayed tooth formation, delayed deciduous tooth exfoliation and late permanent tooth eruption. Prosthetic replacement of teeth may be needed. Hyperdontia Hyperdontia results from development of excess dental lamina and additional tooth germ formation. This may show a hereditary pattern (autosomal dominant) and may be a part of Apert syndrome, cleidocranial dysplasia, Ehlers– Danlos syndrome, Gardner syndrome and Sturge–Weber syndrome. These teeth are referred to as supernumerary teeth. Supernumerary teeth are commonly unilateral. Macrodontia and male predominance are seen. Most develop during first two decades of life. Single tooth hyperdontia is

Figure 70 Lingual

Figure 68 Mesial

Distal

Carabelli cusp Distal

Buccal

Mesial

The location of cusp of Carabelli on the maxillary permanent first molar. Courtesy: Dr Ravikiran Ongole

The Uto-Aztecan feature in the maxillary first premolar. Courtesy: Dr Ravikiran Ongole

Figure 71 Figure 69 Buccal

Mesial

Distal

Lingual

Location of protostylid on the mandibular first permanent molar. Courtesy: Dr Ravikiran Ongole

Orthopantomograph of a patient suffering from ectodermal dysplasia showing hypodontia. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

45


Figure 72

Double mesiodens in the maxillary incisor region. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

seen more in permanent dentition and approximately 90% present in maxilla with a strong predilection for anterior region. Most common sites are maxillary incisors, maxillary fourth molars, mandibular fourth molars, premolars, canines and lateral incisors in that order. Non-syndrome multiple supernumerary teeth occur most frequently in mandible and in premolar region. Supernumerary teeth may be seen in gingiva, maxillary tuberosity, soft palate, maxillary sinus, sphenomaxillary fissure, nasal cavity, and between the orbit and brain. Several terms have been used to describe supernumerary teeth according to their location. Mesiodens: Maxillary anterior incisor region (Figures 72 and 73). Paramolar: Lingually or buccally to a molar tooth (Figure 74). Distomolar/distodens: Distal to third molar (Figure 75). Supernumerary teeth may predispose the area to subacute pericoronitis, gingivitis, periodontitis, abscess formation, odontogenic cysts and tumors. Early removal of accessory tooth is recommended. Supplemental teeth are supernumerary teeth. However they resemble the morphology of the tooth they are associated with (Figure 76).

Disturbances of Eruption of Teeth Premature eruption Deciduous or permanent teeth may erupt prematurely. This may involve single tooth or the entire dentition. Prematurely erupted teeth were earlier known by various other names such as ‘congenital teeth’, ‘fetal teeth’ and dentitio praecox. Massler and Savara suggested the terms natal and neonatal teeth. According the new terminology deciduous 46

Figure 73

Mesiodens. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 74

A buccally placed paramolar. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

teeth found in infants at birth is called natal teeth and those erupting within 30 days after birth called neonatal teeth. Sponge and Feasby further subdivided these teeth into mature or immature. It is believed that the incidence of natal and neonatal teeth is approximately between 0.3% and 0.5%. These teeth generally erupt in the same position as that of deciduous teeth in the arch. These teeth are commonly seen in the mandibular incisor region. Based on the reports of various authors, the site of eruption of natal and neonatal teeth are: mandibular incisor region (85%), maxillary incisor region (11%), mandibular canine region (3%) and maxillary canine and molar regions (1%).


Figure 75

Histopathological evaluation of ground sections show hypomineralized enamel and loss of normal architecture of the enamel rods. The normal architecture of dentinal tubules is lost. The teeth have large pulpal chambers. The presence of these prematurely erupted teeth in infants can cause difficulty in suckling. Riga–Fede disease is a well-recognized lesion associated with natal and neonatal teeth. It is characterized by the presence of a traumatic ulcer on the lingual surface of the tongue or lingual frenum. The ulcer is formed secondary to the trauma caused by these teeth during suckling. Delayed eruption

Intraoral radiograph showing a ‘microdontic’ distomolar placed paramolar. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 76

Grossly delayed eruption of teeth may affect both deciduous and permanent dentition and can be localized or generalized. Local causes include retained deciduous tooth and gingival hyperplasia. Systemic causes include rickets, cretinism and cleidocranial dysplasia. In most cases the cause may be difficult to ascertain. One such factor may be the lack of eruptive force. Treatment of local factors or primary conditions would lead to eruption of the affected teeth. Eruption sequestrum When a molar erupts, the bone overlying the cusps is resorbed earlier, leaving a tiny irregular spicule of bone, or sometimes a complex odontoma in the central occlusal fossa. This may be asymptomatic or cause slight soreness. It appears as a tiny irregular radiopacity overlying the central occlusal fossa but separated from tooth itself. The bone would ultimately disappear by sequestration during the eruption. If it remains in the soft tissue it can be removed.

Supplemental teeth bilaterally on the lingual aspect of the mandibular premolars. Courtesy: Dr Sumanth

Etiopathogenesis The etiology for the occurrence of these teeth is still not known. Various theories have been proposed to explain the occurrence of these teeth. Some authors believe that excessive development during the initiation and proliferation stage will produce these teeth. Another theory put forth suggests that there could be hyperactivity of osteoblastic cells within the tooth germ. It is also believed that a superficial positioning of tooth germs during developmental period may cause premature eruption of these teeth. Endocrine disturbances may also be an etiologic factor. When the entire dentition is affected, hyperthyroidism should be considered. The prematurely erupted teeth are well-formed and normal in all respects, except that they may be somewhat mobile.

Transposition of teeth Peck et al described dental transposition as the positional interchange of two adjacent teeth, or the development or eruption of a tooth in a position normally occupied by a non-adjacent tooth. The transposition can either be complete (crowns and the roots of the involved teeth exchange positions in the dental arch) and incomplete (crowns are transposed, but the roots remain in their original positions). It is estimated that approximately 1% of the population exhibit transposition of teeth. It can be seen in the maxillary or mandibular teeth. Transposition can either be unilateral or bilateral. The common teeth that show transposition are canine-first premolar in the maxilla (Figure 77) and the mandibular canine-lateral incisor. Though literature review reveals almost all cases of transpositions affecting the permanent dentition, Duncan et al (1996) reported the fusion and transposition of the maxillary right central and lateral primary incisors. Etiology Some authors believe that dental transposition occurs because of interchange of developing tooth buds. 47


Figure 77

Orthopantomograph showing bilateral transposition of canine—first premolar in the maxillary arch. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Several theories have been proposed to account for dental transposition, including the interchange of developing tooth buds, inherited condition, altered eruption paths, trauma and the presence of retained primary teeth. It is also believed that root dilacerations of the adjacent teeth may be a potential etiological factor of canine-premolar transpositions. Peck and Peck classified dental transpositions based on the teeth involved as: ❍ ❍ ❍ ❍ ❍ ❍

Maxillary canine-first premolar (Mx.C.P1) Maxillary canine-lateral incisor (Mx.C.I2) Maxillary canine to first molar site (Mx.C to M1) Maxillary lateral incisor-central incisor (Mx.I2.I1) Maxillary canine to central incisor site (Mx.C to I1) Mandibular lateral incisor-canine (Mnd.I2.C).

Since they are asymptomatic no active management is necessary. Transmigration The term transmigration is used to describe the preeruptive migration of a tooth across the midline of the jaw. It is believed that transmigration is unique to the mandibular permanent canines. However Aras et al (2008) and Aydin et al (2003) reported transmigration of maxillary canines. Various authors have proposed diagnostic criteria for transmigration. Some believe that an impacted mandibular canine that has crossed the midline more than half of its length should be considered as transmigrated. Others suggest that the tendency of a canine to cross the mandibular midline is a more important consideration than the distance of migration after crossing the midline. Mupparapu (2002) proposed a classification system to trace the pathway of transmigration. However, this classification system is presently being improved upon by many authors to accommodate various patterns of transmigration. 48

Classification of transmigrated canines Type 1: The canine is impacted mesioangularly across the midline, labial, or lingual to the anterior teeth with the crown portion of the tooth crossing the midline. Type 2: The canine is horizontally impacted near the inferior border of the mandible below the apices of the incisors. Type 3: The canine has erupted either mesial or distal to the opposite canine. Type 4: The canine is horizontally impacted near the inferior border of the mandible below the apices of either premolars or molars on the opposite side. Type 5: The canine is positioned vertically in the midline with the long axis of the tooth crossing the midline. Over retained deciduous canines or missing permanent canines in a patient can be radiographically evaluated to assess for impacted or transmigrated teeth.

Impacted Teeth Impaction of a tooth occurs when its eruption is impeded by a physical barrier. Impaction of deciduous teeth is rare; it generally involves the second molars, probably due to ankylosis. In the permanent dentition, third molars are impacted most frequently (mandibular commoner than maxillary). This is followed by maxillary cuspids and mandibular premolars. In permanent teeth, the causes for impaction include insufficient maxillofacial development, overlying cysts or tumors, trauma, thickened overlying bone or soft tissue. Impacted teeth may erupt partially or completely encased within the bone. The former may be associated with pericoronitis and the latter may cause resorption of roots of adjacent tooth, periodic pain or trismus; dentigerous cysts and adenomatoid odontogenic tumors are common in these. Multiple impacted teeth may be related to syndromes and metabolic disorders such as cleidocranial dysostosis, Gardner syndrome, Yunis–Varon syndrome, tricho-dento-osseous syndrome, GAPO [growth retardation, alopecia, pseudoanodontia (failure of tooth eruption) and progressive optic atrophy] syndrome and mucopolysaccharidoses. However literature review also shows reports of multiple impacted teeth in non-syndromic individuals (Figure 78). Impaction may be classified according to angulation of tooth in relationship to the remaining dentition: mesioangular impaction (Figure 79), distoangular, vertical (Figure 80) and horizontal (Figure 81). There can be variation of angulation in sagittal plane, the impacted third molars may be deflected buccally or lingually (Figure 82). When the crown points toward the inferior border of mandible or when it is completely within the ramus of mandible it is referred to as inverted impaction (Figure 83). Occasionally interesting patterns of impacted teeth are seen such as ‘sleeping molars’ (Figure 84) and ‘kissing molars’ (Figure 85).


Figure 78

Figure 80

Orthopantomograph showing multiple impacted teeth in a non-syndromic individual. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 79 Cropped orthopantomograph showing vertically impacted mandibular third molar. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 81

Orthopantomograph showing mesioangularly impacted mandibular third molars bilaterally. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Impacted teeth are usually considered for removal when they are symptomatic or causing resorption of adjacent and undergoing a cystic degeneration.

Orthopantomograph showing horizontally impacted mandibular third molars bilaterally. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Ankylosed Deciduous Teeth (Submerged Teeth) In this condition, there is fusion of cementum or dentin with the alveolar bone preventing shedding of the deciduous teeth. Proposed causes include changes in local metabolism, trauma, infection and genetic influence. These are commonly seen in mandibular first molars. The affected teeth lie well below the occlusal plane; a sharp solid sound is heard on percussion in contrast to the dull sound of the normal teeth. Radiographically partial absence of periodontal ligament is observed. The adjacent teeth often incline toward affected tooth, leading to occlusal and periodontal problems (Figure 86). Supra-eruption of the opposing tooth may also be seen. Impaction of underlying permanent tooth may also occur. Since forceps extraction is not possible, surgical removal is recommended.

Figure 82

Orthopantomograph showing buccoversion of an impacted mandibular third molar. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

49


Figure 83

Developmental Disturbances in Structure of Teeth Developmental defects affecting the structure of enamel Overview of amelogenesis The development of enamel occurs in two phases: 1. 2.

Orthopantomograph showing the crown of the third molar directed toward the lower border of the mandible. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

The secretory phase The maturation phase

In the first phase, ameloblasts secrete enamel matrix by the secretion of enamel proteins like amelogenins and enamelins, and also aid in its immediate partial mineralization. The second phase, the maturation of enamel takes place by introduction of more mineral that is accommodated by the removal of water and organic matter. The defects that arise in the structure of enamel may be traced back to occurring at any of these phases. Accordingly, most systems of classification of developmental defects of enamel relied on this convenient yet simplistic view of enamel formation. The defects in enamel may thus be broadly classified as follows: 1.

Figure 84 2.

Hypoplastic enamel, a quantitative defect of enamel (as a result of defective/deficient enamel matrix formation), and Hypomineralized enamel, a qualitative defect of enamel (as a result of defective mineralization/maturation of enamel).

The entire process of amelogenesis is influenced by a number of environmental influences and genetic mutations, causing aberrant enamel formation. The further categorization of enamel hypoplasia is done on the basis of the cause as follows: Orthopantomograph showing bilateral sleeping molars. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

1. 2.

Hereditary enamel hypoplasia (amelogenesis imperfecta) Environmental enamel hypoplasia.

Figure 86

Figure 85

Orthopantomograph showing kissing molars on the left side. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

50

Orthopantomograph showing submerged mandibular right side first molar. The radiograph also shows adjacent teeth tipping over the submerged tooth. Multiple impacted teeth are also seen. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore


Genes associated with amelogenesis Numerous genes are expressed in an orderly fashion during the various stages of the formation and maturation of enamel. The protein products of these genes regulate gene expression and ameloblast function. More than a thousand genes may potentially be involved in odontogenesis with hundreds involved in amelogenesis alone. With such a highly regulated process orchestrated by so many genes, it is not surprising that 25–80% of the general population suffers from enamel defects. Below are mentioned a few candidate genes for the causation of structural defects in enamel. AMELX: Tooth-specific gene expressed in preameloblasts, ameloblasts and in remnants of the epithelial root sheath. Its product amelogenin forms the bulk of the protein in developing enamel and is crucial for the regulation of the size and shape of enamel crystallites. ENAM: Expressed predominantly by the enamel organ. Its gene product is enamelin that may interact with amelogenin to determine the length of enamel crystallites. KLK4: Kallikrein-4 codes for a calcium-independent serine protease that is secreted during the maturative phase of enamel development. Mutation of KLK-4 results in poorly mineralized enamel. MMP-20: A gene that codes for a calcium-dependent proteinase that is a member of the MMP family. Its product, enamelysin is a proteinase that cleaves amelogenin and plays a major role in processing the enamel matrix proteins. DLX3: A homeobox gene that is homologous to the distal-less (Dll) gene of drosophila and is critical for craniofacial, tooth, brain, hair and neural development. Ameloblastin (product of AMBN), Tuftelin (product of TUFT1), Amelotin (product of AMELOTIN) and Dentin Sialophosphoprotein (DSPP) are a few other gene products that are involved in amelogenesis.

is the significant time when crowns of all permanent teeth (except those of the third molars) develop. Hypoplasia of the primary teeth and the cusp tips of the first molars would reflect ameloblast damage in utero. Once teeth have fully calcified, they are immune to these external factors, namely, a. Ingestion of fluoride b. Chemicals c. Nutritional deficiencies d. Exanthematous diseases/infections e. Birth-related injuries f. Metabolic disorders g. Celiac disease. Clinical features While the appearance of the hypoplastic enamel varies depending upon the specific etiology, mostly teeth affected by enamel hypoplasia appear to have deficient thickness of enamel. This may manifest as any/all of the following: 1. 2. 3. 4.

Affecting a single tooth, a group of teeth, or all of the teeth. Pits or grooves on the enamel surface (Figure 87). An overall reduction in enamel thickness. White in color and opaque (lacking the translucency of normal enamel), later changing color after eruption to yellowish–brown.

Local infection or trauma Local trauma or infection (e.g. abscess formation) can affect ameloblasts overlying a developing crown, resulting in enamel hypoplasia or hypocalcification. The affected permanent tooth is also known as ‘Turner’s tooth’ and the condition referred to as ‘Turner’s hypoplasia’.

Environmental Enamel Hypoplasia Ameloblasts are sensitive to various forms of injury and insults, either local or systemic, during the process of amelogenesis. The effect of the external factors (like metabolic and genetic conditions) leaves a lasting impression on the formed enamel that cannot be erased as enamel does not ‘heal’ unlike other tissues in the body. With knowledge of the chronology of various stages in the formation of a tooth and a wellelicited history from the patient, a good clinician will be able to trace the event that led to the hypoplasia of enamel. The known environmental factors influencing ameloblast function during amelogenesis are: 1.

2.

Localized causes: a. Local infection or trauma b. Irradiation Systemic causes: Systemic causes may have an effect on permanent teeth if they occur between the time soon after birth and before the age of 6 years, as this

Figure 87

Grooves and pitting defects in enamel hypoplasia. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

51


Most commonly seen to affect permanent maxillary incisors or maxillary or mandibular premolars, as a result of periapical infection of the deciduous predecessor or trauma involving the deciduous tooth being forced into the follicle of the underlying permanent tooth. The affected tooth exhibits an irregular surface with pits and most often has a smaller crown than normal. The tooth may show a mild brownish discoloration. The severity of the hypoplasia depends upon the severity of the infection and the stage of development of the underlying permanent tooth.

Figure 88

Irradiation Radiation in the region of the developing teeth and jaws results in discoloration of enamel besides anodontia and microdontia. Ingestion of fluoride The ingestion of excessive amounts of fluoride (more than one part per million) results in a characteristic form of enamel hypoplasia called as ‘mottled enamel’, first described by GV Black and Frederick McKay in 1916. Mottled enamel is mostly endemic in areas where the drinking water contains excessive amounts of naturally occurring fluoride. The severity of mottling however varies even in an endemic area and may depend on the duration of exposure, timing of exposure relative to enamel formation and the frequency of exposure to high concentrations of fluoride in water. Mild-to-moderate fluorosis manifests as occasional white flecks or enamel spots to white opaque, lusterless areas that cover larger areas of the crown. Enamel opacities are seen to occur symmetrically around the dental arch. Severe fluorosis manifests as pitted, irregular, brownstained teeth that may have a corroded appearance (Figure 88). Histologically, fluorosed enamel shows a well-calcified surface layer on subsurface areas of diffuse hypomineralization. The perichymata are accentuated. Generally, the teeth affected by endemic fluorosis are relatively caries-resistant. The patient’s only concern is likely to be esthetic. Chemicals Certain therapeutic agents like anticancer drugs, tetracycline, thalidomide, vitamin D as well as compounds like lead, mercury and fluorine are known to cause enamel hypoplasia in addition to other defects like microdontia and hypodontia. Nutritional deficiencies Rickets is the most common known cause of enamel hypoplasia. Generalized malnutrition and deficiencies of vitamins A, C and D are known to cause enamel hypoplasia. The affected enamel appears pitted. Exanthematous diseases/infections These include measles, chicken pox, scarlet fever, CMV, rubella, congenital syphilis, respiratory infections. The 52

Yellowish-brown intrinsic staining of teeth associated with dental fluorosis. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

occurrence of exanthematous diseases and nutritional deficiencies tends to principally affect the permanent incisors, canines and first molars as they form within the first 18 months of life. Thus, the type of enamel hypoplasia that they cause can also be termed ‘chronological hypoplasias’. The enamel appears pitted and may even show a horizontal band of hypoplasia. Congenital syphilis Dental abnormalities as a result of congenital syphilis are fortunately rarely seen nowadays. Hutchinson’s incisor was the term used to denote a characteristic appearance of the anterior teeth in congenital syphilis, where the crowns of the teeth tapered toward the incisal edge, giving it a ‘screw-driver’ appearance. The central portion of the incisal edge was deficient as a result of hypoplasia of the middle labial lobe of the incisor. Mulberry molars is the term used to describe the molar teeth affected by congenital syphilis that have smaller than normal occlusal tables and a nodular occlusal surface that resembles the surface of a mulberry. They have also been referred to as Moon’s molars or Fournier’s molars. Birth-related injuries Hypoxia, premature birth, prolonged labor are some of the birth-related conditions that may result in enamel hypoplasia. It has been noted that the average width of the neonatal line in primary tooth enamel is wider in children born after difficult labor, and is narrower in children born through cesarean section. (The neonatal line is a zone of hypocalcification that serves as a histologic landmark corresponding to the event of birth and denotes the transition from intra-uterine to extra-uterine environment). Metabolic disorders Enamel hypoplasia of varying severity is seen in general systemic conditions like hypocalcemia, hypothyroidism, maternal diabetes and toxemia of pregnancy.


Celiac disease A genetically influenced immune-mediated disorder characterized by damage to the small bowel mucosa as a result of contact with the protein gluten. The cause of enamel defects seen in celiac disease is not known, but it is postulated that the gluten-induced immunological process that occurs between the age of 6 months and 7 years results in malabsorption with attendant hypocalcemia, and damage to the delicate enamel organ. Aine has classified the specific enamel defects seen in children with celiac disease and categorized them from grades I to IV.

Figure 89

Amelogenesis Imperfecta Amelogenesis imperfecta (AI) represents a group of inherited, congenital defects that primarily affect only enamel formation and are not accompanied by morphologic or metabolic defects in other body systems other than tooth form or eruption. Amelogenesis imperfecta has also been known as hereditary enamel dysplasia; hereditary brown enamel and hereditary brown opalescent teeth.

Generalized yellowish-brown discoloration of teeth in amelogenesis imperfecta. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 90

Etiology The trait of AI can be transmitted by either an autosomal dominant, autosomal recessive, or X-linked mode of inheritance. Mutations in the amelogenin gene (AMELX) and enamelin gene (ENAM) are believed to cause X-linked AI and autosomal inherited forms of AI respectively. Recent reports have mentioned the presence of mutations in the KLK4, MMP-20 and DLX3 genes in the etiology of AI. Clinical features The incidence varies between 1:718 (Sweden) and 1:14,000 (Michigan, USA); the data varies widely depending on the geographical clustering of patients. Affects both dentitions (deciduous and permanent); sometimes only a part of the dentition may be affected. Teeth exhibit a yellow to dark brown discoloration (Figure 89); the consistency varying from cheesy to hard. The teeth exhibit pits and grooves and in some cases, enamel may be entirely absent (Figure 90). Classification Amelogenesis imperfecta has been subjected to numerous classifications but the one proposed by Witkop Jr (1989) is the most popular and widely used classification to date. It is based on the predominant clinical and radiographic appearance of the defect and on the mode of inheritance of the trait (Table 6).

Yellowish-brown intrinsic staining of teeth associated with pitting defects in the enamel. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Revision of the concepts of inheritance/ genetics In an autosomal recessive mode of inheritance, both parents carry a single mutated (defective) gene but are protected by the presence of a normal gene which is generally sufficient for normal function. Two defective copies of the gene are required to produce a disorder (i.e. both copies of the gene in each cell are altered). Each child has a 50% chance of being a carrier like both parents and a 25% risk of inheriting the disorder. In an autosomal dominant mode of inheritance, the affected parent has a single mutated gene which dominates 53


Table 6

Amelogenesis imperfecta: classification

Type

Clinical appearance

Type I

Hypoplastic

Type IA Type IB Type IC Type ID Type IE Type IF Type IG

Hypoplastic, pitted Hypoplastic, local Hypoplastic, local Hypoplastic, smooth Hypoplastic, smooth Hypoplastic, rough Enamel agenesis

Type II

Hypomaturation

Type IIA Type IIB Type IIC Type IID

Hypomaturation, pigmented Hypomaturation Snow-capped teeth Snow-capped teeth

Type III

Hypocalcified

Type IIIA Type IIIB

Hypocalcified Hypocalcified

Type IV

Hypomaturation-hypoplastic with taurodontism

Type IVA

Hypomaturation-hypoplastic with taurodontism Hypoplastic-hypomaturation with taurodontism

Type IVB

Mode of inheritance Autosomal dominant Autosomal dominant Autosomal recessive Autosomal dominant X-linked dominant Autosomal dominant Autosomal recessive

Autosomal recessive X-linked recessive X-linked Autosomal dominant

Autosomal dominant Autosomal recessive

Autosomal dominant Autosomal dominant

its normal counterpart. Each child has a 50% risk of inheriting the faulty gene and the disorder. In other words, one copy of the altered gene in each cell is able to cause the disorder. In an X-linked disorder, one normal copy of a gene on the X chromosome is generally sufficient for normal function. Women who have a defective gene on one of their two X chromosomes are protected by the normal copy of the same gene on the second chromosome. This benefit is not available to men since they have one X and one Y chromosome. Each male child of a mother who carries the defect has a 50% risk of inheriting the faulty gene and the disorder. Each female child has a 50% chance of being a carrier like her mother. Males with an X-linked form of disease are generally more severely affected than females with similar mutations. The Lyonization effect/Lyon hypothesis/X chromosome inactivation Since the female has two X chromosomes, a mechanism exists to ensure that only one of them (even if both are normal) will remain active for functioning, and the other X chromosome gets ‘switched-off’ or ‘inactivated’. A recessive disorder is thought to arise from a defect in genes that code for enzymes, while a dominant disorder results from mutation in a gene that codes for a structural protein. 54

Other systems of classification applied to AI include: 1. Weinmann et al (1945); based on phenotype: hypoplastic and hypocalcified. 2. Darling (1956); five phenotypes based on clinical, microradiographic and histopathological findings. 3. Witkop (1957); five types based on phenotype. 4. Schulze (1970); based on phenotype and mode of inheritance. 5. Witkop and Rao (1971); based on phenotype and mode of inheritance. 6. Winter and Brook (1975); based primarily on phenotype with mode of inheritance as system for subclassification. 7. Witkop and Sauk (1976); based on phenotype and mode of inheritance. 8. Sundell and Koch (1985); based only on phenotype. 9. Witkop (1989); based on phenotype and mode of inheritance; the most widely followed system of classification of AI. 10. Aldred and Crawford (1995); based on molecular defect, mode of inheritance, biochemical defect and phenotype. 11. Hart et al (2002); subclassification based on the molecular defect associated with AMELX. 12. Aldred et al (2003); based on mode of inheritance, phenotype (clinical and radiographic), molecular defect and biochemical result.

Type I/Hypoplastic AI Clinical features There is a deficiency of enamel matrix with subsequent normal mineralization. The enamel does not develop to normal thickness; at places the enamel is so thin that crowns do not meet at contact points. The decreased crown height leads to anterior open bite (in about 50% of cases). Enamel matrix defects vary from pinpoint to pinhead size pits arranged in rows or columns on labial or buccal surfaces of permanent teeth. Sometimes pits and grooves of hypoplastic enamel are seen in a horizontal fashion across the middle-third of teeth. In type IE, the carrier females have alternating bands of normal thick and abnormal thin enamel (Lyonization effect). Enamel agenesis is seen in Type IG where the tooth has a rough granular surface and has no contact with adjacent teeth. Radiographic features The enamel, although thin, shows normal contrast from dentin. Square-shaped crowns. Type II/Hypomaturation AI Clinical features Enamel is of normal thickness but has a mottled appearance. It is slightly softer than normal


Figure 91

reveals a family history, presents with all teeth similarly affected, reports a relevant medical history that resulted in metabolic dysfunction at the time of enamel formation or if the clinician can identify a chronological distribution to the appearance of teeth. Differential diagnosis ❍

Orthopantomograph showing enamel having the same radiodensity as that of dentin. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

enamel, and is easily penetrated by the point of a probe and chips away from the crown. Enamel appears clear to cloudy, mottled yellow to brown. Enamel in Type II B has random alternating vertical bands of either opaque white or opaque yellow enamel with bands of translucent normal enamel. The snow-capped teeth (Type II C) have opaque white enamel on the incisal or occlusal thirds of the crowns of teeth. Radiographic features The enamel has approximately the same radio density as dentin (Figure 91). Type III/Hypocalcified Type AI Clinical features Enamel initially develops with normal thickness, is orange yellow in color at the time of eruption. It is friable and soft and consists of poorly calcified matrix which is rapidly lost by attrition leaving cores of dentin. The teeth are sensitive to temperature changes. Cervical enamel is better calcified. Anterior open bite is frequently seen. Radiographic features Enamel is less radiopaque than dentin. Crowns have a moth-eaten appearance with a radiopaque line representing calcified enamel in the cervical area. Type IV This is a combination type wherein features of the hypoplastic and hypomaturation types of AI are seen in combination with taurodontism. Histological features of AI Light microscopic studies of enamel have their limitations and ground sections of teeth affected by AI show a reduction in enamel thickness. Ultrastructural study of enamel in hypoplastic AI shows increased enamel porosity and changes in prism morphology and crystallite organization. Diagnosis Identification of AI is made primarily by clinical examination. A differential diagnosis may be made if the patient

❍

❍

❍

❍

Dentinogenesis imperfecta: Increasing attrition leads to deposition of secondary dentin resulting in the obliteration of the pulp chamber in AI. DI may be excluded from the diagnosis as it exhibits bulbous crowns, narrow roots, obliteration of pulp chambers in the absence of attrition and normal radio density of enamel. Dental fluorosis: Type II C (snow-capped teeth) may be mistaken for fluorosis but does not have the accentuated perichymata seen in fluorosis. If fluorosis is suspected, usually the premolars and second permanent molars may be spared and the history will reveal excessive fluoride intake. Tricho-dento-osseous syndrome: Type IV A of AI is differentiated from tricho-dento-osseous syndrome in the absence of nail, hair and bone changes. Widespread enamel defects similar to those seen in AI may also be seen in conditions like epidermolysis bullosa, tuberous sclerosis and oculo-dento-osseous dysplasia. Molar-incisor hypoplasia: This condition (also called ‘cheese molars’) peculiarly affects the first permanent molars and the permanent incisors, with no symmetrical affliction to strongly suggest a chronological disturbance. It has been suggested that the changes seen are due to a combination of genetic predisposition and environmental insult.

Management The three principles of management of patients with AI involve: 1. 2. 3.

Alleviation of pain and anxiety Restoration and maintenance of the remaining dentition with regard to esthetics Maintenance/restoration of the occlusal vertical height.

The management of young patients with AI is preferably done in three phases. 1.

The temporary phase, undertaken during the primary or mixed dentition. Posterior teeth in the primary and early mixed dentition are generally restored with stainless steel crowns, while anterior teeth in the primary dentition may be restored with composites or polycarbonate crowns. (Since the enamel prisms in teeth affected by AI are irregular, the affected enamel may be pre-treated by sodium hypochlorite solution to enhance bonding). 55


2.

3.

The transitional phase, when all permanent teeth have erupted; this phase continues till adulthood. The anterior teeth in adolescents may be restored using porcelain veneers. The permanent phase, which lasts through adulthood. The anterior teeth may now be restored with porcelain jacket crowns. The anterior open bite may at times require surgical management.

The treatment of AI generally extends over many years and requires the patient’s commitment to regular restorative procedures and meticulous oral hygiene. Frequent topical fluoride applications and dietary control are needed to prevent caries. The roughened enamel surfaces may retain plaque. The exposed dentin may be sensitive. Association of AI with syndromes/conditions It is worth recalling the proposal made by Witkop (1989) that ‘the term amelogenesis imperfecta be limited to those inherited, congenital defects that primarily affect only enamel formation and are not accompanied by morphologic or metabolic defects in other body systems other than tooth form or eruption’. Not withstanding the classification of AI proposed by Witkop in 1989 based on this premise, there are a number of conditions where enamel defects resembling AI do occur, but have no place in Witkop’s classification. Aldred et al (2003) have argued that the definition of AI should be changed to incorporate the statement that the enamel defects may be associated with morphologic or biochemical changes elsewhere in the body’. The reported occurrence of autosomal recessive AI (hypoplastic AI with delayed eruption/failure of eruption of permanent teeth) in some cases of nephrocalcinosis has raised the issue of AI being considered an indicator for renal examination (ultrasound), as unrecognized and untreated nephrocalcinosis is associated with significant morbidity. Occurrences of hypoplastic/hypomineralized AI in association with cone rod dystrophy (autosomal recessive inherited) have been reported. Most of the reported cases are seen to have occurred in close-knit communities that practice consanguineous relationships. The ocular symptoms include photophobia, nystagmus and reduced central vision, with a gradual loss of night vision. Kohlschutter–Tonz syndrome is a CNS degenerative disease with convulsions, dementia, epilepsy, spasticity and characteristic ‘yellow teeth’ that are consistent with hypocalcified AI. Usher syndrome is a genetically inherited disorder characterized by progressive hearing loss and retinitis pigmentosa with progressive loss of vision. A few cases have been reported of patients with Usher syndrome having enamel defects (thin enamel in permanent teeth) that resemble the hypoplastic AI. 56

Developmental Defects Affecting the Structure of Dentin An overview of dentinogenesis At the late bell stage of tooth development, the cells of the inner enamel epithelium induce the adjacent cells of the dental papilla to differentiate into odontoblasts, which are the cells responsible for the formation and mineralization of the most abundant dental tissue, the dentin. The process of dentinogenesis involves the deposition of predentin that subsequently mineralizes to form dentin. The first layer of predentin that is deposited acts as a signal to the overlying inner enamel epithelial cells to differentiate into ameloblasts and begin secreting the enamel matrix. Seventy percent of dentin is mineralized, while the remainder is made up of organic material and water (20% and 10% by weight respectively). The organic component is made up by collagen (mainly type I with small amounts of types III and V) and non-collagenous matrix proteins (mainly dentin phosphoprotein/phosphophoryn, dentin sialoprotein, dentin matrix protein, osteonectin, osteocalcin, etc). The process of dentinogenesis thus involves: 1.

2. 3.

The differentiation of odontoblasts from ectomesenchymal cells of the dental papilla following an organizing influence of the inner enamel epithelium. Formation of organic matrix Mineralization of the formed matrix to the extent of nearly 70%.

Dentinogenesis Imperfecta Dentinogenesis imperfecta (DI) is a hereditary developmental defect of dentin formation resulting in the appearance of opalescent teeth and occurring in the absence of any systemic disorder. It is the most common disorder affecting the structure of dentin. Dentinogenesis imperfecta has also been referred to as Capdepont’s teeth and hereditary opalescent dentin. Etiopathogenesis ❍

Hereditary (autosomal dominant trait) with variable expressivity. ❍ Mutations in the DSPP gene (that encodes for dentin sialophosphoprotein, needed for normal dentin formation) mapped to chromosome 4q, resulting in abnormally soft dentin. ❍ Mutations in the COL1A1 and COL1A2 genes that regulate the structure of Type I collagen that is a component of several soft (skin, joint ligaments) and mineralized tissues (bone, dentin). Classification The original classification by Shields, Bixler and El-Kafrawy (1973) proposed three types of DI which correlates with


Table 7

Dentinogenesis imperfecta: classification

Classification by Shields et al

Classification by Witkop

Gene mutation

DI type I

Dentinogenesis imperfecta

Mutation in COL1A1 and COL1A2 genes

DI type II

Classical hereditary opalescent dentin

Mutation in DSPP gene at 4q 21.3

DI type III

DI found in the Brandywine tri-racial isolate in Maryland

Mutation in DSPP gene

the classification given by Witkop (1979) as depicted in Table 7. [Subsequently, investigators were unable to satisfactorily differentiate clinically and histologically between types II and III when seen in adults. Many researchers now conclude that types II and III are essentially the same with the latter being merely a variation of type II]. Shields type I was initially known as ‘DI occurring in association with osteogenesis imperfecta’, but recently, the term for ‘dentinogenesis imperfecta’ is reserved for similar cases seen in association with osteogenesis imperfecta. The preferred term for only the dental defect in the absence of systemic disease is ‘hereditary opalescent dentin’. However, in the absence of a universal consensus and for reasons of convenience, the terms ‘hereditary opalescent dentin’ and ‘dentinogenesis imperfecta’ will be used synonymously. Clinical features Affects approximately 1 in 6,000 to 1 in 8,000 children, with a predilection for occurrence in whites. Teeth exhibit an unusual translucency and opalescence, and the color of the affected teeth varies from yellowish brown to bluish gray. Affected teeth have bulbous crowns with prominent cervical constriction, and narrow roots. Deciduous teeth are affected more severely, while the permanent second and third molars that develop later are least affected in DI. Enamel fractures easily or rapidly undergoes attrition exposing the underlying dentin (this may be due to the dentinoenamel junction being straight instead of scalloped, thus rendering it unable to withstand shearing forces). Affected teeth are less susceptible to decay (as a result of defective dentin providing fewer pathways for invasion of dental caries). Radiographic appearance Short, blunt roots with partial or total obliteration of the pulp chambers and root canals. Crowns of teeth appear bulbous with cervical constriction (Figures 92–94). Shell teeth are a rare radiographic variant of DI first seen in the Brandywine tri-racial isolate in Maryland, USA.

Figure 92

Orthopantomograph showing bulbous crowns, short and blunt roots Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 93

Intraoral periapical radiograph showing short and blunt roots of maxillary posterior teeth. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Shell teeth are so called because they appear like thin shells of dentin covering large pulps. The enamel may be of normal thickness. The deficiency in thickness of dentin is due to insufficient or defective dentin formation and it may extend to involve even the crown. Histological features Other than a thin layer of mantle dentin, the rest of the dentin has fewer tubules, which are wide and irregular. Areas of atubular dentin are also seen partly or totally obliterating the pulp chamber and root canals. The dentinoenamel junction is smooth instead of being scalloped. Vascular inclusions are sometimes seen in the dentin (probably remnants of pulp tissue). Biochemical analysis of dentin shows increased water content and a decreased mineral content when compared to normal dentin. Following the loss of enamel, the defective dentin rapidly wears away because of the low micro hardness. 57


Figure 94

A defect in Hertwig’s epithelial root sheath causes it to fragment and these fragments get incorporated into the dental papilla where they induce the formation of globules of dysplastic dentin. Clinical features Type I/radicular dentin dysplasia The crowns of affected teeth in both dentitions are normal in shape, size and color. Premature exfoliation of erupted affected teeth (due to their short roots). Affected teeth may be more resistant to dental caries. Pattern of tooth eruption is normal.

Intraoral periapical radiograph of mandibular posterior teeth showing bulbous crowns, short and blunt roots with total obliteration of the pulp chambers and root canals. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Management The rapid loss of enamel and wearing away of dentin has to be compensated in order to maintain vertical dimension for function. However, like many other structural defects in teeth, it is increasingly difficult to retain the affected teeth. The risk of pulp exposure is high in such teeth, and the cervical constriction renders it liable to cervical fracture when teeth are covered by crowns or used as abutments.

Dentin Dysplasia The term ‘dentin dysplasia’ was given by Rushton to describe a rare hereditary condition affecting dentin formation that was first described by Ballschmiede in 1920 as ‘rootless teeth’. The enamel is normal, while the dentin is atypical and there is abnormal pulpal morphology. It has also been referred to as rootless teeth. Dentin dysplasia is of two types; Type I/radicular dentin dysplasia (rootless teeth) is so called because the crowns of the primary and permanent teeth seem normal while the roots appear short/stunted. Type II/coronal dentin dysplasia shows a defect in the crowns of primary teeth, but the lengths of the roots seem normal. Etiopathogenesis Hereditary (autosomal dominant trait). Mutations in the DSPP gene (that encodes for dentin sialophosphoprotein) may be responsible for some cases of type II dentin dysplasia. (This is similar to the mutation seen in DI type II). 58

Type II/coronal dentin dysplasia Rarer than Type I. The crowns of affected teeth in the primary dentition appear opalescent yellow, brown or bluish, whereas the permanent teeth appear normal in color. Periapical lesions are infrequent when compared to Type I. Radiographic appearance Type I/radicular dentin dysplasia The roots are extremely short, blunt and tapering or may be absent in both dentitions. Primary teeth show total pulp obliteration, while the permanent teeth show pre-eruptive pulpal obliteration resulting in crescent-shaped pulpal remnants (chevrons of pulp) parallel to the cementoenamel junction. Periapical radiolucencies (representing chronic granulomas, cysts or abscesses. These lesions may have developed as a result of microscopic communication between the residual pulp and the oral cavity in the absence of clinically apparent dental caries) may be associated with teeth that appear to be vital. Type II/coronal dentin dysplasia Root length is normal in both dentitions. The primary teeth show obliteration of pulp chambers. Permanent teeth exhibit enlarged pulp chambers (thistletube shape in anterior teeth and premolars or flame-shaped in molars) with multiple foci of radiopacity/pulp stones. Histological features Type I/radicular dentin dysplasia Enamel, mantle dentin and most of the coronal dentin appear normal. Deeper layers of dentin and all of the root dentin are dysplastic and shows atypical, amorphous, tubular patterns. Numerous calcified, spherical bodies (denticles?) disrupt the tubular course of dentin formation with the result that dentinal tubules are displaced giving rise to the classic ‘lava flowing around boulders’/‘water streaming around boulders’/‘cascading waterfall’ appearance. Type II/coronal dentin dysplasia The primary teeth show altered dentin, resembling the changes seen in DI. The permanent teeth have normal enamel and coronal dentin, while the roots exhibit atubular, amorphous dentin


and large areas of interglobular dentin. (The atypical dentin seen in coronal dentin dysplasia has a large amount of Type III collagen). Differential diagnosis Teeth affected by DI may resemble those of dentin dysplasia. The differentiating features include: Dentin dysplasia


Color

Yellow to brown to bluish

Yellow to brown to bluish

Crown morphology

Normal, shape and size of crown

Bulbous crown with cervical constriction

Obliteration of pulp chamber

Occurs 5–6 years after eruption of the tooth (type II)

Occurs before tooth eruption

Thistle tube-shaped pulp chamber

Mostly present

Absent

Root morphology

Normal appearing roots (type II) No roots (type I)

Short, narrow roots

Management Meticulous maintenance of oral hygiene is the key to prolonged retention of teeth affected by dentin dysplasia, although the presence of short roots and periapical lesions may make it seem a daunting task for the dentist. Endodontic and periodontal treatment is accomplished reasonably well in teeth affected by coronal dentin dysplasia.

Making Sense of It All! Is it DGI? Or is it DD? Or are they all the same? This is no doubt puzzling as for more than 30 years, the two entities were classified using clinical, radiographic, and histopathologic features. This nosology seemed to suit everyone fine, even though Shields et al (1973) made a mention that ‘the heritable dentin defects can be viewed as a continuum’. Recent research has focused on the genetic mutations that underlie these non-syndromic heritable defects of dentin. Mutations in the DSPP gene (dentin sialophosphoprotein gene) cause varied defects in dentin and the defects are seen to correlate with the severity of the mutation. Accordingly, a new concept is emerging of referring to DI and dentin dysplasia as ‘DSPP-associated dentin defects’. Beattie et al (2006) recommend the setting-up of a gene-based classification system that would group all of the DD-II, DGI-II, and DGI-III cases that are associated with DSPP defects into a single category, and then make distinctions based upon severity. According to the same designations as are currently in use, the DD-II phenotype would be the least

severe, DGI-II intermediate, and the DGI-III phenotype the most severe form of the disease. While not studied in as much depth and interest as the DSPP, the DMP1 (dentin matrix acid phosphoprotein gene) is another candidate gene for these dentin defects. DI type I is the dental phenotype associated with osteogenesis imperfecta and people with this disorder may best be categorized as having osteogenesis imperfecta with DI.

Regional Odontodysplasia Regional odontodysplasia is a rare, localized, developmental disorder of dental origin with affected teeth having characteristic clinical and radiographic appearances. This condition has been described under various names by different authors, but Zegarelli (1963) is credited with coining the term ‘odontodysplasia’ to describe a ‘peculiar dental anomaly of unknown cause’. Later, Pindborg (1970) preferred the term ‘regional odontodysplasia’ to describe the segmental and localized nature of this condition. Regional odontodysplasia has also been termed as ghost teeth, odontogenesis imperfecta, odontogenic dysplasia, unilateral dental malformation, AI non-hereditaria segmentalis and localized hypoplasia (Turner teeth). The term ‘regional odontodysplasia’ best describes the segmental and localized nature of this condition that is of unknown etiology and affects enamel, dentin and pulp. Etiology The cause of this rare dental developmental disorder is not precisely known, but a few theories have been proposed. 1.

2.

3.

A somatic mutation in early tooth development (probably in the developing dental lamina) that disrupts odontogenesis. This may explain the involvement of both deciduous and permanent dentitions. A disturbance in vascular supply that creates local ischemia, thereby affecting odontogenesis. Many cases of odontodyplasia have been reported to be associated with hemangiomas or vascular nevi adjacent to the affected teeth. (Some researchers have even proposed that the irregularities in the dental hard tissues are a result of the ‘blood overflow from vessels’ that affects the local concentration of magnesium and sodium around the crystals). Activation of a latent viral infection of the tooth germ during odontogenesis.

Other theories that have been proposed but are unsatisfactory to explain the occurrence of ghost teeth are a hereditary basis, medications taken during pregnancy, irradiation, and failure of migration of neural crest cells, systemic disorders, Rh incompatibility, nutritional and metabolic disorders. 59


Clinical features Age at presentation is variable (4–23 years); the condition is often diagnosed at the time of eruption of primary and permanent teeth. Affects both primary and permanent dentitions. Generally, the disturbance is localized to one arch, most often the maxillary left quadrant (incisors and canines). Females are affected more often than males (1.7:1); there is no racial predilection observed. Pulp or periapical pathology may be associated with the affected teeth even in the absence of gross dental caries (the pathogens may gain access to the pulp through the clefts in the defective enamel and dentin). Patient may present with delayed/incomplete eruption of teeth and unesthetic appearance of affected teeth. Affected teeth appear hypoplastic and small, discolored yellow to brown with the enamel surface having shallow furrows to severe pits and grooves. The gingiva surrounding the affected teeth may be enlarged.

Figure 95

Orthopantomograph showing irregularly shaped teeth with incomplete root formation in regional odontodysplasia. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Differential diagnosis

Radiographic appearance The affected teeth have a ‘ghost-like’ appearance because of a decreased radiopacity and lack of distinction between the enamel and dentin. The teeth have an irregular shape with hypoplastic crowns. Affected teeth have reduced thickness of dentin with large pulp chambers, presence of pulp calcifications, incomplete root formation and wide open apices (Figure 95). Unerupted teeth may be surrounded by a pericoronal radiolucency (representing an enlarged follicle) with abnormal foci of calcification interspersed. The trabeculae of the alveolar bone adjacent to the affected teeth may show rarefaction. Periapical abscesses may be seen in relation to the affected teeth. Histological features Undecalcified ground sections of the affected tooth have thin, pitted enamel with disorganized/altered prismatic structure. The dentin is thinner than normal, and contains large areas of interglobular dentin, containing clefts that may communicate with the pulp. Areas of amorphous dentin and cellular dentin may also be seen with occasional capillaries. The dentin has fewer tubules than normal. The predentin zone is very wide. The pulp chambers are enlarged and contain pulp stones. Dental follicles are often enlarged and contain epithelial rests and calcifications. Scanning electron microscopy reveals thin enamel with irregular enamel prisms and irregular crystalline aggregates.

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Regional odontodysplasia (RO)


Hereditary basis

Absent

Present

Enamel hypoplasia

Present

Absent

Involvement of teeth

Isolated segment of the arch in either dentition/ few teeth involved

All primary teeth involved

The teeth affected by RO may also be mistaken for odontomes or as being involved by dental caries. Management Depending upon the vitality of the pulp, pulpotomy or apexification may be performed to stimulate root formation. Affected primary teeth may be treated by pulpotomy and restored with steel crowns. However, most dentists prefer to extract the affected teeth for esthetic reasons and rehabilitate the patient with prosthesis. This seems a safer option as the longer the affected teeth are retained; the higher is the risk of development of pathology. However, the clinician must weigh the choice against the psychological effects of a youngster having to remove teeth with a resultant decrease in alveolar bone height, potentially decreasing the ability to optimally restore/rehabilitate the affected area. The possibility of the future use of implants may be discussed with the patient.

CHAPTER

Orofacial Pigmentation Disorders Ajit Auluck, Manuel Thomas

➧ Pigmented Lesions of Oral Mucosa

Molecular and Pathologic Correlation of Pigmentation Metal Pigmentation Diffuse and Multiple Pigmented Lesions Focal/Localized Pigmented Lesions

PIGMENTED LESIONS OF ORAL MUCOSA Oral mucosa can have a variety of discolorations like blue, black, brown or yellow because of endogenous pigments or exogenous materials. Recognition and diagnosis of pigmented lesions of the oral mucosa is an important aspect of clinical dental practice because it may be suggestive of an underlying systemic or metabolic disorder, or it can be an initial stage of malignancy. Therefore, dentists must determine the cause of pigmentation, ask relevant questions in the history to determine the cause and request appropriate investigations for early diagnosis and prompt treatment.

Molecular and Pathologic Correlation of Pigmentation A pigment is any organic or inorganic coloring substance. A pigmented lesion can be defined as an area of altered coloration of the oral mucosa either because of physiologic or pathologic process because of deposition of endogenous or exogenous pigments or embedded foreign material in the tissues. Exogenous substances cause oral mucosal pigmentation because these substances are embedded in the oral tissues either by direct trauma or iatrogenic implantation, amalgam being the most common. Cavity preparation of a tooth with an existing restoration (secondary caries) by a rotary bur can forcefully entrap some fine amalgam particles into the oral tissues. Amalgam can also enter oral tissues while removing old or fractured restorations. It can also accidentally enter into an extraction socket during extraction of a restored

➧

3

Pigmentation of Teeth Extrinsic Discoloration Intrinsic Discoloration

tooth. Amalgam particles can be left behind in the oral tissues after root canal treatment or retrograde amalgam filling. The silver particles from the embedded amalgam restorations slowly leach out and stain reticulum fibers causing gray/ black discoloration of mucosa which is called as amalgam tattoo. Lead pencils contain graphite which is another source of exogenous pigmentation which usually occurs in the palate. Rarely when the graphite fragment gets embedded in the palatal tissues following trauma, the mucosa covering this fractured fragment gets discolored and appears as a bluish black focal pigmented area. In heavy metal poisoning also we can observe oral mucosal pigmentation because of formation of metal sulfides which get precipitated in inflamed areas of gingiva causing bluish black discoloration. Table 1 summarizes the type of exogenous substances that can cause oral mucosal pigmentation. Oral mucosal pigmentation can also occur due to variety of endogenous pigments. Each of these endogenous pigments can result in a distinct oral discoloration suggestive of various disease processes which are described in Table 2. Blue, bluish red and purple type of oral pigmentation generally occur as a consequence of blood or vascular disorders. Black, brown or gray discoloration of the oral mucosa is because of melanin or hemosiderin pigments. Yellow discoloration of oral mucosa is because of bilirubin deposition or ingestion of large amount of beta-carotene. The pigmented lesions can either be localized or diffuse depending upon their etiology or disease process which they manifest. Blood pigments can cause red, bluish red or brown pigmentation of oral mucosa. These pigments are deposited into

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the connective tissues after lysis of erythrocytes causing extravasation of hemoglobin. The extravasation of blood into soft tissues is attributed to trauma, capillary fragility, platelet defects, or clotting disorders. This extravasated hemoglobin is acted upon by the enzymes to form hemosiderin, which is further broken down into bilirubin and biliverdin, all of which cause oral pigmentation. Therefore, the same endogenous pigments may result in different types of oral pigmentations over a period of time. An early hematoma is bluish red in color while a late hematoma becomes dark brown in color. Blood pigments are usually cleared from the skin or mucosa within 2 weeks. Melanin causes blue or blue black discoloration of oral mucosa. Melanin is produced from an amino acid tyrosine by the melanocytes within the membrane-bound organelles called as melanosomes. These melanocytes are found in the basal layers of the oral epithelium. Melanin is also produced by the nevus cells, which originate from the neural crest cells and are found in the skin and mucosa. Color of pigmented lesions caused by melanin deposition may be brown, blue, gray or black, depending on the amount of melanin produced as well as on the location of melanin within the tissues. Oral lesions can occur either due to excessive production of melanin pigment or due to proliferation of melanocytes. Sometimes there is no increase in the number of melanocytes but there is only an increase in the synthesis or production of melanin pigment. Over a period of time the

Table 1

Type of exogenous foreign materials causing pigmentation of oral mucosa

Source

Color

Etiology

Silver, amalgam

Gray, black

Iatrogenic implantation, trauma

Graphite

Gray, black

Tattoo, trauma

Lead, mercury, bismuth

Gray

Ingestion of paints, medicines, poisoning

Chromogenic bacteria

Black, brown, green

Superficial colonization

capacity of cells to store melanin pigment is exceeded and then melanin spills into the underlying connective tissues into the adjacent basilar keratinocytes. This process is called as basilar melanosis and melanin incontinence. In the oral cavity we can observe melanosis over the healed areas which had an earlier injury. When the traumatized oral epithelium regenerates, usually there is overproduction of melanin by the melanocytes that repopulate this region causing post inflammatory pigmentation. Certain hormones and drugs can also influence production of melanin. The adrenal cortical–hypothalamic axis is affected by hypofunction of the adrenal cortex. As serum corticosteroid levels decreases, adrenocorticotropic hormone (ACTH) production by the posterior pituitary increases. ACTH also has a melanocyte stimulatory function so melanin production increases and it causes diffuse melanosis of the oral tissues. Therefore oral mucosal pigmentation can also occur in endocrine disorders. Certain drugs like minocycline can also increase the production of melanin within the cells causing diffuse pigmentation of oral mucosa and is called as drug-induced melanosis. Oral pigmented lesions can also occur due to the proliferation of melanocytes as observed in the cases of nevi and melanoma. Melanocytic nevi develop during childhood and rarely arise in adult life. Most nevi originate from the melanocytes in the basal layer of epithelium and proliferate along the junction with the connective tissue. These are called as junctional nevi. Later these melanocytes drop off into the connective tissue to form islands of cells and are called as compound nevi. Later all these cells are completely detached from basal epithelium and form clusters in the dermis or submucosa and are called as intradermal nevi. Rarely do we observe blue nevi in oral cavity and they are comprised of spindle-shaped melanocytes which synthesize copious amounts of melanin pigment. Occasionally, bluish discoloration of oral mucosa can be due to optical phenomenon as a consequence of accumulation of fluid within the epithelial layers. For example a ranula appears blue in color because the mucous absorbs most of the visible wavelength except blue. In albinism the gene for tyrosinase is mutated. In vitiligo, depigmented patches are caused by diminished number of

Table 2 Type of endogenous pigments, the discoloration caused by them and disease process they indicate

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Pigment

Color

Disease process

Hemoglobin

Blue, red, purple

Varix, hemangioma, Kaposi sarcoma, angiosarcoma, hereditary hemorrhagic telangiectasia

Hemosiderin

Brown

Ecchymosis, petechiae, thrombosed vein, hemorrhagic mucocele, hemochromatosis

Melanin

Brown/black/gray

Melanotic macule, nevus, melanoma, hormonal imbalance, drugs

Bilirubin

Yellow

Jaundice/liver disorder

Carotene

Yellow

Precursor of vitamin A

Chapter 3 – Orofacial Pigmentation Disorders

melanocytes. However, these entities are rarely seen in the oral cavity.

Metal Pigmentation Pigmentation of the oral cavity caused by foreign materials or metals is called exogenous pigmentation. The importance of recognizing oral mucosal pigmentation caused by heavy metals lies primarily in the identification and treatment of the cause to avoid severe systemic toxic effects. Depending on the type of metal implicated, a number of systemic signs and symptoms may be associated with chronic exposure of metals. Amalgam tattoo Amalgam tattoo is the most common solitary focal pigmentation lesion of the oral mucosa. These lesions are generally less than 1 cm (rarely amalgam tattoos can be large) and appear as flat, gray-black to blue-black color macules. They are usually found in close approximation to a restoration. Majority of the lesions are located on the buccal mucosa, gingiva and alveolar mucosa with mandibular region being more affected as compared to the maxillary region (Figure 1). All these lesions are asymptomatic and are discovered during routine dental examination. If particles are large enough they can be viewed with help of a radiograph (taken with reduced exposure parameters for soft tissues). The amalgam granules and fragments are found mainly in the lamina propria but were sometimes also seen

Figure 1

in the submucosa. Histopathologically, we may observe a giant cell reaction surrounding these amalgam particles. Mercury poisoning Mercury poisoning can be because of acute or chronic exposure of mercury vapors. Clinical features include gastric disturbances, diarrhea, excitability, headache and mental depression. Patients complain of gastric disturbances, diarrhea, excitability, headaches and mental depression. Patient may have tremors of lips and extremities, dermatitis and nephritis. Oral manifestations include increased salivation (ptyalism) as mercury is excreted in saliva. Tongue may be enlarged and painful (glossodynia). There may be hyperemia and swelling of gingiva, ulcerative stomatitis, loosening and exfoliation of teeth. Acrodynia (Swift disease, Pink disease) is idiosyncratic reaction to large doses of amalgam. It is an uncommon mercurial toxicity reaction in which skin is also involved. It usually occurs after ingestion of mercury from powder, ammoniated mercury ointment, calomel lotion. It is mainly seen in the children below the age of 5–6 years. Manifestations are widespread involving the hand, feet, nose and cheeks which become red or pink in color, cold and clammy like a raw beef. Skin may have maculopapular rashes with pruritis. Patients may complain of irritability, photophobia and muscular weakness. Children may be able to remove their hair in patches. Oral manifestations include profuse salivation, gingiva is painful and ulcerated, teeth may become loose and exfoliate and bruxism is a common finding. Arsenic Arsenic in both organic and inorganic forms may produce acute or chronic symptoms. Oral manifestations may include increased salivation, gingivitis, and oral ulcerations. Exposure produces severe edema of the eyelids, gastrointestinal irritation, and both central and peripheral neuropathies. Arsenic levels can be assessed by complete blood count, urine analysis and hair and finger nail clippings. The condition can be managed by removing the offending agent followed by gastric lavage and chelation therapy with d-penicillamine. Bismuth

Amalgam tattoo on the left buccal mucosa in close vicinity to the restoration. The lesion also shows faint white keratotic striae indicative of a lichenoid reaction. Courtesy: Dr Ajit Auluck

Bismuth is used in treatment of syphilis and dermatological disorders. Patients usually have systemic complaints and it is characterized by ‘bismuth grip’, muscular cramps in the abdomen. Orally, we usually see bismuth line which is a bluish black line in marginal gingiva confined to gingival papilla. Bismuth may react with hydrogen sulfide produced by

63


the bacteria to form bismuth sulfide that gets precipitated around periphery of an ulcer or erupting molar. Patient may also complain of burning sensation and metallic taste in the mouth.

Figure 2

Lead Lead (plumbism) is an occupational hazard seen in plumbers due to acute or chronic exposure because of inhalation of lead vapors or dust. It is also seen among the children who chew wood painted with lead. Clinical features include gastrointestinal symptoms like nausea, vomiting and constipation. Patients may have encephalitis or peripheral neuritis characterized by wrist drop or foot drop. Patients may have hypochromic anemia with basophilic stippling in red blood cells. Oral manifestations include linear bluish black discoloration seen in the gingival margin called Burtonian line. Gingivitis, ulcerative stomatitis, excessive salivation, metallic taste, or rarely bismuth may get deposited in the deciduous teeth too.

Grayish black pigmentation of the oral mucosa characteristic of physiologic pigmentation. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Silver Argyria (silver poisoning) is caused due to chronic exposure due to occupational hazard by silver nitrate. It can result in pigmentation of both the skin as well as the mucous membrane. Exposure to silver causes a violet marginal line, often is accompanied by a diffuse bluish-gray discoloration throughout the oral mucosa. It can also be associated with neurologic and hearing damage. Histologically we can observe silver particles staining the reticular fibers.

Diffuse and Multiple Pigmented Lesions Racial/physiologic pigmentation Physiologic pigmentation of the oral tissues is clinically manifested as multifocal or diffuse melanin pigmentation with variable prevalence in different ethnic groups. Gingiva appears darker in color among Africans, Asians, Caucasians and Hispanics and other dark skinned people. The variability in the color of the oral tissues is not due to the difference in the number of melanocytes is same but this color difference is due to the difference in the activity of the melanocytes. In dark skinned people melanocytes are more active as compared to the fair skinned people. Physiologic pigmentation is seen as diffuse macular pigmentations that may be brown, gray or black in color and can appear anywhere in the mouth with buccal surface and gingiva being most commonly involved. On the gingiva it appears as well-demarcated, ribbon-like, dark brown continuous band that does not extend to involve the marginal gingiva. Occasionally pigmentation may also be seen on the tongue, lips and lingual gingiva as diffuse brown patches with ill-defined or diffuse borders (Figure 2). 64

Racial pigmentation mainly occurs in the childhood. However during early years it may not attract patient’s attention and may be observed after puberty. Racial pigmentation is asymptomatic and does not require any treatment. Drug-induced pigmentation Many medications when taken over a long period of time can cause oral mucosal pigmentation. Drug-induced pigmentation can be due to increased synthesis and accumulation of melanin pigments, deposition of the drug or its metabolites into the oral tissues or deposition of iron after damage to the dermal vessels (Table 3). Chloroquine and other quinine derivatives which are usually used in the treatment of malaria and cardiac arrhythmia can cause pigmentation of oral tissues due to a direct stimulating effect on the melanocytes (Figure 3). According to some of the studies these drugs usually cause pigmentation of the palatal tissues. Minocycline is another drug causing pigmentation of oral tissues. It is a synthetic tetracycline that is commonly used in the treatment of acne vulgaris. Tetracycline causes pigmentation of only the bones and teeth but minocycline can also cause pigmentation of soft tissues. It usually causes diffuse brownish discoloration of the hard palate, gingiva, mucous membranes and tongue. Oral pigmentation can also be due to intake of birth control pills. Chloasma is the term which is used to describe perioral and periorbital pigmentation in such patients (Figure 4). The pigmentation usually occurs as a diffuse brown macular pigmentation which is asymptomatic and lesions resolve upon cessation of drug intake. These lesions


Table 3 List of drugs that can induce oral pigmentation

Figure 4

Bleomycin Busulphan Clofazimine Chloroquine Chlorpromazine Cyclophosphamide Doxorubicin Estrogen 5-Fluorouracil Gold Hydroxychloroquine Ketoconazole Minocycline Tetracycline Quinacrine hydrochloride

Perioral and periorbital pigmentation. Courtesy: Department of Oral Medicine and Radiology, KLE Society’s Institute of Dental Sciences, Bangalore

Zidovudine

Figure 5 Figure 3

Smoker’s melanosis of the buccal mucosa associated with leukoplakia. Courtesy: Dr Ajit Auluck Brownish-black pigmentation of the lips and buccal mucosa caused by chloroquine. Courtesy: Dr Ajit Auluck

usually occur due to the hormonal changes which influence melanocyte stimulation. Smoker’s melanosis Tobacco smokers have more intense pigmentation of oral mucosa as compared to non-smokers. Smoker’s melanosis is more common in females. Women are more commonly affected than men because of synergistic effect between the female sex hormones and smoking. Smoking may cause oral pigmentation in light-skinned individuals and

accentuate the pigmentation in dark-skinned patients. Clinically, there may be multiple diffuse brown pigmented macules of less than 1 cm in diameter. These lesions can occur anywhere in the mouth but may be usually localized on the attached labial anterior gingiva and the interdental papillae of the mandible. These lesions are completely asymptomatic and benign in nature (Figure 5). Microscopically there is evidence of basilar melanosis but there is no melanocyte proliferation. The increased melanin production may be a biologic defense mechanism against the noxious agents present in the tobacco smoke. The intensity of the oral pigmentation is directly related to the duration and amount of smoking. Smoker’s melanosis 65


Figure 6

Figure 7

Diffuse pigmentation of palate in a patient with Addison’s disease. Courtesy: Dr Ajit Auluck Perioral pigmentation of the lip in Peutz–Jeghers syndrome. Courtesy: Dr Ajit Auluck

usually disappears within 3 years of smoking cessation. Biopsy must be advised whenever there is a surface elevation or increase in the pigment intensity or rapid increase in the size of the lesion. Endocrine disorders Adrenal cortical insufficiency can occur secondary to pathologic processes such as neoplasms that may cause damage to the adrenal glands. Due to the deficiency of the adrenocortical hormones in the blood there is an increased production of ACTH by the anterior pituitary gland. But ACTH stimulates the production of melanocyte-stimulating hormone which results in diffuse pigmentation of all the tissues. As a consequence the skin darkens and becomes bronzed. Also multifocal diffuse pigmentations appear in the mucous membranes of the oral cavity, conjunctiva, and genital regions. In the oral cavity pigmentation may appear as diffuse brown patches on the gingiva, buccal mucosa, palate and tongue (Figure 6). This may resemble physiologic pigmentation. Physiologic pigmentation can be differentiated from pigmentation caused by Addison’s disease as the later develops and progresses during adult life and not present since birth. It is also accompanied by systemic manifestations like weakness, nausea and vomiting, abdominal pain, constipation or diarrhea, weight loss and hypotension. Oral pigmentation may be the first sign of Addison’s disease. Therefore complete examination must be done for patients with diffuse pigmentation of oral cavity and associated with systemic signs and symptoms. Patients presenting with such features should be sent for medical evaluation and laboratory tests to assess levels of ACTH, plasma cortisol and serum electrolytes. A biopsy of these oral lesions shows acanthosis with silverpositive granules in the cells of the stratum germinativum. 66

Melanin pigment can be seen in the basal layer of the epithelium. Management involves treatment of the underlying cause and corticosteroid replacement therapy. A tumor of the posterior pituitary or certain small cell carcinomas can also secrete excessive amounts of ACTH which can cause pigmentation of oral tissues. In ACTH secreting tumors (paraneoplastic syndromes) the patient manifests features of the Cushing’s syndrome. In both these conditions there occurs diffuse pigmentation of oral tissues along with associated systemic features. Café au lait pigmentation It manifests as bronze or tan diffuse multifocal macular pigmentations that appear on the skin as well as the oral mucosa. These pale brown macules may vary considerably in size. They have widespread distribution and can occur on the face, neck or the oral cavity. Because of the pale brown color these lesions are called as café au lait spots. It is usually associated with neurofibromatosis (von Recklinghausen’s syndrome), Albright’s syndrome (polyostotic fibrous dysplasia) and Peutz–Jeghers syndrome. Café au lait pigmentations in neurofibromatosis have smooth borders and are associated with axillary freckling. It is an autosomal dominant inherited disease with multiple skin nodules. In Peutz–Jeghers syndrome patients have intestinal polyposis along with oral macular pigmentations that appear around the mouth (Figure 7) and on the fingers. When such lesions are observed, a detailed history of the patient should be taken about gastrointestinal complaints as well as the family history for intestinal polyps. These pigmented melanotic spots do not require any treatment and are not associated with any risk for malignant transformation. However, the patient should be monitored for the


Figure 8

Figure 9

Post inflammatory pigmentation of tongue with lichen planus. Courtesy: Dr Ajit Auluck

Diffuse pigmentation of tongue in HIV patient. Courtesy: Dr Ajit Auluck

Figure 10

development of internal malignancies especially of gastrointestinal tract. Similar pigmented spots are also associated with McCune– Albright’s syndrome that is characterized by polyostotic fibrous dysplasia and precocious puberty. Café au lait spots associated with it have regular borders in contrast to neurofibromatosis. HIV infection In patients infected with human immunodeficiency virus (HIV), progressive hyperpigmentation of the skin, oral mucosa, fingernails, and toenails is reported. Such pigmentation is related to primary adrenocortical deficiency and to antiretroviral therapy like zidovudine (azidothymidine) therapy. Clinically, oral pigmentation appears as irregular macules with brown or dark brown color. The tongue, buccal mucosa, and palate are the most commonly affected sites (Figure 8).

of oral cavity can be involved but the buccal mucosa and the attached gingiva are the most frequently involved sites.

Hemochromatosis

Post inflammatory pigmentation

Hemochromatosis is also called bronze diabetes. It is a chronic disease characterized by the deposition of excess iron (ferritin and hemosiderin) in the body tissues. Deposition of these can result in fibrosis and functional insufficiency of the involved organs. Hyperpigmentation may appear both in the skin as well as of the mucous membranes of oral cavity and conjunctiva. The oral mucosa shows diffuse homogeneous pigmentation which may vary from gray-brown to deep brown in color. Although any part

Long-standing inflammatory mucosal diseases like lichen planus can cause diffuse pigmentation of the oral cavity (Figure 9). Most commonly post inflammatory pigmentation is seen more frequently among the dark-skinned individuals. Clinically, multiple brown-black pigmented areas are observed adjacent to the reticular or erosive lesions of lichen planus. Post inflammatory pigmentation can also occur following periodontal surgery and biopsy (Figure 10). Histologically, there is increased production of melanin by

Post inflammatory pigmentation of buccal mucosa following traumatic ulceration. Courtesy: Dr Ajit Auluck

67


Figure 11

Figure 12

Yellowish discoloration of sclera in a patient with jaundice. Courtesy: Dr Ajit Auluck

Figure 13 Yellowish discoloration of palate in a patient with jaundice. Courtesy: Dr Ajit Auluck

the melanocytes and accumulation of melanin laden macrophages in the superficial connective tissue. Cyanosis Rarely generalized discoloration of oral mucosa can also be associated with cyanosis in which entire oral mucosa may become blue black in color when reduced hemoglobin level reaches above the critical value of 5 g/100 ml. Beta carotene Yellowish discoloration of oral mucosa can also be due to consumption of large amounts of beta carotene in patients having metabolic disorders that impairs conversion of beta carotene to vitamin A. Liver disease Yellowish discoloration of oral mucosa can also be due to liver diseases (jaundice) when bilirubin level increases more than 2–3 mg/dl (Figure 11). To distinguish between the two conditions we must examine the sclera of the eyes. In jaundice sclera will also be yellow in color as bilirubin pigments stain the reticular fibers of sclera whereas betacarotene will not stain the sclera (Figure 12).

Focal/Localized Pigmented Lesions Hemangioma and vascular malformations Hemangiomas occur due to proliferation of cells lining the blood vessels and are tumor like hamartomas which usually occur in children. Vascular malformations occur due to structural defects in the vessels without the proliferation of endothelial cells. Both hemangioma as well as vascular 68

Hemangioma of the tongue. Courtesy: Dr Ajit Auluck

malformation starts at birth but hemangioma resolves with age while vascular malformation does not resolve with age. If hemangiomas are associated with seizures then skull radiographs should be advised which may reveal tram line calcifications suggestive of Sturge–Weber syndrome. Hemangiomas may appear as flat or slightly raised. The color can range from red to bluish purple depending on the type of vessels involved (capillaries, veins or arteries) and also the depth of the lesion in the tissues (Figure 13). If the lesions are superficial to the overlying epithelium they are reddish blue in color and if they are deep then they are blue in color. Hemangiomas can be diagnosed with diascopy test which they usually blanch on pressure. Diascopy test is performed by pressing glass side gently on the lesion. A positive diascopy result is indicated by blanching and suggests that blood is present within vascular spaces and is displaced out of the lesion by application of pressure. However, lack of blanching does not exclude the possibility of a vascular lesion as some cutaneous hemangiomas may not respond positively to diascopy test.


Figure 14

Figure 15

Ecchymosis of the palate. Courtesy: Dr Ajit Auluck

Traumatic hematoma of the buccal mucosa. Courtesy: Dr Ajit Auluck

Lingual varices are usually seen in adults on the ventral surface of the tongue. These are pathologic dilatations of veins and venules. They become more pronounced with age. These are painless and can rupture leading to uncontrolled hemorrhage/bleeding. Varices resemble hemangiomas but can be easily distinguished as hemangiomas resolve with age while varices become more pronounced with age. Varix has finite growth potential while hemangiomas may grow larger in size. Hemangiomas on palpation may have bruit and thrill which is absent in varices. Hematomas can also cause various types of discoloration of oral mucosa. Early hematoma is superficial and can cause bluish swelling of mucosa. They are slightly elevated, often fluctuant and rubbery in consistency. Blood cannot be evacuated from hematomas with digital pressure. But late hematomas are blue-black in color as hemoglobin breaks down to form hemosiderin (Figure 14). Eruption hematoma is a dome-shaped blue swelling that appears around a developing tooth. None of these hematomas have pain or any other associated complaints. Petechiae are minute pin point macules that occur due to erythrocyte extravasation, lysis of RBCs and subsequent breakdown of pigments. When these areas of discoloration are larger than 2 cm then they are called ecchymosis (Figure 15). Usually petechiae and ecchymosis are seen at the junction of soft and hard palate. In normal patients we do not see them but they are seen in patients with bleeding disorders (hemophilia), clotting disorders, vessel wall defects, platelet disorders, vomiting, coughing or fellatio.

Dilated vessels are also seen in hereditary hemorrhagic telangiectasia (Rendu–Osler–Weber syndrome) which is genetically transmitted as an autosomal dominant disease and cause microaneurysms due to weakening of the adventitial coat of blood vessels. Rarely, there may be vascular neoplasms that may appear as pigmented lesions or masses in the oral mucosa. Angiosarcoma is a malignant vascular neoplasm that presents as nodular tumor and arises from the pericytes of the blood vessels. Kaposi’s sarcoma is also a tumor of vascular origin mainly seen in HIV patients. Presence of Kaposi’s sarcoma in HIV patients is diagnostic of AIDS. It is a malignancy which never metastasizes. A human herpesvirus (HHV-8, also called Kaposi’s sarcoma-associated herpesvirus) has been implicated in its etiology. Kaposi’s sarcoma is usually seen on the palate, gingiva or tongue. Initially lesions will appear as flat or slightly elevated brown to purple lesions while later lesions may become dark red or purple that may ulcerate, bleed or undergo necrosis. Therefore for establishing a definitive diagnosis we must advice a biopsy which may show proliferation of spindle-shaped cells surrounding poorly formed vascular spaces with numerous extravasated red blood cells. Graphite Graphite is commonly introduced into the oral mucosa following an accidental injury with a graphite pencil. The lesion appears as an irregular gray to black macule mainly seen in the anterior palatal region of children. A history of injury confirms the diagnosis. Melanotic macule They appear as an asymptomatic macule on the vermillion border of the lower lip. However, they can also occur on the 69


Figure 16

Table 4

Warning signs in a mole suggestive of early melanoma

A—Asymmetry: One half of the lesion does not match the other half B—Border irregularity: The edges are ragged, notched, or blurred C—Color variegation: Pigmentation is not uniform and may display shades of tan, brown, or black; white, reddish, or blue discoloration is of particular concern D—Diameter: A diameter greater than 6 mm is characteristic, although some melanomas may have smaller diameters; any growth in a nevus warrants an evaluation E—Evolving: Changes in the lesion over time are characteristic; this factor is critical for nodular or amelanotic (non-pigmented) melanoma, which may not exhibit the classic criteria above

Melanotic macule of the buccal mucosa. Courtesy: Dr Ajit Auluck

Histologically, only increased melanin pigmentation is seen in the basal cell layer without an increase in the number of melanocytes. Pigmented nevi

Figure 17

Melanotic macules on the gingiva. Courtesy: Dr Ajit Auluck

gingiva, buccal mucosa and the palate (Figures 16 and 17). The color may be gray, brown, blue, black or a combination of all these. Oral melanotic macules are formed due to focal increase in the melanin production. There is no increase in the number of melanocytes but there is only increase in the amount of melanin production. Oral melanotic macules are usually smaller than 1 cm in size. Usually they occur as solitary lesions, which are homogenous in color and have smooth borders. They are benign in nature and do not transform into malignancy. If there is a sudden increase in size of the lesion, change in color or size increases more than 1 cm, a biopsy must be advised to exclude possibility of melanoma (Table 4). 70

These are relatively uncommon cause of oral mucosal pigmentation and may appear as blue or black focal pigmented areas. Histologically, there is increase in the number of nevus cells in the epithelium, connective tissue or both. Accordingly, nevi are classified as junctional nevi, intradermal nevi or intramucosal or compound nevi. Usually melanocytic nevi develop during childhood. Most nevi originate from the basal layer of melanocytes and proliferate in the epithelium along the junction with the connective tissue and are called as junctional nevi. Later, these melanocytes drop off into the connective tissue to form islands or cluster of melanocytes and are called as compound nevi. Eventually all the cells leave the surface epithelium and reside in the dermis or submucosa so called as intradermal or intramucosal nevi. Blue nevi arise from dermal or mucosal melanocytes that persist in the connective tissue during embryonic neural crest migration and therefore do not arise from junctional activity at the epithelium and connective tissue interface (Figure 18). In blue nevi there are spindle-shaped melanocytes which synthesize huge amounts of melanin pigment. Blue nevi can also occur along with ocular pigmentation along the distribution of trigeminal nerve and is called nevus of Ota (Figure 19). Malignant melanoma Described in Chapter 13 on page 368. Clinical evaluation of pigmented lesions When a patient presents with a pigmented oral lesion a detailed medical and dental history must be recorded. A complete extraoral and intraoral examination should be done and relevant laboratory tests must be advised.


Figure 18

Extensive blue nevus of the buccal mucosa. Courtesy: Dr Ajit Auluck

carefully recorded as they may help to ascertain the nature of the lesion. Usually benign pigmented lesions are small, symmetric, uniform in color and show regular borders. Occasionally benign lesions can be slightly elevated. But if the lesions have irregular borders, color variation or surface ulceration then it is most likely to be a malignancy and biopsy must be advised in such cases. Surface characteristics and morphological appearance of the lesions may not point toward the true nature of the lesion so if there is any pigmented lesion seen in oral cavity whose etiology cannot be ascertained, we must advice a biopsy. Clinical tests such as diascopy or appropriate laboratory investigations such as blood tests or radiographs may be advised to confirm a clinical impression and reach a definitive diagnosis. Flowcharts 1 and 2 summarize the approach to the diagnosis and differential diagnosis of pigmented oral lesions.

PIGMENTATION OF TEETH Figure 19

Extraoral photograph showing oculodermal pigmentation. Courtesy: Dr Ajit Auluck

The history should include details like the onset and duration of the lesion, the presence of associated skin lesions, associated systemic signs and symptoms, history of intake of medications and habits. During extraoral examination record the pigmented lesions on the face, perioral skin as well as the lips. A complete intraoral examination of oral cavity should be done. The number, distribution, size, shape and color of all pigmented lesions should be

Discoloration of the tooth is one of the most frequent reasons why a patient seeks dental care. Tooth discolorations are usually esthetically displeasing and psychologically traumatizing. There are many factors that could steal the sparkle from a smile. An understanding of the etiology of tooth discoloration is important to a dentist in order to come to the correct diagnosis, which allows the dental practitioner to explain to the patient the exact nature of the condition. In some instances, the mechanism of staining may have an effect on the outcome of treatment and influence the treatment options the dentist will be able to offer to patients. The causes for tooth discoloration can be classified according to the location of the stains, either as extrinsic or intrinsic. Extrinsic discoloration lies on the tooth surface or in the acquired pellicle. The intrinsic discoloration occurs when the chromogens are deposited within the bulk of the tooth, which may be of local or systemic origin. The coronal aspect of the tooth consists of enamel, dentin and pulp. Any change to these structures during odontogenesis or post eruption can cause an alteration in the outward appearance of the tooth because of the change in the light transmitting and reflecting properties.

Extrinsic Discoloration Extrinsic discolorations are defined as discolorations located on the outer surface of the tooth structure and caused by topical or extrinsic agents. This can be divided into two groups; direct staining by the compounds incorporated into the pellicle layer and producing the stain as a result of the basic color of the chromogen, and indirect staining were 71


Flowchart 1 Any discoloration of the oral mucosa

Heavy metal poisoning Amalgam/graphite tattoo

Exclude extrinsic causes of pigmentation

Drugs like minocycline, oral contraceptives Stains due to chromogenic bacteria

Observe the lesion and note the color and other clinical characteristics

Tobacco and food stains

Blue/black melanin pigmentation

Blue red/brown pigmentation due to blood pigments or iron

Blanch on pressure

Do not blanch on pressure

Tumor masses

Diffuse pigmentation

Focal pigmentation

• Hemangioma • Varices • Early hematoma • Telangiectasia • Kaposi’s sarcoma

• Petechiae • Ecchymosis • Hemochromatosis

• Neuroectodermal tumor of infancy • Malignant melanoma

• Physiologic pigmentation • Endocrine disorders • Smoker’s melanosis • Drug-induced pigmentation • Post inflammatory pigmentation • HIV infection

• Melanotic macule • Nevi • Amalgam tattoo

Clinical approach for diagnosis of pigmented lesions in the oral cavity

there is chemical interaction at the tooth surface with another compound that produces the stain. Direct staining has multifactorial etiology with chromogens derived from dietary sources or habitually placed in the mouth. It is the polyphenolic compounds found in the food that are thought to give rise to the color of the stains. Indirect extrinsic tooth staining is associated with cationic antiseptics and metal salts. The agent is without color or a different color from the stain produced on the tooth surface. Traditionally, extrinsic tooth discoloration has been classified according to its origin, whether metallic or non-metallic. Table 5 summarizes the extrinsic causes of tooth discoloration.

Classification of Extrinsic Stains Nathoo (1997) proposed the Nathoo classification system of extrinsic dental stains. According to this classification system three categories of extrinsic stains are described. 72

Nathoo type 1: The chromogen binds to the tooth surface. The color of the chromogen is similar to that of dental stains caused by tea, coffee, bacteria, and metals. Nathoo type 2: The colored material changes color after binding to the tooth. The stains actually are Nathoo type 1 food stains that darken with time. Nathoo type 3: The colorless material or prechromogen binds to the tooth and undergoes a chemical reaction to cause a stain. These stains are caused by carbohydrate-rich foods, stannous fluoride, and chlorhexidine. Factors responsible for extrinsic discoloration Diet factors Deposition of tannins found in tea, coffee, and other beverages cause brown stains on the surface of the teeth. Commercially available soft drinks and food products containing permitted synthetic food colors (red color: Ponceau 4R, carmoisine, erythrosine, yellow color: tartrazine pyrazolone, sunset yellow FCF, blue color: indigo carmine, brilliant blue FCF, green color: fast green FCF) and additives can temporarily cause discoloration of the teeth and the oral mucosa (Figure 20).


Flowchart 2 Bluish/black discoloration of oral mucosa Usually due to metals/melanin pigment

Localized pigmentation

Exclude pigmentation due to metals like amalgam, graphite, lead etc. In oral cavity, usually amalgam tattoos are seen in close vicinity of restorations

Diffuse pigmentation

Physiological pigmentation Present since birth Smoker’s melanosis

Melanotic macule Small size, mostly on lips, increase in melanin synthesis

History of smoking Endocrine disorders like Addison’s disease/Cushing’s syndrome

Nevi

Look for systemic signs and symptoms

Increased proliferation of melanocytes, usually from birth

HIV associated melanosis Advice ELISA for HIV

Malignant melanoma Dark, irregular borders, asymmetric and rapid growth

Associated with syndromes like Albright’s syndrome, Peutz–Jeghers syndrome

Post inflammatory pigmentation due to healing of lesions like lichen planus

General examination to find other associated features

Algorithm for differential diagnosis of pigmented lesions in the mouth with characteristic features which help in diagnosis *Biopsy must be advised if there is increase in size, change in color or any proliferative changes associated in pigmented lesions

Oral hygiene related factors Accumulations of dental plaque, calculus and food particles cause brown or black stains. Chromogenic bacteria have been suggested as an etiologic factor in the production of stains typically at the gingival margin of the tooth (Figure 21). The most common is a black stain caused by Actinomyces species. The stain is composed of ferric sulfide and is formed by the reaction between hydrogen sulfide produced by bacterial action and iron in the saliva and gingival exudates (Figure 22). Green stains are attributed to fluorescent bacteria and fungi such as Penicillium and Aspergillus species. Orange stain is less common than green or brown stains and is caused by chromogenic bacteria such as Serratia marcescens and Flavobacterium lutescens. Habit related Tobacco from cigarettes, cigars, pipes, and chewing tobacco causes tenacious dark brown and black stains that cover the cervical one-third to midway on the tooth toward the gingival margin (Figure 23).

Chewing of pan (a combination of betel nut of the areca palm, betel leaf, and lime) results in the production of red colored substance that causes red-black stain on the teeth, gingiva, and oral mucosal surfaces (Figure 24). Drug related Cationic antiseptics such as chlorhexidine, cetylpyridinium chloride and other mouth washes (the essential oil/phenolic mouthrinse ‘Listerine’, delmopinol mouthrinses) can cause staining after prolonged use. Chlorhexidine, for example, produces brown to black discoloration (Figure 25). Most evidence indicates that the likely cause of staining is the precipitation of anionic dietary chromogens onto the adsorbed cations. Some systemic medications (e.g. minocycline, doxycycline, co-amoxiclav, linezolid) have also shown to cause extrinsic staining. Metallic compounds are also implicated in dental discolorations because of the interaction of the metals with dental plaque to produce surface stains. Iron-containing 73


Table 5

Extrinsic causes for tooth discoloration

Classification

Factors responsible

Examples

Color

Non-metallic stains Direct stains

Diet

Tea, coffee and other foods

Brown to black

Oral hygiene

Dental plaque, calculus and food particles Chromogenic bacteria

Yellow/brown Brown/black/green, orange

Habits

Tobacco smoking/chewing Pan chewing

Dark brown/black Red-black

Non-metallic stains Indirect stains

Medications

Cationic antiseptics (e.g. chlorhexidine) Essential oils/phenolic mouthrinse Systemic antibiotics (e.g. minocycline)

Yellow brown Yellow Green-gray

Metallic stains Indirect stains

Medications

Iron containing oral solutions Copper salts in mouthrinse Potassium permanganate in mouthrinse Stannous fluoride Silver nitrate

Black Green Violet to black Golden brown Gray

Occupation

Exposure to iron, manganese, silver Exposure to mercury and lead dust Copper and nickel Chromic acid fumes

Black Blue green Green Deep orange

Figure 20

Figure 21

A

B

Accumulation of calculus and food particles at the cervical margin of the tooth causing yellowish brown stains. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

oral solutions used for treatment of iron deficiency anemia cause black stains (Figure 26). Green discoloration can result from the use of mouthrinses containing copper salts. Potassium permanganate mouthwash (violet-black stain), silver nitrate (black stain), and stannous fluoride (brown stain) also can induce dental discolorations. Ice cream candy color staining of the oral mucosa. Courtesy: Dr Prem Prakash Kar, Dr Snehal Thatte, Dr Shomshukla Bhowmick

74

Occupation related Industrial exposure to iron, manganese, and silver may stain the teeth black. Mercury and lead dust can cause a blue-green stain; copper and nickel,


Figure 22

Figure 24

Black stains caused by chromogenic bacteria. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 23

Brown and black staining of teeth and orange-red staining of the buccal mucosa in a patient with a habit of chewing ‘pan’. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 25

Tenacious brown stains on the cervical margin of the teeth in a tobacco chewer. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Extrinsic stains due to prolonged use of chlorhexidine mouthrinse

green-to-blue-green stain and chromic acid fumes may cause deep orange stain. Predisposing factors Factors that predispose children and adults to extrinsic stains include enamel defects, salivary dysfunction, and poor oral hygiene. Microscopic pits, fissures, and defects on the outer surface of the enamel are susceptible to the accumulation of stain-producing food, beverages, tobacco, and other topical agents.

Since saliva plays a major role in the physical removal of food debris and dental plaque from the outer and interproximal tooth surfaces, diminished salivary secretion can lead to extrinsic discoloration. Decreased output may be caused by local disease (e.g. salivary obstructions and infections), systemic disease (e.g. Sjögren syndrome), head and neck radiation therapy for cancer, chemotherapy, and multiple medications (e.g. anticholinergics, antihypertensives, antipsychotics, antihistamines). 75


Intrinsic Discoloration There are several causes of intrinsic tooth discolorations which have either an endogenous or exogenous origin. These changes may occur during or after odontogenesis. During odontogenesis, teeth may become discolored from the changes in the quality or quantity of enamel or dentin, or from the incorporation of discoloring agent into the hard tissues. Post-eruption discolorations occur when the discoloring agent enter the hard tissues. They may originate from the pulp cavity or the tooth space. Pre-eruptive causes of intrinsic discoloration (Table 6) Metabolic causes The diseases that have the potential to cause neonatal hyperbilirubinemia may cause the Figure 26

Black colored extrinsic stains due to use of iron tonic. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Table 6

76

incorporation of bilirubin into developing teeth, producing jaundice like yellow-green tint within the dental hard tissue known as chlorodontia. These diseases include sickle cell anemia; thalassemia; hemolytic disease of the newborn due to Rhesus factor, ABO, or other erythrocyte antigen incompatibility (erythroblastosis fetalis/icterus gravis neonatorum); biliary atresia; bile duct obstruction; biliary hypoplasia; and cholestasis associated with sepsis. Congenital erythropoietic porphyria (Günther’s disease) is a rare, autosomal recessive disorder of porphyrin metabolism, resulting in an increase in the formation and excretion or porphyrins. The porphyrin pigments have an affinity for calcium phosphate and are incorporated into teeth during dental formation and this causes a characteristic reddish-brown discoloration of the teeth, called erythrodontia. The affected tooth shows a red fluorescence under ultraviolet light. Alkaptonuria, also known as phenylketonuria or ochronosis is an inborn error of metabolism of tyrosin and phenylalanine causing a build-up of homogentisic acid. This results in a brown discoloration of the permanent dentition. Disturbance during development of a tooth Enamel hypoplasia may result due to the disturbance of the developing tooth germ following trauma, infection or nutritional deficiency giving rise to localized or generalized enamel defects (Figure 27). Periapical odontogenic infections of the primary teeth can disrupt normal amelogenesis of the underlying permanent successors and can cause localized enamel hypoplasia. Trauma to developing, yet unerupted, teeth can also disturb amelogenesis and may result in enamel hypoplasia, which is visualized as a localized opacity on the erupted tooth. Such teeth commonly are referred to as Turner’s teeth.

Intrinsic causes for tooth discoloration (pre-eruptive)

Classification

Factors responsible

Examples

Color

Pre-eruptive

Metabolic disorders

Hyperbilirubinemia Porphyria Alkaptonuria

Yellow-green Reddish brown Brown

Disturbance of tooth germ

Localized Turner tooth Generalized Infection (maternal or childhood) Nutritional deficiency Molar incisor hypomineralization (MIH)

White to yellow to brownish

Genetic disorder

Amelogenesis imperfecta Dentinogenesis imperfecta Dentin dysplasia Systemic syndrome e.g. epidermolysis bullosa

Yellow brown Blue brown Yellow Yellow

Medication

Tetracycline Minocycline Ciprofloxacin Fluoride

Yellow, brown, blue or greenish Blue-green Greenish Chalky white to brown/black


Figure 27

Generalized chalky white opacifications of the teeth in enamel hypoplasia. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Crown formation begins in utero; therefore, the potential for extensive intrinsic discoloration of the primary dentition may be present throughout pregnancy. Although rare, maternal rubella or cytomegalovirus infection, maternal vitamin D deficiency, drug intake during pregnancy and toxemia of pregnancy can lead to tooth discoloration, which generally manifests as a focal opaque band of enamel hypoplasia. Such defects will be chronologically laid down in the teeth depending on the state of development at the time of interference and the effect is directly related to the degree of systemic upset. There may be pitting or grooving which predisposes to extrinsic staining of the enamel in the region of tooth disturbed, often then becoming internalized. Crown formation of the permanent dentition occurs until the child is aged approximately 8 years. Systemic postnatal infections (e.g. measles, chicken pox, streptococcal infections, scarlet fever) can also cause enamel hypoplasia. The band like discolorations on the tooth are visualized where the enamel layer has variable thickness and becomes extrinsically stained after tooth eruption. Vitamins C and D, calcium, and phosphate are required for healthy tooth formation. Deficiencies can result in exposurerelated or dose-related enamel hypoplasia. Molar-incisor hypomineralization (MIH) is an idiopathic condition characterized by severe hypomineralized enamel affecting incisors and permanent first molars. The enamel defects can vary from white to yellow to brownish areas but they always show a sharp demarcation between sound and affected enamel. The nature of the enamel is porous and brittle, breaking down shortly after eruption under masticatory forces, often resembling enamel hypoplasia, but distinguished by having irregular

Figure 28

Generalized yellowish discoloration of teeth in amelogenesis imperfecta. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

borders with normal enamel as opposed to smooth borders with hypoplastic lesions. The suggestions as to the possible etiologies, including environmental changes during the limited time period, infections during the early childhood, dioxin in breast milk and genetic factors, have yet to be eliminated from the possible causes. Genetic defects and hereditary diseases Genetic defects in enamel or dentin formation include amelogenesis imperfecta (AI), dentinogenesis imperfecta (DI), and dentinal dysplasia (DD). These hereditary diseases can be associated with intrinsic tooth discoloration. Amelogenesis imperfecta is a hereditary disorder which affects the enamel formation in both primary and permanent dentition. Type I is hypoplastic AI. The teeth typically have an abnormally thin enamel layer that reveals the yellow color of dentin beneath the enamel (Figure 28). Hypoplastic teeth with rough or pitted enamel surfaces are also at a greater risk for extrinsic staining. Type II is hypocalcified AI. The enamel in the hypocalcified type is yellow to orange, soft, and lost soon after eruption. Therefore, hypocalcified teeth develop dark stains and are at high risk for dental caries. Type III is hypomaturation AI. Teeth with hypomaturation have soft enamel with a mottled opaque white, yellow, or brown discoloration. Type IV AI involves hypomaturation or hypoplastic dentition with taurodontism. Dentinogenesis imperfecta, an inherited disorder, is classified into three types. DI type I is associated with osteogenesis imperfecta and is characterized by opalescent primary teeth. DI type II (hereditary opalescent dentin) affects both the dentition. The pulp chambers often become obliterated and the dentin undergoes rapid wear once the 77


enamel has chipped away. The teeth have a typical amberlike translucency or opalescence against reflected light, and there color varies from different shades of yellow to bluish-brown. DI type III (brandywine isolate hereditary opalescent dentin) is a very rare autosomal dominant disorder which occurs in a racial segregate in Maryland, United States. It is similar in appearance to type I and II but with radiographic appearance of shell teeth with multiple pulpal exposure in the primary dentition. Dentin dysplasia occurs in two types. In type I DD the primary and permanent dentition are of normal shape and form but may have an amber translucency. Teeth with type II DD are characterized by thistle shaped pulp chamber and pulp stones with brown tooth discoloration. Defects in enamel formation may also occur in a number of systemically involved clinical syndromes such as vitamin D dependent rickets, epidermolysis bullosa, Ehlers– Danlos syndrome and pseudohypoparathyroidism. Patients with epidermolysis bullosa may have enamel hypoplasia and pitting, which produce a yellowish tint and the patients are at risk for caries.

Figure 29

Yellowish discoloration of teeth due to use of tetracycline

Figure 30

Medications Tetracycline, a broad spectrum antibiotic, is known to cause intrinsic discoloration when prescribed during tooth development. Tetracycline staining results from systemic administration of the drug, which chelates with the calcium ions on the surface of the hydroxyapatite crystals as a stable orthophosphate complex. Dentin has been shown to be more heavily stained than enamel. The severity of the discoloration produced depends on the type of tetracycline used, the dosage and the period of time it was taken for, as well as the age at the time of administration. Tetracycline should be avoided from 29 weeks in utero until full term, in breast feeding mothers and in children up to the age of 12 years to avoid discoloration of the developing teeth. It has been shown that the discoloration occurs with the greatest frequency in the developing dentition when total administration is over 3 g, or the treatment exceeds 10 days. The various analogs of tetracycline produce different color changes, for instance, chlortetracycline produces a slate gray color and oxytetracycline causes a creamy discoloration. Teeth affected by tetracycline have a yellowish or browngray appearance which is worse on eruption and diminishes with time (Figure 29). The affected teeth also fluoresce under ultraviolet light, giving off a bright yellow color. Exposure to the sunlight can change the color to brown; the anterior teeth are particularly susceptible to this photooxidation induced color change. In severe cases of tetracycline involvement enamel hypoplasia may result. Tetracycline discoloration has been classified according to the extent, degree and the location of the tetracycline involvement (Jordan and Boksman). 78

Bluish discoloration of teeth due to minocycline. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Degree I: There is minimal expression of tetracycline stain uniformly confined to the incisal three-quarters of the crown and is light yellow in color. Degree II: There is more variability of staining ranging from a highly uniform deep yellow to gray banded discoloration in which a distinctive difference in discoloration is noted between the cervical region and the incisal fourfifths of the crown. Degree III: There is very dark blue or gray uniform discoloration. Minocycline is a semi-synthetic derivative of tetracycline. It is commonly used to treat acne vulgaris. The ingestion of minocycline can lead to a green-gray or blue-gray intrinsic staining of teeth (Figure 30). Unlike with other tetracyclines,


staining occurs during and after the complete formation and eruption of teeth. Staining of the adult dentition appears to occur in 3–6% of patients taking long-term minocycline at more than 100 mg daily. The staining caused by minocycline is different from that caused by tetracycline. The onset of discoloration can occur any time from 1 month to many years after the initiation of the treatment. Four theories have been put forward to explain the possible mechanism by which minocycline causes tooth discoloration. The first is the extrinsic theory, where it is thought that minocycline attaches to the glycoprotein in acquired pellicle. It oxidizes on exposure to air or as a result of bacterial activity, and so causes degradation of the aromatic ring forming insoluble black complex. The pigmentation may be incorporated into the dentin and is possibly a demineralization/remineralization phenomenon related to the high local levels of the drug. The second is the intrinsic theory, where the minocycline bound to the plasma proteins is deposited in collagen-rich tissues, such as the teeth. This then oxidizes slowly over time with exposure to light. The third possibility is that the drug chelates with iron to form an insoluble complex. The fourth suggestion is that minocycline could be deposited in dentin during dentinogenesis, and the process of secondary dentinogenesis can be accelerated in bruxists. Doxycycline has recently been reported to cause extrinsic staining of teeth, possibly by binding to glycoproteins in the dental pellicle in patients with poor oral hygiene in whom oxidation occurs (e.g. sunlight exposure, bacterial) or via mechanisms similar to those for minocycline. Ciprofloxacin, a quinolone given intravenously to infants at dosages of 10 to 40 mg/kg/day to treat infections with Klebsiella, has been associated with greenish discoloration of the teeth when they erupted.

DENTAL FLUOROSIS Dental fluorosis is characterized by enamel discoloration resulting from subsurface hypomineralization due to the excessive ingestion of fluoride during the early maturation stage of enamel formation. Fluoride sources are numerous and include naturally or artificially fluoridated drinking water, commercially available beverages, foods prepared in fluoridated water, chewable vitamins, oral healthcare products (e.g. toothpastes, mouthrinses, oral fluoride supplements), and professional fluoride products prescribed by dentists. The severity is related to age and dose, with the primary and permanent dentitions both being affected by endemic fluorosis. The enamel is often affected and may vary from areas of flecking to diffuse opaque mottling superimposed on to chalky white or dark brown/black appearance (Figure 31). The dark discoloration thought to be post-eruptive by a process of internalization of the extrinsic stains into the porous enamel.

Figure 31

Yellowish brown intrinsic staining of teeth in fluorosis. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Post-eruptive Causes (Table 7) Dental conditions and caries Tooth wear is the progressive loss of enamel and dentin due to attrition, abrasion and erosion. As the enamel thins the teeth become darker as the color of the dentin becomes more apparent. Once the dentin is exposed the potential of chromogens to enter the body of the tooth increases. The various stages of carious process can be recognized by the change in color as the disease progresses. The pathogenesis of dental caries begins with an incipient lesion confined to the enamel layer. Incipient carious lesions are associated with plaque accumulation and manifest as chalky white areas of discoloration secondary to hypocalcification. As caries progresses into the dentin, the overlying translucent enamel reveals the color of the underlying caries and appears yellowish brown. Extensive caries that involve destruction of both enamel and dentin produce a color that ranges from light brown, to dark brown or almost black (Figure 32). The brown color is attributed to the formation of Maillard pigments (reaction between proteins and small aldehydes produced by cariogenic bacteria), melanins, lipofuscins, and uptake of various food colors and bacterial pigments. In some patients, the caries process can self-arrest, and remineralization may occur; however, the brown discolorations usually remain. The natural darkening and the yellowing of the teeth and the change in their light transmission properties with age are due to the combination of the factors involving both enamel and dentin. The enamel undergoes both thinning and textural change, while the deposition of secondary and tertiary dentin and pulp stones all contribute to the darkening process of aging. 79


Table 7

Intrinsic causes for tooth discoloration (post-eruptive)

Classification

Factors responsible

Examples

Color

Post-eruptive

Dental conditions

Dental caries • Incipient • Active • Arrested Tooth wear Aging

Chalky white Yellowish brown Dark brown to black Yellowish Yellowish

Pulpal causes

Pulpal trauma with hemorrhage Calcific metamorphosis Internal resorption

Gray-brown Yellowish to yellowish brown Pinkish

Dental materials

Amalgam Composite glass ionomer cement (GIC) Intracanal medicaments (e.g. iodoform, ledermix) Obturating materials and sealers

Blue-gray Yellowish brown Brownish gray Grayish

Figure 32

Grayish black discoloration in the proximal aspect of the tooth indicative of dental caries. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Pulpal causes Bacterial, mechanical, or chemical irritation to the pulp may result in tissue necrosis and the release of disintegration by-products that might penetrate the tubules and discolor the surrounding dentin. Trauma that occurs to erupted teeth also causes discoloration. After acute trauma, intrapulpal hemorrhage will give the tooth a reddish tinge. Occasionally, in younger patients, the color may return to normal as the inflammation subsides. More often, the discoloration changes to gray-brown in a matter of days as the pulp becomes necrotic. Hemolysis of the red blood cells would follow and release the heme group to combine with the putrefying pulpal tissue to form black iron sulfide. In vitro studies have recently shown that the major cause of discoloration of 80

Figure 33

Discolored upper central incisors following trauma. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

non-infected traumatized teeth is the accumulation of the hemoglobin molecule or other hematin molecules. In the absence of infection, the release of iron from the protoporphyrin ring is unlikely. Excessive formation of irregular dentin in the pulp chamber and along the canal walls may occur following certain traumatic injuries. This is known as calcific metamorphosis. As a result of this, the translucency of the crown gradually decreases, giving rise to yellowish or yellowish brown discoloration (Figure 33). Root resorption following trauma often presents as a pink spot lesion at the cementoenamel junction in an otherwise symptomless tooth, known as the ‘pink tooth of Mummery’. The resorption may be internal, being of pulpal origin or external of periodontal origin.


Dental Materials

Clinical examination

Dental restorations most commonly cause intrinsic discoloration. Amalgam restorations can generate corrosion products, leaving a blue-gray color in the tooth, especially in large cavity preparations with undermined enamel known as amalgam blue. Metal pins and prefabricated posts are sometimes used to reinforce composite restoration on the anterior dentition. Discoloration from inappropriately placed pins and posts is caused by the metal seen through the composite or the tooth structure. Microleakage around composite or glass ionomer restoration causes staining. Open margins may allow chemicals to enter between the restoration and the tooth structure and discolor the underlying dentin. Several intracanal medicaments are liable to cause internal staining of the dentin. Phenols or iodoform based medicaments sealed in the root canal and the chamber are in direct contact with dentin, allowing penetration and oxidation. These compounds discolor dentin gradually. Tetracyclines (e.g. ledermix-triamcinolone acetonide and demethylchlortetracycline) used within the tooth for endodontic therapy may also cause dark gray-brown discoloration. Obturating materials are frequent cause for single tooth discoloration. Incomplete removal of obturating material and sealer remnants in the pulp chamber, mainly those containing metallic components, often result in dark discoloration.

The scratch test is usually used to distinguish between extrinsic and intrinsic discoloration. Discolored tooth surfaces are scratched with care by using a dental explorer, scaler, or similar sharp instrument to assess surface texture. Light scratching with a dental instrument removes weakly adherent plaque that causes extrinsic discoloration. If the discoloration requires removal with a sharp dental scaler, the discoloration is considered to be tenacious. Intrinsic discoloration cannot be removed by using the scratch test. Extrinsic staining of a single tooth is unusual. The distribution is usually generalized. The stains are usually found on surfaces with poor toothbrush accessibility. Whereas in case of intrinsic discoloration distribution is either generalized to all teeth or localized to certain teeth or tooth surfaces. An intrinsic etiology usually exists when a single tooth is discolored. Regarding other physical findings, teeth with extrinsic tooth discoloration usually demonstrate no signs of pulpal disease. Teeth with intrinsic discoloration may demonstrate signs of pulpal disease. A single discolored tooth with a history of trauma will usually be non-vital. Radiographs may reveal periapical pathology. Under ultraviolet light, teeth with tetracycline staining and congenital porphyria may fluoresce yellow or red, respectively.

Diagnosis History The patient’s history of tooth discoloration provides useful information regarding the etiology. The history includes the following: ❍

❍ ❍ ❍ ❍

Dental history: Previous dental treatment, oral hygiene practices, use of mouthwash, amount and scheduling of fluoride intake, history of dental trauma. Medical history: History of maternal or childhood diseases, use of medications. Family history: Genetic disorders. Diet history: Nutritional deficiencies, diet that can cause staining of the teeth. Social history and personal history: Occupational exposure to metals and use of tobacco.

Management The treatment of tooth discoloration consists of identifying the etiology and implementing the required therapy. Scaling and polishing of the teeth remove many extrinsic stains. For more stubborn extrinsic discoloration and intrinsic stain, various bleaching techniques may be attempted. Tooth bleaching can be performed externally, termed night guard bleaching or vital tooth bleaching, or intracoronally in root-filled teeth, called non-vital tooth bleaching. Teeth discolored by dental caries or dental materials require the removal of the caries or restorative materials, followed by proper restoration of the tooth. Partial (e.g. laminate veneers) or full-coverage dental restorations may be used to treat generalized intrinsic tooth discoloration in which bleaching is not indicated or in which the esthetic results of bleaching fail to meet the patient’s expectations.

81

CHAPTER

4

Bacterial, Viral and Fungal Infections Ravikiran Ongole, Praveen BN

Bacterial Infections

Viral Infections

➧

Scarlet Fever

➧

Infectious Mononucleosis

➧

Diphtheria

➧

Acute Lymphonodular Pharyngitis

➧

Tularemia

➧

Measles (Rubeola)

➧

Erysipelas

➧

German Measles (Rubella)

➧

Impetigo

➧

HIV and AIDS

➧

Melioidosis

➧

Sinusitis

➧

Tetanus

Fungal Infections and Protozoal Diseases

➧

Actinomycosis

➧

Histoplasmosis

➧

Noma

➧

Blastomycosis

➧

Botryomycosis

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Mucormycosis

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Rhinoscleroma

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Aspergillosis

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Cat-scratch Disease

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Cryptococcosis

Many of the systemic diseases are caused by a wide range of bacteria, viruses and fungal organisms. Some of these microbial diseases can exhibit oral manifestations. However, some of the microbial diseases such as dental caries and periodontal diseases are localized to the oral cavity. Systemic microbial diseases with oral manifestations are discussed in this chapter.

BACTERIAL INFECTIONS SCARLET FEVER Scarlet fever is also known by the names scarlatina, scarlatinella and scarlatiniform rash. It is caused by an infection with a pyogenic exotoxin-producing group A -hemolytic streptococci. The upper respiratory tract is the usual portal of entry. Most cases occur between 1 and 10 years of age and may occasionally be seen in adults. The organism expresses an erythrogenic toxin that acts on the blood vessels to produce the typical skin rash. Clinical features The incubation period of the bacteria ranges from 1 day up to a week. Patients will present with fever and skin rashes 82

within the first 2 days of the infection. The fever and rash usually resolve in about 7 days. Other associated clinical features include headache, tonsillitis, pharyngitis and lymphadenopathy. The scarlet fever rash appears bright red and mimics a sunburn appearance. Normal pin head-sized areas of the skin may project through the rash giving rise to a sandpaper like surface texture, which is popularly referred to as ‘sandpaper rash’ or ‘sunburn with goose bumps or goose pimples’. The skin rashes are commonly seen over the trunk, extremities, neck, groin and specifically along Pastia’s lines (darkening of the normal skin fold/creases, such as the axillary crease, anticubital crease). Once the rash resolves, a 3–8 months phase of desquamation begins, which is characterized by peeling away of the skin in large flakes. Oral manifestations Patients may present with circumoral pallor. The soft palate, pharynx, tonsillar region and the tongue are commonly affected. The oral cavity appears extensively erythematous and edematous (stomatitis scarlatina). Occasionally a yellowish-white exudate may be seen in the tonsillar crypts. During the first 2 days of the infection the dorsal surface of the tongue exhibits a white coat through which the

Chapter 4 – Bacterial, Viral and Fungal Infections

fungiform papillae are visible. Such an appearance is referred to as ‘white strawberry tongue’. After about 4 days the white coat on the tongue desquamates to reveal an erythematous dorsal surface with hyperplastic fungiform papillae, which is referred to as ‘red strawberry tongue’. The complications of untreated scarlet fever may occur either due to streptococcal toxin (myocarditis), or bacterial invasion (septic arthritis, meningitis, osteomyelitis) or by an allergic reaction (rheumatic fever, glomerulonephritis). The diagnosis can be made based on the characteristic clinical presentations, culture of the secretions from the pharynx or tonsillar regions and detection of antigens specific for group A -hemolytic streptococci.

dead cells, leukocytes and bacteria) initially forms on the tonsils and subsequently spreads to involve the larynx, pharynx, uvula, soft palate and occasionally the gingiva. Removal of this mildly adherent membrane leaves a raw bleeding surface. Some patients may exhibit transient paralysis of the soft palate. Extensive involvement of the respiratory tract may lead to respiratory obstruction. The other serious complications include effects of the toxin on the cardiovascular system, nervous system and renal system to cause myocarditis, polyneuritis and acute interstitial nephritis.

Management

Immunization of the infants with DPT vaccine (weakened form of diphtheria toxin) along with booster doses every 10 years, throughout life will effectively prevent the occurrence of diphtheria. Diphtheria is treated with antitoxin along with antibiotics such as intravenous penicillin or erythromycin.

A single episode of scarlet fever will usually confer permanent antitoxin immunity. However, recurrences are not unusual. This is due to the fact that toxin produced by other strains is not neutralized and the bacterial immunity is temporary. Penicillin is the drug of choice. Erythromycin may be used in patients who are allergic to penicillin. Acetaminophen or ibuprofen may be used to alleviate pain and manage fever. Analgesic mouthrinses (benzydamine hydrochloride) may be used for stomatitis.

DIPHTHERIA Diphtheria is an acute infectious disease caused by toxinproducing Corynebacterium diphtheriae or Klebs-Löffler bacillus (after Klebs who discovered the bacillus and Löffler who isolated the bacillus in pure culture). The bacteria reside in the upper respiratory tract of the infected individual and cause local infection of the upper respiratory tract and occasionally the skin and the heart, kidneys, and peripheral nerves. It spreads through droplet infection and direct contact. The incubation period lasts for a few days, following which the bacterium expresses an exotoxin that causes tissue necrosis that subsequently spreads peripherally. General clinical and oral manifestations Tonsillitis is usually the first clinical finding. Patients present with fever, malaise, headache, sore throat, foul taste/breath and cervical lymphadenopathy. The exotoxin causes necrosis of the soft tissues producing a thick, grayish white membrane. As the infection progresses patients may complain of difficulty in speech, swallowing and breathing. Diphtheria involving the skin causes excoriation of the skin of the nasal and perinasal regions. The grayish pseudo membrane (diphtheritic membrane— covers necrotic ulcerated areas of the mucosa and contains

Prevention and management

TULAREMIA (Rabbit Fever, Deer-fly Fever, Francis’ Disease, Tick-Borne Disease, Ohara’s Disease) Tularemia is caused by gram-negative pleomorphic bacterium, Francisella tularensis (named after the extensive work on tularemia done by Dr Edward Francis). It is transmitted to men from animals (chiefly rabbits and also by muskrats and squirrels) by contact with diseased or dead animals, by the bites of deer flies, fleas, and ticks; by contact with contaminated animals or their products; by ingestion of contaminated food or water or by inhalation of aerosolized bacteria. Young and middle-aged individuals who are actively involved in outdoor activities are more susceptible to the disease. Clinical manifestations The incubation period of tularemia usually varies from 3 to 4 days. The initial symptoms include fever, chills, myalgias and malaise. Disseminated form of the disease can cause tularemic meningitis, pericarditis, peritonitis, endocarditis and osteomyelitis. Occasionally a severe form of tularemia, typhoidal tularemia may be seen. Based on the type of the tularemia, specific clinical manifestations are seen (Table 1). Oral manifestations In the initial stages solitary nodular masses may be appreciated which may eventually form abscesses or ulcerate. Generalized stomatitis along with extremely painful necrotic ulcers may be seen affecting any part of the oropharynx. Regional lymphadenopathy is usually a prominent feature. 83


Table 1

Clinical manifestations and types of tularemia

Type of tularemia

Mode of transmission

Clinical features

Ulceroglandular tularemia

Bite of infected insects and animals (ticks, rabbits)

Ulcers at the site of inoculation (fingers, hands, feet) Inflammation of the regional glands. Tender nodes

Glandular tularemia

Similar features as that of the ulceroglandular variety except that there is no evidence of ulcer

Pneumonic tularemia

Inhaling of airborne bacteria from soil or inhalation of the bacteria by healthcare workers

Pneumonia is the characteristic feature. Other symptoms include dry cough, dyspnea, and pleuritic chest pain

Oropharyngeal tularemia

Eating undercooked meat of an infected animal or drinking contaminated water

Vomiting, diarrhea and other digestive problems

Oculo-glandular form

Occurs following exposure of the conjunctiva to infected blood

The affected eye is tender and erythematous. Occasionally purulent exudate may be seen along with inflamed regional glands

Management Tularemia responds well to antibiotics. The drugs of choice include aminoglycosides (gentamicin, streptomycin) fluoroquinolones (ciprofloxacin, gatifloxacin) and chloramphenicol.

ERYSIPELAS Erysipelas is an acute inflammation of the skin, with marked involvement of cutaneous lymphatic vessels. It is usually caused by -hemolytic Streptococcus pyogenes of group A. Erysipelas has to a lesser extent been caused by group B, C, or G streptococci, and occasionally by Staphylococcus aureus. It has also been referred to as St. Anthony’s fire after the name of the Egyptian monk who is believed to have had the powers to cure this disease. Clinical features The typical lesion of erysipelas is evident as an erythematous, well defined area that may be warm to touch. Occasionally a butterfly rash mimicking lupus erythematosus may be seen when the bridge of the nose is involved. Fever of sudden onset is a typical feature. Erysipelas is usually seen in young or old patients and in systemically compromised patients. The typical rash of erysipelas can affect skin on any part of the body. However previous sites of trauma are the most commonly affected. The common sites affected include the legs, cheeks, eyelids and bridge of the nose. The infection causes destruction of the cutaneous lymphatic vessels. This in turn increases the susceptibility for future recurrences (30% recurrence rate). Management Long-term antibiotic therapy with narrow spectrum penicillins (benzylpenicillin) or macrolides may help in preventing recurrent erysipelas infection. 84

IMPETIGO Impetigo is a highly contagious superficial skin infection caused by -hemolytic streptococci and Staphylococcus aureus. Impetigo is considered as the most common bacterial dermal infection in children. It is more common in children receiving dialysis. Clinical features Impetigo usually affects children in the age group of 2–6 years. It spreads via direct skin contact. The incidence of impetigo is greatest in the summer months, and the infection most often occurs in areas with poor hygiene and in crowded living conditions. There are two types of impetigo: non-bullous (impetigo contagiosa) and bullous. The host response to the infection results in the nonbullous type of impetigo. On the other hand, the bullous form is not dependent on the host response but results from the direct action of the staphylococcal toxin. Non-bullous impetigo The skin of the face and the hands and legs are commonly affected sites. The infection begins as a solitary red macule or papule that almost immediately turns into a vesicle. The vesicle ruptures to form an erosion, and the contents dry to form characteristic honey-colored crusts that may be pruritic. These lesions may spread to surrounding areas by autoinoculation. Bullous impetigo Bullous impetigo is described in detail in Chapter 7 on Vesiculobullous Disorders.

MELIOIDOSIS Meliodosis is a potentially fatal bacterial infection caused by exposure to soil or water contaminated with the bacterial species Burkholderia pseudomallei. The causative


organism, Burkholderia pseudomallei, was thought to be a member of the Pseudomonas genus and was previously known as Pseudomonas pseudomallei. Alfred Whitmore, a pathologist and his assistant CS Krishnaswami in 1911, first described melioidosis as a ‘glanders-like’ disease among morphia addicts in Rangoon, Myanmar (formerly Burma). Stanton and Fletcher in 1932 renamed this disease as meliodosis, which is a derivative from the Greek words ‘melis’ (distemper of asses) and ‘eidos’ (resemblance). Melioidosis is regarded as endemic to southeast Asia and northern Australia. In the Indian subcontinent a survey conducted by Kang et al (1996) revealed a seroprevalence of 7% in a rural rice-growing area near Vellore. Risk factors Diabetes, thalassemia, excessive consumption of alcohol, renal disease, and frequent history of occupational or recreational exposure to mud or pooled surface water are common risk factors resulting in melioidosis. Clinical features Melioidosis can present in an acute or chronic form. The average incubation period of acute melioidosis is about 9 days. However patients can exhibit a period of latency. Such patients do not present any clinical symptoms. Literature review reveals that the longest duration between presumed exposure and clinical presentation was 62 years. Such prolonged periods of incubation were recognized in American soldiers involved in the Vietnam War, and was referred to as the ‘Vietnamese time-bomb’. The typical clinical presentations of acute melioidosis usually include pain and fever. Other clinical findings are cough or pleuritic chest pain suggestive of pneumonia, bone or joint pain suggestive of osteomyelitis or septic arthritis, or cellulitis, thyroid, lymph node and scrotal abscess and ocular infection. Parotid abscess has been reported specifically in Thai children. The chronic form of melioidosis is seen in about 10% of the patients. A chronic form is characterized by the presence of symptoms for longer than 2 months. Patients may present with chronic pneumonia, ulcers on the skin surface and chronic dermal infections. Since the chronic form closely resembles tuberculosis, some authors term chronic melioidosis as ‘Vietnamese tuberculosis’. Diagnosis and management The bacterium can be cultured from the tissue fluid from the abscesses and the patient’s blood and sputum. The drugs of choice include antibiotics such as trimethoprim– sulfamethoxazole and ceftazidime orally. However serious infections are best managed with intravenous tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole.

TETANUS The word tetanus comes from the Greek tetanos, which is derived from the term teinein, meaning to stretch. Tetanus, commonly called lockjaw, is an acute neurologic disease that results from wound contamination with Clostridium tetani, an anaerobic, gram-positive, motile, spore-forming rod characterized by generalized muscle rigidity and spasm, sometimes associated with autonomic dysfunction. Pathophysiology It is believed that although most wounds may be contaminated with the spores of Clostridium tetani, the germination and toxin production occurs only in wounds with low oxidation reduction potential, such as those with devitalized tissue, foreign bodies, or active infection. The bacteria produce two exotoxins: tetanolysin (role still unclear) and tetanospasmin. Tetanospasmin is the neurotoxin responsible for the clinical manifestations of the disease. The toxin spreads hematogenously to the peripheral nerves and travels in a retrograde fashion along the nerve fibers to reach the central nervous system where it blocks the release of gamma-aminobutyric acid (GABA) from presynaptic inhibitory neurons. This loss of inhibitory impulses results in the cardinal clinical manifestations of reflex irritability and autonomic hyperactivity. Clinical features Tetanus is usually seen in young adults who are prone to traumatic injuries. Four types of tetanus are recognized based on the clinical presentation: localized, generalized, cephalic and neonatal. The localized form of tetanus is characterized by a limited area of muscular spasm that is confined to the area of the entry of the bacilli. The cephalic subtype of tetanus is characterized by cranial nerve palsies that often precede trismus. Patients present with cranial nerve palsy (usually facial nerve is affected). Approximately two thirds of cases progress to generalized tetanus. The incidence of cephalic tetanus ranges from 0.9 to 3.0%. The cephalic form results from injuries sustained to the head and neck region, tooth extraction or chronic tympanitis. Some patients may present with incomplete Bell’s palsy. Generalized tetanus is the most common form of the disease and carries the highest mortality. Incubation periods for the generalized form range from a few hours to greater than 1 month. Trismus or lockjaw is the initial presentation in 75% of cases. Facial muscle spasm may cause the classic sneering grin of risus sardonicus. Motor findings progress to involve the neck, trunk and extremities, eventually leading to abdominal rigidity and opisthotonus. The muscle spasms may be sustained or paroxysmal. In severe cases the spasm of 85


intercostal, diaphragmatic and pharyngeal muscles leads to breathing difficulties which may eventually lead to death. Neonatal tetanus is a fatal yet preventable disease that accounts for 14% of annual neonatal deaths worldwide. The neonatal form of tetanus has a high mortality rate. It results from unhygienic delivery practices, application of harmful substances on the umbilical cord, and lack of maternal TT immunization. Risk for contamination and subsequent occurrence of neonatal tetanus remains high for several days after delivery until the baby’s cord wound heals. The incubation period varies from 3 to 10 days. Neonate’s failure to suckle is often the first sign of infection in the neonate, and typically occurs between the 3rd and 10th day of life. In spite of efforts by the infant, spasms of the masseter muscle impede feeding. The newborn becomes irritable and cries constantly. Exhaustion may subsequently bring about cessation of audible crying. Sometimes the lips are pursed as if to whistle. Variable degree of muscle spasm develops leading to asphyxia. Differential diagnosis Fascial space infections causing trismus, dystonic reactions induced by such drugs as phenothiazines and metoclorpropramide, hypocalcemia, meningitis, encephalitis, rabies and strychnine poisoning can be considered in the differential diagnosis for tetanus. Diagnosis A simple bed side test may be used effectively to diagnose tetanus. The spatula test is said to have a sensitivity of 94% and specificity of 100%. The posterior pharyngeal wall is touched with a spatula. The test is considered positive if there is a reflex spasm of masseter and negative if there is a normal gag reflex. Enzyme immunoassays for antitoxin levels can also be used. A level of 0.01 IU/ml or greater is considered protective, making the diagnosis of tetanus less likely. Prevention and management The first step should include rapid-sequence intubation with midazolam and succinylcholine. Passive immunization with human tetanus immune globulin (5,000 IU) will help to neutralize free tetanospasmin. It should be given after airway control and before wound debridement. Finally the source wound should be thoroughly debrided, with removal of all foreign bodies and devitalized tissue. Metronidazole, 500 mg IV every 6 hours, is recommended as the first-line antibiotic. As a part of the supportive measures, sympathetic overactivity can be managed with a labetalol infusion at 0.25– 1 mg/min. Diazepam may be used to sedate the patient. The WHO recommends that an individual should receive 3 doses of DTP in infancy, followed by a TT-containing 86

booster at school-entry age (4–7 years), in adolescence (12–15 years), and in early adulthood.

ACTINOMYCOSIS Actinomycosis is subacute to chronic, suppurative granulomatous disease that tends to produce draining sinus tracts. It is caused by anaeroboic gram-positive, non-acid fast bacilli. The common isolates in humans include Actinomyces naeslundii, A. israelii, A. meyeri, A. viscosus and rarely A. odontolyticus. Kalfas et al (2001) identified a new species, Actinomyces radicidentis that was isolated from apical periodontitis. Von Langenbeck noted the first case of human actinomycosis in 1845. Bollinger and Harz in 1877, named the genus Actinomyces when they described the etiologic agent of bovine actinomycosis (‘lumpy jaw’) and called it Actinomyces bovis. Clinical features Actinomycosis is mostly found in young adults. Women are less frequently affected than men. Based on the site of involvement, actinomycosis can be grouped into the cervicofacial (55%), pulmonary (15%), abdominal and pelvic (25%) and cutaneous and genitourinary actinomycosis (5%). Cutaneous actinomycosis is extremely rare and these are said to arise from wounds contaminated with saliva or as a consequence of hematogenous dissemination following a dental procedure. However primary cutaneous actinomycosis have also been reported. The genitourinary form has been reported in patients using intrauterine contraceptive devices. The presenting symptoms of pulmonary actinomycosis are fever, cough, thoracic pain and dyspnea. The sputum is mucopurulent or even sanguineous. With the appearance of fistulae, the disease spreads to the mediastinum, the pericardium, and finally to the skin of the chest. Actinomycosis is believed to be acquired by endogenous implantation into deep tissues where anaerobic conditions prevail. Actinomyces israelii is an anaerobic normal inhabitant of the mouth, especially in the teeth and tonsils. In the cervicofacial region, puncture wounds, dental extractions, or compound fractures are some of the routes of infection. The cervicofacial variant is characterized by the appearance of solid sub- or supramandibular nodules or swellings and the overlying skin becoming purple to violet. Clinical presentation of cervicofacial actinomycosis is characterized by the presence of suppurative or ‘wooden’ indurated mass with discharging sinuses. Pus from the discharging sinuses contains tiny yellow sulfur granules. Common initial symptoms of infection including pain, fever, erythema, edema, and suppuration may be absent.


Actinomycosis often involves lymphatic nodes but by the direct extension of a primary lesion. Occasionally, the masticatory muscles and tongue may be involved resulting in trismus and dysphagia.

Noma is considered to represent the ‘face of poverty’ because many of the risk factors that are associated with poverty. The World Health Organization (1998) has reported an estimated worldwide incidence of 140,000 cases per year.

Radiographic features Actinomycotic osteomyelitis affecting the maxilla and mandible have been reported. Radiographs reveal ill-defined radiolucencies with a radiopaque periphery. Periapical actinomycosis is believed to be a non-resolving periapical lesion associated with actinomycotic infection and has been suggested as a contributing factor in the perpetuation of periapical radiolucencies after root canal treatment. A diagnosis is usually made by identifying the typical actinomycotic colonies in a surgical specimen. Occasionally, the periapical actinomycotic lesion may appear radiopaque mimicking condensing osteitis. Investigations Sinus tracts may reveal the presence of yellowish granules (1–6 mm in diameter) referred to as ‘sulfur granules’. On histological examination, the sulfur granules consist of a central tangled mass of gram-positive mycelia surrounded at the periphery by gram-negative, club-shaped rods. The hematoxylin and eosin stained specimen shows the ‘ray phenomenon’. The periphery of the granule shows filaments that are radially oriented and embedded in eosinophilic material.

Clinical features Noma is usually seen in children between the age of 3 and 12 years mainly in the developing countries especially sub-Saharan Africa. Children at risk for noma have been seen to have low plasma concentrations of zinc, retinol, ascorbate, and essential amino acids with increased plasma and saliva levels of free cortisol. Many authors believe that noma, occurs secondary to the extension of necrotizing ulcerative gingivitis. In the initial stages ulcerative areas from the gingiva extend to involve the adjacent soft tissues. Subsequently the necrotic areas spread both into deeper tissue planes and superficially. The overlying skin turns deep blue to black and eventually sloughs away. Extensive necrosis can lead to exposure of bone and osteomyelitis. Patient may present with pain, fever, malaise, foul odor and regional lymphadenopathy. The differential diagnosis for noma must include mucocutaneous leishmaniasis, lupus erythematosus, leprosy, agranulocytic ulcerations, injuries associated with physical trauma (including burns), syphilis, oral cancer and yaws. Other variants of Noma

The sinus tracts have to surgically excised and abscess drainage should be facilitated. Long-term antibiotic therapy with penicillin or tetracycline is recommended.

‘Noma neonatorum’ is characterized by gangrenous process of the nose, oral cavity, eyelids, and perineum usually seen in premature infants at births or within the first month of life. The causative organism for noma neonatorum is usually Pseudomonas. Noma pudendi is the term used for noma affecting the anogenital area and causing necrosis of the genitalia.

NOMA (Cancrum Oris, Gangrenous or Necrotizing Stomatitis)

Complications and management

The word noma is derived from the Greek word ‘nomein’ that means ‘to devour’. It is rapidly progressive opportunistic infection which is caused primarily by Fusobacterium necrophorum, Fusobacterium nucleatum and Prevotella intermedia. Other reported organisms isolated from the Noma lesions include -hemolytic Streptococci, Actinomyces spp., Peptostreptococcus micros, Veillonella parvula, Staphylococcus aureus, Corynebacterium pyogenes, Bacteroides fragilis, Bacillus cereus and Pseudomonas species. The predisposing and/or risk factors for noma include poverty, malnutrition, immunosuppression (including HIV infection), poor oral hygiene, unsanitary environment, leukemia, and infectious diseases caused by measles and herpesviridae.

Extensive necrosis can cause premature loss of deciduous teeth, damage to the permanent tooth buds, sequestration of the jaws, trismus, and bony or fibrous ankylosis of the temporomandibular joint. Occasionally, infection from the oral cavity can extend to other parts of the body causing systemic complications such as toxemia, dehydration and bronchopneumonia. Untimely intervention can lead to death. Local wound care along with restoration of the hydration, nutritional and electrolyte imbalance should be given adequate importance. Penicillin along with metronidazole are the antibiotics of choice in the management of noma. However, clindamycin and gentamicin are the drugs of choice in the management of neonatal noma.

Management

87


BOTRYOMYCOSIS (Bacterial Pseudomycosis) Botryomycosis arises from chronic infections produced by low-virulence organisms in an altered host environment. Staphylococci have been the most common organisms implicated, but various other bacteria have also been identified in lesions of human botryomycosis. The disease, later referred to as botryomycosis, was first described involving the lung of a horse by Bollinger in 1870. Sebastiano Rivolta in 1884 coined the term botryomycosis (‘botryos’ from Greek for bunch of grapes) after he found globular granules in a tumor from the cut spermatic cord of a horse. Clinical types and features Winslow (1959) categorized botryomycosis into two types based on their site of involvement: integumental and visceral. The integumental botryomycosis affects the exposed body surfaces such as the hands, feet or the head. It occurs in the site of a contaminated wound, foreign body or trauma and manifests as a localized granulomatous infection. Occasionally it causes osteomyelitis. The visceral form is relatively rare. It is usually seen in immunocompromised individuals. It affects the lung, liver, kidney, spleen, brain, prostate, bowel and the lymphatic tissues (tonsil, lymph node). The typical botryomycotic lesions are indurated fibrotic masses that may form draining sinuses and fistulas. Literature review reveals a few reports of botryomycosis affecting the orofacial region. Small and Kobernick (1967) reported a patient with botryomycosis of the tongue. Rawal and Rawal reported a patient with gingival botryomycosis and Alavandar (1979) reported botryomycosis affecting the mandible. Histopathologic features Hematoxylin and eosin stained specimens show chronic suppurative and granulomatous inflammation with giant cells, epithelioid macrophages and scattered microabscesses. Within the areas of the purulent inflammation, Bollinger’s granules are seen. These are relatively small, but frequently microscopically visible, pale yellow or yellow-white granules consisting of irregular aggregates or colonizations of gram-positive cocci, usually staphylococci. Bollinger’s granules are surrounded by an amorphous, eosinophilic, refringent matrix called the Splendore-Hoeppli phenomenon (this phenomenon is also seen around colonies of certain bacteria, fungi, helminthes, actinomyces, mycetoma, nasofacial and subcutaneous phycomycosis and around silk sutures). 88

Management Surgical resection along with antibiotic therapy is the treatment of choice.

RHINOSCLEROMA (Respiratory Scleroma) Rhinoscleroma is an endemic, chronic, slowly progressive granulomatous disease caused by Klebsiella rhinoscleromatis (a gram-negative rod-shaped bacteria, 2.5 m in length). In 1882, von Frisch identified K. rhinoscleromatis as the etiologic agent. In 1870 Ferdinando Von Hebra, a dermatologist described the disease for the first time. It was later named respiratory scleroma. The word ‘skleroma’ in Greek meaning hard tumefaction, was adopted in 1932 at the International Clinical Otorhinolaryngology Conference (in Madrid), emphasizing involvement of upper and lower airways. Rhinoscleroma is contracted by direct inhalation of droplets or contaminated material. Clinical stages Humans are the only identified host of K. rhinoscleromatis. It usually affects individuals in the 2nd to 4th decades of life. It affects people living in crowded conditions with poor hygienic and nutritional conditions (including iron deficiency anemia). Rhinoscleroma affects women more commonly than men (13:1). The nose is the most common site of infection, although the nasopharynx, paranasal sinuses, and pharynx may also be involved. Other affected organs include the paranasal sinuses, eustachian tubes, middle ear, orbital tissues and the brain. Rhinoscleroma occurs in three overlapping stages: catarrhal-atrophic (sometimes called ozaena), granulomatous (proliferative or nodular) and sclerotic (cicatricial or fibrotic). In the catarrhal stage, patient may complain of foul smelling purulent nasal discharge and nasal obstruction. On clinical examination atrophy and crusting of the nasal mucosa or hyperemia and exudates in the respiratory tract mucosa are evident. In the granulomatous stage, epistaxis, nasal deformity and destruction of the nasal cartilage (Hebra nose), hoarseness of voice, anosmia and anesthesia of the soft palate are common signs and symptoms. Clinical examination may reveal a bluish red and rubbery granulomatous lesion. These lesions over a period of time turn into a pale hard granulomatous mass. In the sclerotic stage, clinical examination shows granulomatous lesions surrounded by dense fibrotic tissue.


Diagnosis The diagnosis of rhinoscleroma is made by the bacterial isolation by culture on blood or MacConkey agar. Histopathological specimens can be stained with periodic acidSchiff, Giemsa and Warthin–Starry stain. The presence of Mikulicz cells (clear cytoplasm vacuolated histiocytes containing the bacillus) and degenerated plasmocytes in Russel bodies are diagnostic of rhinoscleroma. The hypertrophic stage of rhinoscleroma has characteristic mild to marked high signal intensity on both T1- and T2-weighted MR images. Management Nasal or pharyngeal obstruction is best managed surgically along with antibiotic therapy. Many authors recommend the use of cephalosporins and clindamycin. Shaer et al (1981) have shown that the topical application of 2% acriflavine solution is an effective and safe treatment option for rhinoscleroma. Tracheostomy may be required if laryngeal scarring causes airway obstruction.

CAT-SCRATCH DISEASE

couple of months. The lymph nodes can enlarge to a size of about 10 cm. Other systemic manifestations include parotitis, osteomyelitis, hepatosplenomegaly, neurological conditions (seizures, altered behavior or consciousness, peripheral facial nerve paresis, myeloradiculitis) and hematological conditions (hemolytic anemia, thrombocytopenia and eosinophilia). When a pet’s saliva contaminated (as the cat constantly licks its fur) fur is groomed, organisms from the fur are transferred to the individual’s hand. Such contaminated fingers, when used to rub the eyes might cause self-inoculation of the organisms to the conjunctiva. Conjunctival involvement will result in preauricular lymphadenopathy. This association of conjunctival involvement and preauricular lymphadenopathy in cat-scratch fever is referred to as ‘Parinaud oculoglandular syndrome’. Several skin reactions have been reported, including erythema nodosum, erythema marginatum and erythema multiforme. B. henselae and B. quinata are implicated in the causation of bacillary angiomatosis and peliosis in immunocompromised hosts such as in AIDS. Orally these lesions mimic Kaposi’s sarcoma and appear as vascular lesions and within bone may cause alveolar bone loss. Diagnosis

Cat-scratch disease arises from the inoculation of the gram-negative bacillus Bartonella henselae following a cat’s scratch, lick or bite. It is estimated that almost 40% of the domestic cats may have an asymptomatic B. henselae infection accompanied by bacteremia, which can persist for more than a year. It is believed that domestic cats tend to rapidly develop antibodies and therefore appear healthy in spite of the bacteremia. The first description in the literature of cat-scratch disease is credited to Henri Parinaud in 1889. Dr Robert Debré in 1931 described a case of a boy with a cat-scratch on his hand associated with a suppurative epitrochlear lymph node. He is credited with recognizing the cat as the vector of this illness and coined the term ‘catscratch disease’. Regnery and coworkers (1992) identified B. henselae as the causative organism for cat-scratch disease. Cat-scratch disease is considered as a self-limiting granulomatous condition characterized by suppurative regional lymphadenitis. Clinical features The incubation period varies from 7 to 15 days. It usually affects individuals in the second decade of life. Patients may present with mild fever, fatigue and malaise. The initial lesion occurs as a pustule or papule seen at the site of the trauma (cat-scratch or bite). These initial lesions are followed by regional lymphadenopathy that lasts for a

Neville and coworkers enumerated certain criteria for the diagnosis of cat-scratch fever. Evidence of at least three of the following four criteria is considered to be positive for cat-scratch disease: 1. 2.

Contact with a cat, presence of a scratch or a primary dermal or ocular lesion. Positive Hangar–Rose skin test (cat-scratch disease skin test).

This skin test was first developed by Hanger and Rose in 1946. Aspirated material from a lymph node of a patient with known cat-scratch disease is pasteurized, standardized, and tested for sterility. It is then injected subdermally and skin reaction is noted. 3. 4.

Unidentifiable cause for lymphadenopathy. Presence of pleomorphic bacilli with Warthin–Starry method or Brown–Hopps method.

However, serological test (ELISA for IgM antibodies to B. henselae) is the gold standard for the diagnosis of cat-scratch disease. Elevated serum titers are seen 1–3 weeks after the onset of the disease process. Management The condition is self-limiting and usually resolves in about 6 months duration. Suppurative nodes may be aspirated to evacuate the pus. The recommended surgical procedure to evacuate the pus is to introduce the needle into the skin 89


1 to 2 cm away from the swelling and then burrow beneath the surface of the skin to reach the affected node. The technique helps to hasten the healing and prevent formation of a persistent sinus. Antibiotics such as gentamicin, penicillin, ciprofloxacin and rifampin may be used when systemic involvement is apparent. Other bacterial infections with oral manifestations such as tuberculosis, syphilis, leprosy and gonorrhea have been described in Chapters 8, 21 and 22.

VIRAL INFECTIONS INFECTIOUS MONONUCLEOSIS (Monoglandular Fever, Kissing Disease) Infectious mononucleosis (IM) is a clinical syndrome caused by Epstein–Barr virus-4 (EBV, human herpes virus-4). EBV replicates primarily in beta-lymphocytes but also may replicate in the epithelial cells of the pharynx and parotid duct. Children and young adults are usually affected. The virus is transmitted via intimate contact. Children may acquire the virus through sharing of saliva contaminated fingers, toys and serving spoons. Direct transfer of contaminated saliva may occur in adults following kissing (hence the name kissing disease) or sharing of straws. The incubation period is 4–8 weeks. Clinical features The characteristic clinical features of IM include, malaise, fatigue and anorexia. These symptoms are immediately followed by high fever (about 104F) which lasts for almost 2 weeks. The most striking feature of IM is the presence of lymphadenopathy. Any or all lymphatic chains may be enlarged. Lymphadenopathy is always bilateral and symmetrical in all patients. Bilateral posterior and anterior cervical lymphadenopathy is highly suggestive of EBV infectious mononucleosis. Other clinical features include the presence of tonsillar enlargement, hepatosplenomegaly, jaundice, rhinitis and pharyngitis. Hoagland’s criteria (1975) for the diagnosis of IM include: at least 50% lymphocytes and at least 10% atypical lymphocytes in the presence of fever, pharyngitis, and adenopathy, and confirmed by a positive serologic test. Oral manifestations include hard and soft palate petechiae, necrotizing ulcerative mucositis, necrotizing ulcerative gingivitis and pericoronitis. Occasionally, the parotid gland may be affected along with facial nerve palsy. 90

Warwick et al (2003) reported a patient with IM, ruptured spleen and Cullen’s sign (periumblical ecchymosis). They also suggest that the presence of abdominal pain is an uncommon symptom in infectious mononucleosis and its occurrence is therefore a danger sign that may forewarn a potentially life threatening complication of ruptured spleen. The complications of IM include myocarditis and cardiac conduction abnormalities, neurologic abnormalities, meningitis, encephalitis, cranial nerve palsies, retrobulbar neuritis, acute interstitial nephritis, hemolytic anemia, thrombocytopenia and upper airway obstruction. Syndrome association Chronic fatigue syndrome and Lemierre’s syndrome have been reportedly associated with IM. The association of IM and chronic fatigue syndrome is still very questionable and debatable. Diagnosis The Paul-Bunnell test is a serological test that detects heterophile antibodies by agglutination of sheep or horse red blood cells. However, in the 1st week of infection, the falsenegative rate is as high as 25%. VCA-IgG and VCA-IgM tests are useful in diagnosing patients who have highly suggestive clinical features but negative heterophile antibody test results. Antibody to Epstein–Barr nuclear antigen (EBNA), while typically not detectable until 6–8 weeks after the onset of symptoms, can help distinguish between acute and previous infections. Elevated hepatic transaminase levels may be seen in about 50% of the IM patients. Management Infectious mononucleosis usually resolves in about 6 weeks. IM is best managed with extensive palliative and supportive healthcare. Patient should be adequately hydrated. Fever and malaise may be managed with acetaminophen and NSAIDs. Though steroids have been used frequently, they are best used only in an emergency to relieve the patient of respiratory compromise secondary to pharyngeal edema. Antibiotics like penicillins are best avoided as these patients have a higher risk of developing a morbilliform skin rash.

ACUTE LYMPHONODULAR PHARYNGITIS Acute lymphonodular pharyngitis is caused by Coxsackie virus A10. It is characterized by prodromal fever, anorexia, headache and sore throat. Like most viral infections, the condition is self-limiting and generally resolves in about 2 weeks.


Clinical features Acute lymphonodular pharyngitis is usually seen in children and young adults. Clinically, the hyperplastic lymphoid aggregates are evident as discrete yellow to dark pink colored nodules or white to yellow papules surrounded by an erythematous ring, generally 1–5 in number. These lesions are typically found on the tonsillar pillars, uvula, soft palate and oropharynx. Histopathological evaluation of these nodules may reveal epithelial necrosis and inclusion bodies (intranuclear or cytoplasmic) and multinucleated cells. Management The condition is self-limiting and the management is aimed at supportive care. Non-aspirin containing analgesics are beneficial.

MEASLES (Rubeola) Measles is caused by an RNA virus, paramyxovirus. Measles is an acute and highly communicable disease and infection confers lifelong immunity. The disease process is marked by the presence of prodromal fever, cough, conjunctivitis and coryza (profuse discharge from the nasal mucous membrane). Measles may often occur as an epidemic. The virus is transmitted via direct contact or by droplet infection and the respiratory tract forms the portal of entry. Measles is usually considered as a serious disease in malnourished, immunocompromised or vitamin deficient individuals. Clinical features Following a 14-day incubation period skin rashes begin to appear. About 2–3 days before the typical skin rash appears the patient may exhibit prodromal upper respiratory symptoms and conjunctivitis along with lymphadenopathy. The skin rash fades away in about 7 days. Pale skinned individuals may exhibit areas of altered pigmentation following resolution of the skin rash. During this stage of the infection the pathognomonic Koplik’s spots begin to appear on the buccal mucosa. Koplik’s spots are small, irregular, red spots with a minute bluish white speck in the center of each seen on the buccal mucosa and lingual mucosa. They are named after Henry Koplik (1858–1927), an American pediatrician who first described them in 1896. Patients are usually irritable and photophobic at this stage. These spots represent sites of virus replication and sites of inflammation of the mucous glands. As the disease progresses, bacterial superinfection may lead to diarrhea, bacterial pneumonia, cancrum oris,

convulsions and subacute sclerosing panencephalitis may develop. Diagnosis Measles can be diagnosed based on the characteristic skin rash and the Koplik’s spots. The diagnosis can be confirmed by the measles virus sandwich-capture immunoglobulin M (IgM) antibody assay. Prevention and management Infants below 1 year of age are protected by the maternal antibodies. Live attenuated measles vaccination given to a child older than 1 year provides immunity. The measles-mumps-rubella (MMR) vaccine is given in two doses. The first dose is given to children at the age of 1 year. The second dose is given usually between 4 and 6 years of age. Supplementation by vitamin A during an acute attack, minimizes the morbidity and mortality risks.

GERMAN MEASLES (Rubella) Rubella is caused by Rubivirus, an RNA virus of the Togaviridae family. Rubella runs a milder course and it affects the skin, lymphatic system and the joints. However, infection of the mother during pregnancy may lead to serious complications for the developing infant. The disease spreads via the respiratory route and mainly by droplet infection and to a lesser extent by direct contact with contaminated throat or nasal secretions. Clinical features The incubation period lasts for approximately 18 days. It typically affects children and to some extent young adults. The initial prodromal symptom period is followed by lymphadenopathy. Suboccipital and posterior auricular nodes are typically enlarged. The other clinical findings include skin rashes and pharyngitis. The most important complication of rubella is the congenital rubella syndrome. The maculopapular rash appears pink and appears first on the face and then spreads rapidly downwards to involve the trunk and the extremities. These eruptions are generally transitory and persist only for about 3 days, thus accounting for the famous synonym ‘3-day measles’. Oral manifestations The common oral manifestation is the presence of minute red macules and petechiae on the soft palate and uvula (Forchheimer spots: non-specific for rubella) of pinpoint red macules and petechiae can be seen over the soft palate and the uvula just before or with the exanthem. 91


Mothers suffering from rubella during the first trimester are likely to have children who exhibit pitting and enamel hypoplasia and rarely complete aplasia. Eruption of teeth may be retarded. Some authors have reported cleft lip and palate in some of these children. Prevention and management Rubella is best prevented by mumps-measles and rubella vaccination. The disease is self-limiting. As individuals are highly contagious in the first 1 week, following appearance of the skin rash, they should ideally abstain from group activities during this period. Maintenance of hydration and bed rest is generally sufficient. Non-aspirin containing NSAIDs may be given for managing the prodromal symptoms.

HIV AND AIDS Human immunodeficiency virus (HIV) is a lentivirus (a member of the retrovirus family) that can lead to acquired immunodeficiency syndrome (AIDS). HIV infects cells of the human immune system and destroys them or prevents them from functioning. Such individuals whose immune system is defective are much more vulnerable to opportunistic infections. Retroviruses have an inherent advantage of both mutation (typical of RNA viruses) and latency (typical of DNA viruses).

Discovery of HIV Disease syndromes similar to the clinical manifestation of AIDS have been described in the ancient Ayurvedic literature. Sushrutha in 800 BC and later Charaka and Vagbhatta describes a conditions with ‘loss of muscle mass, fever, skin eruptions and ulcers, complexion changes, neurological disorders, exhaustion, coma and death, and stated that in irremediable stages treatment should be given up’. In 1981, homosexual men with symptoms of a disease that now are considered typical of the acquired immunodeficiency syndrome (AIDS) were first described in Los Angeles and New York. The men had an unusual type of lung infection (pneumonia) called Pneumocystis carinii (now known as Pneumocystis jiroveci) pneumonia (PCP) and rare skin tumors called Kaposi’s sarcoma. The patients were noted to have a severe reduction in CD4 cells. These cells, often referred to as T cells, help the body fight infections. Shortly thereafter, this disease was recognized throughout the United States, western Europe, and Africa. In 1983, researchers in the United States and France described the virus that causes AIDS, now known as the human immunodeficiency virus (HIV) and belonging to the group of viruses called retroviruses. In 1985, a blood test became available 92

that measures antibodies to HIV that are the body’s immune response to the HIV. This blood test remains the best method for diagnosing HIV infection. American researcher Robert Gallo and French scientist Luc Montagnier are both credited for discovering HIV. In the later parts of 1986 in India, first cases of HIV were diagnosed among sex workers in Chennai, Tamil Nadu. It was noted that contact with foreign visitors had played a role in initial infections among sex workers. In 1987 a National AIDS Control Program was launched to co-ordinate national responses. Its activities covered surveillance, blood screening, and health education. By the end of 1987, out of 52,907 who had been tested, around 135 people were found to be HIV positive and 14 had AIDS. Most of these initial cases had occurred through heterosexual sex, but at the end of the 1980s a rapid spread of HIV was observed among injecting drug users in the three north-eastern states of India, namely Manipur, Mizoram and Nagaland. In 1992 the government set up NACO (the National AIDS Control Organization), to oversee the formulation of policies, prevention work and control programs relating to HIV and AIDS. In 1982, AIDS was originally defined by US Center for Disease Control as ‘the disease, at least moderately predictive of a defect in a cell mediated immunity occurring in a person with no known cause for diminished resistance to that disease’. HIV infection in children was first recognized in 1983. Pediatric AIDS can be defined as disease occurring in children less than 13 years of age. The etiologic agents of AIDS and HIV infections belong to the family of human retroviruses and the subfamily of lentiviruses. The four recognized human retroviruses belong to two distinct groups: i. ii.

The human T lymphotropic viruses [HTLV-1 and 2] The human immunodeficiency virus [HIV-1 and 2]

The most common cause of HIV disease throughout the world is HIV-1, which was identified in May 1983, and HIV-2 was first identified in 1986 in west African patients and was originally confined to west Africa. The major difference in the genomes of HIV-1 and 2 is that the HIV-2 lacks the vpu gene. HIV is more closely related to an SIV (simian immunodeficiency virus) isolated from chimpanzees in 1990. HIV-2 is much more closely related phylogenetically to the simian immunodeficiency virus found in sooty mangabees.

Structure of the HIV-1 Virion HIV-1 virion is spherical in shape and contains an electron dense core surrounded by a lipid envelope derived from the host cell membrane during budding of the virus from the infected cell.


The virus core contains several core proteins, two strands of genomic RNA, and the enzyme reverse transcriptase that is characteristic of all retroviruses. The viral envelope is studded with two viral glycoproteins, gp120 and gp41. The gp41 projects outward and is important for the fusion of the virus to its target cells and gp120 helps in binding of host cell CD4 receptor. The virion is approximately 10 kb in length, and it contains the gag, pol and env genes, that code for the core protein, reverse transcriptase and envelope proteins respectively. Each structural region comprises three structural proteins/ antigens. Env gene makes gp160, gp120 and gp41 glycoproteins. Gag gene is responsible for p55, p24, and p17 antigens and pol for p31, p51, p66 antigens.

Subtypes HIV-1 Virus The strains of HIV-1 can be classified into three groups: the ‘major’ group M, the ‘outlier’ group O and the ‘new’ group N. These three groups may represent three separate introductions of simian immunodeficiency virus into humans. More than 90% of HIV-1 infections belong to HIV-1 group M. Group O is believed to be restricted to westcentral Africa and group N (discovered in 1998) is seen in Cameroon is extremely rare. Within group M there are known to be at least nine genetically distinct subtypes (or clades) of HIV-1. These are subtypes A, B, C, D, F, G, H, J and K (Table 2). Occasionally, two viruses of different subtypes can meet in the cell of an infected person and mix together their genetic material to create a new hybrid virus (a process similar to sexual reproduction, and sometimes called ‘viral sex’). Many of these new strains do not survive for long, but those that infect more than one person are known as ‘circulating recombinant forms’ or CRFs. For example, CRF A/B which is a mixture of subtypes A and B. Lentivirus HIV-1

HIV-2

Group M

Group N

Table 2

Predominant types of HIV-1 in various parts of the world

Region

Predominant type

Other subtypes

South America

B

Australia

B

C, F

Western Europe

B

A, C, D

Eastern Europe

B, C, G, D

F

Africa

A, B, D, C, E, F, G, H, O

Uganda

A, B, C, D, G

Zaire

A, D, H

Kenya

A

Nigeria, Gabon

G, H

Cameroon

A, B, E, G, H, F

Central Africa

A, C, D, E

Zambia, Malawi (Southeast Africa)

C

China

Bb

Southeast Thailand, Myanmar

Bb, E

Indonesia

E

India

C

C

A, B, F

nucleic acids in the reverse direction, i.e. DNA from RNA and hence termed ‘reverse transcriptase’ and the virus as retroviruses.

Basic Genetics of HIV HIV contains nine genes made of 9,749 base pairs. Gag (codes for internal structural proteins and capsid proteins using about 2,000 base pairs), pol (codes for the three enzymes necessary for replication using about 2,900 bp) and env (codes for the surface proteins gp120 and gp41 that protrude from the lipid envelope and attach to cellular receptors using about 1,800 bp). Other genes are tat (transactivator protein), rev (regulator of expression of virus protein), vif (virus infectivity factor), nef (misnamed negative regulator factor, but really an enhancing factor), vpr (virus protein R), and vpu (virus protein U).

Group O

Stages of Infection (Figures 1–17) Clades A, B, C, D, F, F2, G, H, J, K

The hallmark of the life cycle of HIV infection is the reverse transcription of genomic RNA to DNA by the enzyme reverse transcriptase. Crispian Scully (1997) stated that HIV is an RNA virus containing an enzyme, which can transcribe

Step 1: Entry of the HIV virion into the host T-cell, is triggered by the binding of membrane proteins to receptors on the T-cell surface. Step 2: The membrane proteins on the virus are units called gp120. These gp120 unit binds to the receptors called CD4 on the T-cell. The union of gp120 and CD4 initiates another event. 93


Figure 1

Figure 3 gag p17 gag p24

HIV

RNA

4 CD gp 40 gp 120

Envelopment of virus into host cell

T-cell

Co-receptor CCR5 combines with CD4

Figure 4 Binding of HIV virion into host T cell

Figure 2 HIV

Endocytosis

T-cell

CD

4

Complete envelopment of virus

T-cell

5 CR

Figure 5

C

Capsid

gp120 unit binding to CD4 receptor HIV

Step 3: CD4 changes its shape so that another membrane protein of the T-cell called CCR5 fits. CCR5 is a co-receptor that is essential in enabling the virus to enter the cell. Patients with defective co-receptors do not show signs of HIV infection in spite of repeat exposures. Step 4: These events lead to the envelopment of the virus into its host cell. Step 5: This process is known as endocytosis. Step 6: Once inside the host cell capsid begins to shed its coat. 94

T-cell

Capsid within host cell

Step 7: Shedding of the capsid is necessary for the exposure of viral RNA and enzymes. In HIV, the viral genome is in the form of RNA. There are two strands of RNA connected at one end. The capsid also contains important enzymes for the events leading to infection of the host cell.


Figure 6

Figure 8

Enzymes Double stranded viral DNA RNA Capsid (shedding the capsid)

Shedding of capsid

Formation of double stranded DNA

Figure 7

Figure 9 Viral RNA

Viral DNA

Reverse transcriptase Viral DNA Host cell nuclear envelope

Reverse transcription Host DNA

Step 8: The first event is called reverse transcription. From a strand of RNA, the enzyme reverse transcriptase catalyzes the formation of viral DNA. Step 9: Reverse transcriptase also helps in the formation of the second strand of viral DNA. Step 10: The viral genetic material is ready to enter the host cell nucleus and become integrated into the host DNA. Step 11: The viral DNA is integrated with the help of another enzyme called retroviral integrase. The integrated DNA is now called a provirus. Step 12: The provirus serves as a template for the synthesis of viral RNA. Upon completion, the newly formed viral RNA moves out into the cytoplasm. Step 13: The viral RNA carries information that codes for viral proteins and enzymes. Therefore, it is also called messenger RNA. The codes on the viral RNA are translated into proteins and enzymes in the form of a long chain called a polypeptide chain. Step 14: The polypeptide chain includes important proteins for the envelope, capsid, enzymes, and other parts of

Viral DNA entering host cell nucleus

Figure 10

Viral DNA

Host DNA

Retroviral integrase [PROVIRUS]

Viral DNA integrating with host DNA

95


Figure 11

Figure 13

Ribosome Viral RNA

Synthesis of viral RNA Protease breaking polypeptide chain

Figure 12 Figure 14 Viral RNA

Host cell

T-cell nucleus

Capsid begins to form Polypeptide chain

Early stages of capsid formation Formation of polypeptide chain

Figure 15

the new virus to be formed. The enzyme protease helps to cut this chain into individual components. Step 15: With all the components ready to leave the host cell the capsid forms to envelop these pieces. Step 16: Assembly of the capsid initiates the insertion of membrane proteins on the host cell’s plasma membrane. Step 17: As the new virus leaves or buds from the surface of the host cell, it forms an envelope with the inserted membrane proteins. Step 18: Numerous new viruses can be formed from one T-cell and move on to infect other T-cells in various parts of the body. 96

Membrane proteins

Host cell

Formation of membrane proteins on host cell


Figure 16 Plasma membrane

Budding Host cell

Newly formed virion leaving host cell

Figure 17

New HIV molecule Host cell

Newly formed HIV molecule

Step 19: The T-cells are eventually destroyed, leaving the body with a compromised immune system and susceptible to attack by foreign bodies.

Transmission Transmission of HIV-1 occurs mainly through one or more of three routes: 1. 2. 3.

Sexual contact Passage of the virus from infected mothers to the newborn Through blood and parenteral inoculation.

Sexual contact It is the predominant mode of transmission. The rate of infection is increased with the number of sexual partners

and with the frequency of anal receptive intercourse, which predisposes to rectal trauma in the receptive partner. It is believed that the virus is carried in lymphocytes present in the semen and enters the recipient’s body through abrasions in rectal mucosa. HIV-1 has been found in vaginal and cervical secretions and in monocytes and endothelial cells within the submucosa of the uterine cervix of infected individuals through which the transmission to the male partners takes place. Zagury D Bernard and Leibwitch et al (1984) stated that HIV spreads to women from men through the semen and from cervical secretions of infected woman to men. This was based on the isolation of HIV from semen and cervical secretions, which makes it biologically possible for HIV to spread heterosexually from men to women and women to men. Faltz, Mc Clure and Doughaty et al (1986) stated that infection can occur without trauma to the vagina. This was substantiated by experimental vaginal HIV infection of a chimpanzee and from the case reports of infection through artificial insemination of the virus. Pandian et al (1987) reported a relatively higher risk for those engaged in anal intercourse than those having only vaginal intercourse but emphasized that anal intercourse was not always necessary for transmission. Greenblatt et al (1987) stated that a factor that may influence transmission is genital ulceration. He stated that an African study found an increased risk of being infected on those with a history of genital ulceration. Mayer and De Glottal (1987) stated that anecdotal cases of HIV transmission by oral sexual activity have been reported but has never been convincingly demonstrated. Nobut Gilmole (1992) reported that among the sexual modes of HIV transmission, intercourse is the most predominant factor, as more than 60% of HIV transmission worldwide were attributed to vaginal intercourse. He also stated that everybody is susceptible to HIV infection although some people have been reportedly exposed to the virus and inexplicably they have not been infected. He stated that susceptibility to HIV may need to be facilitated by mucosal injury caused by trauma, sexually transmitted diseases or genital ulcers. Anne M Johnson (1988) stated that there is some evidence that the risk of transmission increase both with the duration of the sexual relationship and the frequency of sexual contact. WHO (1997) stated that individuals vary on their susceptibility to infection for reasons that are not known. Through sexual intercourse some may get infected by a single exposure from infected partners while others may not become infected even after repeated exposures. The receptive partner is at greater risk than the insertive partner in both vaginal and anal intercourse. Male to female transmission was higher than transmission from female to males. This was substantiated on 5-year follow-up study 97


at San Francisco where 20% of female partners of HIV positive men got infected whereas only one case of female to male transmission was observed. As per their observation they stated that anal sex was more hazardous than vaginal sex because there was greater degree of trauma in anal intercourse as anal mucosa is thin and vascular. So the highest risk is for person who is passive or receptive partner in anal intercourse. They also opined that oral sex, deep kissing may carry a risk of infection and risk of acquiring infection is much higher in those suffering from sexually transmitted disease especially so in the presence of ulcerative lesions of the genitalia. Passage of the virus from infected mothers to the newborns Carrew, Jaffe, Hardy A Metal (1988) stated that the proportion of HIV-infected pregnant women whose infants are subsequently found to be infected ranges from 16 to 33%, but the specific determining perinatal infection remains unexplained. Oxdely (1988) stated that a rare case of transmission through breast milk has been documented. Philiop A Piczzo and Karina M Balter (1991) stated that the exact time during pregnancy or delivery when HIV transmission occurs is not well established. Although the presence of virus had been documented in fetal tissues after 8–15 weeks’ gestation, HIV was found predominantly during intrapartum period. This might occur because of ingested maternal blood or because of maternal-fetal transmission during labor and delivery. Goryle, Selik and Chersov (1990) stated that the most common means of transmission of HIV to a child from an infected mother is either during pregnancy or at birth. They stated that although the vertical transmission of HIV from an infected mother to an infant is unique, few cases may represent a blood borne transmission. In 1996, Indian Council of Medical Research stated about the selected factors associated with mother to child transmission of HIV-1. It was classified into: 1.

2.

98

Proved or possible modes of transmission ❍ Maternal immune deficiency ❍ Chorioamnionitis ❍ Breast feeding ❍ Vaginal delivery ❍ Low maternal serum vitamin A concentration ❍ Instrumental injury during labor and/or delivery (episiotomy, forceps, etc.) ❍ Premature rupture of membranes ❍ Prematurity ❍ Prolonged labor Controversies ❍ Maternal immune response against HIV ❍ Viral strain characteristics

Ramos-Gomez (1997) stated that HIV can be transmitted perinatally from mother to newborn infant in three ways: 1. 2. 3.

Transplacentally during pregnancy During delivery as the infant passes through the birth canal Postnatally during breast feeding

An estimated 94% of pediatric HIV infection is acquired perinatally and around half of these reported perinatal infection occurred when the infant through the birth canal. WHO and NACO (1997) in their publication stated that most of the children acquire HIV from their mothers through the three possible routes: transplacentally, intrapartum and breast feeding. The other routes like blood transfusion and role of contaminated syringes also contributed in a small way. They stated that transplacental is a major source of infection and parental transmission accounting for 80% of all AIDS cases. Frequency of transmission from mother to child was around 25% and transmission was more in mothers with HIV symptomatic group than asymptomatic group. They stated that intrapartum transmission was due to contact of child with maternal blood during delivery. They also stated that the transmission can occur through breast feeding, as the virus has been isolated in breast milk. The mother to child transmission can be now prevented by the recent use of antiretroviral drugs. These are said to prevent the virus transmission from mother to child if the virus status of the mother is detected in early stages of pregnancy and prompt use of antiretroviral therapy. Through blood and parenteral inoculation Volken Wah, Hans H Kramer and Thomas et al (1986) reported a case of HIV infection that appeared to have occurred through horizontal transmission with two siblings. They stated even minor bites by HIV infected children may carry the risk of transmitting the virus. They cautioned the parents and teachers and other people responsible for HIV infected children should be aware of this possibility and try to prevent spread of virus by this route. Fashy, Schmith and Sash et al (1989) stated that risk of HIV transmission to healthcare workers by accidental parenteral exposure to infected blood has been estimated to be 0.36% and 0.41% of such injuries. Gershon, Valhov and Nelson (1990) stated that in a study of more than 1,300 dental healthcare workers 94% had sustained an accidental inoculation type injury with a median number of three parenteral injuries per year.


However the risk of HIV infection in this study was only 0.08%. Desjarlair and Friedman (1995) stated that transmission by parenteral exposure to infected blood such as through the sharing of uncleaned injection equipment during injecting drug appeared to be the most efficient means of HIV transmission. They also stated that the prevalence of HIV infection has risen rapidly among equipment sharing during drug abuse in many countries, emphasizing the spread by the HIV by this mode. Mast and Grebreding (1995) stated that volume of blood involved in percutaneous exposure may prove an important determinant of risk. The type of gauge of needle used, the depth of penetration and glove use, effect the amount of blood transferred during needle prick injuries. They also stated that the titer of virus in the contaminant is hypothesized to be an important variable affecting the infection. They stated that mean circulating viral titer in patients with AIDS was 100–1,000 times higher than in patients with HIV infection who are asymptomatic and exposure of blood from patients with AIDS was associated with higher risk of transmission.

HIV and Saliva Malamad et al (1997) in their review article ‘Inhibition of HIV infectivity by saliva’ stated that viral inhibitory factors are present in a variety of human saliva. They proposed that the inhibitory factors are produced within the salivary glands probably in greater concentration in submandibular saliva and may indicate the presence of multiple factors. They concluded from their study that saliva does not lyse HIV. Shugars and Wahi (1998) in their article ‘How oral cavity resists transmission of HIV’ stated that the thick epithelial layer of intact oral mucosa is a barrier to infection. They stated that saliva lubricates the mucosa, dilutes the microbial burden and also washes microbes into the gastrointestinal tract where they are destroyed. When trauma or disease ruptures the physical barrier of the mucosa, HIV can potentially enter susceptible cells. They stated that rare cases of transmission have been reported through blood, blood contaminated oral mucosa or saliva. Further they stated that saliva inhibits HIV by several endogenous inhibitors and oral secretion can neutralize HIV via virus specific antibody response. Various salivary components like lactoferrin, lysosome, lactoperoxidase exert antimicrobial effects. Mucins and thrombospondin can entrap viruses. Defensins—SLP-I and thrombospondin work to inhibit HIV from entering susceptible cells. They conclude that mouth is made resistant to HIV transmission by the combination of a thick epithelial layer, low number of CD4 bearing target cells and variety of endogenous inhibitors antiviral antibodies. They also stated that these inhibitory mechanisms may fail when mucosal surface is not intact.

ACQUIRED IMMUNE DEFICIENCY SYNDROME Centers for Disease Control and Prevention (CDC) in 1993 had defined acquired immunodeficiency syndrome (AIDS) as the occurrence of one or more group of life-threatening opportunistic infections, malignancies, neurologic diseases, and other specific illnesses in patients with HIV infection and/or with CD4 counts less than 200/mm3. CDC stated that this definition was a surveillance definition that was established to track the incidence of this disease and the relative occurrence of diseases that are likely to occur in severely immunosuppressed individuals. It is stated that in that part of the world where CD4 enumeration is not as readily available, clinical diagnoses, in conjunction with serologic tests for HIV, could be used to define patients with AIDS and to track the spread of this epidemic.

Revised Classification System of HIV Disease (CDC, 1993) The CDC disease staging system assesses the severity of HIV disease by CD4 cell counts and by the presence of specific HIV-related conditions. The definition of AIDS includes all HIV-infected individuals with CD4 counts of 200 cells/l (or CD4 percentage 14%) as well as those with certain HIV-related conditions and symptoms. CD4 (mm3)

A

B

C

500

A1

B1

C1

200 to 400

A2

B2

C2

200

A3

B3

C3

Category A ❍ ❍ ❍

Asymptomatic HIV infection Persistent generalized lymphadenopathy Acute retroviral syndrome

Category B ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍

Bacillary angiomatosis Candidiasis Cervical dysplasia Constitutional symptoms (fever, diarrhea 1 month) Oral hairy leukoplakia Herpes zoster Idiopathic thrombocytopenic purpura Listeriosis Pelvic inflammatory disease Peripheral neuropathy

Category C (AIDS defining conditions) ❍ ❍

CD4 count less than 200 cells/l Candidiasis (pulmonary, esophageal) 99


❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍

Cervical cancer Coccidiodomycosis Cryptosporidiosis Cytomegalovrius Encephalopathy Herpes simplex (chronic, esophageal) Histoplasmosis Isosporiasis Kaposi’s sarcoma Lymphoma Mycobacterium avium/Mycobacterium kansasii Pneumocystis carinii Recurrent pneumonia Progressive multifocal leukemia.

WHO (1997) suggested the criteria for HIV infection. This criterion was based on the clinical diseases and was classified into cardinal findings, characteristic findings and associated findings. Cardinal findings Adults

Children

Kaposi’s sarcoma

Kaposi’s sarcoma (rare in children) Pneumocystis carinii pneumonia Lymphoid interstitial pneumonitis Esophageal candidasis

Pneumocystis carinii pneumonia Toxoplasma encephalitis Esophageal candidiasis Cytomegalovirus retinitis

Diarrhea (continuous or intermittent more than 1 month) Generalized extrainguinal lymphadenopathy Skin infection (severe or recurrent) Cough for more than 1 month dermatitis

Stages

CD4 count range

Oral thrush

Severe prurigo (itching without lesion) Non-Hodgkin’s lymphoma Recurrent bacterial/viral infections Herpes zoster, past or present Progressive neurological disease Herpes zoster: multidermatomal

Oral hairy leukoplakia Miliary, extrapulmonary or Non-cavity pulmonary tuberculosis Cryptococcal meningitis Non-cavity pulmonary tuberculosis

Acute infection

1,000–750 750–200

2–15 weeks

Early symptomatic

500–100

1–5 years

Late symptomatic

50–200

1–4 years

Advanced disease

50–0

0–2 years

Weight loss more than 10%

CD4 Strata

Complication

500/mm

Persistent generalized lymphadenopathy Candida vaginitis Guillain–Barre syndrome Polymyositis Aseptic meningitis Pneumococcal pneumonia Pulmonary tuberculosis Thrush Zoster Cryptosporidiosis, self-limited Cervical intraepithelial neoplasia Kaposi’s sarcoma B cell lymphoma Anemia Idiopathic thrombocytopenic purpura Mononeuritis multiplex Oral hairy leukoplakia P. carinii pneumonia Disseminated or chronic herpes simplex Miliary/extrapulmonary Tuberculosis Candida esophagitis CNS lymphoma Wasting HIV-associated dementia Peripheral neuropathy Cryptococcosis Disseminated histoplasmosis and microsporidiosis Disseminated/chronic herpes simplex Disseminated M. avium CMV retinitis

3

200/m3 (usually 100/m3)

Fever (continuous or intermittent more than 1 month) 100

Children Neurologic findings (dementia) Focal motor deficits

1–4 weeks

Correlation of CD4 cell count and AIDS complications

Associated findings Adults

Duration

Asymptomatic

Characteristic findings Children

Drug reactions (previously not seen) Failure to thrive fever (continuous/intermittent than 1 month) Generalized lymphadenopathy

Stages in HIV disease

200–500/mm3

Adults

Progressive headache

50/mm3


Tuberculosis and HIV It is suggested that the clinical presentation of tuberculosis is dependent on the degree of immune suppression and those patients with CD4 cell counts above 200/mm3 more likely to have classical upper lobe disease and cavitary changes characteristic of reactivation disease. Extrapulmonary tuberculosis frequently occurs with HIV infection and usually seen in 70% of patients with CD4 cell count less than 100/mm3. WHO (1997) stated that in India, 60% of AIDS patients have tuberculosis infection.

5.

6.

Oral manifestations In 1986 the European community took the initiative to establish a classification system for oral manifestations in HIV infection. The classification was presented by Pindborg. He classified the oral manifestations into six categories based on associated agents like fungal, bacteria, viral, neoplasm, neurological and unknown cause. 1.

2.

3.

4.

Fungal infection a. Candidiasis i. Pseudomembranous ii. Erythematous iii. Hyperplastic iv. Angular cheilitis b. Histoplasmosis c. Cryptococcosis d. Geotrichosis Bacterial infection a. HIV Necrotizing gingivitis b. HIV Gingivitis c. HIV—Periodontitis Caused by: Mycobacterium avium intercellulare, Klebsiella pneumoniae, Enterobacterium cloacae, Escherichia coli d. Actinomycosis e. Cat-scratch disease f. Sinusitis g. Exacerbation of apical periodontitis h. Submandibular cellulitis Viral infection a. Herpes simplex b. Cytomegalovirus c. Epstein–Barr Hairy leukoplakia d. Varicella zoster i. Herpes zoster ii. Varicella e. Human papilloma virus i. Verruca vulgaris ii. Condyloma acuminatum iii. Focal epithelial hyperplasia Neoplasms a. Kaposi’s sarcoma

b. Squamous cell carcinoma c. Non-Hodgkin’s lymphoma Neurologic disturbances a. Trigeminal neuropathy b. Facial palsy Unknown cause a. Recurrent aphthous ulceration b. Progressive necrotizing ulceration c. Toxic epidermolysis d. Delayed wound healing e. Idiopathic thrombocytopenia f. Salivary gland enlargement g. Xerostomia h. Melanotic hyperpigmentation

Diagnostic criteria In 1989, WHO Collaboration Center for Oral Manifestation of the HIV under ‘WHO Global Program on AIDS’ and ‘European Clearing House of Oral Problems related to HIV’ defined the diagnostic criteria for oral manifestations. These diagnostic criteria were proposed for epidemiological surveys. The diagnostic criteria were given for the most common oral manifestations. Following are the diagnostic criteria suggested. 1. Candidiasis i.

Pseudomembranous: The pseudomembranous is presented as a white or yellow removable plaque leaving a red surface. Pseudomembranous may be located in all parts of the oral cavity. ii. Erythematous: It is defined as red area without removable plaques often located on palate, dorsum of the tongue and buccal mucosa. Smears from red area must be positive for candida hyphae on PAS staining. iii. Angular: Fiery and commissures. Smears from red area must be positive for candida on PAS staining. 2. Periodontal disease a.

b.

c.

Gingivitis: They defined gingivitis as the disease characterized by fiery red edematous attached gingiva and may affect the alveolar mucosa. No ulceration must be present. Necrotizing gingivitis: This is characterized by gingival pain, swelling, ulcerations, necrosis or as distribution of interdental papillae covered with a fibrous slough. The patient suffers from fever and halitosis may be present. Periodontitis: This is characterized by aggressive irregular bone destruction. Any infection that gives the impression of affecting periodontal structure other than gingiva. 101


3. Hairy leukoplakia

– Focal epithelial hyperplasia – Verruca vulgaris ❍ Varicella zoster virus ❍ Herpes zoster ❍ Varicella

Hairy leukoplakia presents as a white, non-removable lesion on margin of the tongue. The surface is corrugated, but might be non-corrugated if it is seen on the inferior surface of the tongue or on the buccal mucosa. To establish a reliable diagnosis, a biopsy must be performed. Biopsy from hairy leukoplakia shows hair-like projections, hyperparakeratosis, koilocytic like cells and no inflammation. The surface layer of the epithelium shows numerous hyphae of candida.

Group 3: Lesions seen in HIV infection

4. Oral Kaposi’s sarcoma

❍ ❍

A characteristic macroscopic appearance of either erythematous or violaceous plaque-like lesions, or a bulky tumor predominantly seen in palate or on the gingiva.

❍

❍ ❍

Revised classification by the European Community Clearing House (1992) European Community Clearing House in 1992 revised the classification of oral lesions associated with HIV infection. The manifestations were divided into three main groups: i. Lesions strongly associated with HIV infection ii. Lesions less commonly associated with HIV infection iii. Lesions seen in HIV infection Group 1: Lesions strongly associated with HIV infection ❍ ❍ ❍ ❍ ❍

Candidiasis: Erythematous Pseudomembranous Hairy leukoplakia Kaposi’s sarcoma Non-Hodgkin’s lymphoma Periodontal disease – Linear gingival erythema – Necrotizing (ulcerative) gingivitis – Necrotizing (ulcerative) periodontitis

Group 2: Lesions less commonly associated with HIV infection ❍

❍ ❍ ❍

❍ ❍ ❍

102

Bacterial infections – Mycobacterium avium intercellulare – Mycobacterium tuberculosis Melanotic hyperpigmentation Necrotizing (ulcerative) stomatitis Salivary gland disease – Dry mouth due to decreased salivary flow rate, unilateral or bilateral swelling of the major salivary glands Thrombocytopenic purpura Ulceration NOS (not otherwise specified) Viral infections – Herpes simplex virus – Human papilloma virus (warty-like lesions) – Condyloma acuminatum

❍

❍ ❍

Bacterial infections – Actinomyces israelii – Escherichia coli – Klebsiella pneumoniae Cat-scratch disease Drug reactions (ulcerative, erythema multiforme, lichenoid, toxic epidermolysis) Epithelioid (bacillary) angiomatosis Fungal infections other than candidiasis – Cryptococcus neoformans – Geotrichum candidum – Histoplasma capsulatum – Mucoraceae (mucormycosis/zygomycosis) – Aspergillus flavus Neurologic disturbances – Facial palsy – Trigeminal neuralgia Recurrent aphthous stomatitis Viral infections – Cytomegalovirus – Molluscum contagiosum

Laboratory diagnosis There are two main approaches for the diagnosis of HIV infection, the direct and the indirect. The direct method seeks information on the presence of virus itself by classical isolation method and identifying the presence of virus specific genes by molecular biology techniques. George Babu in his review states that the classical method of isolation for HIV is time consuming, expensive, requires special containment laboratory and highly trained personnel. He also states that molecular biology technique such as polymerase chain reaction (PCR) is expensive and should be done by highly trained personnel but it is less expensive than classical virus isolation and less time consuming. He further states that PCR finds application under special circumstances such as the presence of early stages of infection. The indirect methods are based upon the observation that infected persons make antibody eventually. In most cases, the IgG class of antibody can be detected on the serum 6–8 weeks after infection. ELISA Test 1. The first system to have been introduced is ELISA (enzyme linked immunosorbent assay) for screening and western blot test for confirmation of HIV antibody.


2.

3.

ELISA is done in a 96-well polystyrene microtiter plates, the plates being coated with HIV specific antigen and allowed to react with patients serum. The other rapid tests include DOT tests (e.g. tridot insti, HIV—check and agglutination tests (e.g. Combaids, Immunocomb). Western blot test is used to detect the presence of nine antibodies to the nine HIV specific antigens. In asymptomatic stage, the presence of one antibody (gp160, gp120 or gp41) one from core region (p17, p24 or p55) and one from polymerase region (p31, p51 or p66) is required. In a symptomatic person, the presence of gp41 with one band from any of the two regions is adequate.

Management The management of HIV disease is two pronged: one aimed at managing the conditions arising out of the immunosuppression and opportunistic infections and the other targeted at the virus itself. I. Management of the viral infection Antiviral therapy is instituted in patients with AIDS regardless of the CD4 count and in patients who are asymptomatic but with CD4 count less than 200 cells/ mm3 (Table 3). Four groups of drugs can be used to combat the virus. A combination of these drugs may be used in the management of HIV infection. These regimens are referred to as highly active antiretroviral therapy (HAART). The commonly employed regimens used include:

HAART may be associated with adverse side effects such as IRIS (immune reconstitution inflammatory syndrome, which is characterized by worsening of the already existing opportunistic infection, appearance of new opportunistic infections and autoimmune disorders. Other side effects of HAART include: bone marrow suppression, bleeding disorders, liver and renal toxicity, hypersensitivity reactions and severe forms of erythema multiforme. Charles Barr (1995) recommended the following therapy for oral disease associated with HIV/AIDS. I. Fungal disease Candida albicans 1. Nystatin vaginal tablets: 100,000 IU/tablet to dissolve one tablet in the mouth 3 times daily for 1–2 weeks. 2. Mycostatin pastilles: (Nystatin) 200,000 IU/pastille. One pastille dissolved in mouth to 5 times daily for 1–2 weeks. 3. Mycelex troches (Clotrimazole): 10 mg troche one troche dissolved in the mouth 5 times daily for at least 14 days. 4. Nizoral (Ketaconazole): 2,000 mg/tablet one tablet daily with food until lesions disappear if response is poor—2 tablets daily. 1.

2.

a. 1 NNRTI 2 NRTI b. 1 or 2 PI 2 NRTI c. Triple NRTI. 3. Table 3 Antiviral therapy for management of HIV infection Drug

Examples

Mechanism of action

Fusion inhibitors

Enfuvirtide

It is an anti-HIV peptide that inhibits entry of the virus into host cells

Nucleoside reverse transcriptase inhibitors (NRTIs)

Abacavir Didanosine Lamivudine Stavudine Zalcitabine Zidovudine

They terminate the elongation of the growing DNA chain and reduce or prevent replication of HIV in infected cells

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Nevirapine Efavirenz Delavirdine

They inhibit a vital step in the transcription of RNA genome into double stranded viral DNA

Protease inhibitors (PIs)

Indinavir Ritonavir Atazanavir

They inhibit the cleavage of viral proteins

Zovirax (acyclovir)—200 mg tablets. Two tablets 4–5 times daily. Recurrence is frequently noted after therapy is discontinued. Podophyllin resin—25% solution. Dab solution on lesions with cotton applicator 2–3 times daily. To rinse mouth with plain water for 30–60 seconds following last application last application. Allow 1 week for beneficial effect. Second application may be necessary depending on thickness of lesion. Retin A (tretinoin)—topical retinoid solution 0.05% apply to involved area for 1–2 minutes daily for several days.

Herpes simplex virus-1 Zovirax (acyclovir) 200 mg tablets 2 tablets 4–5 times daily until healing occurs. Varicella zoster virus Zovirax (acyclovir) 200 mg tablet or 800 mg tablets: to take 4 g/day. Cytomegalovirus Cytovene (ganciclovir sodium), intravenous 7.5–15 mg/kg/day for 10–14 days. Human papilloma virus Surgical excision by scalpel. Cryotherapy, CO2 base, or electrocoagulation. II. Bacterial disease A. Linear erythematous banding 1. Irrigation with 10% povidone iodine solution 2. Prophylaxis 3. Antifungal therapy (if suspect candiasis) 103


4. 125 chlorhexidine gluconate 5. Frequent systemic follow-up. B.

Necrotizing (ulcerative) gingivitis and periodontitis 1. Irrigation with 1% povidone iodine solution 2. Debridement of necrotic gingival tissue, scaling, root planing 3. Antibiotic therapy 4. Hydrogen peroxide—water rinses 5. 12% chlorhexidine gluconate rinse 6. Frequent systemic follow-up of the case.

Sterilization Steam: Autoclave instruments at a temperature of 121C, at 15 lb/sq in pressure for 15–20 minutes on specially modified cooker. Flame: Heating with flame until red-hot to sterilize instruments such as knives and other skin piercing instruments. Disinfection a.

III. Neoplasia Kaposi’s sarcoma 1. Chemotherapy: Wet Velban (Vinblastine sulfate) 0.1 ml of a 0.2 mg/ml solution for each 0.5 cm lesion. Drug is injected 0.2 intralesionally after local anesthesia. 2. Localized radiation therapy: Fractionated radiotherapy of approximately 800 to 1,500 cGy 3. Intro A (Interferon): 3–5 million IU injected into lesion 3 times per week 4. Sotradecol (sodium tetradecyl sulfate): Intralesional injection of a 3% solution at 0.2 cc/cm 5. CO2 laser. VI. Aphthous ulcers 1. 2.

3. 4. 5. 6.

Lidex (Fluocinonide) ointment 0.05% or clobetasol ointment. Apply to lesion Dexamethasone 0.5 mg/5 ml swish 1–2 teaspoonful around mouth for at least 1 minute and expectorate, 4 times daily until lesion disappears Prednisone–10 mg tablets. One tablet up to 6 times daily for 1 week depending on healing Thalidomide 200 mg every 12 hours for 5 days Tetracycline oral suspension–125 mg/5 ml swish and expectorate Levamisol: 50 mg every 8 hours for 3 years.

b.

WHO also recommends that the needle, syringe should not be recapped, bent or broken by hand to avoid needle prick injuries or skin puncture. They suggested that it should be collected in a container with bleach solution and destroyed. For reusable syringe and needles, they suggested that these should be decontaminated by soaking in 0.1% sodium hypochloride solution for 20–30 minutes. They also stated that when autoclaving is not possible, sterilization can be achieved by specially modified cooker at 15 Ibs/sq inch pressure at 121C temperature for 15–20 minutes or by boiling in water for 20 minutes. Diana Shin Flemming and John C Fahley (1996) have mentioned about CDC classification of dental instruments into three categories on their risk of transmitting infection: 1.

Universal precautions WHO (1997) recommended ‘Universal Safety Precautions’ for preventing the spread of HIV infection. They stated that ‘Universal Safety Precaution’ means that all body fluids and blood of patients should be considered as infections and all precautions should be taken since it is not known who is infected with HIV. The universal precaution starts with: ❍ ❍ ❍ ❍ ❍ ❍ 104

Hand washing. Creating appropriate barrier by use of gloves, masks, gowns, eye protectors. Careful handling of sharp objects. Proper sterilization and disinfection. Disposal of instruments after use/decontamination of instruments including syringes, needles and equipment. Proper disposal of infected waste.

Boiling: Completely immerse instruments in water, for about 20 minutes, WHO states that boiling is sufficient to inactivate (destroy) HIV. Chemical: HIV is highly fragile and easily inactivated by the following chemicals: 1. Ethanol—70% 2. Glutaraldehyde—2% 3. Household bleach—1% solution 4. Formaldehyde—8% (dilute formalin 1:5) 5. Chlorine sodium—10% solution 6. Isopropyl alcohol—3.5% solution

2.

3.

Critical: These are surgical and other instruments used to penetrate soft tissue or bone which should be sterilized after each use. These devices include forceps, scalpels, bone chisels, scalers and burs. Semicritical: These instruments are those which do no penetrate soft tissue or bone but contact oral tissues which should be sterilized after each use; if not feasible it should receive high level disinfection (e.g. Mouth Mirrors, Amalgam condensers). Non-critical: These are the instruments or medical services such as external components of X-ray heads that come contact only with skin; these could be disinfected by detergent or washing depending upon the nature and degree of contamination.

SINUSITIS Inflammation of the paranasal sinus mucosal lining is referred to as sinusitis. When all the paranasal sinuses


(frontal, maxillary, sphenoid and ethmoid) are inflamed the term pansinusitis may be used. Based on the duration of the clinical presentation sinus diseases can be categorized into: ❍ ❍ ❍

Acute: defined as disease lasting less than 1 month. Subacute: presence of disease for 1 to 3 months. Chronic: is longer than 3 months duration.

Acute Sinusitis Sinusitis occurs when the mucous membranes of the upper respiratory tract namely the nares, pharynx, sinuses and larynx become inflamed. The swelling obstructs the sinus openings and prevents mucus from draining normally. This creates a moist environment which aids in harboring infection. The most common cause for sinusitis is a viral infection. However sinusitis can also occur as a result of a bacterial or fungal (secondary to aspergillosis, mucormycosis, candidiasis, histoplasmosis and coccidiomycosis) infection. When the upper respiratory tract infection persists for longer than 2 weeks, a bacterial etiology is more likely. Other causes for sinusitis include allergies, deviated nasal septum, nasal polyps, antroliths (Figure 18) and as complications of systemic conditions such as cystic fibrosis, gastroesophageal reflux or immunodeficiency diseases. The severity of sinusitis may exacerbate when exposed to polluted air or when an individual smokes. Clinical features Patients suffering from sinusitis include facial pain (especially in the periorbital region, maxillary sinus region and forehead), fever, fatigue, nausea, nasal congestion, erythema over the sinus region (owing to increased blood Figure 18

flow), referred tooth pain, halitosis and reduced smell and taste. Usually acute sinusitis when untreated will result in a medically irreversible chronic phase of sinusitis. In rare instances, acute sinusitis can trigger an asthmatic attack, may spread to the brain to cause meningitis and can cause visual disturbances.

Chronic Sinusitis Chronic maxillary sinusitis is defined as sinusitis lasting longer than 12 weeks. Patients may report of chronic facial pressure in the maxillary region, headache, rhinorrhea, postnasal drip, light headedness, decreased sense of smell, or toothache. In children, the symptoms of sinusitis are less specific than in adults. Symptoms include persistent nasal congestion and cough lasting for more than 10 days, high fever and purulent nasal discharge. Children are less likely to present with facial pain or headache. Clinical and radiographic diagnosis Apart from history, clinical examination of the sinuses will help in diagnosing sinusitis. In many individuals the sinuses are tender in palpation. Another simple chair side test that can be employed is transillumination to assess the maxillary and frontal sinuses. The paranasal sinuses can be assessed using plain radiographs such as Waters’ view (facilitates viewing of the maxillary, frontal sinuses and sphenoid sinuses), Caldwell view (visualization of the frontal and ethmoid sinuses), lateral view (to visualize the sphenoid sinus and the posterior frontal sinus wall) and the submentovertex view (sphenoid sinuses are visualized). The typical radiographic findings in a paranasal sinus view include: localized thickening of the mucosal lining at the base of the sinus, generalized thickening of the mucosal lining (Figure 19), partial filling of the sinus (fluid level appearance) and a complete cloudy or hazy sinus (Figure 20). CT of the osteomeatal complex has been used to assess pansinusitis. It has been frequently reported that sinus CT scanning has a high sensitivity but a low specificity for demonstrating acute sinusitis. CT scanning may be used to assess significant mucosal thickening, air-fluid levels (Figure 21), osteomeatal complex obstruction, polyposis (Figure 22), or calcification suggestive of fungal sinusitis. Management

Intraoral periapical radiograph showing antrolith. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Acute sinusitis is best managed medically using nasal decongestants and systemic antihistamines. Patients should be instructed to use steam inhalation. In most infections amoxicillin is sufficient to neutralize pathogens such as S. pneumoniae, H. influenzae and M. catarrhalis. However when the infection does not subside in a week’s 105


time, following culture, the antibiotic coverage can be widened to include clavulanic acid. In extreme cases when the medical line of management fails to provide adequate drainage of the sinus, surgical drainage may be undertaken. Surgical treatment includes antral lavage, middle meatal antrostomy and endoscopic enlargement of the osteomeatal complex. Herpes simplex virus infections, varicella zoster infections, herpangina, herpangina, hand, foot and mouth disease, mumps, condyloma acuminatum and molluscum contagiosum are described in Chapters 7, 8, 11 and 22.

FUNGAL INFECTIONS AND PROTOZOAL DISEASES HISTOPLASMOSIS Histoplasmosis was first described by an American physician, Samuel Darling in 1906. Histoplasmosis is caused by the dimorphic fungus (present as yeast at body temperature and as mold in the natural environment) Histoplasma capsulatum. The mold typically inhabits soil in humid areas containing bat or bird excrement. When humans inhale these

Figure 19 Figure 21

CT scan showing thickening of the mucosal lining of the ethmoid sinus

CT scan showing fluid level appearance in the right maxillary sinus

Figure 20 Figure 22

Paranasal sinus view showing complete haziness of the left maxillary sinus

106

CT scan showing a large polyp in the right maxillary sinus


air borne spores, they travel to the lungs. It is primarily a lung disease. There are two varieties of H. capsulatum that are pathogenic to humans, H. capsulatum var capsulatum and H. capsulatum var duboisii. Histoplasmosis is an endemic infection in most of the United States. Pathogenesis Following deposition of the spores in the alveoli at the normal body temperature the spores germinate into the yeast form. The yeast form of the organism is promptly ingested by pulmonary macrophages. The yeasts become parasitic, multiply within these cells, and migrate to hilar and mediastinal lymph nodes. They subsequently gain access to the blood circulation and eventually disseminate to various organs. Macrophages throughout the reticuloendothelial system ingest and sequester the organism. In an immunocompetent host, in about 2 weeks after exposure, cellular immunity develops, and the macrophages become fungicidal and eliminate the infection. The sites infected (such as the lung, liver, spleen, bone marrow and lymph nodes) show evidence of necrosis, leading to caseation, fibrous encapsulation, calcium deposition and within a few years of the initial exposure, calcified granulomas are formed. However, in an immunocompromised host due to defect in the cellular immunity, a lethal progressive disseminated form of infection is seen. Clinical features There are three clinical forms of histoplasmosis: acute pulmonary, chronic pulmonary and disseminated form. Most of the infected individuals are either asymptomatic or present very mild illness. Only less than 1% of the individuals exhibit symptoms.

Acute Pulmonary Histoplasmosis Patients may present with malaise, fever, headache, chills, weight loss, myalgias, sweating, non-productive cough and pleuritic chest pain. However, when large number of spores are inhaled patients may present with dyspnea and hypoxia. Occasionally, hepatosplenomegaly, adenopathy, erythema nodosum, and erythema multiforme may be seen. Acute pulmonary infection may lead to mediastinal granuloma, pericarditis and arthritis (symmetrical and multiple joints are involved). Chest radiographs may reveal solitary or multiple patches of air space, especially in the lower zones of the lung. Severe infections may reveal presence of hilar and mediastinal adenopathy and small diffuse pulmonary nodules. The symptoms of the acute form of the disease resolve spontaneously.

Chronic Pulmonary Histoplasmosis It is usually seen in elderly white males who have a preexisting lung disease such as emphysema. Patients present with malaise, productive cough, fever, and night sweats mimicking the clinical features of tuberculosis. The form of histoplasmosis causes necrosis and loss of lung tissue. Chest radiograph may reveal cavitation and infiltration in the upper lobe of the lungs. Progressive thickening of cavity walls and retraction of adjacent lung tissue occur over time. Radiographs typically reveal the absence of adenopathy.

Disseminated Histoplasmosis The disseminated form of histoplasmosis is a rare disease and occurs primarily in immunocompromised persons (patients with HIV infection, lymphoreticular neoplasms, corticosteroid therapy, cytotoxic therapy and immunosuppressive agents). The spectrum of illness in disseminated disease ranges from a chronic, intermittent course in immunocompetent persons to an acute and rapidly fatal infection that usually occurs in infants and severely immunosuppressed persons. Fever is the most common symptom; however, headache, anorexia, cough, weight loss, and malaise are frequent complaints. Hepatosplenomegaly, lymphadenopathy and oropharyngeal ulcerations are typically encountered. The buccal mucosa, tongue and palate are the most common sites affected. Solitary painful ulcers are seen. These erythematous ulcers exhibit firm rolled-out margins that resemble malignant ulcers. The disseminated form of the disease also affects the nervous system, gastrointestinal system and the renal system. Diagnosis Histoplasmosis can be diagnosed by culture, fungal stains, serologic tests for antibodies, and antigen detection. In order to demonstrate the yeast of H. capsulatum special stains such as PAS and Grocott-Gomori methenamine silver have to be used. Prognosis and management Histoplasmosis is a self-limiting disease. However the untreated disseminated form may result in death in almost 90% of the individuals. Analgesics and antipyretics may be used to manage fever and myalgias. Intravenous amphotericin B is used as the drug of choice. Other drugs that have been used with good results are ketoconazole and itraconazole.

BLASTOMYCOSIS (Gilchrist Disease) Blastomycosis was first described in America by the American dermatologist, Thomas Caspar Gilchrist in 1894. 107


It is caused by Blastomyces dermatitidis, a dimorphic fungus. It is believed to thrive in organic matter and soil which have high moisture content. Following inhalation of the spores, three forms of the disease are manifested: acute, chronic and a disseminated form. Clinical manifestations Blastomycosis is typically seen in men engaged in outdoor activities usually in the 3rd and 4th decades of life. The acute form of blastomycosis is characterized by fever, malaise, myalgias, weight loss, cough, and pleuritic chest pain. The chronic form is much more commonly seen than the acute form. It is characterized by symptoms mimicking those of tuberculosis such as night sweats, low-grade fever, productive cough and weight loss. Rarely, dissemination to other body sites such as the skin, bone, CNS, genitourinary system and oral cavity may be seen. Cutaneous lesions may appear as erythematous nodules that subsequently ulcerate. Oral features Intraoral lesions of blastomycosis appear as irregular pink or white areas. The ulcers may be painful and appear irregular with rolled borders. Histologic findings On histological section blastomyces can be easily discernible with PAS stan, H and E stain, PAP and methenamine silver stains. It can be cultured using Sabouraud’s agar. Management For mild cases itraconazole and ketoconazole can be used effectively. Patients who are refractory to ketoconazole can be treated with amphotericin B.

MUCORMYCOSIS (Zygomycosis, Phycomycosis) Mucormycosis is an opportunistic deep fungal infection caused by ‘bread mold fungi’ of the genera Mucor, Absidia, Rhizopus and Cunninghamella, also collectively known as Phycomycetes. Zygomycosis was first described by Platauf in 1885 as ‘Mycosis mucorina’. The class ‘Zygomycetes’ is subdivided into two orders, which contain the agents of human Zygomycosis, the Mucorales and the Entomophthorales. Among the Mucorales, Rhizopus (most common), Mucor, Absidia, Rhizomucor, Cunninghamella, Saksenaea, Cokeromyces and Apophysomyces have been implicated in causing human disease. 108

The hallmarks of disease with these organisms are angioinvasion, thrombosis, infarction and necrosis of the involved tissue. Predisposing factors The predisposing factors for mucormycosis include diabetes, hematological malignancies (leukemia, lymphoma), bone marrow or organ transplant, prolonged use of steroids, patients on deferoxamine therapy (Rhizopus species thrive well in iron rich environment), severe and prolonged neutropenia, deficient T cell immunity and low birth weight. Diabetes with ketoacidosis is a very potent predisposing factor. Mucormycosis thrives very well in acid pH and glucose rich medium. Hyperglycemia enhances fungal growth and impairs neutrophil chemotaxis, while lactic acidosis decreases phagocytosis. Clinical features Mucormycosis may manifest as a rhinomaxillary form or a more severe rhinocerebral form. It also manifests as pulmonary, gastrointestinal, cutaneous or a disseminated form. In the early stages of the disease, patients exhibit facial cellulitis, anesthesia, nasal discharge, epistaxis, fever, headache and lethargy. Involved tissues become red, then violaceous and finally black as vessels are thrombosed and tissues undergo necrosis. Extension into the orbital region can lead to periorbital edema, proptosis, tearing and ocular or optic nerve involvement spreading along the cribriform plate can result in intracranial involvement. Oral manifestations and radiographic features The most common oral sign of mucormycosis is ulceration of the palate, which results from necrosis due to invasion of a palatal vessel. It characteristically causes denudation of underlying bone, occasionally forming an oroantral fistula. Ulcers have also been reported on the lip, gingiva and alveolar ridge. Gingiva has a peculiar erythematous hyperplasia and is termed strawberry gingivitis. Paranasal sinus radiographs may reveal thickening of the sinus mucosal lining and occasionally air-fluid levels. In severe forms of the disease bone destruction may be seen. Diagnosis Special stains like calcofluor white stain; Gomori methenamine silver stain, periodic acid Schiff and Papanicolau stains are required. Cytological specimens may show ribbon like, wide, aseptate hyphal elements exhibiting angioinvasion and necrotic debris. Management Underlying predisposing factors should be corrected. The necrotic lesions have to be surgically debrided. Amphotericin B is the first line drug of choice for most


cases of zygomycosis. Some authors suggest the use of hyperbaric oxygen therapy as it may aid in inhibiting the growth of fungal spores.

ASPERGILLOSIS Aspergillosis was first described in 1729 by a priest botanist, Micheli. In 1893, Morrel Mackenzie published the first case of aspergillosis affecting the maxillary sinus. It is a saprophyte that belongs to the class of myocetes. Aspergillus flavus, A. niger and A. fumigatus are pathogenic to humans. It is believed that aspergillosis is the second most common opportunistic infection to affect immunocompromised individuals. Aspergillus is usually present in decaying matter, soil and water. It is contracted via inhalation. Aspergillus may cause hypersensitivity reactions and in some individuals it exhibits direct angioinvasion. Aspergillus primarily affects the lungs resulting in allergic bronchopulmonary aspergillosis, chronic necrotizing Aspergillus pneumoniae, aspergilloma (fungus ball/mycetoma) and invasive aspergillosis. However, in immunocompromised host the fungi is no longer restricted to the lung. This disseminated form causes endophthalmitis, endocarditis, and abscesses in the myocardium, kidney, liver, spleen, soft tissue, and bone and oral involvement. Oral findings Involvement of the oral cavity may be seen in the disseminated form of the disease. The tongue, soft and hard palate and an occasional report of pulp and periodontal tissue involvement have been described in literature. Involvement of the maxillary sinus may result in an extension to the adjacent structures and the palate to form a very painful ulcer surrounded by a zone of necrotic black tissue. Diagnosis Aspergillus may be identified in branched septate hyphae about 4 m in diameter in potassium hydroxide preparations. Aspergillus may be cultured in Sabouraud’s agar media. The hyphae demonstrate a tendency to invade adjacent blood vessels. Management The ulcerated lesion should be debrided, systemic amphotericin B therapy is the drug of choice.

CRYPTOCOCCOSIS (European Blastomycosis, Torulosis, Busse-Buschke Disease) Cryptococcosis is an opportunistic fungal infection caused by Cryptococcus neoformans. It is usually present in bird

droppings, rotting wood and soil. Otto Busse, a pathologist, in 1894, isolated C. neoformans from the tibia of a 31-yearold woman. Abraham Buschke also isolated C. neoformans from the same patient, thus giving rise to the Busse– Buschke disease in recognition for their discovery. Cryptococcosis is an acute, subacute, or chronic infection by C. neoformans, chiefly affecting the central nervous system, causing a pulmonary, disseminated, or meningeal mycosis. The risk factors for developing serious forms of cryptococcosis include patients with AIDS, post organ transplantation, reticuloendothelial malignancy, long-term corticosteroid treatment and individuals suffering from sarcoidosis. Cryptococcus neoformans is the second most common cause of opportunistic fungal infection in patients with AIDS. It is considered as a sentinel infection that signals the perturbation of the host’s immune status.

Types There are two varieties of C. neoformans: C. neoformans var neoformans consisting of serotypes A and D (causes disease in immunocompromised hosts) and C. neoformans var gatti consisting of serotypes B and C (causes disease in normal hosts). The yeast is typically found in pigeon feces. Some of these organisms are restricted to tropical and subtropical areas, and are isolated from certain species of eucalyptus trees and the air beneath them. Infections occur through inhalation of yeast like organisms which enter smaller respiratory passages and then remain dormant depending on the host reaction. Organisms are then reactivated from such previous dormant infections in the lung or lymph node. Clinical features Cryptococcosis is seen more commonly in men due to their occupational exposure or a lack of estrogens. The infection usually affects the respiratory system and the nervous system. However a wide dissemination into multiple body sites may also occur. It is estimated that 40–85% of the patients present with involvement of the brain parenchyma. Patients may initially complain of headache, fever and nuchal pain suggesting meningeal irritation. As the disease progresses, stupor, coma and dementia may be seen. Papilloedema may be seen. Complications of CNS involvement include internal hydrocephalus, focal motor deficits, and symptoms of raised intracranial pressure. When the lung is involved, a primary pulmonary complex, similar to TB may be seen. Symptoms of acute pneumonia with cough, fever, and lobar pulmonary infiltrates affecting alveoli may be seen. Pleural effusion without parenchymal lesions are rare. Cutaneous involvement results in the formation of papules, abscesses, cellulitis, acneiform lesions, draining sinuses, 109


or subcutaneous swellings. Ocular involvement is seen as choroidal infection and endophthalmitis. Direct traumatic inoculation into the bone may result in osteomyelitis and arthritis. Oral features Oral lesions of cryptococcosis appear as nodular or granulomatous lesions which subsequently ulcerate. These ulcers typically reveal indurated borders and rolled-out edges. The common sites that are affected include the hard and soft palate, tongue, gingiva and the tonsillar pillars. Cryptococcus infection has also been reported involving extraction sockets. Diagnosis The organism can be isolated in culture, recognized histopathologically and its polysaccharide capsular antigen can

110

be detected in cerebrospinal fluid. The organism grows in blood and chocolate agar within 3–5 days. Histopathological examination requires the uses of Pap stain, India ink preparation, alcian blue, Mayer mucicarmine stain and Masson-Fontana silver stain. These stains help in the detection of the polysaccharide capsule of the yeast. India ink preparation is useful when greater than 10 colony forming units (CFU)/ml of yeasts are present. Alternatively, cryptococcal antigen in cerebrospinal fluid can be detected by latex agglutination. Management Amphotericin B is the drug of choice. However other drugs that have fewer side effects compared to amphotericin such as flucytosine, fluconazole and itraconazole can be used. Oral candidiasis and paracoccidiodomycosis are described in Chapters 6 and 8.

CHAPTER

5

Orofacial Pain Joanna Baptist, Ajay Nayak, Ravikiran Ongole

➧ Pain Physiology

Common Terminologies Associated with Pain Properties of Pain Pain Pathways Gate Control Theory

➧

Myofascial Pain

➧

Neuralgias Trigeminal Neuralgia Glossopharyngeal Neuralgia Postherpetic Neuralgia Geniculate Neuralgia Occipital Neuralgia

➧

Classification of Orofacial Pain

➧

Clinical Assessment of Pain

➧

Pain from Orodental Structures

➧

Atypical Odontalgia

➧

Barodontalgia

➧

Atypical Facial Pain

➧

Paranasal Sinus-related Pain

➧

Burning Mouth Syndrome

PAIN PHYSIOLOGY

2.

The International Association for Study of Pain (IASP) in 1994 defined pain as the subject’s conscious perception of modulated nociceptive impulses that generate an unpleasant sensory and emotional experience associated with actual damage or described in terms of such damage. The experience of pain is usually a protective mechanism of the body. On a short-term basis, pain warns the individual that he or she is in danger so that one can alter the situation. For example when a person accidentally touches something hot he or she will alter the situation by spontaneously withdrawing from the source of injury. Long-term pain will result in immobilization of the affected part such that the individual can recover from the injury faster (for example, muscle spasm). Pain at times can be non-beneficial, such as pain associated with cancer, psychogenic pains and neuralgias which only adds to the misery of the patient. However, interestingly these pains help the physician in diagnosis.

3.

Common Terminologies Associated with Pain 1.

Nociceptors: These are receptors that are sensitive to painful stimulus and are responsible for initiating the generation of pain.

4. 5. 6. 7. 8.

Nociception: It is defined as a noxious stimulus or has potential to turn noxious over a period of time. Allodynia: Pain that is produced by a stimulus that is not normally painful. Hyperalgesia: Increased sensitivity to painful stimuli. Hypoesthesia: Reduced sensation in response to stimulus. Anesthesia: Absence of sensation in response to a stimulus. Causalgia: Persistent burning pain caused by deafferentation of sensory innervation. Neuralgia: It is the pain that is experienced in the tissues along the distribution of the nerve.

Properties of Pain Weber and Fechner’s law Weber and Fechner proposed that gradation of stimulus strength is discriminated approximately in proportion to the logarithm of stimulus strength. This law can be mathematically expressed as R ⫽ ␣ log S where R ⫽ intensity of the reaction (i.e. the pain perceived), ␣ ⫽ constant and S ⫽ the intensity of the stimulus. 111


According to this law, exponential increase in the intensity of stimulus does not cause exponential increase in pain perceived. Though the pain perceived increases with increase in stimulus; the pain experienced is only in terms of log of the intensity of the stimulus. For example, if a pin prick (1 unit of tissue damage) of 1 unit of intensity of stimulus results in 1 unit of pain perception; a musculocutaneous laceration (100 units of tissue damage) causing 100 units of intensity of stimulus results in 2 units of pain perception and not 100 units. Similarly, a crushing injury (1,000 units of tissue damage) causing 1,000 units of intensity of stimulus results in 3 units of pain perception and not 1,000 units. This law ensures that an individual would perceive pain of all intensities but at the same time will not cause significant morbidity due to pain. Adaptation As long as nociceptors (pain receptors) are stimulated, pain continues to be perceived as these receptors have very little or no property of adaptation. It is interesting to note that the inability to adapt to pain is beneficial in terms that a person is appraised of the injurious stimulus that causes pain as long as it persists. For example, olfactory receptors get adapted to a particular smell when stimulated for a long period of time thereby the smell is not perceived any longer. Though pain is not adaptable, the brain itself along with the spinal cord can suppress the input of pain signals to the nervous system by activating a pain control system called ‘analgesia system’. Pain localization Pain is poorly localized. It is said that superficial somatic pain is more localized than deep visceral pain. However this is not exactly true as the superficial injury not only excites the nociceptors but also the tactile receptors, thus helping in localizing the pain. If the superficial nociceptors were alone to be stimulated, it would still cause quite poorly localized pain.

Nociceptors Pain receptors are called nociceptors (from Latin, nocere—to hurt). All nociceptors are free nerve endings (however other cutaneous receptors when stimulated excessively can result in pain). Either present in skin or any other tissues. They are more concentrated in superficial layers of skin, periosteum, arterial walls, joint surfaces, the falx and the tentorium of the cranial vault. Deep tissues are sparsely supplied with nociceptors. Two general types of nociceptors are characterized by the neurons associated with them. 112

1. 2.

A␦ fibers (wrapped in Schwann cells) C fibers

A␦ fiber

C fiber

1–6 ␮m diameter

1.5 ␮m diameter

Myelinated

Non-myelinated

5–30 m/s conduction velocity

0.5–2 m/s conduction velocity

Carries the first pain that is experienced—sharp

Carries steady dull pain

Stimulation of nociceptors Mechanical, chemical and thermal stimuli excite pain receptors. Fast pain is conducted by A␦ fibers which is elicited by the mechanical and thermal stimuli. The slow dull pain is conducted by the C fibers which are elicited by all three types of stimuli. It is almost always caused by release of chemicals liberated by the injured tissue. These are endogenous chemicals called algogenic (pain producing) substances. Algogenic substances stimulate nociceptors to produce pain. These chemicals are pain producing peptides, bradykinins, serotonin (5 HT), potassium ions, prostaglandins, acetylcholine and proteolytic enzymes. It is interesting to note that commonly used NSAIDs suppresses pain by inhibiting prostaglandin synthesis. These prostaglandins by themselves cannot excite the nociceptors, i.e. prostaglandins are not algogenic but they enhance the sensitivity of the nociceptors toward the algogenic power of bradykinins and other chemical mediators of pain.

Sequelae of Pain Apart from nociception there are various other sequelae of pain that alter other systems of the body. Pain affects an individual psychologically as well as physically. Psychological sequelae An uninhibited individual would react to acute pain by mourning and crying as seen in young children and animals. However, most individuals develop frustration, mental irritation or depression in response to long standing pain. A patient with long standing atypical facial pain will most often come to the physician with a frowning face and would often get irritated with prolonged history taking. Thus such patients should be treated both by medicines and psychological counseling. Muscular sequelae Injury or disease causing pain results in spasm of skeletal muscle in the vicinity of the affected region. This is protective as it immobilizes the affected region and thereby puts it to forcible rest which is most essential for rapid healing.

Chapter 5 – Orofacial Pain

But this spasm also causes ischemia of the muscles which aggravates muscular pain. Patients with internal derangement of temporomandibular joint (TMJ) usually exhibit spasm of the masticatory muscles of the affected side thereby preventing further damage to the affected TMJ. In such conditions apart from treating the affected site of injury, muscular spasms should be managed with physiotherapy, muscle relaxants, massage, etc. Autonomic nervous system sequelae Patients with somatic pain generally present with increased blood pressure, pupillary dilatation and tachycardia which are all the signs of sympathetic over activity. However visceral pain is associated with fall in blood pressure and vomiting.

Figure 1

Thalamus Neospinothalamic tract

Hypothalamus Reticular formation

Paleospinothalamic tract Gasserian ganglion Motor nucleus (v)

Reflex Withdrawal from painful stimuli is the reflex action exhibited by the individual. It is an important sequela of pain that protects the individual from further injury. For example, biting on a stone during mastication would immediately initiate a reflex action to keep the mouth open until an individual realizes the presence of the injurious agent (stone). Such reflex action would protect further injury to the periodontium.

Dual Pain Pathways Peripheral pain fibers are of two types, the fast conducting (A␦ fibers) and slow (C fibers) conducting. The fast pain is felt within 0.1 second of the application of the noxious stimulus. But it takes 1 second or more for slow pain to begin. Occasionally slow pain may take over a few minutes to begin after application of the noxious stimulus. Though both fast and slow conducting fibers have free nerve endings as their receptors, they travel via two distinct pathways for transmitting pain signals to the central nervous system. Because of this dual pain pathway a single painful stimulus would often give a first sharp electrical pain that is generally followed by a slow dull pain. This ‘double’ pain sensation initially would cause an individual to react immediately to safeguard himself/herself. Whereas the slow pain tends to become increasingly painful over a period of time. Once these fibers (A␦ and C) enter the spinal cord, the pain signals take two pathways to the brain. They are the neospinothalamic tract and the paleospinothalamic tract (Figure 1). Neospinothalamic tract (for fast pain) Sensations of mechanical and acute thermal pain are brought to the spinal cord by the first order neurons. They terminate in the lamina I (lamina marginalis) in the dorsal horns where they synapse to excite the second order neurons

Sensory nucleus (v) Spinal tract nucleus (v)

Illustration showing the pain pathway

of the neospinothalamic tract. These fibers cross immediately to the opposite side through the anterior commissure and then travel upward in the anterolateral column of the spinal cord. Few of these second order neurons terminate in the reticular areas of the brain stem (the reticular areas when stimulated causes excessive alertness and increases an individual’s sense perception), while most of the others travel up to the thalamus terminating in the ventrobasal complex along with the dorsal column—medial lemniscal tract. The remaining second order neurons terminate in the posterior nuclear group of the thalamus. From these areas third order neurons relay signals to other basal areas of the brain and to the somatic sensory cortex. Paleospinothalamic tract (for slow pain) This pathway transmits pain, which is carried via the peripheral slow conducting C pain fibers (it also transmits very few A␦ fibers). These peripheral fibers terminate in the laminas I and II (together called substantia gelatinosa) of the dorsal horns. Most of the signals then pass through one or more additional short fiber neurons within the dorsal horns themselves before entering laminas V through VIII, also in the dorsal horn. The next series of neurons gives rise to long axons that mostly join the fibers from the neospinothalamic tract, passing first through the anterior commissure to the opposite side of the spinal cord and then upward to the brain in the same pathway. 113


Analgesia system or pain inhibitory pathway

Figure 2

The analgesia system comprises three major components, namely, 1. 2. 3.

The periaqueductal gray and periventricular areas of the mesencephalon and upper pons Raphe magnus nucleus and nucleus reticularis paragigantocellularis Pain inhibitory complex located in the dorsal horns of spinal cord

The electrical stimulation in the periaqueductal gray area or in the raphe magnus nucleus can almost completely suppress many strong pain signals entering the dorsal spinal roots. Stimulation of areas at still higher levels in the brain that in turn excite the periaqueductal gray can also suppress pain. The nerve fibers originating from periaqueductal gray and periventricular nuclei secrete enkephalin at their terminals. These fibers synapse with the fibers originating from the raphe magnus nucleus. The fibers originating from the raphe magnus nucleus secrete serotonin at their nerve terminals. Finally these fibers terminate at the dorsal horns of the spinal cord. Serotonin (secreted by the fibers originating from the raphe magnus nucleus) causes the cord neurons to secrete enkephalins. Enkephalin causes presynaptic inhibition and post synaptic inhibition of A␦ and C pain fibers at the site of synapse of the dorsal horns. This inhibition is caused by the blocking of calcium channels of nerve membrane at their terminals.

Gate Control Theory This theory explaining pain modulation was proposed by Ronald Melzack and Patrick David Wall in 1965. They hypothesized that pain perception was not just solely due to activation of nociceptors but due to interaction between pain conducting and non-pain conducting neurons. Nonpain conducting nerve fibers interfere with the pain conduction thus altering pain perception. There have been various modifications of the original gate control theory. A revised version of the gate control hypothesis proposes that the projection neuron of the spinothalamic pathway when activated results in sensation of pain (Figure 2). The projection neuron synapses with both non-nociceptive mechanoreceptors (A␣ and A␤ fibers) and the nociceptive C fibers, hence activated by both. The interneuron is spontaneously active and this activation of interneuron causes inhibition of projection neuron; thus inhibiting pain perception. In turn, the interneuron synapses with the projection neuron, C fibers, A␣ and A␤ fibers. When the non-nociceptive mechanoreceptors (myelinated and fast conducting A␣ and A␤ fibers) are stimulated they cause two effects: (i) activation of interneuron and (ii) activation of projection neuron. 114

Dorsal horn Spinal cord Aα or Aβ fiber (Non-nociceptive) C fiber (nociceptive)

+ + +

−

−

Interneuron Projection neuron

To spinothalamic tract

Illustration showing gate control theory

Though it activates the projection neuron simultaneous activation of interneuron causes inhibition of projection neuron thus resulting in lack of pain sensation. When C fibers are activated they again cause two effects: (i) inhibition of interneuron and (ii) activation of projection neuron, therefore resulting in pain perception. When both non-nociceptive mechanoreceptors and nociceptors are simultaneously activated, the mechanoreceptors being myelinated fast conducting fibers, the signals from these fibers reach interneuron and projection neuron first before C fibers can conduct signals. In these instances the A␣ and A␤ fibers stimulate the interneuron before C fibers can inhibit the same. Thus the net effect is no pain. This would explain the benefits of physiotherapy and massage in the effective management of painful conditions. It is interesting to note that free nerve endings of unmyelinated nerve fibers when relatively mildly stimulated produce itch and tickle. Unlike pain, itching occurs in superficial tissues and not in deep structures like viscera. It is common knowledge that scratching relieves itching as the fast conducting mechanoceptive fibers activated by scratching suppress the itching sensation. Studies indicate that the C fiber system responsible for itching may not be the same responsible for pain. Surprisingly tickling sensation in general is regarded as pleasurable whereas itching and pain are regarded as unpleasant sensations.

Concept of Referred Pain Referred pain is a spontaneous heterotopic pain that is felt in an area innervated by a different nerve from the one that mediates the primary pain.


Characteristics of referred pain 1.

Referred pain usually occurs within a single nerve root, passing from one branch to the other. Referred pain in the trigeminal area rarely crosses the midline unless it originates at the midline. Usually if the referred pain is felt outside the nerve that mediates the pain, it is generally felt cephalad to the nerve (upward and toward the head) and not caudally. However in severe pain the excitatory effects are felt caudal to the site of initiating input.

2. 3.

CLASSIFICATION OF OROFACIAL PAIN

Bell (1989) has classified orofacial pain as follows: Axis I (Physical conditions) 1.

2.

The American Academy of Orofacial Pain has classified orofacial pain as follows: 1.

2.

3.

4.

5.

Intracranial structures – Neoplasm – Aneurysm – Hematoma – Hemorrhage – Abscess – Edema Extracranial structures – Teeth – Ears – Eyes – Nose – Throat – Sinuses – Tongue – Glands Musculoskeletal disorders – TMJ disorders – Masticatory muscle disorders – Fibromyalgia – Cervical disorders – Generalized polyarthritides Neurovascular disorders – Migraine headaches – Cluster headaches – Tension type headaches – Cranial arteritis Neurologic disorders – Paroxysmal neuralgias • Trigeminal neuralgia • Glossopharyngeal neuralgia – Continuous neuralgias • Atypical odontalgia • Traumatic neuroma • Neuritis • Postherpetic neuralgia

Somatic pain – Superficial somatic pain (cutaneous, mucogingival) – Deep somatic pain – Musculoskeletal pain (muscle, TMJ, osseous and periosteal, soft connective tissue, periodontal) – Visceral pain (pulpal, vascular, neurovascular, visceral mucosal, glandular, ocular and auricular) Neuropathic pain – Episodic (trigeminal, glossopharyngeal, geniculate, nervous intermedius neuralgias and neurovascular pains) – Continuous (neuritis, deafferentation pain and sympathetically maintained pain)

Axis II (Psychologic conditions) 1. 2. 3. 4.

Mood disorders Anxiety disorders Somatoform disorders Other conditions

Types of Pain Acute pain It is generally a physiologic response to an injury. It persists as long as the noxious stimulus is present. Acute pain almost always subsides within the time period required for the process of normal healing. Chronic pain Merskey and Bogduk (1994) described chronic pain as a persistent pain that is not amenable, as a rule, to treatments based on specific remedies, or to the routine methods of pain control such as non-narcotic analgesics. In common parlance chronic pain is regarded as pain that persists way beyond the normal time required for the process of normal healing. Pain is said to be chronic in nature when it lasts over 3 months. It is generally associated/ influenced by psychological, emotional, social and cultural factors.

CLINICAL ASSESSMENT OF PAIN The diagnosis and management of orofacial pain begins with a comprehensive patient history. The most expeditious way to obtain such a history is via a detailed patient questionnaire and detailed patient–physician interview. 115


Figure 3

Figure 4 None (0)

Mild (1)

Moderate (2)

Severe (3)

Throbbing Shooting Stabbing Sharp Cramping Gnawing Hot–burning Aching Heavy Tender Splitting Tiring–exhausting Sickening Punishing–cruel

McGill pain questionnaire (short version) Illustration showing the pain diagram. Patient is encouraged to mark areas on the picture that represent the painful sites in the patient

Figure 5 The interview is followed by a complete oral and head and neck examination, appropriate chair side investigations, radiographic imaging and lab studies. Assessment of pain can be achieved by certain subjective and objective methods. Some widely accepted subjective methods include the use of McGill Pain Questionnaire (long/ short), visual analog pain scale (VAS), brief pain inventory. The faces pain scale and the pain diagram. During the patient interview the clinician should obtain the following data: mode of onset, duration, location of the pain, quality or character of the pain, intensity of the pain, frequency of the painful episodes, aggravating and relieving factors if any, radiation or referral patterns, any other associated symptoms and history of any medical consultations/use of medications for the same. The location of pain and referral patterns can be identified by the patient using a pain diagram (Figure 3). The pain quality or character can be expressed using the widely accepted McGill Pain Questionnaire (Figure 4). This questionnaire will help the patient to describe how exactly he/she feels about the pain by selecting an appropriate adjective from a list in the questionnaire. The intensity of pain can be quantified using the visual analog scale (VAS). The VAS is a 10 cm long line with 0 marked on one end (represents no pain) and 10 at the other end (represents worst possible pain). The linear scale has markings from 0 to 10 at 1 cm intervals. The patient is encouraged to mark a point along this scale that correlates with the intensity of pain experienced. For convenience pain 116

0

10

No pain

Worst possible pain

Visual analog scale

intensity can be categorized as mild (score 1–3), moderate (score 4–6) and severe for scores 7–10 (Figure 5). However the ‘Faces Pain Scale’ can be used in child patients for assessing the intensity of pain (Figure 6). Following the history, physical examination should be undertaken. A thorough physical examination of the head and neck, including the TMJ, maxillary sinus, masticatory muscles along with the accessory muscles, salivary glands and the oral cavity should be performed. Intraoral examination should include the evaluation of teeth, periodontium and the oral mucosa.

PAIN FROM ORODENTAL STRUCTURES Pulpal Pain Dental pain is the single-most common cause why a patient visits a dental clinician, a fact that will be vouched for by any practicing clinician. Pulpal pain forms a major component of


Figure 6

0

2

4

6

8

10

Faces pain scale. Score the chosen face 0, 2, 4, 6, 8 or 10, counting left to right, so ‘0’ = ‘no pain’ and ‘10’ = ‘very much pain’. Do not use words like ‘happy’ and ‘sad’. This scale is intended to measure how children feel inside, not how their face looks. From PAIN, 2001, 93, 173–183 ‘The Faces Pain Scale–Revised: toward a Common Metric in Pediatric Pain Measurement’, by CL Hicks, CL von Baeyer, PA Spafford, I van Korlaar and B Goodenough. Reprinted with permission of the International Association for the study of Pain®.

this dental pain and needs to be comprehensively understood for making accurate diagnosis and according the right treatment options. Pulpal pain is classified as a visceral type of pain and manifests features characteristic to such a type of pain. The pulp responds to any form of noxious stimuli by way of inflammation. Pulpal pain can be brought about by a variety of causes, the most common being, dental caries, trauma, chemical irritants and even rarely, anachoresis. Clinical features The patient manifesting pulpal pain describes it as an aching sensation that is not localizable to the patient. The patient will point out to a region of the jaw and mention about the pain, but when asked to specifically point out the tooth, will be unable to do so. The absence of proprioception in the pulp leads to such a scenario. On examination of the region, some clinical finding of deep caries, pulpal involvement by caries or fracture of tooth, or deep cervical abrasion may be seen. The underlying inflammation of the pulp shows typical sign of pain on movement of the part, especially since the pulp is tightly enclosed in a chamber of dentin. This is evidenced by the history of postural changes in pain that may be reported by the patient. The pain is usually intermittent and aggravated by contact of the tooth with sweets, cold and/or hot food stuff. The sweets cause a change in the fluid dynamics within dentin due to their hygroscopic nature and the thermal changes get mediated via the A␦ and C nerve fibers, leading to a crossing beyond the pain threshold of the pulpal receptors. Reversible pulpitis gives a typical finding of pain occurrence on application of the noxious stimuli that characteristically disappears immediately on withdrawal of the stimulus. Irreversible pulpitis, on the other hand, shows persistence of pain for some time, even after removal of the noxious stimulus. This differentiation is quite necessary as the treatment options for both vary considerably, as the pulp and/or the tooth need to be sacrificed in the irreversible

situation, while the pulp can be salvaged in the reversible type. As the inflammation is totally confined within the pulp space, no tenderness is elicited on percussion of the tooth. Pulpal pain rarely remains unchanged for long periods of time. It either resolves by itself, a rare scenario, or progresses to chronicity and/or pulpal necrosis. Once the pulp undergoes necrosis, no painful stimuli are transmitted and leads to relief from all symptoms. This may give rise to a false feeling of cure to the patient and leads to neglect. During the process of pulpal necrosis, thermal stimuli may evoke differences in response. Pain may be aggravated by both heat and cold when both the A␦ and C nerve fibers are intact. As the condition progresses, heat will cause the pain to occur while cold may actually relieve it. Diagnosis Pulpal pain is of prime suspect when there is poor localization of the pain by the patient. At times, the patient may not even be able to differentiate if the origin is maxillary or mandibular jaw. Definite clinical lesions like dental caries, faulty restorations, fractured teeth or others may point to the source. Thermal, mechanical, chemical and electric stimulation of a suspected tooth may provide the noxious stimulation and induce the pain that the patient can then identify. Vitality tests are not always reliable, because they indicate the nervous response rather than the intactness of the vascular supply and the presence of healthy pulp in one root canal and necrotic pulp in another can provide conflicting interpretations. Sequential analgesic blocking can usually definitively identify the source tooth. However if the pain is found to occur in a particular region of the jaw, but exact localization is not possible clinically, then waiting for the natural pain localization to occur by extension into the periodontal ligament may be another option. In rare situations, a direct exploration of the tooth may be justified in severely painful conditions wherein the patient is unwilling to wait for natural localization of the pain. This would seem better than a radical option of 117


extracting the tooth. Radiographic examination will not yield any direct characteristic signs of pulpal inflammation. However extension of any pathology into the pulp, such as caries, restorations, etc. may be seen as a possible causative agent and help in diagnosis.

Periodontal Pain Pulpal pathology leading to necrosis of the pulp after a while spills into the periodontium via the apical foramen and/or the accessory foramina. The discussion here pertains to the apical portion of the periodontium via the pulp being affected rather than the progressive effects of the gingival or periodontal diseases. The periodontal ligament behaves and responds to noxious stimulation in a manner similar to other ligaments of the body. Therefore periodontal pain is felt as a deep somatic pain of the musculoskeletal type. The receptors of the periodontal ligament can precisely locate stimulus due to the property of proprioception. The causes of pain originating in the periodontal ligament are as varied for pulpal pain. Inflammatory reaction, trauma, endodontic procedures, improperly contoured restorations, faulty occlusal contacts, orthodontic appliances and surgical procedures are the most common. Parafunctional oral habits may also be a contributing factor. Clinical features The periodontal ligament pain is described by patients as sharp jabs or pricking type of pain. The pain is usually intermittent in nature and occurs whenever there is loading of the ligament, such as during chewing. The functional action causes movement of the tooth that compresses the ligament, leading to displacement of the edema fluid and irritation of the free nerve endings causing pain. This feature can be observed clinically by percussing the suspect tooth, which simulates the functional action. Any tenderness if present during percussion indicates periodontal ligament involvement. The patient will usually precisely identify the tooth and mention it to be sore or a feeling of elongation being present. Clinically the tooth may be seen to be slightly out of occlusion. There may be associated tenderness in the vestibule and at times a frank swelling may be present in the gingival region or in the vestibule. Diagnosis The exact location being pointed out by the patient is the first clue in suspecting periodontal ligament involvement. Clinical test of percussion along with presence of any of the contributing factors further helps in diagnosis. Vitality testing can be of help if the cause is related to pulpal pathology, because a necrotic or dead pulp definitely favors a diagnosis of apical periodontal pathology of some degree. Radiographic findings of a widening of the periodontal space with or 118

without a breach of lamina dura and altered trabecular pattern are a definitive indication of periodontal pathology. Dental pain

Dental hypersensitivity

Caused due to noxious stimulation of the nerve endings

Caused by normal physiologic stimulation of nerve endings

May be intermittent or continuous, depending upon the stage of pathology

Usually always transient

May manifest at any age from youngsters to elderly

Usually seen in the elderly population

Not associated with any particular habits

Parafunctional oral habits play a role in its occurrence

May or may not respond to cold test

Always occurs in response to a cold test

BARODONTALGIA Barodontalgia is the pain or injury associated with teeth as a result of alteration in the pressure gradients. Historically, the term aerodontalgia was used to describe pain experienced by air crew in flight. Over a period of time it was noticed that deep sea divers also suffered tooth pain due to pressure changes, prompting the use of the term barodontalgia. Barodontalgia can be explained by Boyle’s law, which states that ‘at a given temperature, the volume of a gas is inversely proportional to the ambient pressure’. As an individual descends deeper and deeper below the water surface, pressure exerted by water on the diver increases and reduces the volume of gases in enclosed spaces such as teeth and the paranasal sinuses. Similarly during a high altitude flight the atmospheric pressure outside the aircraft decreases thereby permitting the volume of gases to increase. These changes in pressure affect air crew and passengers of a non-pressurized aircraft. Barodontalgia arises when gases that are confined within closed spaces are unable to contract to adjust the internal pressure to correspond to the outside pressure. The phenomenon begins to occur at an altitude of approximately 3,000 m and at a water depth of 10 m where the ambient pressures are 0.75 and 1 atm, respectively. Individuals may experience a simple sharp or squeezing tooth pain. Occasionally the pressure change may cause the rupture of the alveolar mucosa. Strohaver (1972) categorized barodontalgia into direct and indirect types. In the direct type, reduced atmospheric pressure contributes to a direct effect on a given tooth. However in the indirect type, dental pain is secondary to stimulation of the superior alveolar nerves by a maxillary barosinusitis. Direct barodontalgia is generally manifested by moderate to severe pain, which usually develops during ascent, is well localized, and the patient can frequently identify the


involved tooth; indirect barodontalgia is a dull, poorly defined pain that generally involves the posterior maxillary teeth and develops during descent.

procedures such as pulpectomy and capping of an exposed pulp. In these individuals endodontic treatment is recommended.

Etiology Kollmann (1933) proposed three hypotheses to explain the occurrence of barodontalgia: expansion of trapped air bubbles under a root filling or against dentin that activates nociceptors; stimulation of nociceptors in the maxillary sinuses, with pain referred to the teeth; and stimulation of nerve endings in a chronically inflamed pulp. In most cases of barodontalgia the individual’s tooth is already affected by some sort of pathology such as acute or chronic periapical infection, caries, deep restorations, residual dental cysts, sinusitis and a history of recent surgery. The term barosinusitis has been used in literature to describe pain in the tooth caused by congestion of the maxillary sinus and most often the pain is experienced during descent. Whereas barodontalgia is usually experienced during ascent and the tooth is affected usually by periapical pathology.

Underwater Diving During underwater diving the air from the pressurized tanks may be forced into the tooth via the carious lesions or defective margins of restorations. With the fall in atmospheric pressure during ascent, trapped gases may expand and enter dentin tubules, thereby stimulating nociceptors in the pulp or causing the movement of pulp chamber contents through the apex of the tooth, resulting in pain. Calder and Ramsey (1983) suggest that the physical properties of the gas mixture used during deep sea diving may contribute to barodontalgia. In scuba tanks, oxygen’s natural diluent gas, nitrogen, is replaced by helium, resulting in a gas of lower viscosity. This gas can enter tissues, including teeth, and can sometimes become trapped in closed spaces, such as the pulp chamber and root canal. There are two mechanisms by which gases can be trapped in spaces: if there is a space between a tooth and its restoration, gas may be forced into it during an increase in pressure; and dissolved gas may diffuse from tissues into spaces as pressure decreases. Occasionally, the trapped gas will expand and the resulting stress may cause tooth fracture. This process has been called odontecrexis (Greek word meaning ‘tooth explosion’). The Fédération Dentaire Internationale (FDI) recommends an annual check-up for divers and pilots, with oral hygiene instructions. Also it recommends that the patients should not dive or fly in non-pressurized cabins within 24 hours of a dental treatment requiring anesthetic or for a week following a surgical treatment. Some authors suggest that when treating people who are subjected to large pressure changes it is best to avoid

PARANASAL SINUS-RELATED PAIN The paranasal sinuses are placed in close proximity to the oral cavity, especially the maxillary sinus and have some common innervations. This can cause pathologies in and about the sinus to be referred to the dental structures and vice versa. Therefore a careful consideration of their close relationship must be made in chronic painful conditions. Primary pain that occurs at the opening of the sinuses into the nasal cavity has secondary reference zones in the maxillary posterior teeth of the same side and some areas of the face. It should however be noted that the sinus lining mucosa is actually insensitive to pain, but the junction of the sinus lining with the nasal mucosa is richly innervated and when stimulated causes intense pain. Hence any exudate present within the sinus causes a feeling of fullness or pressure in that sinus rather than pain or headache. When the patient bends forward, the exudates can wash over the sensitive ostium causing pain that may radiate to the maxillary teeth. Many a times, sepsis from the maxillary teeth may in itself be a cause for the sinus inflammation. If the teeth are secondarily involved by extension of prior sinus disease, the dental pain will be of the periodontal type due to the effect on the periodontal ligament with almost no features of pulpal pain. Pain of maxillary sinus origin will be usually felt as a constant, dull non-pulsatile ache in the maxillary teeth of the affected side and sometimes on the face. There may be accompanying ear pain, malaise, nasal congestion and nasal discharge. Inflammation of the sinus will usually cause radiographic findings of haziness or cloudiness of the sinus and/or hyperplasia of the sinus lining.

MYOFASCIAL PAIN Pains of muscular origin are one of the frequent sources of chronic pain anywhere in the body and the head and neck region is not bereft from it. The pain originating from the skeletal muscles, tendons and fascia surrounding these constitute the term myofascial pain (MFP). The intimate relation of the muscles in and around the oral cavity, both anatomically and functionally accords the orofacial musculature an important consideration in the differential diagnosis of chronic orofacial pain. Pathology originating in the dental structures can cause effects manifested in the musculature. The group of muscles involved, their number and their relative location determine the severity of pain felt by the patient. According to Bell (1989), ‘it is a good rule to follow 119


in diagnosing pains about the face and mouth is initially to assume that the pain is dental until proven otherwise, then muscular until proven otherwise’. Myofascial pain is a regional muscle pain disorder that manifests characteristic local areas of hypersensitive bands of muscle tissue known as ‘trigger points’. The exact nature of a trigger point is not known, but it has been hypothesized that certain pain inducing events sensitize the free nerve endings in the muscles that cause the occurrence of the hypersensitive areas. Some investigators believe that the individual muscle spindles manifesting the trigger point are innervated by the sympathetic nervous system which may be the cause of muscle pain in emotional situations. The trigger point has an ability to cause referred pain in a definite anatomical area when stimulated. Each trigger point is thought to be less than 1–2 mm in diameter. The complete range of etiologic factors for MFP is difficult to determine, but both local and systemic causes have been consistently identified in most patients, such as trauma, emotional stress, fatigue, hypovitaminosis and infections especially of the upper respiratory tract. Clinical features A patient manifesting MFP will complain of increased fatigue, stiffness and pain in a particular group of muscles. The patient may describe a feeling of subjective weakness and restriction in the normal range of muscle motion. The pain typically increases as the day progresses and is particularly more following a stressful day. The clinical presence of the characteristic trigger point is the hallmark of this condition. When such a trigger point is detected and palpated the patient gives a typical behavioral reaction, acknowledging the tenderness felt in the area of pain reference, known as the ‘jump sign’. When the painful muscle is stretched it is found to be restricted in motion and the patient may adopt a faulty posture to obtain relief from the pain. In some situations, multiple trigger points may induce referred pain in the same region or a single trigger point may cause radiating pain in two or more muscles. If the muscle soreness persists for a long time, a cyclic painspasm-pain pattern may form. Therefore accurately locating the source of pain, the trigger point, and the zone of reference is equally important. There may be accompanying tingling or numbness of the associated area. Patient may complain of pain in the TMJ region, the ear, scalp or the neck. Rarely in some patients, autonomic changes may be present, such as pallor, sweating, flushing, lacrimation, nasal congestion, increased salivation and nausea.

stretching exercises and analgesic injection into the trigger points are most commonly employed. The details of all modalities used in management of MFP are beyond of the scope of discussion of this book.

NEURALGIAS Neuralgia is a clinical condition involving a pain of a severe intensity, with a throbbing or stabbing character in the course or distribution of a specific nerve.

Trigeminal Neuralgia Trigeminal neuralgia (TN) is frequently encountered neuropathy in dental practice affecting the fifth cranial nerve. Though it has been known by various names in the literature such as tic douloureux, trifacial neuralgia, Fothergill’s disease, the currently accepted terminology is ‘trigeminal neuralgia’. It is a well-recognized disorder characterized by a severe, paroxysmal burst of pain in one or more branches of the trigeminal nerve often induced by touching trigger points, in or about the oral cavity. TN is diagnosed primarily on the basis of the history of characteristically unilateral pain attacks that are consistent with specific clinical criteria for the diagnosis. However the typical sequence of events that occur in a patient manifesting TN begins with the initial symptoms of pain that may be misdiagnosed as pain of odontogenic origin. A careful history-taking is of paramount importance stressing upon the onset (whether insidious or sudden), the duration and frequency of painful episodes, and other associated symptoms. The exact cause of TN pain attacks is not known in spite of accurate description of the condition over the years by several researchers. However, an interesting finding, that some benign tumors in the brain and/or vascular anomalies leading to compression and possible demyelination of the trigeminal nerve root at the entry into the pons, produce symptoms clinically characteristic of classic TN. This finding strongly implies that injury to the nerve root may be an important initiating factor. When such a pathologic component is present, it is known as symptomatic TN, but in the absence of any such causative factor, the condition is known as idiopathic TN. Oral causes, such as periodontal lesions and traumatic lesions have been long discarded. Clinical features

Management Management of MFP depends upon the identification of the trigger point and the referred zone. Conservative methods based upon physiotherapy principles should be applied that can be supplemented with drugs. Basic muscle 120

Trigeminal neuralgia has most often a sudden onset and progresses to become a chronic condition. Although no mortality is associated with the condition, the quality of life of the sufferer is severely affected. TN does not show any specific racial predilection and is known to occur


throughout the world in more or less the same frequency ranges irrespective of the ethnicity, geographic location or climatic conditions. It manifests in both males and females, with a slight female preponderance (2:3 males to females). The condition usually occurs above the age of 50 years, mostly in the 60–70 years range. When this condition manifests in adolescents or young adults, a demyelinating lesion in the pons should be ruled out as that is one of the most common occurrences. The patient gives a typical history of paroxysms of lancinating painful episodes involving the face that are strikingly unilateral. The pain may be described like being stabbed by a knife or an electric shock-like kind of pain. The patient is usually able to precisely point out the area affected by the pain and charts out an area supplied by the branches of the trigeminal nerve on the face. The most commonly affected divisions are the maxillary and mandibular divisions, either singly or in combination. The ophthalmic division may also be involved, though with less frequency. There has been an unexplained finding of predominant right side involvement in most studies. The attacks in each patient occur with same intensity and same areas of the face, brought about by routine activities such as chewing, smiling, talking, etc. The patient may point out to an exact location on the skin, called as trigger point, the stimulation of which causes the occurrence of an attack. These trigger points are located most commonly around the mouth, ala of the nose and periorbital or molar regions. Majority of the patients complain of lancinating pain shooting from the corner of the mouth to the angle of the jaw. There may also be a history of jolts of pain from the upper lip or canine teeth to the eye and eyebrow, without actual involvement of the orbit itself. The painful episode is usually brief lasting from a few seconds up to 2 minutes. Though the episode may be brief, some patients can experience volleys of multiple attacks within a short span of time. When an attack might get precipitated in the dental office, the patient is seen clutching the face, especially the region affected and show an expression of deathly pain (indicates the severity). Several patients, in the past, have been reported to have suicidal tendencies to rid themselves of the pain. The severe pain as it fades away may give rise to a burning ache that may last for a prolonged time after the attack. White and Sweet (1955) described a set of criteria for diagnosing TN popularly known as ‘Sweet criteria’ and currently accepted by the International Association for the Study of Pain (IASP) and the International Headache Society (IHS): 1. 2. 3. 4.

The pain is paroxysmal and sudden in nature. Light touch to the face on the trigger zones provokes the pain. The pain is confined to the trigeminal nerve distribution. The pain is unilateral in manifestation.

5.

The clinical neurologic (sensory) examination is normal.

The IHS has defined classic TN as ‘a unilateral disorder characterized by brief electric shock-like pains, abrupt in onset and termination, limited to the distribution of one or more divisions of the trigeminal nerve. Pain is commonly evoked by trivial stimuli including washing, shaving, smoking, talking and/or brushing the teeth (trigger factors) and frequently occurs spontaneously. Small areas in the nasolabial fold and/or chin may be particularly susceptible to the precipitation of pain (trigger areas). The pains usually remit for variable periods’. This definition covers most essential clinical presentations of TN. Differential diagnosis There are few other conditions that can mimic such a characteristic condition. However, in some cases, especially in the initial stages, may need other conditions to be ruled out. Chief among these are odontogenic causes, TMJ-related disorders, atypical facial pain, glossopharyngeal neuralgia, multiple sclerosis. The specific age group and sex distribution usually helps differentiate TN from other causes like atypical facial pain and TMDs that usually begin at a much younger age. A valuable clue to the diagnosis of TN is the occurrence of the pain attack with certain activities, such as rubbing the face or shaving a trigger area, whereas in other facial pain syndromes, they massage the face or apply heat or ice, which is strikingly missing out in the history reported by TN patients. Investigations Usually all laboratory values are seen to be within normal limits. Any kind of electrophysiological testing in the affected area of the face also usually does not reveal any profound abnormalities. However some clinicians insist on an elective MRI scan of the brain to detect any missed out clues, intracranially, and only then proceed with the treatment. Treatment Given the older age manifestation of TN, medical therapy is usually better tolerated than any form of surgical intervention, which can be attempted only if and when the pharmacologic therapy fails. Two broad groups of pharmacologic agents, anticonvulsants and skeletal muscle relaxants, are usually employed in the management of TN. Among the anticonvulsants, carbamazepine is the drug of choice for TN. A 100-mg tablet usually accords substantial relief within 2 hours, and therefore it is used as a first choice agent. So predictable and powerful is the relief that if the patient does not respond at least partially to carbamazepine, it should lead to a 121


reconsideration for the diagnosis of idiopathic TN. If the initial dosage does not relieve the discomfort adequately, administer a higher dose by increments of 100 mg (200 mg/ day) up to a maximum dosage of 1,200 mg/day. This drug may cause bone marrow depression, drowsiness, dizziness, blurred vision, vertigo, subjective feeling of dryness in the mouth as a spectrum of its side effects. Therefore monitoring the bone marrow activity by obtaining a complete blood count prior to initiating therapy and routinely thereafter is indicated. The main disadvantage of this drug is that, though very effective, it does not address the etiology of the neuralgia and needs to be prescribed on a longterm basis for symptomatic relief. Baclofen is the skeletal muscle relaxant employed in treating TN based upon the CNS depressant properties. Baclofen is most often used after therapy with carbamazepine has been initiated as the effects are synergistic with those of carbamazepine permitting a reduction in the dosing of carbamazepine, thereby reducing any of its adverse effects. Baclofen is introduced as 5 mg t.i.d. for 3 days, followed by increase to 10 and 20 mg/day every 3 days, up to a maximum dosage of 80 mg/day. Several other drugs have been tried in the management of refractory TN, but their role has been unclear and not supported by strong enough evidence to be routinely employed. Another drug, pimozide has also been used in the doses of 2–12 mg/day in managing TN. This drug is however recommended only for very severe and intractable cases given the higher rate of adverse side effects. Drugs like gabapentin, lamotrigine, topiramate have been used with some success in few clinical trials, but their usefulness remains yet to be ascertained at this point in time. Over time, the drugs used for the treatment of TN often lose effectiveness as patients experience pain in spite of the routine medications. For such patients, in whom medical therapy has failed, surgery is a viable and effective option. There are various surgical options that may be explored as options by the neurosurgeon, the description of which is beyond the scope of this book (Flowchart 1). Prognosis Trigeminal neuralgia is not a life-threatening condition. The disease manifests typically as clusters of attacks that wax and wane in frequency. Exacerbations most commonly occur in fall and spring seasons. After an initial attack, the disorder may remit for months or even years. Thereafter the attacks may become more frequent, more easily triggered, disabling, and may require long-term medication.

Glossopharyngeal Neuralgia Glossopharyngeal neuralgia (GPN) is a neuropathy similar to TN, but occurs due to affliction in the distribution of the 122

ninth cranial nerve. Harris (1926) coined the term glossopharyngeal neuralgia. This condition though less frequently seen in comparison to TN, is nonetheless equally painful and causes a great deal of deterioration in the quality of life in affected persons. The exact cause of this condition is unknown as yet, with some reports of nerve compression leading to the condition. However, this still remains to be ascertained as the definitive cause of GPN. Clinical features Glossopharyngeal neuralgia characteristically manifests in the older age group usually beyond 60 years of age. It does not exhibit any specific gender predilection. A patient suffering from GPN will give a history of severe shooting pain occurring in episodes. The attacks have no specific pattern and may vary in frequency from a few per day to rarely once in few months. The severity too can oscillate from between intolerable to relatively milder attacks. The pain is usually localized to areas around the posterior parts of the oral cavity and the pharynx in a typical unilateral manifestation. The pain attacks may be initiated by some specific functions like speech, swallowing, yawning or coughing (associated with tongue movements). Clinical examination usually yields no specific information, but careful probing may reveal certain sensitive areas or trigger points, that are usually located in the oropharyngeal walls or the peritonsillar area (including the soft palate). Thus palpation of the lateral aspect of the throat can easily provoke an attack confirming the diagnosis. Rarely, the pain from GPN may be felt in the ear region only, caused due to involvement of the tympanic plexus of the ninth cranial nerve. The close proximity of the glossopharyngeal nerve to the vagus nerve may cause accompanying vagal manifestations like syncope, arrhythmia and at times, even cardiac arrest. Differential diagnosis Since the trigger zones of GPN lie around areas of jaw usage, the clinician may easily confuse it with odontogenic causes, TMJ-related problems or masticatory muscle disorders. Masticatory pain may be easily differentiated by avoiding movements of the mandible and allowing free movements of the tongue. GPN will not be prevented as tongue movements would precipitate the attack. Another definitive method is to apply a topical anesthetic on to the pharyngeal mucosa that would completely stop the pain impulses arising from the stimulation of trigger zones. Any relief by this method would certainly point to a diagnosis of GPN. Eagle’s syndrome, associated with an elongated styloid process compressing the glossopharyngeal nerve may produce symptoms similar to those of GPN. A radiographic examination of the neck can help rule out calcific enlargement of the styloid process. Also pain on rotation of the head


Flowchart 1 Trigeminal neuralgia

New case

Refractory cases

Resistance Carbamazepine (Mazetol, Tegretol) 100 mg b.i.d.

Increase the dose of carbamazepine up to 600 mg b.i.d./day

Phenytoin sodium (Eptoin, Dilantin) 100 mg

1. Percutaneous radiofrequency thermocoagulation 2. Microvascular decompression

Sustained release carbamazepine (Mazetol SR, C-Lep SR) 400 mg b.i.d./day

Second line of drugs (no established efficacy – cochrane) 1. Lamotrigine 50 mg/day (Lyzin) 2. Pimozide 2 mg b.i.d./day (Mozep, Pimojet) 3. Baclofen 25 mg b.i.d./day (Spinofen, Lioresal)

1. Combination therapy carbamazepine (half the last dose) + phenytoin sodium 100 mg 2. Oxycarbazepine 300 mg (Oxep, Oxetol) b.i.d./day up to 1,200 mg/day 3. Gabapentin 300 mg (Gabantin, Gabapin) 1st day 300 mg, 2nd day 300 mg b.i.d., 3rd day 300 mg t.i.d. and then maintain the dosage. Can be given up to 2,400 mg/day

Note: All available medications have been enlisted. however, the physician should choose the appropriate mode of treatment/drug based on the clinical situations

Management of trigeminal neuralgia

to one side (causing impingement of the nerve) is a feature more suggestive of Eagle’s syndrome rather than GPN. Another situation that may compound the diagnosis of GPN is its rare but simultaneous occurrence with TN. This situation may necessitate ruling out any brain lesions causing these conditions. Again topically anesthetizing the pharyngeal mucosa will cause partial relief and the patient will point out to the persistent pain in the areas of the trigeminal nerve distribution. When GPN manifests exclusively in the tympanic plexus, the excruciating ear pain may be confused with geniculate neuralgia, ear-related or TMJ-related disorders. Investigations Laboratory tests do not exhibit any abnormality. In case of concurrent GPN and TN, an elective MRI scan of the brain

may be performed to detect any intracranial or extracranial tumors or any vascular anomalies. A panoramic radiograph may be obtained to check for the status of the styloid process calcification. Treatment The medical management of GPN is similar to that of TN. The anticonvulsant, carbamazepine, is the drug of choice, according relief to most of the affected persons. Baclofen also aids in the management by providing a synergistic action along with carbamazepine. The dosage schedules used in managing TN are the same when applied to GPN. Failure of medical therapy necessitates considering surgical options that have been known to provide relief, but come with associated risks accompanying any surgical intervention modality. 123


The occurrence of severe pain during swallowing may lead to the avoidance of any food and drinks by the patient. This can adversely impact the general health of the patient due to a significant lack of nutrition. Also the older age manifestation may predispose to more severe effects of malnutrition in GPN patients. Therefore adequate dietary adjustments need to be made and counseling must be provided regarding proper diet schedules. Prognosis Glossopharyngeal neuralgia is not a life-threatening condition. The disease produces episodic pain attacks that vary in frequency. Some patients may suffer only few attacks with natural remissions for prolonged periods. However frequent pain in most cases requires long-term medication.

Postherpetic Neuralgia The virus herpes virus varicellae or human herpes virus-3 (HHV-3) causes the infections varicella and herpes zoster in man. The primary infection with this virus leads to the clinical manifestation of varicella or chicken pox. Once the primary infection resolves, the virus enters into the sensory nervous system and can remain latent there for many years. In the head and neck, the trigeminal ganglion is the preferred site that harbors the virus during its latency. Due to some reason, activation of such latent viral particles causes the secondary infection called herpes zoster. Spontaneous pain, pain provoked by trivial stimuli, and altered sensation accompany herpes zoster and which may continue long after its characteristic rash has healed is known as postherpetic neuralgia (PHN). Herpes zoster infection by itself is a painful condition and the pain continues up to a month in most patients. But when the lesions have clinically healed and the pain still persists beyond a period of 3 months, the diagnosis points to PHN. The exact cause of PHN is not known, as it does not occur in every patient who manifests zoster infection. The sensory alterations and pain that occur in PHN have been thought to occur as a result of both peripheral and central disturbances in the nervous pathways. Many risk factors have been noted in clinical studies that predispose for development of PHN, such as advancing age, the site of zoster rashes (a particularly higher risk for trigeminal manifestation), a severe prodromal pain before the zoster manifestation and a very severe degree of rashes. Clinical features Postherpetic neuralgia usually affects the elderly group of patients over 60 years. As the age advances, the risk for developing PHN increases. The general debilitation of the health and/or any accompanying immunocompromised 124

states leads to manifestation of zoster and consequently PHN. Generally it is not seen in patients below 40 years and the incidence between 40 and 60 years is quite less as compared to in those patients above 60 years. No specific gender predilection is noted and it manifests in both male and female patients. The patient provides a typical history of unilateral pain or burning sensation that affects a region in a dermatomal pattern. Clinical examination will reveal either healing or already healed lesions of zoster infection. In rare instances, subclinical reactivation of herpes zoster can occur (without clinical manifestation of the rashes) known as zoster sine herpete. If PHN occurs in conjunction with such a situation, the diagnosis may be slightly confusing. Management The condition is never fatal, but patients may experience significant pain for a prolonged period of time thereby decreasing their quality of life. The main goal of therapy is to achieve relief from the constant gnawing pain the patient experiences. Though most of the times complete resolution is not achieved, some degree of reduction can be hoped for, sufficient enough for the patient to bear while performing routine daily activities. The various drugs that have been employed in managing PHN are: the tricyclic antidepressants (amitriptyline, nortriptyline), corticosteroids (dexamethasone, prednisone, and methylprednisolone), and anticonvulsants (gabapentin). The antiviral drugs (famciclovir) that are used to treat the zoster infection have shown to decrease the incidence of PHN as compared to patients who have not received antiviral therapy. Topical therapy with capsaicin and lignocaine has been effective in few patients. Those patients who do not respond to the medications within the first year are unlikely to have any relief from the pain and are labeled as refractory. These patients need to be educated and counseled about the condition.

Nervus Intermedius (Geniculate) Neuralgia Nervus intermedius is the sensory branch of the VII cranial (facial) nerve that supplies the external auditory meatus, ear auricle and regions around it. The neuralgia occurring in this nerve is referred to as nervus intermedius neuralgia or geniculate neuralgia or VII nerve neuralgia. This condition is very rare as compared with the other neuralgias in the head and neck region. It may be associated with herpes zoster infection of the geniculate ganglion (Ramsay Hunt syndrome). The patient describes paroxysmal pain occurring in the external auditory meatus or the walls of auditory canal. Rarely the pain may be felt only in the tympanic membrane or within the middle ear. The patient may describe a feeling of a hot stick inserted within the ear. Rarely the pain may be felt in the soft palate, tongue or even within


the facial musculature. However careful examination will reveal that the pain occurs when the ear auricle is stimulated and cause radiation of pain to the structures mentioned before. Management of the condition is similar to trigeminal neuralgia with the use of anticonvulsants like carbamazepine in doses of up to 1,200 mg/day. In Ramsay Hunt syndrome a short course (2–3 weeks) of high-dose steroid therapy has been found to be particularly useful.

Occipital Neuralgia Paroxysmal sharp pain occurring in the region supplied by the greater and lesser occipital nerves constitutes occipital neuralgia. The pain is felt in the posterior region of the skull up to the vertex. Rarely the patient may manifest temporal or at times even retro-orbital pain. Usually this condition arises due to the compression of the nerves, following trauma, infection or neoplasms. Given the frequency of musculoskeletal pains occurring in the same region the clinician needs to carefully differentiate these from each other. The presence of trigger points in the cervical region causing radiating pain up to the occipital region favors a musculoskeletal disorder. Local anesthetic blocking of the taut trigger points helps in easy differentiation. No satisfactory management strategies have been outlined in literature due to the paucity of true occipital neuralgia cases.

ATYPICAL ODONTALGIA Atypical odontalgia (AO) is a clinical condition that poses quite a challenge to the dental clinician. As the name suggests it is toothache that cannot be attributed to any cause that are usually suspected. It is therefore also known as phantom pain. Various other terminologies have been applied to this condition in the past, such as, atypical facial neuralgia, migrainous neuralgia, idiopathic toothache, etc. that have only added to confusion rather than clear many of the impending doubts regarding this condition. Therefore the use of these alternative terminologies is best avoided. AO is a frequently encountered condition in clinical practice. Patients usually end up getting various dental treatment procedures performed for the problem and often seek exacting therapy from the clinician. The multiple procedures performed previously may at times mislead the dentist into assuming the diagnosis provided by the previous clinician. It is still a poorly understood phenomenon with unclear pathophysiology and as a consequence diagnostic confirmation is achieved by excluding other known causes or those with a somatic etiology. Some authors have suggested a deafferentation pain model for explaining the clinical behavior, however till date, this has not been conclusively proven. Another school of

thought, that too has not been validated, has believed that some form of trauma has to be involved that may lead to some unexplained changes in either transmission or recognition of the pain impulse. The association of AO with psychological disorders has led to some belief that the pain may be a component of the spectrum of the psychosomatic disorders. Clinical features Atypical odontalgia is a very frequently encountered clinical situation and patients present with symptoms of toothache. The patient is usually a middle aged lady in her early forties but may manifest in significantly older women too. The exact reason for this age and gender predilection has not been understood. The patient usually points out specifically to a single tooth or very rarely a group of adjacent teeth. The teeth most commonly affected are the premolars and molars of the maxillary jaw, AO is very rarely reported in the mandibular teeth. On examination, there is no abnormality detected in the complaint tooth. Many a times, the tooth may have been treated endodontically, but does not otherwise show up any cause for concern. The tooth may have been extracted and then in such cases, the patients insist that the procedure has not alleviated the pain and the pain still persists, as if the tooth is still present, giving rise to the term, phantom pain of the tooth. The pain described is of a dull, aching, throbbing or burning and persistent type. The patient will usually describe a feeling of unpleasant sensation being present throughout the day that does not increase during functions such as eating or swallowing. AO does not cause any disturbance in sleep and patients report of occurrence of pain immediately after awakening. The presence of the pain is usually not altered by local provocation such as during pulp testing, percussion, etc. Very rarely the pain may spread to the adjoining structures within the oral cavity, such as jaw bones and even rarely may involve the broader facial region. Graff-Radford and Solberg have outlined the following criteria that may help in identifying AO: 1. 2. 3. 4. 5.

Pain in a tooth or tooth site Continuous or almost continuous pain Pain persisting for more than 4 months No sign of local or referred pain Inconsistent results of a somatic nerve block

All investigative modalities such as laboratory or radiographic tests turn up with negative results. The patient usually undergoes a lot of attempted therapies without having accorded a definitive diagnosis. Differential diagnosis Other pathologies manifesting similar symptoms need to be ruled out before arriving at a diagnosis of AO, as 125


the diagnosis is primarily based upon exclusion. ‘Common pathologies are commoner than thought to be, while rare ones are rarer than thought to be’. This statement applies accurately in disorders of the oral cavity too and therefore it is necessary for the clinician to emphatically rule out the common causes of toothache such as pain of pulpal, periodontal or myofascial origin and pain referred from contiguous structures. Atypical odontalgia can be differentiated from pulpal pain by the following features: patient cannot usually point out to a specific tooth with pulpal pain because of the absence of propioceptive ability of the pulp. Pulpal pain tends to worsen over a period of time, while AO is more or less persistent and of the same intensity. Local provocation of heat, cold or electricity will give altered results from the corresponding or opposing teeth in pulpal-related pain, but not so in AO. Anesthetic blocks cause instantaneous relief from pulpal pain. Finally the attempted dental therapies should have alleviated pulpal pathology, but AO manifests with persistence of the pain. Similarly periodontal pain will show up clinical findings of periodontal disease and also some radiographic evidence of periodontal destruction. Anesthesia usually relieves periodontal pain but not AO. Myofascial pain usually involves the broader orofacial region with the major component being involvement of the musculature as opposed to the single tooth or tooth site of AO. The presence of trigger points leading to either spontaneous pain or pain on palpation is not a feature of AO and movements of the musculoskeletal system such as during talking, chewing, smiling cause exacerbation of myofascial pain, again not encountered in AO. Pain referred from the maxillary sinus may be mistaken for AO, therefore needs careful consideration. Sinus pain usually involves the whole of the maxillary jaw or at least a quadrant on one side. Application of pressure below the eyes and over the sinus region, and lowering or bending down the head lead to an increase in pain of sinus origin, AO however usually does not demonstrate any change in the intensity of pain. Imaging studies can usually point out the sinusitis leading to the pain, but AO will not show up any imaging findings. In the rare instances, when AO may involve a region more than a single tooth, trigeminal neuralgia (TN) may need to be ruled out. TN occurs as lancinating pain in bursts of paroxysms, while AO is a dull ache that is continuous in nature. No specific trigger zones exist for AO unlike TN and TN usually manifests in a much older age group. Treatment Management of deafferentation pains is usually not easily accomplished and AO is no exception. The pharmacologic therapy is usually the best suited strategy and all dental procedures must be completely avoided once a diagnosis of AO has been made, because any somatic treatment would 126

be of no value in causing any pain relief. The patients usually agree to this after having suffered through numerous procedures not having provided relief. Any psychologic association if suspected should be dealt with in conjunction with a psychologist. Atypical odontalgia does not respond to opioid as well as non-opioid analgesics. The tricyclic antidepressants are the most favored drug employed in managing AO. The exact mode of action of these medications is not known, but it has been suggested that the analgesic properties of these drugs are more likely acting than their antidepressant effects. Amitriptyline is prescribed in doses ranging from 25 to 75 mg per day initially and if needed may be used up to 200 mg per day. The beneficial effect of the drug needs to be carefully titrated against the risk of adverse effects such as dizziness, drowsiness, headache, xerostomia, constipation, appetite and weight changes, nausea, weakness, hypotension. But patients not achieving relief with high doses are unlikely to have any satisfactory remission of the condition. In those cases that do achieve relief, complete elimination of pain is rare and therapy needs to be continued for a prolonged duration, a minimum of 3 months. Other tricyclic antidepressants such as imipramine, nortriptyline, and dothiepin have also been used. However, their effects are not very different from amitriptyline. Phenothiazines have also been used with some success in some clinical trials, however, their role is more supplementary to the tricyclic drugs. Tardive dyskinesia is a major potential side effect of phenothiazines that has not allowed for a major role of these drugs in AO. Once pain control of a desirable degree is achieved, all these drugs should be tapered off gently and then discontinued.

ATYPICAL FACIAL PAIN This condition has been the cause of much confusion and has led to many contradictions in the literature. The term atypical facial pain (AFP) suggests that it is a painful condition not satisfying certain typical manifestations of well-known conditions. In the current scenario, AFP has been completely rejected as a diagnostic terminology by the International Association for the Study of Pain (IASP), for the simple reason that it does not describe any definitive condition and has been used injudiciously in the literature to signify conditions that were not understood or correctly diagnosed. AFP has been as a ‘wastebasket’ for dumping any painful condition that has not conformed to the set of criteria for other orofacial pain conditions and thus is a diagnosis of exclusion rather than inclusion. AFP has thus been encompassing a wide group of facial pain problems. Although rarely as severe as trigeminal neuralgia, facial pain is continuous for AFP patients. Recent studies propose


that AFP is an early form of trigeminal neuralgia. Indeed, some patients have components of both AFP and TN symptoms. Earlier literature has linked AFP to ‘psychological pathology’. Recent studies however have shown no such link exists. Clinical features The causes for AFP may be varied but they lead to strikingly similar symptoms. Facial pain, typically manifests in middle-aged women who often describe some kind of a vague, intractable, burning, aching or cramping, occurs on one side of the face, often in the region of the trigeminal nerve that may extend into the upper neck or back of the scalp. The pain is usually of a diffuse pattern and presents as a continuous manifestation with few, if any periods of remission. On examination, however, no frank noticeable pathology is detected. The discomfort leads to a definite decrease in the quality of life. Invariably the patient will have visited a number of clinicians and undergone numerous dental procedures, in hopes of getting a cure. Many clinical and laboratory tests would have been performed and most of them would have yielded negative results. Though a psychological basis has been often attributed to this condition by various authors, the findings of various studies have been conflicting and the occurrence of psychogenic findings is not different from that of the general population. Diagnosis Diagnosing AFP is a challenging task. As mentioned earlier, the diagnostic path for AFP is usually based upon a process of elimination. When a patient complains of above described symptoms the clinician must first rule out any other conditions. The conditions needing careful considerations are oral (dental), paranasal sinus-related, myofascial and neurologic causes. Tests to be performed include radiographs of the skull, advanced imaging modalities, especially including the brain and the skull base. A careful otolaryngologic evaluation and a neurological consultation should be comprehensively obtained. AFP patients are considered complex and end up with a partial or incomplete diagnosis, the reason being that the patients are not completely evaluated, but only examined by a given specialist, and what implies in the application of only that specific field of treatment. Thus a multidisciplinary systematic evaluation for patients with suspicion of AFP is an absolute must. Management Treatment of AFP can be difficult and perplexing for both the doctor and patient. Pharmacotherapy is usually the first resorted treatment that may be complemented by surgical procedures. Drugs like amitriptyline and gabapentin have

been used with some degree of success. Other alternative modalities that have been employed include hot and cold compresses and acupressure and/or acupuncture. These have been able to provide some degree of relief to majority of the patients. Usually there are no associated long-term consequences due to this condition other than altered quality of life, but the patients usually get used to the pain and continue with routine activities.

BURNING MOUTH SYNDROME Burning mouth syndrome (BMS) is not a very common condition, yet can be encountered occasionally by the dental clinician. BMS is a poorly understood phenomenon that may present with a dilemma to the attending clinician in both diagnosing and managing such patients. BMS is a chronic intraoral painful condition that is not characteristically associated with any clinical lesions. It is known by various other synonyms, like burning tongue syndrome, glossodynia, glossopyrosis, stomatodynia, and stomatopyrosis. However it would be incorrect to label the condition as glossodynia or glossopyrosis when the entire oral mucosa is involved and in such a scenario BMS would be the appropriate term. The IASP defines BMS as ‘a burning pain in the oral mucosa’ and glossodynia as ‘a burning pain in the tongue only’. The exact etiologic or precipitating cause of BMS is not yet known in spite of various proposed hypotheses on the matter. Over the years, local, systemic and psychologic factors have been the broadly suggested causes. Local causes include candidal infection, denture wear, decreased salivary output, and parafunctional oral habits. Systemic factors that have been suspected are various nutritional deficiency disorders (iron deficiency anemia, vitamin deficiencies), hormonal changes like menopause, diabetes, thyroid and parathyroid disorders and drugs. Patients with BMS have been described to have higher levels of anxiety, depression, cancerophobia and mood disorders as compared to control groups. Eli Eliav et al (2007) conducted a study to assess the role of chorda tympani in patients with BMS. The striking feature of their study was the presence of chorda tympani nerve dysfunction in patients with BMS. They concluded that BMS is a form of neuropathic pain, which may be related to chorda tympani nerve dysfunction. They proposed that the evidence of elevated taste detection threshold levels (via electrogustatory testing) and raised taste/tingling detection thresholds ratio may help clinicians diagnose BMS. Clinical features The typical BMS patient will describe the problem as a burning, scalding or a tingling feeling in the oral mucosa. 127


There may be accompanying persistent bad or altered taste sensations. BMS usually affects the elderly, above the age of 50 years and with a strong predilection for women. The condition seems to occur between 3 and 12 years of reaching menopause and presence of other systemic diseases just adds to the increased risk of developing the condition. Evaluation of a suspected BMS patient should include details regarding the onset, location, and character of the pain. Any related oral symptoms of salivary changes should also be noted. The pain and/or burning sensations typically start upon awakening and increase in intensity with the progression of the day and the condition rarely interferes with sleep. The patient describes the typical sensation as if the mouth or the tongue were scalded or on fire. The burning sensation may be aggravated by hot and/or spicy foods but is not specifically caused by them. In some patients the symptoms begin in a particular oral location and then gradually spread to cover the entire mucosa. The tip of the tongue and the inner surface of the lips are the most common starting locations. Functions such as eating and drinking can bring about temporary relief. However in majority of cases, no such clinical lesions will be detected. The patient may give details of systemic symptoms that might correlate the oral condition with hot flushes of menopause. The patient’s social and psychologic history should also be taken into account and noted if any particular event relates to the onset of the symptoms. Queries related to

cancer arising from the condition need to be resolved. BMS patients often end up visiting many clinicians for getting the problem resolved and often sound dejected. Whether there is an underlying psychologic cause for the pain or if the psychologic component is a consequence of the painful condition has not been accurately ascertained. Petruzzi et al (2007) described five patients who had burning mouth syndrome along with vulvodynia. They termed this condition vulvostomatodynia. The condition is characterized by burning sensation in the tongue, lips, vestibule and other mucosal sites in menopausal and post menopausal women. Differential diagnosis Oral lesions such as local oral infections, oral lichen planus and the like should be ruled out. The oral mucosa should, therefore, be thoroughly examined for any mucosal lesions that may be a cause for the symptoms. The presence of the burning sensation may be an initial sign of the neuralgias; however these will be typically unilateral in manifestation. The combined occurrence of burning sensation and decreased salivation should lead the clinician to investigate any underlying salivary gland pathology. Common systemic diseases causing burning sensations in the oral mucosa such as diabetes and anemia must be assessed by appropriate laboratory evaluation.

Flowchart 2 Burning mouth syndrome

Initial visit

Chronic cases

Topical: A. Capsaicin gel 0.025% (Capsain-p) B. Alpha-lipoic acid as mouthrinse b.i.d./1–2 months (ALA-100, Aladin 100 mg)

Systemic: A. Multivitamins – B12, methyl cobalamin and folic acid (MCBM-69, Neurokind-G and Nuvolt-G t.i.d.; Nurokind plus, Nuvolt: o.d.)

Systemic: A. Amitriptyline 25 mg b.i.d. (Amitone, Amitryn, Amitrol, Tadamit) for 15 days, o.d. for 15 days B. Gabapentin 300 mg (Gabantin, Gabapin) 1st day 300 mg, 2nd day 300 mg b.i.d., 3rd day 300 mg t.i.d. and then maintain the dosage. It can be given to a maximum of 2400 mg/day C. Alprazolam 0.25 mg b.i.d. (Restyl, Alcalm, Anxit SR-0.5 mg) for a week and slowly withdraw the drug D. Clonazepam 2 mg o.d. at bed time for 15 days (Clozep, Lonazep MD, Melzap) E. Nortriptyline 25 mg o.d. for not more than 3 months (trip)

Note: All available medications have been enlisted. However, the physician should choose the appropriate mode of treatment/drug based on the clinical situations

Management of burning mouth syndrome

128


Management Any treatable cause of the burning sensations in the oral mucosa should be identified and treated comprehensively before labeling any patient to be suffering from BMS. However, once all such conditions have been ruled out and a diagnosis of BMS has been arrived at, the situation should be explained to the patient and counseling regarding the benign nature of the condition should be offered. The decrease in the quality of life should be explained as in some patients the conditions undergoes spontaneous remission while in the majority of cases it persists as a chronic condition. Due to an unclear etiopathogenesis, definitive pharmacologic therapy is not available for the condition and all modalities are essentially palliative in nature. Topical, systemic and psychologic therapies have been used with varying degrees of success. Topical therapies with anesthetic products such as lignocaine and benzydamine hydrochloride seem to be effective in a handful

of cases and even in these rapidly lose effectiveness. Topical clonazepam when used in doses of 1 mg used for 3 minutes thrice daily has imparted relief to some patients, yet its routine use has not been validated. Systemic therapies with alpha-lipoic acid, capsaicin, amisulpride and antidepressants have been tried with inconsistent results. Gabapentin that has been effective in other chronic pain disorders has demonstrated little or no effect on BMS patients. Cognitive behavioral therapy (to replace patterns of negative emotions and thoughts with more realistic and positive ones) has helped few patients who have had underlying psychological causes. However, labeling all cases as psychologically based often leads to inefficient management of BMS patients by both dental and medical clinicians. Therefore, no single or sure-shot treatment strategy has been evolved for this enigmatic condition and it would be wrong to label each case of BMS to suffering from the same causative mechanism, for therein lies the pitfall of successfully managing BMS (Flowchart 2).

Trigeminal Pain Pathway Trigeminal nerve is the primary sensory nerve of the maxillofacial region. Pain is conducted along the afferent fibers of the branches of the trigeminal nerve into the semilunar or gasserian ganglion. The impulses from the ganglion are carried to the sensory root of the nerve into the pons. The sensory root either ends directly in the main sensory nucleus or branches out into the ascending fibers (carry general tactile sensation) and descending fibers (transmit pain and temperature). Pain impulse, therefore descends from pons, through the medulla down to the level of second cervical segment and terminates. The secondary neurons emerge from the spinal nucleus, after which the axons cross the midline and ascend to join the fibers of mesencephalic nucleus to form spinothalamic tract of the fifth nerve. These axons continue to ascend and terminate in the posteroventral nucleus of the thalamus. Few of these second order neurons activate the reticular area of the brain stem causing excessive alertness, increase the individual’s sense of perception and reaction to pain. The third order neurons project from the posteroventral nucleus carrying pain impulse to the posterocentral convolutions of the cerebral cortex.

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SECTION

III

Mucocutaneous Disorders

6 7 8 9

Red and White Lesions Vesiculobullous Disorders Oral Ulcerative Diseases Dermatological Diseases

133 174 196 218

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CHAPTER

6

Red and White Lesions Ashok L

Color of Oral Mucosa ➧

Hereditary Benign Intraepithelial Dyskeratosis (Witkop’s Disease) Focal Epithelial Hyperplasia (Heck’s Disease) Dyskeratosis Congenita White Sponge Nevus

Description of Red and White Lesions White Lesion Red Lesion

➧ ➧

Etiologic Classification of Red and White Lesions

➧

Red Lesions of the Oral Cavity

White Lesions of the Oral Cavity

➧

Red Lesions of the Tongue Migratory Glossitis Median Rhomboid Glossitis Deficiency States Foliate Papillitis Erythroplakia Discoid Lupus Erythematosus

Frictional Keratosis/Traumatic Keratosis Chemical Burns and Thermal Burns Leukoplakia Lichen Planus Candidiasis Oral Submucous Fibrosis Psoriasis

In day-to-day clinical practice oral physicians often encounter a wide spectrum of oromucosal lesions. These lesions range from harmless mucosal alterations like change in the color and texture of the oral mucosa, needing simple therapeutic remedies and patient counseling to lesions of a life-threatening nature. Red and white colored alterations of the oral mucosa are commonly seen in dental practice. Recognizing and differentiating these mucosal alterations from normal anatomic variations is imperative for the effective management of these lesions.

Color of Oral Mucosa As the oral mucosa is translucent, it reflects the contents of the underlying connective tissues. Normal color of the oral mucosa is pink, the intensity being varied in different parts of the oral cavity and depends upon various factors like, ❍ ❍ ❍

Thickness of the oral mucosa Degree of keratinization Amount of vascularity and fibrous content in the connective tissue

❍ ❍

Formation of pseudomembranes Pigmentation producing cells like melanocytes.

DESCRIPTION OF RED AND WHITE LESIONS White Lesion White lesion is a non-specific term used to describe any abnormal area of the oral mucosa that on clinical examination appears whiter than the surrounding tissue. It is usually slightly raised, roughened or of different texture from the adjacent normal mucosa (e.g. linea alba buccalis, frictional keratosis, leukoplakia, chronic hyperplastic candidiasis etc). This normal color of the mucosa may turn into white due to the increased thickness of the epithelium with increased production of keratin (hyperkeratosis) and production of abnormal keratins and imbibition of fluid by the upper layers of the mucosa. In situations like coagulation of tissue surface (occurs in burns), results in the formation of white pseudomembrane, which remains attached to the mucosa but can be scraped off easily. Generally white lesions result 133

Section III – Mucocutaneous Disorders

from various factors like, trauma, infections, immunologic injury to the mucosa or other genetically determined factors.

5.

Red Lesion Red lesion refers to an area of reddened mucosa that may appear smooth and atrophic or exhibits a granular, velvety texture (e.g. erythroplakia, median rhomboid glossitis, erythematous candidiasis, etc). These lesions may occur alone or in combination with a white lesion. Such lesions may be termed as a mixed lesion or a red and white lesion (e.g. speckled leukoplakia, erosive lichen planus, etc). Individual variations in the color of the oral mucosa are probably an expression of one or more genetically controlled factors. Healthy masticatory mucosa (gingiva, palate, dorsal surface of the tongue) is light pink in color. The lining mucosa (mucosa over the vestibule, cheeks, lips, floor of the mouth, and ventral surface of the tongue) is reddish pink in color. Palatoglossal arch region is dusky red in color due to increased vascularity and often misdiagnosed as sore throat. The histological reason behind the appearance of a red lesion may be due to dilated blood vessels, influx of new blood vessels, hemorrhage under the epithelium or a relatively thin outer epithelium.

ETIOLOGIC CLASSIFICATION OF RED AND WHITE LESIONS 1.

2.

3.

4.

134

Normal mucosal variations Leukoedema Fordyce granule Linea alba buccalis Genetically linked white keratotic lesions Oral genodermatoses White sponge nevus Hereditary benign intraepithelial dyskeratosis Pachyonychia congenita Post inflammatory white lesions Traumatic keratosis Mechanical trauma Thermal burn Chemical burn (aspirin burn, uremic stomatitis) Radiation mucositis Reactive mucosal hyperplasias (stomatitis nicotina palati) White and red lesions due to infections Syphilis Measles (Koplik’s spots) Candidiasis Bacterial stomatitis

6.

7.

Premalignant lesions Leukoplakia Lichen planus Lichenoid reactions–drug induced, graft-versushost disease Erythroplakia Actinic keratoses Discoid lupus erythematosus Chronic hyperplastic candidiasis Premalignant conditions Oral submucous fibrosis Oral psoriasiform lesion Dyskeratosis congenita Syderopenic dysphagia Syphilitic glossitis Miscellaneous Intraoral skin grafts (people of Afro-Asian origin) will not generally exhibit a white coloration of the skin graft. The graft will appear black or brown depending on the extent of melanin pigmentation (Figure 1).

WHITE LESIONS OF THE ORAL CAVITY White lesions of the oral cavity can be categorized clinically as keratotic (non-scrapable) or non-keratotic (scrapable) lesions. Table 1 gives a list of scrapable and non-scrapable lesions.

Frictional Keratosis/Traumatic Keratosis Frictional keratosis is defined a white patch with a rough surface which is clearly related to a source of mechanical irritation and that will disappear over a period of time with the removal of the stimuli. Lesions belonging to this category include linea alba buccalis, and cheek, lip or tongue biting or chewing. Linea alba buccalis is a non-scrapable white line that is present on the buccal mucosa usually along the plane of occlusion (Figure 2). It may either be seen unilaterally or bilaterally. Linea alba occurs due to the constant friction or irritation of the buccal mucosa by the facial surfaces of teeth. It is more pronounced with respect to the posterior teeth and may have a scalloped architecture. It is asymptomatic and usually does not require any form of management. Chronic cheek, lip, tongue chewing usually presents as thickened and shredded whitish areas. Habitual oral mucosa chewing can sometimes lead to areas of localized erosion and ulceration. The lesions may present bilaterally or unilaterally. Individuals with chronic cheek biting (morsicatio buccarum) have either a habit of sucking the cheeks frequently

Chapter 6 – Red and White Lesions

Figure 1

Figure 2

Linea alba on the buccal mucosa. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore Skin graft. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Table 1

Non-scrapable and scrapable lesions

Keratotic lesions (non-scrapable)

Non-keratotic lesions (scrapable)

Linea alba buccalis Frictional/traumatic keratosis Homogeneous leukoplakia Reticular lichen planus Chronic hyperplastic candidiasis Dyskeratosis congenita White sponge nevus

Chemical burn/thermal burn Pseudomembranous candidiasis Syphilitic mucous patch Diphtheritic patch

or push the cheek in between teeth with their finger. Similarly individuals with chronic lip chewing habit (morsicatio labiorum) and chronic tongue nibbling habit (morsicatio linguarum) present with macerated appearance of the labial mucosa and lateral surface of the tongue respectively. The lower labial mucosa is usually affected in lip chewers (Figure 3A, B). Habitual chewing may be associated with individuals under stress. However most of the individuals are unaware of the parafunctional habit. The management of these conditions should be targeted at educating the patient regarding the ill-effects of the parafunctional habit. Frictional keratosis is also caused by the rough flange of denture, sharp cusp of a tooth or sharp edge of broken teeth (Figure 4). Histologically traumatic keratotic lesions will show varying degree of hyperkeratosis and acanthosis.

Management Removal of the etiologic agent will generally result in complete resolution of the lesion within 2 weeks. Biopsy may be considered in lesions that persist for a longer duration, to rule out any dysplastic changes.

Chemical Burns and Thermal Burns Chemical trauma to the oral mucosa may be due to improper use of medicaments or the use of harsh chemical substances such as strong acid or alkali. Chemical burn usually results from the patient applying analgesics like aspirin or acetaminophen or home remedies such as clove oil to the mucosa adjacent to a decayed tooth to alleviate pain. Chemical substances like phenol, silver nitrate, concentrated hydrogen peroxide, root canal medicaments can also produce an area of necrosis. Thermal burns are generally caused due to the accidental intake of hot food or beverages. These mucosal burns are characteristically seen on the anterior one third of the tongue and palate. The clinical appearance of these burns in most cases depends upon the severity of the tissue damage. Chronic mild burn usually produces keratotic white lesion whereas intermediate burn causes localized mucositis and the more severe burns coagulates the surface of the tissue and produces a diffuse white lesion. In such cases the tissue can be scraped off, leaving a raw bleeding painful surface (Figure 5). Differential diagnosis Acute pseudomembranous candidiasis and gangrenous stomatitis can be considered in the differential diagnosis for chemical and thermal burns. 135


Figure 3 A

B

(A) Whitish macerated appearance of the upper labial mucosa. (B) Whitish thickened and shredded area on the lower labial mucosa. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 4

Frictional keratosis caused by the sharp cusp of the adjacent molar. Courtesy: Dr Praveen, KLE Institute of Dental Sciences, Bangalore

Figure 5

A chemical burn on the buccal mucosa that is characterized by the presence of a white pseudomembrane that reveals an underlying erythematous area when scraped off. Courtesy: Dr Ashok

Management 1.

2. 3.

Topical application of anesthetic agent like benzocaine/ lignocaine gel (choline salicylate 8.7%, benzylkonium 0.01% and lignocaine hydrochloride 2%). Topical application of steroids like triamcinolone acetonide (triamcinolone acetonide oral paste 0.1%). In case of severe pain analgesics can be used.

Nicotine Stomatitis (Stomatitis Nicotine Palatinus, Smoker’s Palate) Thoma in 1941 was the first to use the term stomatitis nicotine because he noticed this lesion to almost exclusively 136

occur in individuals who had the habit of smoking tobacco. This lesion is a reactive hyperplasia to the heat generated by the tobacco smoke that acts as a chronic irritating agent. These mucosal changes are mostly seen in reverse cigarette/chutta and pipe smokers and relatively lesser in cigar, cigarette and beedi smokers. Clinical features Smoker’s palate is usually seen in males. However, in the Indian subcontinent women who have the habit of reverse chutta smoking also exhibit these mucosal changes. It is


Figure 6 A

B

(A) Diffuse grayish white pigmentation of the palate with red pinpoint areas characteristic of smoker’s palate. (B) Multiple papules on the palate with red pinpoint areas in smoker’s palate. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

generally asymptomatic. The palatal mucosa appears as a diffuse grayish white surface or flat topped nodules may be seen with red pinpoint areas situated in the center of each nodule (Figure 6A, B). These red pinpoint areas correspond to the inflamed orifice of the minor salivary gland ducts. Differential diagnosis ❍ ❍ ❍

Palatal papillary hyperplasia Focal epithelial hyperplasia (Heck’s disease) Darier’s disease (follicular keratosis)

Leukoplakia Oral leukoplakia (OL) is the most common precancerous lesion of the oral mucosa. The term leukoplakia was first used by Schwimmer in 1877 to describe a white lesion on the dorsum of the tongue, which probably represented syphilitic glossitis. He proposed the term ‘leukoplakia’ for a diffuse patch on the dorsum of tongue. Since then it has evolved as a clinicopathologic concept over many years; sometimes representing an innocent hyperkeratosis and sometimes dysplastic features. Definition The requirement for a clear definition for oral white lesions has long been recognized. Similar requirements also apply to red lesions or the red component of preponderantly white lesions. The definition of leukoplakia has often been confusing and controversial. Currently the WHO definition and definition given by Axell are widely used.

Auluck et al conducted a survey in 10 different dental colleges in India among 153 specialists including oral surgeons, oral physicians and oral pathologists to check the prevalence of confusion regarding the definition of leukoplakia and its application. It was found that 33.33% of the specialists preferred to follow WHO definition (1978), while 65.35% preferred to follow Axell (1984) definition. The authors described the current ambiguity regarding the accepted definition of oral leukoplakia and emphasized the need for an international collaboration to reach a consensus on the use of the term leukoplakia. WHO definition of leukoplakia (1978) Leukoplakia is a white patch or plaque that cannot be characterized clinically or pathologically as any other disease. The definition indicates that the term leukoplakia does not carry a histologic connotation and should be used only in descriptive clinical context. Axell et al definition of leukoplakia (1984) Leukoplakia is a white patch or plaque that cannot be characterized clinically or pathologically as any other disease and not associated with any physical or chemical causative agent except the use of tobacco. Axell et al definition of leukoplakia (1996) Leukoplakia as a predominantly white lesion of the oral mucosa that cannot be characterized as any other definable lesion; some oral leukoplakia will transform into cancer. This definition is most widely accepted in the western world. Pindborg et al definition of leukoplakia (1997) A predominantly white lesion of the oral mucosa that cannot be characterized as any other definable lesion. 137


Epidemiology The frequency of leukoplakia is highly variable among geographical areas and demographic groups. The prevalence in the general population varies from less than 1 to more than 5%. The prevalence of leukoplakia increases to 8% in men over the age of 70 and the prevalence in women past the age of 70 is approximately 2%. Mehta et al (1961) reported the prevalence of 3.5% in 4,734 Indian population. Manghi et al (1965) reported a prevalence of 6.5% among 2,004 persons. Smith et al (1975) reported a prevalence of 11.7% among 57,518 persons. Yang et al (2001) reported the prevalence of leukoplakia as 24.4% among the aborigines in southern Taiwan. Chang et al (2005) reported the prevalence of 7.44%. In a 10-year follow-up study, a random sample of 30,000 villagers in three areas in India, the annual incidence rates varied from 1.1 to 2.4 per 1,000 men and 0.03 to 1.3 per 1,000 women. In India the prevalence of oral leukoplakia among betel quid chewers with tobacco ranged from 0.4 to 1.8% and among betel quid chewers without tobacco ranged from 0.3 to 0.7%. Table 2 gives the overall impression of the prevalence of oral leukoplakia with a geographic emphasis. Classification and staging system for oral leukoplakia Van der Waal (2000) designed and proposed the classification and staging system. The present classification and staging system is primarily designed for the purpose of uniform reporting of treatment or management results and requires the availability of a biopsy report. It also could serve as means for epidemiological studies. L (size of the leukoplakia) L1 Size of single or multiple leukoplakia together 2 cm L2 Size of single or multiple leukoplakias together 2–4 cm L3 Size of single or multiple leukoplakias together 4 cm Lx Size not specified

Table 2

138

P (pathology) P0 No epithelial dysplasia (includes ‘no or perhaps mild epithelial dysplasia’) P1 Distinct epithelial dysplasia (includes ‘mild to moderate’ and ‘moderate to possibly severe’ epithelial dysplasia) Px Absence or presence of epithelial dysplasia not specified in the pathology report. OLEP (Oral leukoplakia) staging system Stage I L1P0 Stage II L2P0 Stage III L3P0 or L1L2P1 Stage IV L3P1 General guidelines for oral leukoplakia staging system 1.

2.

3.

If there is doubt concerning the correct L or P category to which a particular case should be allotted, then the lower (i.e. less advanced) category should be chosen. This will also be reflected in the stage grouping. In case of multiple biopsies of single leukoplakia or biopsies taken from multiple leukoplakias the highest pathological score of the various biopsies should be used. For reporting purposes the oral subsite according to the ICD-DA should be mentioned.

The letter ‘E’ in the OLEP abbreviation has been used to prevent confusion with the often used abbreviation for oral lichen planus. Some leukoplakias have a white verrucous texture being referred to as verrucous leukoplakia. In the majority of these cases no epithelial dysplasia is present. Yet, such lesions may easily recur (‘proliferative verrucous leukoplakia’) after conservative treatment and may finally lead to the development of a squamous cell carcinoma. Etiopathogenesis 1. Tobacco (smoke/smokeless form) Use of tobacco in the form of factory-made cigarettes, beedi, cigars and cheroots

Prevalence of leukoplakia

Author and year of study

Country

Number of persons examined

Prevalence (%)

Pindborg et al (1965–1966)

India

30,000

Gangadharan and Paymaster (1971)

India

2,03,249

0.7

Mehta et al (1972)

India

1,01,761

0.7

Axel (1976)

Sweden

20,333

3.6

Bouquet and Gorlin (1986)

USA

23,616

2.9

Hogewind and Van der Waal (1988)

Netherlands

1,000

1.4

Banoczy and Rigo (1991)

Hungary

7,820

1.3

Ikeda et al (1991)

Japan

3,131

2.5

Schepman et al (1996)

Netherlands

1,000

0.6

1.5–3.3


and powdered tobacco in pipes or rolled into hand-made cigarettes, are the main etiological agents in the causation of leukoplakia. Much of the tobacco in the world is consumed in the form of smokeless tobacco and it is placed in contact with the mucous membrane. In south-east Asian countries tobacco is mostly consumed mixed with other ingredients like areca nut, betel leaf, slaked lime, catechu and condiments. Smokeless tobacco use is practiced in many forms. Chewing of tobacco containing products or snuff dipping habits vary greatly from one part of the world to another. It is of great importance to quantify the degree of exposure. Over 300 carcinogens have been identified in tobacco smoke or in its water-soluble components which can be expected to leach into saliva. The major and most studied among them include aromatic hydrocarbons, benzopyrene and the tobacco specific nitrosamines, N-nitrosonornicotine (NNN), nitrosopyrrolidine (NYPR), nitrosodimethylamine (NDMA) and 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK). Benzopyrene is a powerful carcinogen and is found in amounts of 20–40 mg per cigarette. The mainstream smokes of a cigarette contain 310 mg of NNN and 150 ng of NNK. These agents act locally on keratinocytes, stem cells, and are absorbed and act in many other tissues in the body. Cigarettes can be classified as low or medium, if the tar yield is below 22 mg and as high if tar yield above 22 mg compared with non-smokers the risk of oral cancer and OL for smokers using low to medium tar cigarettes is 8.5%. A case control study from Brazil also found an increased risk among cigarette or pipe smokers with a strong doseresponse relationship between the number of years smoked and oral cancer risk (Franco et al, 1989). Snuff involves placing moistened, powdered tobacco, treated with natron (sodium sesquicarbonate) in the lower labial, buccal sulcus or the floor of the mouth against the lingual side of the mandible. Snuff has been shown to contain carcinogens such as N-nitrosamines which are derived from tobacco. Many studies have demonstrated that tobacco in any form can predispose to OL (Pindborg et al, 1972; Salonen et al, 1990; Christian et al, 1992). 2. Alcohol Alcohol has also been emerged as a significant risk factor for OL. In Germany, Wilsch et al (1978) found that alcohol consumption was greater among people with leukoplakia as compared to control. In India Gupta et al (1984) studied alcohol habits of over 7,000 individuals with tobacco habits and found that 31% consumed alcohol regularly, 25% occasionally and 44% did not consume alcohol at all. The prevalence of OL was higher among regular and occasional (3.9%) alcohol drinkers than among non-drinkers (2.9%). Although alcohol by itself not an important risk factor for leukoplakia, it might produce synergetic effects when combined with the habit of chewing tobacco or smoking.

Alcohol causes dehydration of the oral mucosa and increases the ambient temperature of the oral cavity thereby making the oral mucosa more vulnerable to the carcinogenic effects of tobacco. Alcohol by itself contains known carcinogens such as hydrocarbons and nitrosamines. It also causes liver induced cellular changes in target tissues (increased acetaldehyde content). 3. Viral infection The possible implication of human papilloma virus in the etiology and potential for malignant transformation of oral premalignant lesion has been studied extensively and it was reported that the likelihood of detecting HPV was 2–3 times higher in precancerous oral mucosa and 4–5 times higher in oral squamous cell carcinoma than in normal oral epithelium. The possible viral etiology of OL had been first suggested by light microscopic demonstration of HPV suggestive changes (Fejerskov, 1977). The first evidence of HPV etiology of oral leukoplakia had been provided by Loning (1985), Syrjanen (1986) and Naghashfar (1985). In a follow-up study of 20 leukoplakias, Lind (1987) established a significant correlation between the presence of HPV antigen and the degree of dysplasia and malignant transformation. High prevalence of HPV in PVL had been found by Maitland et al (1987) who found an overall rate of 42% using probes specific for HPV 16. The differences in detection of HPV may be accounted for different sensitiveness of methods used. D’costa et al (1998) in their study detected HPV 16 in 34% of the potentially malignant lesions and Mao et al (1996) in 36% of precancerous lesions. In oral cavity HPV 16 has been demonstrated in both homogeneous leukoplakia and in verrucous leukoplakia (Loning, 1985; De Villers, 1986; Milde, 1986; Syrjanen, 1988 and Kashima et al, 1990). Studies by Nielsen et al (1996) in the prevalence of HPV in oral premalignant lesions found an overall rate of HPV positive lesions to be 40.8% of which five of them were HPV 16. Elamin et al (1998) suggested that the prevalence of HPV infection is higher in oral lesions from India. The high prevalence of HPV infection in oral premalignant cases indicates that HPV infection would be an early event in the process of malignant transformation of oral epithelial cells. 4. Leukoplakia and diabetes A few studies in the literature have found a significant association between diabetes mellitus and OL prevalence (Albert et al, 1992; Ujpal et al, 2002). Albert et al (1992) reported an OL prevalence of 6.2% among diabetics as compared to 2.2% in a control group. However the analysis did not adjust for age and gender. Diabetes mellitus leads to a number of metabolic and immunologic changes that affect the oral mucosa and it is associated with a variety of oral conditions (Ponte et al, 2001). 139


Thomas et al (2004) have found a significant association between diabetes mellitus and OL prevalence. According to weighted model, diabetics were three times more likely to have OL than non-diabetics. However no association between diabetes and the incidence of oral squamous cell carcinoma has been described previously. Therefore the significance of the apparent association between diabetes and OL is unclear.

Figure 7

5. Candidiasis and leukoplakia There is a longstanding discussion whether Candida infection is a cause of leukoplakia or if it is a superimposed infection in a pre-existing lesion. It has been shown that, upon treatment, nonhomogeneous Candida-infected leukoplakias convert into a homogeneous lesion, and some lesions even regressed. 6. Dietary factors Ramaswamy et al (1996) have shown that serum vitamins A, B12, C, E, beta-carotene and foliate were decreased in leukoplakic patients as compared to controls. Many other studies supporting the protective effects of carotinoids and vitamin A, C and E have been reviewed by Enwon et al (1995) and Garewell et al (1999). Only a very few studies have reported a positive association between estrogens and oral leukoplakia. Hashibe et al (2000) reported an inverse relationship between body mass index (BMI) and OL prevalence in a large population in India. The authors hypothesize that higher estrogen levels in people with higher BMI may explain this relationship. Kushlinskill et al (1988) have demonstrated estrogen receptors in oral squamous cell carcinoma and OL. Thomas et al (2004) recently have demonstrated a strong protective effect of estrogen use on OL prevalence in women. In their study there was no case of OL among women who were using estrogen.

Commissural leukoplakia. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 8

Clinical features 1.

2. 3.

140

Leukoplakia is seen most frequently in middle-aged and older individuals. Sex distribution is also variable. Men are more affected in some countries, while this is not the case in the western world. Less than 1% of men below the age of 30 have leukoplakia. The male-to-female ratio is reported to be about 3:1 to 6:1. Leukoplakia can be either solitary or multiple. Leukoplakia may appear on any site of the oral cavity, the most common sites being: buccal mucosa, alveolar mucosa, floor of the mouth, lateral border of tongue, lips and palate, however the lesions in the floor of the mouth, lateral border of the tongue and lower lip are most likely to show dysplastic or malignant changes. By far the most affected oral sites are the commissures (Figure 7) and the buccal mucosa (Figure 8) showing 60–90% of the leukoplakia. Next are the lip (3.7%), the alveolar ridge (3.0%) (Figure 9), the tongue (1.4%), floor of the mouth (1.3%), vestibular mucosa (1.1%) (Figure 10) and the palate (0.9%).

Homogeneous leukoplakia on the buccal mucosa. Courtesy: Dr Ashok

4.

Early or thin leukoplakia appears as a slightly elevated grayish-white plaque that may be either well defined or may gradually blend into the surrounding normal mucosa (Figure 11). As the lesion progresses, it becomes thicker and whiter, sometimes developing a leathery appearance with surface fissures. Some leukoplakias develop surface irregularities and are referred to as granular or nodular leukoplakias. Other lesions develop a papillary surface and are known as verrucous or verruciform leukoplakia.

Clinical forms of leukoplakia Classically two clinical types of leukoplakia are recognized: homogeneous and non-homogeneous, which can co-exist.


Figure 9

Homogeneous leukoplakia on the alveolar ridge and buccal mucosa. Courtesy: Dr Ashok

Figure 11

Early or thin leukoplakia on the buccal mucosa. Courtesy: Dr Ashok

Figure 10 Figure 12

Keratotic white patch in the labial vestibule due to placement of tobacco (tobacco pouch keratosis). Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Homogeneous leukoplakia is defined as a predominantly white lesion of uniform flat and thin appearance that may exhibit shallow cracks and that has a smooth, wrinkled or corrugated surface with a consistent texture throughout (Figure 12). This type is usually asymptomatic. Non-homogeneous leukoplakia has been defined as a predominant white or white-and-red lesion (erythroleukoplakia) (Figure 13) that may be either irregularly flat, nodular (speckled leukoplakia) or exophytic (exophytic or verrucous leukoplakia). These types of leukoplakia are often associated with mild complaints of localized pain

Homogeneous leukoplakia on the dorsum of the tongue. Courtesy: Dr Sumanth

or discomfort. Proliferative verrucous leukoplakia is an aggressive type of leukoplakia that almost invariably develops into malignancy. This type is characterized by widespread and multifocal appearance, often in patients without known risk factors. In general, non-homogeneous leukoplakia has a higher malignant transformation risk, but oral carcinoma can develop from any leukoplakia. 141


Figure 13

Erythroleukoplakia on the buccal mucosa. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Malignant transformation White lesion in the oral cavity were thought to be precancerous as early as 1870 by Paget, who gave them such appellations as ichthyosis, smoker’s patch and leukokeratosis. Leukoplakia is an example for precancerous lesion. The frequency of dysplastic or malignant alterations in oral leukoplakia has ranged from 15.6 to 39.2% in several studies. Although leukoplakia is more common in men than women, several studies have shown that women with leukoplakia have a higher risk of developing carcinoma. A wide range of rates for the malignant transformation of leukoplakia has been reported from 0.13 to 19.8% but it is estimated that the annual transformation rate should not exceed 1%. Up to 10% of leukoplakia may be malignant at the time of initial examination. The potential for malignancy appears higher in certain risk sites like floor of the mouth and ventral surface of the tongue, where the lesion is associated with Candida species, or where the lesion is verrucous or mixed with red lesions (erythroleukoplakia or speckled leukoplakia). Cawson (1966), Einhorn and Wersall (1967) and Banoczy (1977) inferred that certain features of leukoplakia have been reported to be associated with an increased risk of malignant transformation. These are: ❍ ❍ ❍ ❍ 142

Gender, particularly women seems to be at risk Long duration of the leukoplakia Leukoplakia in non-smokers (idiopathic leukoplakia) Location in the floor of the mouth and or on the tongue

❍ ❍ ❍

Non-homogeneous type of OL Presence of Candida albicans Presence of epithelial dysplasia.

Longitudinal studies of the rate of malignant transformation in leukoplakia were first reported by Sugar and Banoczy (1959) in Hungary. In a study conducted by Gupta et al, 12,212 tobacco users were followed up annually to assess the malignant potential of precancerous lesions in Ernakulam district in Kerala, India. They observed that out of a total of 19 new oral cancers over period of 8 years, 15 (79%) originated from leukoplakia. The location of oral leukoplakia has a significant correlation with the frequency of finding dysplastic or malignant changes at biopsy. In the study by Waldron and Shafer (1975), the floor of the mouth was the highest risk site, with 42.9% of leukoplakias showing some degree of epithelial dysplasia, carcinoma in situ, or unsuspected invasive squamous cell carcinoma. The tongue and lips were also identified as high risk sites, with dysplasia or carcinoma present in 24.2% and 24% respectively. The study by Silverman and colleagues (1984) showed an overall malignant transformation of 17.5%. In their study only 6.5% of homogeneous leukoplakia underwent malignant change, however, 23.4% of speckled leukoplakia and 36.4% of leukoplakias with microscopic evidence of dysplastic changes transferred into cancer. Among the different clinical varieties of leukoplakias, proliferative verrucous leukoplakia has got highest risk of malignancy. In a follow-up study of 54 cases of proliferative verrucous leukoplakia, Silverman and Gorsky found that 70.3% of the patients subsequently developed squamous cell carcinoma. Holmstrup and Besserman (1983) and Silverman (1990) inferred that proper use of antifungal therapy might result in a shift from high risk nodular or speckled leukoplakia to low risk homogeneous leukoplakia. Hernandez et al (2003) have suggested that in patients who display oral premalignant conditions like leukoplakia, immunosuppression must be considered as an important risk factor for oral cancer. Investigations Although an experienced oral physician may be able to diagnose and manage majority of the leukoplakias, it is always prudent to follow a systematic investigative protocol to diagnose leukoplakia. The investigative procedures includes the following: ❍

Toluidine blue staining: Toluidine blue clinically stains malignant lesions, but not normal mucosa. In vivo, the dye may be taken up by the nuclei of malignant cells manifesting increased DNA synthesis. Toluidine blue also serves as a guide to biopsy by localizing tumor cells within the area of the lesion. Toluidine blue


Figure 14

Figure 15

Hyperorthokeratosis and basal cell hyperplasia in leukoplakia. Courtesy: Department of Oral Pathology, MCODS, Mangalore Toluidine blue stained leukoplakic lesion on the gingiva and buccal vestibule. Courtesy: Dr Ashok

❍

staining uses a 1% aqueous solution of the dye that is decolorized with 1% acetic acid. The dye binds to dysplastic and malignant epithelial cells with a high degree of accuracy (Figure 14). ❍ Cytobrush technique: This technique is more accurate than any other cytologic technique used in the oral cavity. The cytobrush technique uses a brush with firm bristles that obtains individual cells from the full thickness of the epithelium. These two techniques are adjuncts and not substitutes for an incisional biopsy. ❍

Biopsy: When a suspicious lesion is identified, an incisional biopsy using a scalpel or a biopsy forceps is recommended. When the lesion is very small excisional biopsy is performed as an investigative procedure and as a treatment modality. ❍ In homogeneous leukoplakia, the value of histological examination to some extent is questioned. The occurrence of epithelial dysplasia is rather low in this type as is the risk of future malignant transformation. However, even the experienced clinician will occasionally be surprised by the histopathological findings of a clinically innocent looking homogeneous leukoplakia. Therefore a biopsy should be performed in homogeneous leukoplakia. In non-homogeneous leukoplakia, i.e. usually symptomatic, epithelial dysplasia or even carcinoma in situ or early squamous cell carcinoma is rather common. The biopsy should be taken at the site of symptoms, if present, and or a site of redness or induration. Biopsies of exophytic, verrucous or papillary lesions should be taken deep enough to include a sufficient amount of underlying connective tissue, and preferably from the margins.

This lesion represents various degrees of epithelial dysplasias. Some lesions exhibit carcinoma in situ with top to bottom basilar hyperplasia, loss of polarity, increased mitosis, hyperchromatism, dyskaryosis and alteration in nuclear cytoplasmic ratio without any evidence of thickening of epithelial layer or without any evidence of disturbance of keratinization process (Figure 15). ❍ The frequency of epithelial dysplasia in leukoplakia varies between less than 1% and more than 30%. The presence of epithelial dysplasia is generally accepted as one of the most important predictors of malignant development in premalignant lesions. ❍ Markers of proliferation in leukoplakia: There are markers for determining future cancer development in oral premalignant lesions. These markers are divided into genomic markers and differentiation markers. The genomic markers include DNA aneuploidy, loss of heterozygosity and changes in expression of oncogenes and tumor suppressor genes (p53), whereas the proliferative markers include keratins and carbohydrate antigens.

Differential diagnosis The keratotic lesions that could be considered in the differential diagnosis of homogeneous leukoplakia includes: ❍ ❍ ❍

Chronic hyperplastic candidiasis Reticular lichen planus White sponge nevus.

Treatment (Flowchart 1) General considerations As a standard rule all possible agents leading to white keratotic lesions should be eliminated such as sharp teeth, candidal infection, etc. so as to rule out other definable lesions. In persisting lesions or in the absence of possible causative factors, a biopsy should be taken to 143


Flowchart 1 Leukoplakia Topical antifungal agents – Candid cream (clotrimazole), thrice/day for a week

No response

Reduction in size

Less than 1 cm

More Morethan thanor or equal equal to to 11cm cm

Excisional biopsy

Incisional biopsy

Dysplasia present

Total Totalexcision excisionof ofthe the lesion lesionwith withgraft graft

Follow Followup uponce oncein in 66months monthsfor for33years years

Continue Continuethe thetopical topical antifungal antifungalagent agentfor for 11month month

Dysplasia absent

IfIfexcision excisionisisnot notpossible possible–– A. Capsules of of lycopene lycopene 44 mg A. Capsules mg b.i.d. bid or 8 mg 3 months 8ormg ODo.d. for for 3 months B. Capsules antioxidants of antioxidants with B. Capsules with selenium bid b.i.d. 6 months selenium forfor 6 months C. Topical bleomycin bleomycin 1% 1% w/v w/v thrice thrice C. Topical a day days day forfor 1515 days

Retinol –A Retinol–A (VitaminAAanalogue) analog) (Vitamin ointment ointmentapplication application b.i.d./1 b.i.d./1month month

Note: All available medications have been enlisted. However, the physician should choose the appropriate mode of treatment/drug based on the clinical situation

Management of leukoplakia

exclude histologically the presence of a definable lesion and to establish the degree of epithelial dysplasia, if present or even the presence of carcinoma or carcinoma in situ. Up to 60% of leukoplakias regress or totally disappear if tobacco use is stopped. OL induced by smokeless tobacco may resolve if the habit is stopped. Some candidal leukoplakias respond, at least partially to antifungal drugs (smoking should also be stopped) and dysplasia may regress. Medical management of oral leukoplakia Chemoprevention Chemoprevention is the interventional use of chemical agents such as minor dietary constituents and pharmaceuticals to halt or slow the carcinogenic process before invasion. These include natural or synthetic compounds, micronutrients or non-nutrients. 1. Carotinoids and retinoids (-carotine, Vitamin E, selenium, canthaxanthin, astaxanthin, phytoene and spirulina-dunaliella) 144

Some carotinoids have antioxidant or anticarcinogenic activities and can block genotoxic activity of oral carcinogens. Retinoids are the synthetic and natural analogs of vitamin A. There are naturally occurring retinoid, including retinol, retinal, retinoic acid and their metabolites. Beta-carotene is a natural precursor of vitamin A. More recently etretinate 13-cis retinoic acid and other retinoid have been successfully used for the treatment of oral leukoplakia. Exactly how retinoids may act to inhibit carcinogenesis is unclear, although some retinoids may enhance anti-tumor immune responses. Retinoids have a pronounced and essential effect on cell differentiation. Retinoids may have an effect by their interaction with growth control mechanisms such as transforming growth factors and also possibly by acting on tumor suppressors either directly or via an interaction with transforming growth factors. Retinoids may inhibit the transformation mediated by papillomaviruses. Oral leukoplakias have


been treated with a range of retinoids and carotinoids. Leukoplakias have been successfully treated with systemic 13-cis retinoic acid. Mulay and Urbach (1958) was the first to use vitamin A therapy for topical therapy of oral leukoplakia. Smith (1962) administered 75,000–300,000 IU of vitamin A daily for a period of 3–18 months. Seventy two percent of hyperkeratosis lesions, 25% of massively keratotic and ulcerative forms of leukoplakia improved but the dyskeratotic forms were unresponsive. However signs of hypervitaminosis were not observed. Silverman et al (1965) reported that short-term large dose treatment with vitamin A (300,000–900,000 IU daily) leads to the improvement of leukoplakia. 2. 13-cis retinoic acid 13-cis retinoic acid (CRA) at 1.5 mg/kg per day for 3 months followed by 0.5 mg/kg daily for 9 months resulted in an initial 55% beneficial response followed by maintenance of effect in 92% of cases. Kaugars and Silverman (1995) in a study of 10 patients with leukoplakia using 50 mg of 13-CRA per day for 3 months showed a 50% reduction in the clinical size of the lesions in three patients. Treatment of three patients was discontinued because of elevated serum triglyceride levels or headache. 3. Beta-carotene Many authors have proposed that beta-carotene supplementation can be used for the treatment of leukoplakia with minimal side effects. Beta-carotene alone in a dose of 30 mg daily for 3–6 months also produced a 71% response rate in 24 patients with oral leukoplakias, with no significant toxicity (Garewall et al, 1991). The same workers have used beta-carotene 60 mg daily for 6 months and report similar benefit (Garewall et al, 1992). Others have found beta-carotene 90 mg daily to produce benefit in 44% after three cycles of use of 3 months each. 4. Fenretinide (n-4-hydroxy phenyl retinamide) Fenretinide (synthetic retinoid) 200 mg daily used for 1 year reduced the relapses and appearance of new oral leukoplakias, compared with controls, with few adverse effects in 39 patients having previously had leukoplakias surgically excised. 5. Vitamin E Vitamin E has synergistic inhibitory activity against carcinogenesis in animal models and may have some beneficial effect in man. Many studies, using vitamin E in oral leukoplakias showed a beneficial clinical response in 46% of 43 patients by 24 weeks, and a histological response with no serious adverse effects. Another study showed a significant decrease in oral leukoplakia after combined treatment with vitamin E, retinol and -carotene (Zaridze et al, 1993). Vitamin E therefore shows promise in the control of leukoplakias. Photodynamic therapy of oral leukoplakia A combined parenteral and locally applied treatment modality in the

form of photodynamic therapy (PDT) using hematoporphyrins has been found to be effective in animal models and has been used to treat head and neck cancers and premalignant lesions in man. PDT was first used in 1990, when acridine and light were combined to kill paramecia and the first oncologic use of PDT was in 1903, when eosin and light were employed in the treatment of skin cancer. PDT involves using specific wavelength of laser light to activate a photosensitizing drug which is administered systemically and is retained selectively in the lesion and this triggers a cold photochemical reaction resulting in the generation of reactive products such as singlet oxygen that damages tissue. Advantages of this type of treatment as reported by Sciubba (1995) includes inactivation of clinically subtle or undetectable alteration, sparing of normal tissue, minimal morbidity and its use as an adjunctive tool to more traditional modalities. However it was pointed out that the major disadvantage of PDT is the cutaneous photosensitivity which can persist for several months after administration of the photosensitizer which can be a major problem in the Indian subcontinent, where oral cancer is most common. Topical chemotherapy of oral leukoplakia Topical treatment of leukoplakia with podophyllin solution (Kovacs et al, 1962) or bleomycin (Hammersley et al, 1985; Malmstrom, 1988; Wong et al, 1989) has induced some regression or even total resolution of dysplasia and of clinical lesions. Hayasaki et al (1977) described the use of bleomycin with iontophoresis in the treatment of cancer, leukoplakia and papillomas of the head and neck region. Their results showed that this method of application was not effective for malignant lesions but was effective at removing leukoplakia of the oral mucosa. Newer treatments Gene therapy Patients with head and neck cancer including oral cancer are more susceptible to chromosome damage when their cells are exposed to mutagens (Schantz et al, 1990) and there are a number of genetic changes now described in oral carcinoma (Scully et al, 1993). Synthetic antisense oligonucleotides complementary to the start codons of human papilloma virus (HPV) type 18 E6 and E7 genes can significantly inhibit growth in vitro of oral carcinoma cell lines (Steele et al, 1992, 1993). Even though laboratory and animal data for the use of gene therapy is very incomplete, many investigators have begun clinical trials in human patients. Tests of several types of gene therapy have begun in various types of cancer, and for oral cancer; the trials include the testing of recombinant p53, the expression of suicide genes and the use of conditionally competent adenoviruses. Since the scientific basis for these trials is rather weak, it can hardly be expected that impressive results are imminent. There are as yet no trials in oral potentially malignant lesions 145


aimed at correcting genetic changes or enhancing the immune response by gene therapy; indeed the whole field of gene therapy has been publicly criticized for its rush to clinical experiments, when the basic studies are still incomplete. Other alternative modalities of treatment Green tea Tea, the dried leaves of the plant ‘Camellia sinensis’ is a popular beverage consumed worldwide. The pharmacological actions of green tea includes; antiinflammatory action, antioxidant action and anticancer action. Tea acts as an inhibitor of initiation of carcinogenesis in the following ways: ❍

Tea polyphenols are effective in reducing the accumulation of free radicals by inducing the production of superoxide dismutase (SOD), a free radical scavenger (Das et al, 2002). ❍ Tea inhibits formation of mutagens in a dose dependaet manner (Weisburger et al, 2002) and reduces lipid peroxidation (Fadhel et al, 2002). ❍ In UV induced responses, epigallocatechin gallate (EGCG) prevents the formation of UVB induced cyclobutane pyrimidine dimers (Katiyar et al, 1999). ❍ EGCG is also a strong inducer of the detoxifying enzyme glutathione-s-transferase. These reports strongly point toward antimutagenic activity of green tea. The gallated flavonoids (especially gallated EGCG and the aflavins) act Khafif et al (1998) reported that green tea extract has been shown to have a chemopreventive or inhibitory role in the treatment of oral leukoplakia. Li et al (1999) conducted a double blind, placebo-controlled trial in 59 patients with oral leukoplakia, and found that oral and topical administration with a black and green tea mixture resulted in a partial regression of the lesion in 37.9% of the treated patients compared to placebo control. The treatment reduced cell proliferation and the rate of chromosome aberration in peripheral blood lymphocytes. Weisburger et al (1999) have proposed that catechins, in particular EGCG are believed to be responsible for the chemopreventive effects of green tea, which act by antioxidant and free radical scavenging activity. Oral lycopene Oral lycopene in the dose of 8 mg/day is beneficial in the treatment of oral leukoplakia. Surgical line of treatment If the lesion is very small, it should be excised as a part of investigation and as a treatment option. Any leukoplakia could transform into a carcinoma, even those which did not show epithelial dysplasia initially (or in which dysplasia happened to be absent from the biopsy taken). The main problem is that the malignant transformation cannot be reliably predicted yet. Regular check-up of these patients is essential both in treated and untreated patients. 146

Lichen Planus The word lichen planus is derived from the Greek literature; lichen meaning ‘tree moss’ and planus refers to ‘flat’. In 1869 Erasmus Wilson, a dermatologist first reported the condition. Oral lesions of lichen planus were first described by Thiebergie. Wickham (1895) described the characteristic appearance of whitish striae and punctuations that develop atop the flat-surfaced papules. Definitions Oral lichen planus (OLP) is a common chronic immunological inflammatory mucocutaneous disorder that varies in appearance from keratotic (reticular or plaque like) to erythematous and ulcerative. Eisen (2005) defined OLP as a relatively common chronic inflammatory disorder affecting the stratified squamous epithelia. It is a skin disease common with in the oral cavity, where it appears as either white reticular, plaque, or erosive lesions with a prominent T-lymphocyte response in the immediate underlying connective tissue. Etiopathogenesis In spite of extensive research, exact etiology is still unknown. The most accepted and current data suggest that OLP is T cell mediated disorder in which there is production of cytokines which leads to apoptosis. Autocytotoxic CD8 and T cells trigger apoptosis of oral epithelial cells (Eversole, 1997; Porter et al, 1997). The immune system is triggered due to the interactions among genetic, environmental, and lifestyle factors. Other possible theories include the genetic background, where the weak association between HLA antigen and lichen planus was found by Powell et al (1986) and Roston (1994). Dental materials and infectious agents like Gram negative aerobic bacillus, spirochetes and increased prevalence of Candida species were suggested by Simon and Hornstein (1980). Vincent et al (1990), Soto Araya et al (2004) reported the strong association of psychological factors like higher level of anxiety, greater depression, and psychic disorders in patients with erosive lichen planus. Clinical features Lichen planus commonly affects 1–2% of the general population, prevalence rate being 0.1–4%. Forty percent lesions occur on both oral and cutaneous surfaces, 35% occur on cutaneous surfaces alone, and 25% occur on oral mucosa alone. Lichen planus commonly affects the adults. However it has also been observed in children as recently reported by Sharma (1999). The age range usually varies from 40 to 70 years.


Figure 16 A

B

Violaceous papular lesions of cutaneous lichen planus on the upper and lower extremity. Courtesy: Dr Ashok

There is definite female predilection with ratio of 2:1. The characteristic manifestation of oral lichen planus is the appearance of white papules that usually coalesce forming a network of lines that may intersect or crisscross each other forming various patterns. Louis Frederic Wickham described the presense of fine, white or gray lines or dots seen on the top of the pruritic papular rash on the skin in lichen planus. These striae are popularly referred to as Wickham’s striae. Skin involvement in lichen planus Skin lesions are characteristically itchy and violaceous to brown papules, very frequently distributed over the flexor aspect of the wrist or ankles, extensor aspect of the lower legs, skin of the lower central back and natal clefts (Figure 16A, B). Scalp involvement results in loss of hair (alopecia) which is referred to as lichen planopilaris. Longitudinal ridging and grooves are seen over the nail (onychorrhexis). Other changes seen in the nail includes distal splitting (onychoschizia), separation of the nail plate from nail bed (oncycholysis), permanent damaged nail matrix (pterygium) and finally permanent nail loss (anonychia). Koebner’s phenomenon is the appearance of the lesions at the site of micro trauma and is well demonstrated in case of skin involvement as well demonstrated in the oral lesions. Hence any mechanical trauma or irritation such as sharp filling margins or rough surfaces or ill-fitting dentures should be evaluated and eliminated. Oral manifestations The basic lesion of OLP is papule arranged in the linear or annular forms and crisscrossing each other forming various patterns like annular and reticular forms.

Andreasen (1968) divided OLP into six types, namely, reticular, papular, plaque like, erosive, atrophic and bullous type. Oral lesions may manifest in one of the following basic clinical forms; hypertrophic (plaque like, papular, reticular), erythematous (atrophic, erosive) and bullous. Reticular form is the most common type. It appears as a series of fine, radiant, white striae known as Wickham striae which may be surrounded by a discrete erythematous border. The most common site of involvement is the posterior buccal mucosa, tongue and gingiva (Figure 17A–D). Plaque-like lesions resemble leukoplakia and occur as homogeneous white patches. In 1892 Kaposi first described a distinctive clinical variant of the disease with blisters, which was termed lichen ruber pemphigoides or bullous lichen planus. This form is rarer than other forms of oral lichen planus. It appears as a small bullae or vesicle that tends to rupture easily. The bulla or vesicle range from few millimeter to several centimeters in size. Erosive lichen planus is the second most common type (Figure 18). Erosions are often extensive, irregular and affect the lingual and buccal mucosa and are often associated with white lesions. Gingival involvement in erosive lichen planus produces desquamative gingivitis (Figure 19), which has greater potential for malignant transformation. Occasionally diffuse melanosis may be seen along with erosive type of lichen planus, which is referred to as pigmented lichen planus. The lesion presents as reticular white lesions (may or may not be associated with erosive areas) surrounded by brownish to grayish black pigmentation (Figure 20A, B). It is believed that the T lymphocytes infiltrate into the basal layers and cause basal cell degeneration thereby stimulating melanogenesis. Histopathological evaluation of pigmented lichen planus shows basilar melanosis and melanin incontinence. 147


Figure 17 A

B

C

D

(A) Reticular lichen planus on the buccal mucosa. (B) Reticular lichen planus on the buccal mucosa. (C) Lichen planus on the palate. (D) Reticular lichen planus on the labial mucosa of the upper lip. Courtesy: Dr Ashok

Atrophic lichen planus presents as diffuse red patches usually surrounded by white striae. Such striae that radiate peripherally are usually evident at the margins of atrophic zones of the lesion (Figure 21A, B). Reticular forms are usually asymptomatic and rarely require treatment whereas erosive and atrophic forms are frequently associated with severe discomfort and burning sensation. It is an absolute necessity to evaluate periodically for malignant transformation.

Figure 18

Association of oral lichen planus with systemic illness Carrozzo et al (2003), Arrieta et al (2000) and Jubert et al (1994) found the frequent association of hepatitis C virus and OLP, and suggested that HCV occasionally replicates in OLP tissue contributing to the pathogenesis of mucosal damage. Lichen planus is often associated with immune mediated diseases like alopecia areata, dermatomyositis, 148

Erosive lichen planus affecting the tongue. Courtesy: Dr Sumanth


Figure 19

Figure 20 A

Desquamative gingivitis in erosive lichen planus. Courtesy: Dr Ashok

B

lichen sclerosis et atrophicus, morphea, myasthenia gravis, ulcerative colitis and primary biliary sclerosis. Syndromes associated with OLP Grinspan syndrome is the association of OLP with diabetes mellitus and hypertension. Graham-Little syndrome and vulvovaginogingival syndrome are other syndromes associated with OLP, in which there is mucosal involvement of gingival and genital region, usually of erosive type. Differential diagnosis Differential diagnosis of reticular/annular type of OLP includes lichenoid drug reaction, electrogalvanic white lesions and frictional keratosis and leukoplakia. Keratotic forms of lichen planus can be differentiated from leukoplakic plaque as the former is usually associated with burning sensation and association with etiologic factors in the latter. Hypertrophic form also resembles hyperplastic candidiasis. Erosive lichen planus resembles lupus erythematosus. Oral lichenoid reactions are identical clinically and histologically with OLP but have an identifiable etiology like drugs and dental restorative materials including amalgams, composite resins, cobalt and gold have been implicated as the causes of lichenoid reactions. Even flavoring agents and plastics can be important in the pathogenesis and management with oral lichenoid reaction. Patch test may be of help but lacks sensitivity and specificity. Erosive lichen planus has to be differentiated from lichenoid reaction, graft-versus-host disease, discoid lupus erythematosus and speckled leukoplakia. Desquamative gingivitis of gingival erosive lichen planus should be

(A) Brown colored pigmentation on the buccal mucosa in pigmented lichen planus. Courtesy: Dr Ashok. (B) Grayish black pigmentation on the buccal mucosa bounded by reticular lichen planus. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

differentiated from other forms like pemphigus, pemphigoid and linear IgA disease. Erythematous lesions of OLP can be excluded from atrophic candidiasis by the presence of whitish striations at the periphery. Investigations Diagnosis is generally achieved by the characteristic clinical presentation and the complete history and the extraoral manifestations. Sometimes biopsy may be complementary. Gingival lichen planus is often difficult to diagnose and 149


Figure 21 A

B

(A) Diffuse red patches surrounded by white striae in atrophic lichen planus involving the buccal mucosa. (B) Diffuse erythematous areas in atrophic lichen planus involving the tongue. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 22

(Max-Joseph space) and, rarely, clinical blistering of the oral mucosa (bullous lichen planus). Immunofluorescence of perilesional mucosa shows the fibrin and shaggy fibrinogen in a linear pattern at the basement membrane zone and cytoids in the absence of deposition of fibrinogen. Malignant potential of OLP First report of a gingival cancer diagnosed in patient with OLP was in 1910 by Hallapeau. The most important complication of OLP is the development of oral squamous cell carcinoma from the non-keratotic forms. The reported frequency of malignant transformation varies greatly, between 0.4 and over 5%, over periods of observation from 0.5 to over 20 years.

Saw tooth rete pegs and subepithelial band of chronic inflammatory cells, characteristic of lichen planus. Courtesy: Department of Oral Pathology. MCODS, Mangalore

direct immunofluorescent studies are confirmatory as they demonstrate presence of autoantibodies. Histopathological features include the essential features like superficial band-like infiltrate of T lymphocytes, basal cell liquefaction, degeneration and epithelial maturation pattern being normal (Figure 22). Additional features include jagged (saw-tooth) and spindly rete ridges, colloid (Civatte, hyaline, cytoid) bodies, and separation of epithelium from the lamina propria. Degeneration of basal keratinocytes and disruption of the epithelial basement membrane and basal keratinocyte anchoring elements in OLP produce weaknesses at the epithelial-connective tissue interface which may result in histological cleft formation 150

Prognosis Cutaneous lesions are self-limiting and pigmentation may fade after few years or remain permanent. Complete remission occurs in 70% of cases after 1 year. Oral lesions are chronic, rarely undergo spontaneous remission, furthermore, erosive oral lesions are difficult to palliate. The spontaneous remission of OLP is much less than 5% of patients over 7.5 years follow up. The reticular form of LP has best prognosis because spontaneous remission occurs in 40% of cases. The erosive form of the lesion can persist for 15–20 years. Management (Flowchart 2) Treatment should be considered after the evaluation of clinical type, associated symptoms, and age. Reticular lesions are asymptomatic and require no therapy but only


Flowchart 2 Oral lichen planus

Symptomatic

Topical antifungal therapy with clotrimazole 1% (Candid) cream t.i.d./day for a week

Relief in symptoms Asymptomatic

No relief in symptoms

Regular follow-up once in 3 months

New cases

Recalcitrant cases

Intralesional steroids: Injection triamcinolone 0.5 ml (Amcort) with once/week for 4 weeks

Topical corticosteroids (increasing order of potency) 1. Triamcinolone acetonide 0.1% (Tess gel, Ledercort ointment) t.i.d./day until symptoms improve (maximum of 1 month) 2. Fluocinolone acetonide 0.025% (Fluzone cream) t.i.d./day for 2 months with tapering dose 3. Clobetasone propionate 0.05% (Clobetol cream, Cosvate gel) b.i.d./day for 2 months 4. Clobetasone 17-butyrate (Eumosone) 0.05% b.i.d./day for 1st month, o.d. for 2nd month 5. Mometasone furoate 0.1% (Mosone cream)

Immunomodulation: chloroquine (Lariago, Laquin) 250 mg b.i.d. for 3 months

Immunosuppression: Azathioprine (Imuzat, Azoran) 1 mg/kg/day (50 – 100 mg) for one month. Dosage can be increased up to 2 mg/kg/day and should not be given more than 3 months

No relief in symptoms Combination therapy (systemic + topical) 1. Tab prednisolone 10 mg (Wysolone, Emsolone) t.i.d. for 2 weeks; 10 mg b.i.d. for 1 week; 10 mg o.d. for 1 week; 5 mg o.d. for 1 week & 5 mg once in 2 days (thrice) 2. Topical triamcinolone acetonide 0.1% (Tess gel) t.i.d./day till symptoms improve or cyclosporine solution (Sandimmune) as mouthrinse twice/day for 15 days

PUVA therapy (Psoralen ultraviolet A rays)

Newer drugs like mycophenolite mofetil 500 mg (Cellmune), tacrolimus, sirolimus, pimecrolimus can be tried (longterm side effects not studied)

Note: All available medications have been enlisted. however, the physician should choose the appropriate mode of treatment/drug based on the clinical situations

Management of oral lichen planus

observation for changes. In general, all treatment should be aimed at eliminating atrophic and ulcerative lesions, associated symptoms, and minimize the risk of malignant transformation. All precipitating factors like mechanical irritants (sharp fillings, metallic restorations, ill-fitting dentures) should

be eliminated. As gingival lesions may exacerbate with the local factors due to Koebner’s phenomenon, an optimal atraumatic oral hygiene program should be instituted. The most commonly employed and useful agents are topical corticosteroids and lack of their adherence to mucosa has made preferable to use rinses. 151


Topical corticosteroids reduce pain and inflammation. Triamcinolone acetonide 0.1% in Orabase, oral suspension of triamcinolone, high potency steroid mouthwashes like betamethasone valerate 0.1%, fluocinolone acetonide 0.1%, clobetasol propionate 0.05% have been used effectively. Systemic corticosteroids should be reserved for recalcitrant erosive or erythematous lichen planus, where the topical approaches have failed or wide spread involvement of skin, genital, esophageal or scalp involvement. Daily dosages of 40–80 mg of prednisolone can be used for brief period of time, i.e. 5–7 days and stopping abruptly or the dosage should be reduced by 5–10 mg per day gradually over a 2–4 week period. When using most potent steroids, the medication is not indicated for more than 15 days. For intractable erosive lesions intralesional injections of triamcinolone acetonide (10–20 mg/ml per vial) for every 2–4 weeks has been found effective, but results in severe pain. Hydrocortisone, methylprednisolone and dexamethasone can also be tried. One third of OLP patients who are treated with topical steroids develop secondary candidiasis, which necessitates treatment with antifungals. Immunosuppressive and immunomodulating agents Many immunosuppressive agents like cyclosporine 100 mg/ml may be used as mouthrinse or finger rub application using very low doses of cyclosporine 48 mg/day in adhesive base was found to be effective in suppressing T cell cytokine production. Treatment of OLP with immunomodulators like levamisole 150 mg per day for 3 days along with prednisolone has shown excellent response and long-term remission. Tacrolimus, a steroid free topical immunosuppressive agent approved for the treatment of atopic dermatitis is 10–100 times effective than cyclosporine. Topical tacrolimus 0.1% has shown resolution of erosive lesion in 14% of patients as observed by an independent study, but causes side effect of burning sensation. The US Food and Drug Administration recently issued a health advisory to inform healthcare providers and patients about a potential cancer risk from the use of tacrolimus. Topical retinoids like isotretinoin gel 0.1% that act by down regulation of fibroblast function has been found to be of little use when compared with topical steroids. Other treatment modalities Psoralens and long wave ultraviolet A (PUVA) therapy with 8-methoxy psoralen and photochemotherapy have shown excellent results. To avoid PUVA side effects photosensitizer with topical 0.01% trioxsalen can be used. But the side effects of therapy include oncogenic potential, nausea, vomiting, dizziness and headache. The psychological factor should also be considered. In highly 152

anxious and depressed patients psychotherapy should be considered. Surgery Excision, C02 laser, cryosurgery and photochemotherapy have been effective for persistent or dysplastic lesions. However surgery may lead to worsening OLP presumably via a Koebner phenomenon and reportedly causes a high rate of recurrence. Miscellaneous treatments Antibiotics like 2% aureomycin mouthwash, antimalarials like hydroxychloroquine sulfate, azathioprine, dapsone, interferons in the form of topical (human fibroblast interferon beta and human fibroblast interferon alpha) and systemic (IFN—3–10 million for 3 weeks) have been found effective but lack enough clinical trials. Thalidomide in the dosage of 100–150 mg per day has shown to be effective in resolution but not preferred due to serious side effects. As no therapy is curative and the goal for symptomatic patients is palliation. Relief can be achieved in the majority of patients with topical steroid alone or in combination with other immunomodulatory topical agents. Atrophic/ erosive forms of OLP have to be systematically and periodically reviewed for malignant transformation. Lichenoid drug reaction Lichenoid drug reactions and lichen planus exhibit similar clinical and histologic findings. Clinically they demonstrate erythematous erosions and ulcerations with focal areas of radiating lines. The lichenoid reactions are distinguished from lichen planus by two factors; the association with the administration of a drug, contact with a metal or foodstuff, or systemic disease, and their resolution when the offending agent is eliminated (Figure 23A, B). The increased prevalence of oral lichenoid drug reactions are perhaps because of increased use of newly introduced drugs and appearance of lesions similar to OLP and spontaneous remission after the withdrawal of the drug. Diagnosis depends upon establishing the relationship between the onset and the use of offending agent and resolution of the symptoms upon withdrawal of the offending agent A careful drug history is complementary to the diagnosis. Histology may be beneficial as lichenoid lesions may have a more diffuse lymphocytic infiltrate and contain eosinophils and plasma cells, and there may be more colloid bodies than in classical LP. Agents causing lichenoid reactions The most commonly used drugs that are implicated in lichenoid reactions include antiarthritics, antihypertensives, antimicrobials, antiparasitics, anxiolytics, non-steroidal


Figure 23 A

B

(A) Erythematous area on the buccal mucosa in relation to an amalgam restoration. (B) Lichenoid reaction on the buccal mucosa in relation to a tooth that was previously restored with silver amalgam restoration. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

anti-inflammatory drugs, oral hypoglycemic agents, uricosuric agents. Lichenoid reaction may develop after months or even years after taking the drug. Dental materials like amalgam compounds, cobalt, gold, acrylic and casting alloys have been known to cause lichenoid reaction. Some authors report that a low frequency of sensitization to mercury and no beneficial effects from the removal of silver amalgam fillings, whereas others suggest that sensitization to mercury is an important cause. In cases where patch test negative patients improve with amalgam, mercury may be acting as an irritant in the pathogenesis of oral lichenoid reaction. Patch testing and biopsies however cannot accurately predict the response to removal of amalgam fillings with those of other material. Betel quid lichenoid lesion A quid-induced lichenoid oral lesion has been reported among betel quid users. It resembles OLP but there are specific differences. It is characterized by the presence of fine, white, wavy parallel lines that do not overlap or crisscross, are non-elevated, and in some instances radiate from a central erythematous area. The lesion generally occurs at the site of placement of the quid. These lesions may regress with decrease in frequency, duration, or change in site of placement of the quid. There may be complete regression of the lesion when the habit is given up.

Candidiasis Candidiasis is a disease caused by infection with a yeast like fungus, Candida (Monilia) albicans, although other

species may also be involved, such as C. tropicalis, C. parapsilosis, C. stellatoidea, C. krusei, C. glabrata, C. pseutropicalis and C. guilliermondii. Candida albicans is a relatively common inhabitant of the oral cavity, gastrointestinal tract and vagina. Candidiasis is the most common opportunistic infection in the world. Up to 60% of healthy, nonhospitalized individuals may harbor this pathogen in the oropharyngeal region. The advent of HIV infection and AIDS has resulted in a resurgence of oral candida infections that are usually seen in very young, the very old, and the very sick. Its occurrence has increased remarkably since the prevalent use of antibiotics, which destroy the normal inhibitory bacterial flora, and immunosuppressive drugs, particularly corticosteroids and cytotoxic drugs. Oral candidiasis or thrush usually remain as a localized disease, but on occasion it may show extension to the pharynx or even to the lungs. The genus Candida is a collection of some 150 asporogenous yeast species. Because of their inability to form asexual stage, they are most often classified among the fungi imperfect in the class Deuteromycetes. C. albicans is a dimorphic fungus existing both in the blastospore phase and the hyphal or mycelial phase. C. albicans is the most dominant species, followed by C. tropicalis, C. glabrata, C. parapsilosis and C. krusei. Other Candida species and genera are rare and transient. Epidemiology Candida is commensal organism and part of the normal oral flora in about 30–50% of the population, and is capable of producing opportunistic infections within the oral cavity when appropriate predisposing factors exist. 153


Etiology and pathogenesis Candida is predominantly an opportunistic infectious agent, the role of candida as opportunistic invader versus etiologic agent in the patients with oral white lesions has not clearly been established. However the demonstration of the catalytic role of some candida strains in endogenous cellular nitrosamine production, the statistically significant association of certain strains with dysplastic red and white lesions, and the hyperplastic effects on epithelium of candida in vitro, indicate that candida may be a carcinogen or a promoting agent. The pathogenesis of different biotypes and strains of C. albicans varies. Candida albicans produces an enzyme called phospholipase; this enzyme is concentrated at the tips of the fungal hyphae and localized in the vicinity of host cellular compartments where active invasion is occurring. A relationship has been suggested between the adherence of C. albicans to surfaces and its ability to colonize and cause the disease. The adhesion of C. albicans to oral mucosal cells might be due to interaction involving divalent cations. The adsorption of macromolecules onto epithelial cells onto epithelial cells is believed to occur via electrostatic interactions involving calcium ions and other ionic groups. The extent and strength of the adhesion depends on the initial surface properties of both the organisms and substratum involved and can be influenced by several factors. Neville et al have identified three general factors that may lead to clinically evident oral candidiasis. These factors are: (i) the immune status of the host, (ii) the oral mucosal environment, and (iii) the particular strain of C. albicans (the hyphal form is usually associated with pathogenic infection). Oral candidiasis has been considered as the disease of the diseased. The following is a list of specific conditions that may predispose a patient to develop oral candidiasis: ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍

Factors that alter the immune status of the host Blood dyscrasias or advanced malignancy Old age/infancy Radiation therapy/chemotherapy HIV infection or other immunodeficiency disorders Endocrine abnormalities Diabetes mellitus Hypothyroidism or hypoparathyroidism Pregnancy Corticosteroid therapy/hypoadrenalism

Factors that alter the oral mucosal environment ❍ ❍ ❍ ❍ ❍ ❍ 154

Xerostomia Antibiotic therapy Poor oral or denture hygiene Malnutrition/gastrointestinal malabsorption Iron, folic acid, or vitamin deficiencies Acidic saliva/carbohydrate-rich diets

❍ ❍

Heavy smoking Oral epithelial dysplasia

Classification of Candidiasis (Greenberg and Glick, 2003) Pseudomembranous type Atrophic (erythematous)—antibiotic stomatitis Atrophic Denture sore mouth Angular cheilitis Median rhomboid glossitis Hypertrophic/hyperplastic Candida leukoplakia Papillary hyperplasia of palate Median rhomboid glossitis (nodular) Multifocal Syndrome associated Familial endocrine neoplasia syndrome Myositis (thymoma associated) Localized Generalized

Clinical presentation Acute pseudomembranous candidiasis Pseudomembranous candidiasis is the most common form of oral candidiasis. The most common sites include buccal mucosa, dorsal tongue and palate. It usually follows antibiotic therapy or immunosuppression. A burning sensation usually precedes the appearance of as soft, creamy white to yellow, elevated plaques, that are easily wiped off from the affected oral tissues and leave an erythematous, eroded, or ulcerated surface which may be tender (Figure 24). Thrush may be seen in neonates and among terminally ill patients, particularly in association with serious underlying conditions such as leukemia and other malignancies and in HIV disease. A possible complication of oropharyngeal thrush is the involvement of the adjacent mucosa, particularly those of the upper respiratory tract and the esophagus. The combination of oral and esophageal candidiasis is particularly prevalent in HIV infected patients. Any mucosal surface may be involved and erythematous or white areas often develop beneath the partial or complete dentures. The lesions may involve the entire oral mucosa or may relatively localized areas where normal cleansing is poor. A prodromal symptom of rapid onset of a bad taste and the loss of taste discrimination is described in adults. Differential diagnosis Differential diagnosis of thrush include food debris, habitual cheek biting, burns and rarely, a genetically determined epithelial abnormality like white sponge nevus. Chronic hyperplastic candidiasis (candida leukoplakia) Hyperplastic candidiasis is seen as chronic, discrete raised


Figure 24

White elevated plaques on the buccal mucosa and erythematous areas where the white patches were scraped off. Courtesy: Dr Ashok

Figure 25

Keratotic white plaques on the dorsum of the tongue in chronic hyperplastic candidiasis. Courtesy: Dr Ashok

lesions that vary from small, palpable translucent whitish areas to large, dense, opaque plaques, hard and rough to touch (Figure 25). The most common sites are the anterior buccal mucosa along the occlusal line, and laterodorsal surfaces of the tongue. The most common appearance is that of asymptomatic white plaques or papules (sometimes against an erythematous background) that are adherent and do not scrape off. Chronic atrophic (erythematous) candidiasis The most common site is the hard palate under a denture (Figure 26), but atrophic candidiasis may also be found on the dorsal

Figure 26

Erythematous velvety area on the palate in a denture wearer suggestive of atrophic candidiasis. Courtesy: Dr Ashok

tongue and other mucosal surfaces. The most common etiology is poor denture hygiene, and/or continuous denture insertion, but it may also be caused by immunosuppression, xerostomia, or antibiotic therapy. The most common appearance is that of a red patch or velvet textured plaque. When atrophic candidiasis occurs on the hard palate in association with a denture, it is frequently associated with papillary hyperplasia. Patient may complain of a burning sensation associated with this type of candidiasis; 15–65% of cases are usually associated with angular cheilitis. And lesions of chronic atrophic candidiasis have also been frequently reported in HIV-positive and AIDS patients. Three progressive clinical stages of denture sore mouth have been described in the literature. Median rhomboid glossitis Median rhomboid glossitis is a form of chronic atrophic candidiasis characterized by an asymptomatic, elongated, erythematous patch of atrophic mucosa of the posterior mid-dorsal surface of the tongue due to a chronic Candida infection (Figure 27). In the past, median rhomboid glossitis was thought to be a developmental defect resulting from a failure of the tuberculum impart to retract before fusion of the lateral processes of the tongue. A concurrent ‘kissing lesion’ of the palate is sometimes noted (Figure 28). Specific predisposing etiologic factor(s) for median rhomboid glossitis have not been clearly established. Angular cheilitis (perleche) Clinical appearance is that of red, eroded, fissured lesions which occur bilaterally in the commissures of the lips and are frequently irritating and painful (Figure 29). The most common etiology is loss of vertical occlusal dimension, but it may also be associated with immunosuppression. 155


Figure 27

A well defined erythematous area on the mid-dorsum of the tongue roughly rhomboidal in shape suggestive of median rhomboid glossitis. Courtesy: Dr Ashok

Figure 28

Figure 29

Erythematous fissures in the corners of the mouth bilaterally as seen in angular cheilitis. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

immune defects, in which there is persistent mucocutaneous candidiasis that responds poorly to topical antifungal therapy. The main types of this rare disorders include familial CMC, diffuse CMC, candidiasis endocrinopathy syndrome, candidiasis thymoma syndrome. Role of candida in oral carcinogenesis

Erythematous areas on the palate in an individual with candidal lesion on the dorsum of the tongue. Commonly referred to as ‘kissing lesion’. Courtesy: Dr Ashok

Chronic multifocal oral candidiasis This term has been given to chronic candidal infection that may be seen in multiple oral sites, with various combinations, including angular stomatitis, median rhomboid glossitis and palatal lesions. All these lesions will be having 1 month duration with no history of predisposing factors like systemic diseases, or patient’s receiving any drugs, or radiotherapy. These lesions are most commonly seen in chronic smokers in their 5th or 6th decade of life. Chronic mucocutaneous candidiasis (CMC) It is the term given to the group of rare syndromes, with a definable 156

Candidal leukoplakias may develop into carcinoma. It is unclear whether the yeast are involved in the development or transformation of leukoplakia. The Candida organisms present in the candidal leukoplakia have higher nitrosation potential than others, which might indicate a possible role of specific types in the transformation of some leukoplakias. The Candida species may be involved in carcinogenesis by elaborating nitrosamine compounds, which act either directly on the oral mucosa or interact with other chemical carcinogens to activate specified protooncogenes and thereby initiate oral carcinoma. Investigations for candidiasis The diagnosis of oral candidiasis is most frequently made on the basis of clinical appearance along with exfoliative cytology examination. Smear examination This involves the histologic examination of intraoral scrapings which have been smeared on microscope glass slides. A 10–20% potassium hydroxide preparation (KOH prep) can be used for immediate microscopic identification of yeast cell forms. Alternatively, the slide containing the cytologic smear can be sprayed with a cytologic fixative and stained using PAS (periodic acidSchiff) stain and other slide with Gram’s stain prior to microscopic examination. Yeast cell appears dark blue after Gram staining and red or purple in PAS staining.


Hematologic investigations Since oral candidiasis is associated frequently with predisposing factors such as nutritional deficiencies, blood dyscrasias or HIV infections, estimation of hemoglobin lymphocyte and white cell counts, blood sugar and serum ferritin are important. Biopsy A biopsy of affected tissue may be indicated, especially when candidiasis is suspected in conjunction with some concurrent pathology, such as candidal leukoplakia, epithelial dysplasia, squamous cell carcinoma, or lichen planus. The sections should be stained with PAS or Gridley’s or Gomori methenamine silver (GMS), because Candida species stain poorly by hematoxylin and eosin. Microbiology It is also possible to culture Candida using a Sabouraud’s dextrose agar, which is used as a primary culture medium to aid in the definitive identification of the fungal organism. To permit the distinction between different yeast species Pagano-Levin medium is useful. Imprint culture technique This technique uses a sterile plastic foam pad of known size (2.52.5 cm) dipped in Sabouraud’s broth and placed on the suspect mucosal surface for 60 seconds. Then the plastic foam is placed directly on Sabouraud’s or Pagano-Levin agar. Candida density at each site is determined by a Gallenkamp colony counter and expressed as colony-forming units (CFU) per mm2. Colony counts in excess of 30 CFU cm2 of mucosa in the dentate and 49 CFU cm2 in denture wearers suggested a candidal infection. Salivary culture technique This involves patients 2 ml of mixed unstimulated saliva into a sterile, universal container. The number of Candida expressed as CFU per mm of saliva is estimated by counting the resultant growth on Sabouraud’s agar. Oral rinse technique Here the patient is asked to rinse the mouth for 60 seconds with 10 ml of sterile phosphate buffered saline or sterile water. The oral rinse is centrifuged at 1,700 g for 10 minutes and the deposit resuspended in 1 ml of sterile PBS. The concentrated oral rinse is now inoculated on appropriate media to assess CFU per mm of rinse sample using a spiral plater prior to incubation. This technique has advantages over the imprint technique because it is simple to perform and it can be used for the quantitation of other organisms such as coliforms. Immunologic tests Immunity in oral candidiasis is predominantly cell mediated. Cell-mediated immunity to C. albicans antigens can be demonstrated in most human subjects both by the appearance of delayed skin hypersensitivity to candida antigens and by in vitro tests of cellular immunity such as inhibition of leukocyte migration or stimulation of lymphocyte transformation to candida antigens. As test of humoral immunity, the candida agglutinin test, the candida complement fixation test, the candida precipitin test, immunofluorescence, and ELISA test have

been used. Among these tests, ELISA is the standard and ideal test, which uses the purified cytoplasmic protein of C. albicans as antigen. The ELISA has been proven to be a sensitive, cheap, and quick method for the quantification of antibody titers and would undoubtedly be the laboratory method of choice. Rationale for treatment Topical versus systemic drugs Topical antifungals are usually the drug of choice for uncomplicated, localized candidiasis in patients with normal immune function. Systemic antifungals are usually indicated in cases of disseminated disease and/or in immunocompromised patients. Medication should be continued for at least 48 hours after the disappearance of clinical signs of candidiasis along with complete healing and the absence of mucosal erythema. Some sources recommend drug therapy should be continued for 10–14 days regardless of the disappearance of clinical signs of candidiasis. Suggested medications for the treatment of candidiasis (Flowchart 3) Topical antifungal medications Nystatin is the first specific antifungal agent effective in the treatment of candidiasis. Nystatin taken systemically may lead to occasional GI side effects such as nausea, vomiting and diarrhea. It can be used in rinse form, oral and vaginal tablets or creams. Nystatin oral suspension 100,000 units/ml; 300 ml: rinse with one teaspoonful (5 ml) for 2 minutes, use q.i.d. (after meals, and at bedtime) and spit out. Patient can be directed to rinse and swallow if there is pharyngeal involvement. Amphotericin B is produced by Streptomyces nidus. It has a broad spectrum of activity in humans and remains a cornerstone of therapy for systemic fungal infections. It is available as cream, lotion and ointment and as an intravenous solution. It is usually fungistatic but fungicidal in higher concentrations. Clotrimazole is the most potent topical agent in azole group of antifungals. It has got GI and neurological toxicity clotrimazole troches, 10 mg 70 troches; one troche dissolves in mouth five times per day for 14 days. Systemic antifungal medications include ketoconazole tablets, 200 mg 1 tab q.i.d. with a meal or orange juice for 14 days. Ketoconazole is the drug being used in the treatment of chronic mucocutaneous candidiasis and candidiasis in immunocompromised patients. Fluconazole tablets, 100 mg, 15 tablets; 2 tablets to start, then 1 tablet q.i.d. for 14 days, oral absorption of fluconazole is rapid and nearly complete within 2 hours. Itraconazole tablets, 100 mg, 1 tablet b.i.d. with a meal or orange juice for 14 days. This drug has a long half-life and fewer side effects than ketoconazole but is expensive. Its use is contraindicated in liver diseases. 157


Flowchart 3 Oral candidiasis

If such rectification is not possible (AIDS, diabetes)

Systemic candidiasis

Rectify the underlying systemic/local cause

Physician opinion sought

Topical route (denture stomatitis, angular cheilitis, median rhomboid glossitis)

Parenteral route

1. Clotrimazole 1% cream (Candid, Canesten) five times/day for 2 weeks 2. Clotrimazole 2% gel (Candid V) five times/day for 2 weeks 3. Clotrimazole 1% solution (Canesten) five times/day for 2 weeks 4. Nystatin 5 lakh unit tablets (Mycostatin) four times/day for 14 days – crush & mix with water & use as mouthrinse & swallow 5. Hamycin 2 lakh unit/ml (Hamycin suspension) 2–3 times/day as mouthrinse for 7–10 days 6. Fluconazole dispersible tablet (Nuforce) with water – to use as mouthrinse 3 times/day for 14 days

Oral route (pseudomembranous, hyperplastic, acute atrophic)

1. Fluconazole 150 mg (Flucole, Candizole) b.i.d. for 14 days 2. Fluconazole 200 mg (Nuforce, Onecan) b.i.d. for 14 days 3. Ketoconazole 200 mg (Ketozole, Fungicide) o.d. for 1–4 weeks 4. Itraconazole 100 mg (Candistat) o.d. for 14 days

Amphotericin B IV infusions 0.3 mg/kg (Fungisome – 10 mg, 25 mg, 50 mg) can be infused over 4–8 hrs


Management of candidiasis

158

All the azole group of drugs are fungistatic, and not fungicidal. This is an important consideration when treating the chronically immunosuppressed, such as those with HIV and patients with candidal meningitis.

Nystatin–triamcinolone acetonide ointment or clotrimazole cream 1% or miconazole cream 2% or ketoconazole cream 2% can be applied to affected areas q.i.d. (after meals, and at bedtime) for 14 days.

Treatment for chronic atropic candidiasis Application of a thin coat of medicines like nystatin ointment or clotrimazole cream 1% or miconazole cream 2%, ketoconazole cream 2% to entire inner surface of denture after each meal for 14 days usually results in remission. Instruct the patient to leave dentures out at night and to soak denture in a 1% sodium hypochlorite solution for 15 minutes with thorough rinsing under running water for at least 2 minutes, before bedtime.

Complementary and alternative medicine Garlic capsules. Garlic may have antifungal and antibacterial properties. One study found that ajoene, a compound obtained from garlic, was as effective in treating the fungus that causes athlete’s foot. Caprylic acid capsules. This fatty acid, derived from coconut oil, has been shown to have antifungal properties. These are generally safe, but should not be used in patients with ulcerative colitis.


Oral Submucous Fibrosis Oral submucous fibrosis (OSMF) is an insidious, chronic disease affecting any part of the oral cavity, and sometimes the pharynx. Occasionally it is preceded and/or associated with vesicle formation and always associated with a juxtaepithelial inflammatory reaction followed by progressive hyalinization of the lamina propria. The later subepithelial and submucosal myofibrosis leads to the stiffness of the oral mucosa and deeper tissues with progressive limitation in opening of the mouth and protrusion of the tongue. Oral submucous fibrosis is one of the most prevalent premalignant condition in India which is easy to diagnose but difficult to manage. At present it is considered as irreversible and incurable. According to Pindborg and Sirsat (1966), OSMF is an insidious chronic disease affecting any part of the oral cavity and sometimes the pharynx. Although occasionally preceded by and/or associated with vesicle formation, it is always associated with juxta-epithelial inflammatory reaction followed by a fibroelastic change of the lamina propria with epithelial atrophy leading to stiffness of mucosa and causing trismus and inability to eat. Epidemiology The disease occurs mainly in Indians. It affects between 0.2–1.2% of urban population attending dental clinics in India. The disease should be a cause of concern in countries with large migrant populations from south-east Asia. Worldwide estimates in 1996 indicate that 2.5 million people are affected by the disease. In ancient medicine Shushrutha described a condition, ‘Vidari’ under mouth and throat diseases. Schwartz (1952), for the first time reported a case of ‘atropia idiopathica tropica mucosae oris’ occurring in Indians in east Africa. Lal and Joshi (1953) first described this condition in India and termed it as OSMF. Etiopathogenesis Pathogenesis of the disease is still not clear, and it is believed to be multifactorial. The exact role of any of the etiologic factor in the development, severity and progress of the disease is not clear as the disease may still progress even if none of these are present. The chewing of betel nut has been recognized as one of the most important etiological factor for the causation of OSMF. The chewing of areca nut in various forms and mixtures is deeply embedded in the social and cultural history of India and other south-east Asian countries. Its use appears in ancient Sanskrit literature. Areca nut contains potent cholinergic muscarinic alkaloids, notably arecoline and guavacoline, with a wide range of parasympatheticomimetic effects, they promote salivation and the passage of wind through the gut, they rise blood pressure and

pulse rate and they elicit a degree of euphoria by virtue of their GABA receptor inhibitory properties which contribute to dependence and habituation. There are also bronchoconstrictor effects, and evidence for a role in precipitating and exacerbating asthma and diabetes. This arecoline plays a major role in the pathogenesis of OSMF by causing an abnormal increase in the collagen production. In genetically predisposed people, betel nut and pan chewing render the oral mucosa susceptible to chronic inflammatory changes with decreased T-lymphocyte count and higher null cell count. Areca nut, chilli and misi are the chief local factors in the production of OSMF. The role of chilli ingestion in the pathogenesis of OSMF is controversial. A hypersensitivity reaction to chilies is believed to contribute to the occurrence of OSMF, explained by some authors as allergen induced eosinophilia due to capsaicin. Misi, a black colored powder containing the substances like soda, borax, powdered alum, charcoal of myrobalan and fillers earth in varying proportion is predominantly used by females in Uttar Pradesh is known to induce OSMF. The flavonoid catechin and tannins from betel nut stabilizes the collagen fibers and makes them resistant to degradation by collagenase. Nutritional deficiency: Malnutrition is more prevalent in OSMF. Several investigators have reported anemia, vitamin, iron and protein deficiencies among OSMF patients. Iron metabolism seems to be the primary factor and deficiency in folic acid, pyridoxine, and vitamin B12 deficiencies are secondary. The genetic factors like increased factors like HLA DR 10, DR3 and DR7 have been reported. Immunological studies have shown raised immunoglobulin like A, E and D. Autoantibodies to gastric and parietal cells, as well as thyroid microsomal, antinuclear, reticulin, and antismooth muscle antibodies have been found in 65% of patients with the disease. Increased levels of proinflammatory cytokines and reduced antifibrotic interferon gamma (IFN-) in patients with OSMF, which may be central to the pathogenesis of OSMF, has been demonstrated. Matrix metalloprotein: The genomic studies have shown the 5A genotype of MMP3 promoter was associated. Studies have shown that six collagen related genes including COL1A1, COL1A2, COLase, LYOXase, TGF-1, and CST3 are found to be located on different chromosomes in OSMF patients. Role of saliva: Trivedi suggested the involvement of trace metal copper in the molecular pathogenesis of OSMF as they found the high levels of copper expression in saliva could act as initiating factor and stimulation of fibrogenesis by up regulation of lysyl peroxide. According to the study conducted by Chaturvedi (1991), saliva was found to contain alkaloids, tannins, nitrates, thiocyanins, nitrosamines and have carcinogenic activity. 159


They found that chewing betel nut releases copper into the saliva that stimulates lysyl oxidase enzyme lead to fibrosis.

b. c.

Molecular pathogenesis of OSMF (Rajalalitha and Vali, 2005)

d.

Collagen is the major structural component of the connective tissues and its composition within each tissue needs to be maintained for proper tissue integrity. The synthesis of collagen is influenced by a variety of mediators, including growth factor, hormones, cytokines and lymphokines. A prominent mediator is transforming growth factor-beta (TGF-). The growth factor has also been implicated in the development of many fibrotic diseases. It causes the deposition of extracellular matrix by increasing the synthesis of matrix proteins like collagen and decreasing its degradation by stimulating various inhibitory mechanisms. So transforming growth factor beta signaling pathway might be critical for pathogenesis of OSMF.

No restriction in mouth opening No restriction in tongue protrusion up to mesioincisal angle of upper central incisor when maximally extended with mouth wide open. Burning sensation only on taking spicy food or hot liquids.

Figure 30

Clinical features Oral submucous fibrosis is very commonly seen among the Indians. Indians who have settled in other countries and to lesser extent in other Asiatic people. Several Europeans in Europe, India and Africa have also been mentioned as victims of the disease. Epidemiological surveys of Indian population have revealed that incidence varied in the range of 0.04–0.4% and in urban population 0.18–1.2%. Overall prevalence of up to 0.4% in Kerala. The common age of occurrence varies from 12–62 years with the mean age being 40 years but there are reports of OSMF even in as younger as 4-year old. There is female predilection, with the ratio being 3:2. First and the foremost feature of OSMF is burning sensation and pallor or blanching of oral mucosa. Intraoral sites of involvement include the buccal mucosa (Figure 30), retromolar area, followed by soft palate, palatal fauces, uvula, tongue (Figure 31) and labial mucosa (Figure 32A, B). There may be stiff and small tongue, blanched and leathery floor of the mouth (Figure 33), fibrotic and depigmented gingiva, rubbery soft palate with decreased mobility and blanched and atrophic tonsils, and shrunken bud like uvula. Mouth opening may become progressively reduced (Figure 34). Other symptoms include increased salivation, change of gustatory sensation, hearing loss due to stenosis of the Eustachian tubes, dryness of the mouth, nasal tonality to the voice. Dysphagia to solids (if the esophagus is involved), impaired mouth movements (e.g. eating, whistling, blowing, sucking) (Figure 35).

Pallor or marble-like appearance of the oral mucosa in OSMF. Courtesy: Dr Ashok

Figure 31

Staging of OSMF Stage 1: Early OSMF a. 160

Mild blanching

Depapillation and pallor associated with the tongue in OSMF. Courtesy: Dr Ashok


Figure 32 B

A

Pallor of the upper and lower labial mucosa in OSMF. Courtesy: Dr Ashok

Figure 33

Figure 34

Pallor of the ventral surface of tongue and floor of mouth in OSMF. Courtesy: Dr Ashok

Difficulty in mouth opening due to the presence of circumoral fibrous bands in OSMF. Courtesy: Dr Ashok

Stage 2: Moderate OSMF a. b. c. d. e. f.

Moderate to severe blanching Mouth opening reduced by 33%, tongue protrusion reduced by 33% and reduced flexibility Burning sensation even in the absence of stimuli Presence of palpable bands Lymphadenopathy either unilateral or bilateral Demonstrable anemia on hematological examination.

Stage 3: Severe OSMF a. b.

c.

Burning sensation very severe More than 66% reduction in the mouth opening, cheek flexibility and tongue protrusion. In much tongue may appear fixed Ulcers over the buccal mucosa

d. e.

Thick palpable bands Bilateral lymphadenopathy, definite nutritional compromise can be established in B complex (angular cheilitis) and iron deficiency group.

Khanna and Andrade (1995) grouped OSMF into different stages: Group 1: Very early ❍ Mouth opening is normal ❍ Burning sensation ❍ Excessive salivation ❍ Acute ulceration and recurrent stomatitis. 161


Figure 35

❍ ❍

Lips circular band felt around the entire mouth Difficult intraoral examination

Group 5: Advance cases with premalignant and malignant changes ❍ OSMF and leukoplakia ❍ OSMF, squamous cell carcinoma Haider (2000) staged OSMF clinically and functionally as follows: Clinical Staging Stage 1: Faucial bands only Stage 2: Faucial and buccal bands Stage 3: Faucial and labial bands Functional Staging Stage A: Mouth opening 13–20 mm Stage B: Mouth opening 10–12 mm Stage C: Mouth opening less than 10 mm. Inability of the patient to blow his cheeks demonstrating inelasticity of the oral mucosa in OSMF. Courtesy: Dr Ashok

Group 2: Early cases Mouth opening: 26–35 mm (interincisal opening) Soft palate and faucial pillars were the areas primarily affected ❍ Buccal mucosa appeared mottled and marble like where dense pale, depigmented fibrosed areas alternated with pink normal mucosa ❍ Red erythematous patches ❍ Widespread sheets of fibrosis. ❍ ❍

Group 3: Moderately advanced Mouth opening 15–25 mm (interincisal opening) Trismus Vertical fibrous bands could be palpated and firmly attached to underlying tissue ❍ Unable to blow out their cheeks and whistle ❍ Soft palate—the fibrous bands were seen to radiate from the pterygomandibular raphe ❍ Or the anterior faucial pillars in a scar like appearance ❍ Lips—atrophy of vermillion border ❍ ❍ ❍

Unilateral posterior cheek involvement with only ipsilateral involvement of the faucial pillars and soft palate and opening reduced to 15–18 mm. Group 4: Advanced cases Stiffness/inelasticity of oral mucosa Trismus Mouth opening 2–15 mm (interincisal opening) Fauces thickened, shortened and firm on palpation Uvula was seen to be involved, shrunken, small, and fibrous band ❍ Tongue movement restricted ❍ Papillary atrophy (diffuse) ❍ ❍ ❍ ❍ ❍

162

Malignant potential and oral submucous fibrosis Various authors in the past have suggested OSMF as a precancerous condition. According to Pindborg, atrophy of the epithelium increases the vulnerability of the action of carcinogens. Due to irritation by exogenous factors, the atrophic epithelium undergoes hyperkeratinization, there is intercellular edema in the prickle cell layers and the basal cells undergo hyperplasia. After this carcinoma can develop at any stage. Congestion of the blood vessels due to excessive fibrosis in the connective tissue compromises the blood supply. Some have demonstrated abnormal expression of P-53 tumor suppressor gene as detected by immunohistochemistry in the epithelium of OSMF. Other diseases associated with OSMF There are reports of concomitant occurrence of oral lichen planus, leukoplakia, pemphigus and squamous cell carcinoma in the literature. Histopathologic changes Epithelial changes Increase in the clinical severity of the disease may be accompanied by epithelial hyperplasia or atrophy (Figure 36), which is associated with an increased tendency for keratinizing metaplasia. Deep invagination of epithelial pegs into underlying lamina propria, liquefaction degeneration of basal cells have been reported. Connective tissue changes The connective tissue changes include hyalinization, with moderate number of chronic inflammatory cells. The most striking feature of connective tissue is the presence of dense collagen bundles, randomly oriented and extending into the underlying striated muscles. Inflammatory cell infiltration includes lymphocytes, monocytes, plasma cells, and occasionally macrophages.


Figure 36

melanocytes, a feature which explains the clinically observable loss of pigment. Absence of fibroblasts within the hyalinized zones, total loss of epithelial rete pegs, and extensive degeneration of muscle fibers. Investigations

Studies have reported thickened basement membrane with marked reduction in the vascularity in the connective tissue which was inversely proportional to increased density of collagen which appeared hyalinized.

Diagnosis of the disease is by clinical findings and confirmed by incisional biopsy. Many investigations have been suggested by various authors, that include hematological, serological, immunological and biochemical factors. Other laboratory findings include a raised ESR, slight eosinophilia, microcytosis and hyperchromic indicative of anemia. Cytologic smears may be performed. A neural network-based oral precancer stage detection method has been proposed. This new technique uses wavelet coefficients from transmission electron micrography images of subepithelial fibrillar collagen in normal oral submucosa and in OSF tissues. These wavelet coefficients are used to choose the feature vector, which, in turn, can be used to train an artificial neural network. This trained network is able to classify normal and oral precancer stages (less advanced and advanced) after obtaining the image as an input. It may be used as an adjunct to hematoxylin and eosin histologic evaluations in the near future.

Histological staging of OSMF


Khanna and Andrade (1995) have classified the histological findings of OSMF into four groups.

Oral manifestations of scleroderma: Scleroderma can be distinguished by other cutaneous, systemic, and characteristic radiographic and laboratory findings. Anemia: Pale oral mucosa can mimic atrophy and fibrosis. Amyloidosis: Hyalinized stroma can be distinguished from amyloid infiltration by using Congo red and thioflavine T staining under polarized and immunofluorescent light. Generalized fibromatosis: Although soft tissue masses are not produced in the usual sense, the fibrosis of OSMF may be confused with generalized fibromatosis.

Atrophic epithelium and the hyalinization and homogenization of collagen fibers. Courtesy: Department of Oral Pathology, MCODS, Mangalore

Group 1: A fine fibrillar collagen network with marked edema, blood vessels dilated and congested. Large aggregate of plump, young fibroblasts containing abundant cytoplasm. The inflammatory cells consist of PMNLs with few eosinophils, normal epithelium with some hyperplastic epithelium. Group 2: The juxta-epithelial area shows early hyalinization. Collagen still appears as separate bundles and thickened. Plump young fibroblasts are present in moderate numbers. The blood vessels are dilated and congested. The inflammatory cells are mononuclear lymphocytes, eosinophils and occasional plasma cells; flattening and shortening of the epithelial rete pegs with varying degree of keratinization. Group 3: Juxta-epithelial hyalinization. Thickened collagen bundles are fairly describable, separated by edema. Blood vessels constriction, fibrocytes with scanty cytoplasm and spindle-shaped nuclei and atrophic epithelium with total loss of rete pegs. Muscle fibers seem to be interspersed with thickened and dense collagen fibers. The degeneration of muscle fibers begin. Group 4: Hyalinization of collagen bundles as smooth sheet, obliteration of blood vessels and decreased/loss of

Treatment (Flowchart 4) Since the exact etiology is unknown, various treatment modalities have been tried from time to time. The treatments of the condition include avoidance of habits but there is no reversal of fibrosis. Management includes the following medications: Corticosteroids These agents can be used in pharmacologic doses for their anti-inflammatory and immunosuppressant properties and their effects on blood and lymphatic systems in the palliative treatment. In patients with moderate OSMF, weekly submucosal intralesional injections or topical application of steroids may help prevent further damage. 163


Dexamethasone (Decadron): Adult dose 4 mg IV/IM. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability. Placental extracts The rationale for using placental extract in patients with OSMF derives from its proposed anti-inflammatory effect, hence, preventing or inhibiting mucosal damage. Cessation of areca nut chewing and submucosal administration of aqueous extract of healthy human PE (Placentrex) showed marked improvement of the condition. Hyaluronidase The use of topical hyaluronidase has been shown to have quicker improvement in symptoms compared with steroids alone. The combination of steroids

and topical hyaluronidase shows better long-term results than either agent used alone. Interferon-gamma This plays a role in the treatment of patients with OSMF because of its immunoregulatory effect. IFN- is a known antifibrotic cytokine. Patients treated with an intralesional injection of IFN- experienced improvement of symptoms. IFN-, through its effect of altering collagen synthesis, appears to be a key factor to the treatment of patients with OSMF, and intralesional injections of the cytokine may have a significant therapeutic effect on OSMF. Surgical care: Surgical treatment is indicated in patients with severe trismus and/or biopsy results revealing dysplastic or neoplastic changes. Surgical modalities that have been used include the following:

Flowchart 4 OSMF

Stage I

Stage II & III

Stage IV

Systemic: 1. Iron supplements (Dexorange Syrup, Haemup Syrup/Capsules) 2. Antioxidant capsules b.i.d. for 3 months (Antoxid, Altomin Xl, Lynet, Revup, Oxyace, Oxidix)

Topical: 1. Benzydamine 0.15% mouth rinse (Tantum) 2. Triamcinolone gel (Tess) or crushed dexamethasone tablets in 20 ml of water & use as mouthrinse Immunomodulators: Levamisole 150 mg o.d. for 3 days – twice in a month for 3 months (Vermisol, Levazole)

Intralesional injections: 1. Dexamethasone + Hyaluronidase 1,500 IU (Hylase) + Lignocaine 2 ml; multiple site injections once/week for 6 weeks 2. Betamethasone + Hyaluronidase 1,500 IU + Lignocaine + Placentrex = 3 ml multiple site injections once/week for 6 weeks

Newer drugs: 1. Pentoxifylline 400 mg b.i.d. for 15 days (Flexital, Flowpent) 2. Interferon gamma injections

No medicinal treatment can be given 1. Surgical relieving of fibrous bands with buccal pad of fat covering the wound 2. Laser surgery

Physiotherapy: 1. Mouth opening exercises 2. Mouth opening appliance 3. Ice cream stick 4. Ultrasound


Management of oral submucous fibrosis

164


Simple excision of the fibrous bands: Excision can result in contracture of the tissue exacerbating the condition. Split-thickness skin grafting following bilateral temporalis myotomy or coronoidectomy: Trismus associated with OSMF may be due to changes in the temporalis tendon secondary to OSMF; therefore, skin grafts may relieve symptoms. Nasolabial flaps and lingual pedicle flaps: Surgery to create flaps is performed only in patients with OSF in whom the tongue is not involved. The use of vitamin supplements, balanced diet and stretching exercises are aimed at increasing the mouth opening. Regular physical examinations, biopsy specimen analysis, and cytologic smear testing should be scheduled to detect oral dysplasia or carcinoma, especially in patients with severe OSMF. Patients with surface leukoplakia require close follow-up monitoring and repeat biopsies. Patients with dysplasia and carcinomas should receive routine treatment for these entities. Complications Oral dysplasia and squamous cell carcinomas are complications of OSMF. In patients with OSMF, the risk of developing oral carcinoma is 7–14% over a 10-year period. If the palatal and paratubal muscles are involved in patients with OSMF, conductive hearing loss may occur because of functional stenosis of the Eustachian tube. Prognosis No treatment is effective in patients with oral submucous fibrosis, and the condition is irreversible. Recent reports claim improvement of the condition if the habit is discontinued following diagnosis at an early stage.

Focal Epithelial Hyperplasia (Heck’s Disease) Heck’s disease is considered among the most contagious of the papillary lesions affecting the oral cavity. Presently the etiology for this condition is said to be a subtype of the human papillomavirus, HPV-13, and possibly HPV-32. It is very commonly seen in Eskimos and American Indians and less commonly in white Europeans. The predisposing factors associated with this condition are poor hygiene, poverty and communal lifestyle. Presence of this condition among close communities and family members suggests an infectious pathogenesis. Dos Santos et al (2004) in their article state the prevalence of this condition affecting the oral mucosa was highest in Waimiri-Atroari Indians, reaching 21% with no differences between the sexes or among different age groups. Patients of a younger age group presented with multiple lesions, which were predominantly nodular, whereas older patients had few or even single lesions, which tended to be flat and papular. Clinical features It is usually seen in children and adults. The condition is characterized by multiple soft, circumscribed, sessile nodules of whitish color or a color mimicking the adjacent oral mucosa (Figure 37). The common sites of involvement are the lips, buccal mucosa and the lateral borders of the tongue (Figure 38).

Figure 37

Psoriasis Description is given in Chapter 9 (Dermatological Diseases).

Hereditary Benign Intraepithelial Dyskeratosis (Witkop’s Disease) Witkop-von Sallmann disease It is a rare genetic disorder characterized by the oral lesions and bilateral conjunctival plaques. The oral lesions are similar to white sponge nevus. They appear as thick corrugated asymptomatic white plaque involving the buccal and labial mucosa. Other intraoral sites include floor of the mouth, lateral tongue, gingiva and palate. The significant feature of this disease is the formation of corneal plaques that may lead to blindness. Differential diagnosis White sponge nevus and pachyonychia congenita can be considered in the differential diagnosis.

Well circumscribed, sessile nodules mimicking the color of the adjacent oral mucosa in Heck’s Disease. Courtesy: Prof Braz Campos Durso, Brazil

165


Figure 38

Well circumscribed, papular lesions on the labial mucosa in Heck’s disease. Courtesy: Prof Braz Campos Durso, Brazil

The diagnosis of Heck’s disease can be made by clinical examination. However histological evaluation may show features of viral infection. The condition is said to be associated with HIV infection. However the association between these two conditions is yet to be substantiated. Suppression of the immune system leaves the patient vulnerable to opportunistic infections, including HPV infections. Management No treatment is necessary as it is self-limiting and regresses completely. However some treatment modalities that have been used include surgical or cryosurgical procedures, electrocoagulation or treatment with carbon dioxide laser. Steinhoff et al (2001) have used interferon- for successfully managing the condition. However, its efficacy in the treatment of oral lesions has yet to be adequately tested.

White sponge nevus involving the buccal mucosa. Courtesy: Thomas S Pilak, Marquette University, USA

White sponge nevus is also known by other names which include white folded gingivostomatitis, familial white folded hypertrophy of the mucous membrane, leukokeratosis oris, hereditary leukokeratosis, leukoderma exofoliativum mucosae oris and naevus spongiosus albus mucosae. Etiopathogenesis The basic defect lies in the epithelial cell maturation and desquamation. Atypical abundance and aggregation of tonofilaments and increased intracellular attachment cause piling up of surface cells and keratin. There is also a decreased shedding of keratin which leads to white sponge nevus. Genetic basis There are mutations in genes controlling keratins, i.e. K4 and K13 on chromosomes 12q13 and 17q21–22. There is also a K4-3bp deletion. Mutations are also seen in K14 and K19 controlling genes. Rugg et al described mutation in genes N-60 and Richard et al reported mutations in gene L119P.

Dyskeratosis Congenita

Clinical features

Description is given in Chapter 9 (Dermatological Diseases).

Usually presents itself at birth or early childhood. There is no sex predilection. Lesions are seen involving the oral mucosa and other mucosal sites such as the nasal cavity, esophagus, larynx, vagina and rectum. The common sites that are affected include buccal mucosa (Figure 39) followed by labial mucosa, alveolar ridge and floor of mouth. Gingiva and tongue are rarely affected. Usually it presents itself as an asymptomatic gray white folded or corrugated spongy mucosal lesions that often have symmetrical weavy pattern (Figure 40). They have soft or spongy texture and white opalescent hue. Size of the lesion can vary from few millimeters to several centimeters. They present usually as a symmetrically bilateral lesion.

White Sponge Nevus White sponge nevus is a hereditary dyskeratotic hyperplasia of the mucous membranes that shows an autosomal dominant inheritance pattern with irregular penetrance. It is characterized by variable and some times severe leukokeratosis of the oral mucosa. Hyde in 1909 gave the first description of this condition. Subsequently in 1935, Cannon named it white sponge nevus. 166

Figure 39


Figure 40

White corrugated spongy mucosal lesions on the labial mucosa in white sponge nevus. Courtesy: Thomas S Pilak, Marquette University, USA

It is usually asymptomatic. However it may become symptomatic by the irritating stimuli like bacterial or yeast infection. Patients can complain of pruritus, burning sensation or pain. Differential diagnosis Various conditions can be considered in the differential diagnosis such as leukoedema, leukoplakia, traumatic keratosis, chemical burn, candidiasis, lichen planus, pachyonychia congenita, Darier’s disease and dyskeratosis congenita. Histopathologic features Histopathological sections reveal epithelial thickening showing both acanthosis and hyperkeratosis. The basal layer is intact and the spinous cell layer is continuous till the surface and shows intracellular edema and pyknotic nuclei are seen. Parakeratin plugging runs deep into the spinous layer. Mild inflammatory cell infiltrate is seen in the submucosa (Figure 41). Treatment Since it is a benign lesion and usually asymptomatic, no treatment is required. However in symptomatic cases tetracycline mouthrinse and penicillins have shown some good results.

RED LESIONS OF THE ORAL CAVITY Individual variations in the color of the oral mucosa are probably an expression of one or more genetically controlled factors.

Figure 41

White sponge nevus. Courtesy: Thomas S Pilak, Marquette University, USA

The color of the oral mucosa depends on the thickness of the oral epithelium, underlying connective tissue contents like fibrous tissue, vascularity, and the functional adaptations of the mucosa toward forces of mastication and the inflammatory process. Healthy masticatory mucosa (gingival, palate, dorsal surface of the tongue) is light pink in color. The lining mucosa (mucosa over the vestibule, cheeks, lips, floor of the mouth, and ventral surface of the tongue) is reddish pink in color. Palatoglossal arch region is dusky red in color due to increased vascularity and often misdiagnosed as sore throat. Classification of red lesions—congenital and acquired Congenital red lesions Vascular malformations like hemangiomas, AV shunts. Acquired red lesions ❍ Erythroplakia ❍ Extravasations of blood (trauma or hemostatic disease) ❍ Atrophy or erosion of the mucosa ❍ Inflammation secondary to vascular dilatation ❍ Infections like (cellulitis, secondary syphilis, candidiasis) ❍ Inflammatory hyperplasias ❍ Allergic and autoimmune diseases ❍ Increase in the hemoglobin pigmentation Traumatic erythematous macules Mechanical trauma to the oral mucosa can produce a variety of clinical lesions depending on the nature and severity and the host response. These may be in the form of erythematic macules, hemorrhagic nodules, echymoses, erosions and ulcers in the order of severity. Common causes include self-inflicted injury like cheek bite or some deleterious habits, sharp margins of the teeth or restorations and ill-fitting prostheses. 167


The most common site of occurrence of the erythematous macules are on the anterior and lateral borders of the tongue, floor of the mouth, posterior palate, buccal mucosa, and the mucosal surface of lips. Clinical configurations of these depend on the offending agent. This could be either elicited by the history or by clinical examination. The caustic drugs (aspirin) or hot foods or beverages result in the coagulation necrosis of the superficial tissue and appear as whitish scrapable membrane over an erythematous base. Erythematous macules at the junction of hard and soft palate should be differentiated from the purpuric macule of oral sex, palatal bruising because of severe cough or severe vomiting, allergic manifestations, macular hemangioma, atrophic candidiasis, infectious mononucleosis and herpangina. The lesions usually regress after the removal of the causative factors. In case of multiple numbers, investigations are needed to rule out the underlying hemostatic disorders. Reddish ulcers or ulcers with red halo Ulcerative conditions like recurrent herpes and recurrent aphthous stomatitis are first manifested as erythematous macules.

RED LESIONS OF THE TONGUE Migratory Glossitis Description is given in Chapter 2 (Developmental Disturbances).

Median Rhomboid Glossitis Description is given in Chapter 2 (Developmental Disturbances).

Deficiency States

Soft tissue odontogenic infection (cellulitis) Odontogenic infections may originate in canals and periapex of the teeth, gingival and periodontal pockets, and the gingival operculum over an erupting tooth and may spread to the surrounding soft tissues like oral mucosa appear red, swollen and tender to palpate.

Certain deficiency states can produce a glossitis of a completely bald or patchy bald tongue. These include iron deficiency anemias, pernicious anemia, Plummer-Vinson syndrome; sprue and vitamin B complex deficiencies, especially those of thiamine, riboflavin, nicotinic acid, pyridoxine, pantothenic acid, and vitamin B12.

Mucositis secondary to systemic diseases Mucosa may have reddish appearance in case of severe esophagitis and other gastrointestinal disorders, uremic stomatitis in case of end stage renal diseases.

Clinical features

Macular hemangiomas and telangiectasias Red macular hemangiomas occur as both syndromic and non-syndromes associated are readily differentiated from erythemas by the history of long duration, non-tenderness, absence of inflammatory components, characteristic emptying of the lesions. Polycythemia Polycythemia also called erythremia is a chronic and sustained elevation of erythrocytes and level of hemoglobin. Primary polycythemia is a neoplastic condition of the hematopoietic system. Secondary polycythemia results from stimulation of bone marrow at high altitudes or by chronic pulmonary diseases like emphysema. In this condition the entire oral mucosa appears deep red and gingival and soft tissues easily bleed and seen as multiple petechiae over the palate. Laboratory investigations including elevated levels of erythrocyte count, raised hemoglobin concentration, hematocrit values quickly establish the diagnosis. 168

Lupus erythematosus Lupus erythematosus is a connective tissue disease of unknown cause in which antibodies to nuclear constituents are produced to result in the involvement of various organs. Two forms of the disease include discoid and systemic lupus erythematosus. In Schiodt’s study of 32 patients of lupus erythematosus with oral lesions, early lesions were characterized by erythema without the striae.

Tongue may be intensely red and then becomes smooth as the filiform or both the types of papillae atrophy. Symptoms vary from tender to burning tongue to extreme glossodynia.

Foliate Papillitis Sometimes enlarged foliate papillae appear red in color due to inflammatory enlargement of the lymphoid tissue or due to upper respiratory tract infections or mechanical irritation and may be mistaken for erythroplakic lesions on the tongue.

Erythroplakia Erythroplakia is a precancerous lesion occurring in the oral cavity, The term ‘erythroplakia’ (erythroplasia) was coined to describe red lesions of the oral mucosa in contrast to oral leukoplakia. The term erythroplasia was originally used by Queyrat to describe a red, precancerous lesion of the penis. The term erythroplakia is used for a clinically and histopathologically


similar process that occurs on the oral mucosa. Erythroplakia is a clinical term that refers to a red patch that cannot be defined clinically or pathologically as any other condition. This definition excludes inflammatory conditions that may result in a red clinical appearance. Definitions Over the years several definitions for erythroplakia have been suggested. Mehta et al, diagnosed erythroplakia ‘when the oral mucosa was the seat of a well-demarcated, red, often fiery red patch, which could not be attributed to other causes’. According to Shafer and Waldron, ‘Erythroplakia of the oral cavity is a specific disease entity which must be differentiated from other specific or non-specific inflammatory oral lesions, although this can only be done in most cases by biopsy’. WHO in 1978 defined erythroplakia as ‘any lesion of the oral mucosa that presents as bright red velvety plaques which cannot be characterized clinically or pathologically as any other recognizable condition’. This definition was confirmed during an international seminar on oral leukoplakia and associated lesions related to tobacco habits in 1983. In 1994, at another symposium on oral white lesions with special reference to precancerous and tobacco-related lesions the definition of OE was changed: ‘The term erythroplakia is used analogously to leukoplakia to designate lesions of the oral mucosa that present as red areas and cannot be diagnosed as any other definable lesion’. An updated definition for erythroplakia was proposed by Bouquot as ‘a chronic red mucosal macule which cannot be given another specific diagnostic name and cannot be attributed to traumatic, vascular, or inflammatory causes’. Erythroplakia is defined as ‘a fiery red patch that cannot be characterized clinically or pathologically as any other definable lesion’. This definition is now widely accepted, although it is based on the principle of diagnosis per exclusion. Incidence/prevalence It is generally accepted that the erythroplakia is much less common than oral leukoplakia and most of the prevalence figures were derived from studies in South and South-East Asia and no such figures have been published from other geographic areas. In a survey of 50,915 Indian individuals, Mehta et al found only nine cases of erythroplakia (0.02%). In 1975 Shafer and Waldron described 58 cases thought to be representative of oral erythroplakia among 64,345 biopsies, representing 0.09%. Two epidemiological surveys of oral mucosal lesions from Malaysia revealed a prevalence of 0.02% for both studies.

In a house-to-house survey in Burma among 6,000 villagers over the age of 15 years, five cases of oral erythroplakia were diagnosed, with a prevalence of 0.83%. Feller et al from South Africa studied 138 cases of oral precancerous lesions, of which eight were oral erythroplakia. A recently published case-control study from Kerala, India, included 100 cases of erythroplakia among 47,773 controls, with a prevalence of 0.2%. With these few data available it was observed that presently erythroplakia has a range of prevalence between 0.02% and 0.83%. Classification Shear suggested a classification of erythroplakia in 1972. He differentiated between clinical and microscopic variations and neoplastic from inflammatory changes. Clinical variations ❍ Homogeneous erythroplakia ❍ Erythroplakia interspersed with patches of leukoplakia ❍ Granular or speckled erythroplakia (embracing the lesion described as speckled leukoplakia) Microscopic variations ❍ Neoplastic – Squamous carcinoma – Carcinoma in situ (intraepithelial carcinoma) and less severe forms of epithelial atypia ❍ Inflammatory – Candida albicans infections (including denture stomatitis) – Tuberculosis – Histoplasmosis – Miscellaneous specific, non-specific and nondiagnosable lesions Etiopathogenesis While erythroplakia does not seem to have a known geographic incidence, studies from India have shown that erythroplakia may be associated with tobacco smoking and chewing habits and that the risk to develop erythroplakia was strongly associated with these. Etiology and pathogenesis of erythroplakia are poorly understood. Predisposing factors are widely unknown, but it was suggested that tobacco and alcohol use are probably involved in most cases. Reports of large case-control study in Kerala, India, shed more light on some of the factors involved in the etiology of erythroplakia. One of these studies evaluated the risk of erythroplakia in relation to chewing tobacco, smoking, alcohol drinking, body mass index (BMI), and vegetable, fruit, and vitamin/iron intake. It was concluded that tobacco chewing and alcohol drinking are strong risk factors for erythroplakia in the Indian population. 169


Figure 42

and velvety surface; they may also be seen with other morphological characteristics, like an irregular, red granular surface interspersed with white or yellow foci, which may be described as granular erythroplakia. Erythroplakia is soft to palpation and does not become indurated or hard until an invasive carcinoma develops in it. Erythroplakia is often asymptomatic, although some patients may complain of a sore or burning sensation. Malignant transformation Erythroplakia has the highest risk of malignant transformation compared to all other oral mucosal premalignant lesions. The malignant transformation rate for erythroplakia varies from 14 to 50%. Differential diagnosis Erythematous candidiasis, atrophic oral lichen planus and denture-induced stomatitis can be considered in the differential diagnosis of erythroplakia.

A red velvety lesion involving the left buccal mucosa suggestive of erythroplakia. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

In another study designed to study the risk factors for multiple oral premalignant lesions, suggested that tobacco chewing was the most important risk factor for multiple oral premalignant lesions and therefore may be a major source of field cancerization on the oral epithelium in an Indian population. Clinical features Oral erythroplakia occurs most frequently in middle age and elderly and appears as a red macule or plaque with a soft, velvety texture (Figure 42). Among 58 cases reported by Shafer and Waldron 37 cases (67.8%) occurred in the sixth and seventh decades (19 men, 18 women). It occurs most commonly in men. The soft palate, the floor of the mouth and the buccal mucosa are the most commonly affected site; the tongue is rarely affected. Shafer and Waldron, however, observed some differences of location between women and men. The most common site of occurrence of oral erythroplakia in men was the floor of the mouth, but in women the combined mandibular alveolar mucosa, mandibular gingiva, and mandibular sulcus was most commonly affected. In men this combined site was the least common site of occurrence. The retromolar area in both men and women and the floor of the mouth in women was the next most common site of involvement. The typical lesion of oral erythroplakia is less than 1.5 cm in diameter and half are less than 1 cm, but lesions larger than 4 cm have also been observed. Some erythroplakias are smooth and some are granular or nodular. Often there is a well-defined margin adjacent to mucosa of normal appearance, although the erythroplakia lesions may have a smooth 170

Treatment and recurrence rate Erythroplakia is a premalignant lesion, which shows highest risk for malignant transformation; therefore early treatment of such lesion is mandatory. Alcohol and tobacco habits should be avoided as a preliminary measure. Regular follow-up examination is recommended for the lesion which shows no or moderate epithelial dysplasia. Surgical excision of the lesion is recommended for those lesions which show severe epithelial dysplasia or carcinoma in situ histologically. Amagasa et al (1985) recorded a recurrence of erythroplakia in 5 of 7 cases.

Discoid Lupus Erythematosus Discoid lupus erythematosus (DLE) is a chronic inflammatory condition of the skin, connective tissue and specific internal organs that has associated circulating autoantibodies to DNA and other nuclear and RNA proteins; circular whitish buccomucosal lesions and erythematous rashes of the sun-exposed skin. Lupus erythematosus is a syndrome whose manifestations range from a localized skin lesion to a destructive systemic disorder without any cutaneous changes. Classification Gilliam classification of skin lesions associated with LE I. LE-Specific skin disease A. Acute cutaneous LE 1. Localized ACLE 2. Generalized ACLE B. Subacute cutaneous LE 1. Annular SCLE 2. Papulosquamous SCLE


C.

II. A.

B. C. D. E. F. G. H.

Chronic cutaneous LE 1. Classic discoid LE a. Localized DLE b. Generalized DLE 2. Hypertropic/verrucous DLE 3. Lupus profundus 4. Mucosal DLE a. Oral DLE b. Conjunctival DLE 5. Chilblain DLE 6. Lichenoid DLE LE—Non-specific skin disease Cutaneous vascular disease 1. Vasculitis 2. Vasculopathy 3. Livedo reticularis 4. Thrombophlebitis 5. Raynaud’s phenomenon Non-scarring alopecia Sclerodactyly Rheumatoid nodules Calcinosis cutis Urticaria Erythema multiforme Lichen planus

Alternatively DLE can be classified as: ❍ ❍ ❍ ❍ ❍ ❍

Systemic lupus erythematosus Bullous form of lupus erythematosus Neonatal form of LE Chronic cutaneous form of LE (CCLE) Subacute cutaneous form (SCLE) Drug-related lupus

Discoid lupus erythematosus (DLE) is named so because the lesions are disc or coin shaped. DLE is also known by the name cutaneous lupus erythematosus and chronic discoid lupus erythematosus. The WHO Collaborating Reference Centre for Oral Precancerous Lesions describes DLE as a benign disorder of the skin, most frequently involving the face, and characterized by well-defined red scaly patches of variable sizes, which heal with atrophy, scarring and pigmentary changes. Discoid lupus erythematosus can present as a localized or generalized form. In the localized form, head and neck are most commonly involved, whereas in the disseminated form the lesions may occur in a wide spread pattern on the trunk and limbs, or may be localized to other body sites. Etiopathogenesis Genetic factors Genetic deficiencies of the complement components including C2, C3, C4, and C5 as well as the C1

esterase inhibitor are associated with DLE. Significant increases of HLA B7, B8, DR3 and DQA0102 and a significant decrease in HLA A2 have been reported for patients with DLE. It also occurs with increased frequency in female carriers of X-linked chronic granulomatous disease. Role of UV light Ultraviolet light is probably the most important environmental factor in the induction phase of LE specific skin disease. Early studies demonstrated that cutaneous LE lesions could be provoked in the clinically normal skin of the patients with both SLE and cutaneous LE by repeated delivery of high doses of UVB radiation to the same test site. More recent studies argue that UVA radiation can also induce cutaneous LE lesions. Environmental factors The onset of lesions may be precipitated by a variety of factors. At a study in Leeds, lesions started with trauma in 11%, with mental stress in 12%, sunburn in 5%, infection in 3%, exposure to cold in 2% and pregnancy in 1%. Drugs like antibiotics (penicillin, streptomycin, sulfonamides, tetracycline), antituberculous drugs (isoniazid, paraaminosalicylate), antihypertensive drugs (hydralazine and methyldopa), antifungal (griseofulvin) and antiarthritic (gold) have known to precipitate lesions of DLE. Clinical features It is usually seen in the 3rd and 4th decades of life. The peak age of onset is 30 years in females and 40 years in males. It is predominantly seen in females in the ratio 3:1. Blacks are reportedly more severely affected. The common sites of involvement include the face, scalp, nose, ears, V area of the neck and extensor aspect of the arms. Any area of the face including the eyebrows, eyelids, nose and lips can be affected. Skin lesions Early lesions The lesion start as patches of erythema, occasionally with an urticarial component; later they become papulosquamous and eventuate in elevated reddish edematous plaques covered with adherent graying scales. The lesions tend to enlarge peripherally and may coalesce to produce bizarre patterns. Chronic lesions Chronic lesions are well defined and circular, oval or irregular in shape. Often they have an elevated erythematous border. The center of the lesion is usually depressed. Dilated follicular openings plugged with horny epithelial plugs are seen. Large areas may be involved. Some of the patches may resolve, but residual scarring is more common. The scars are smooth, atrophic, flat and white. Telangiectasia may be present at the edges of the scars so called telangiectatic lupus erythematosus is merely the morphological form in which telangiectasia predominates. Post inflammatory hyperpigmentation also may occur. Depigmentation may also be seen. Follicular involvement 171


is a prominent feature. Keratotic plugs accumulate in dilated follicles that soon become devoid of hair. When the adherent scale is lifted from more advanced lesions, keratotic spikes similar in appearance to carpet tacks can be seen to project from the undersurface of the scale (carpet tack sign or tin tact sign). Color: Active lesions—red whereas burnt out or scarred lesions are pink or white. Shape is usually round, oval, annular, polycyclic with irregular borders. Distribution—scattered discrete lesions. Malar rash or the butterfly rash is occasionally seen in DLE. Mucosal or oral lesions Lesions of the mucous membranes may be limited to these areas, but usually coexist with skin lesions of DLE. Mucous membrane lesions more commonly occur during acute systemic episodes of lupus erythematosus. They typically consist of gingivitis, mucosal hemorrhage, erosion and shallow ulcerations. ❍

Early lesions—mucosal hemorrhage, erosion, superficial erythematous patches with dilated blood vessels on the borders. The center is depressed or superficially ulcerated. ❍ Chronic lesions—central atrophic areas with small white dots, surrounded by a keratinized border composed of radiating white striae. Different types of DLE ❍ ❍

❍

❍

❍ ❍ ❍

Verrucous DLE: If hyperkeratosis is marked, a warty lesion with a red slightly raised edge results. Tumid DLE: The tissues are swollen, brawny, warm and tense. The surface shows a reddish, mottled appearance due to scarring. Chilblain lupus: Variant of DLE characterized by purplish-blue, tender chilblain-like (chilblains are ulcers affecting extremities that occur due to exposure to cold and humidity) nodules. LE profundus: In this cutaneous infiltrate occurs primarily in the deeper portions of the dermis and gives rise to firm, rubbery, sharply defined nodules varying in size from one to several cm in diameter. LE and EM like syndrome (Rowell’s syndrome). LE and LP overlap syndrome. Rosacea like syndrome.

Discoid lupus erythematosus has negative response for LE cell inclusion test usually patients with SLE typically develop LE cells. This cell or phenomenon consists of a rosette of neutrophils surrounding a pale nuclear mass apparently derived from a lymphocyte. Only rare occasion is the LE cell found in cases of DLE. Immunofluorescence studies Immunofluorescence studies reveal a granular or shaggy pattern of IgG, IgM, IgA, C3 in the basement membrane or in the dermal-epidermal junction. In comparison to IgM, granular deposits of IgG are extensive at the dermoepidermal junction. Such a finding is referred to as lupus band. Lupus band test (LBT) is positive in 90% of active lesions that have not been recently treated with topical corticosteroids. However the test is negative in burnt-out or scarred lesions and in the normal skin (either sunexposed/non-sun-exposed). Histological features Hyperkeratosis with follicular or keratotic plugging, atrophy of the rete pegs, liquefaction degeneration of the basal layer of cells, perivascular infiltration of lymphocytes and their collection about dermal appendages, and basophilic degeneration of collagen and elastic fibers with hyalinization, edema and fibrinoid change, particularly prominent immediately beneath the epithelium. Differential diagnosis 1.

2.

3.

4.

Laboratory findings The laboratory findings for DLE are not specific. Patients can present with anemia, leukopenia, thrombocytopenia, elevated ESR levels, elevated serum globulin levels, high IgG levels, presence of antithyroid antibodies and reduced T-cell counts. Urine examination and blood urea nitrogen has to be done to rule out SLE and to know patient’s renal function. Antinuclear antibodies are rarely present. 172

5.

Systemic lupus erythematosus (SLE): Systemic manifestations are present, LE cells are seen and antinuclear antibodies are present. Polymorphous light eruption (PLE): Absence of antinuclear factor from the serum and of dermal-epidermal immunoglobulin deposits. Lupus vulgaris: Lesions usually occur at an early age, and are rarely symmetrical, may be ulcerated and usually show characteristic apple jelly nodules. Lichen planus: The presence of concentrations of lymphocytes in the immediate underlying lamina propria, deep focal accumulations of lymphocytes with germinal centers and perivascular infiltrates of lymphocytes is helpful in differentiating lesions of LE and those of LP. In more chronic lesions the presence of hyperorthokeratosis and surface depressions containing keratin (keratin plugging) suggests LE than LP. Seborrheic dermatitis, actinic keratosis and drug eruptions.

The differential diagnosis for oral lesions include lichen planus and leukoplakia. The classic oral discoid lesion has three outstanding features according to Schiodt which can be differentiated from other lesions; they are: a central atrophic area with small white dots, a slightly elevated border zone of irradiating white striae and telangiectasia.


Prognosis The untreated skin lesions tend to be persistent, usually heals with scarring. Less than 5% of the cases may convert into SLE. Squamous cell and less commonly basal cell carcinomas occasionally occur in scars of DLE, particularly on the scalp, ears, lips and nose. Management General measures Patient can be advised against excessive exposure to sunlight, UV light and heat. They can be instructed to use umbrellas or broad brimmed hats. Sunscreen creams or lotions can be used regularly. Topical therapy 0.025% fluocinolone cream or 0.1% triamcinolone acetonide cream has shown to be effective. Intralesional corticosteroid injections (triamcinolone acetonide 5–10 mg/ml) at 6 weekly interval are helpful in resistant cases. Oral therapy Oral prednisolone 0.5 mg/kg rapidly tapered over 6 weeks or hydroxychloroquine, initially 200 mg twice daily, reducing to 200 mg/day after response. Alternatively chloroquine sulfate 200 mg twice daily can be used. Other drugs that have been used include

aureomycin 6–9 mg/day, isotretinoin 20–80 mg/day and dapsone 100 mg/day. When all of the above have failed in patients with severe and persistent disease, then the following drugs can be given. Pulsed methylprednisolone 500–1,000 mg/day for 2–3 days or cyclophosphamide 50–200 mg/day or intravenous pulses of above drugs at 10 mg/kg, at 3–4 weekly intervals. Note: For a long time the terms precancerous lesions and conditions have been used extensively in literature. However, many authors believed that the use of the prefix ‘pre-’ implied that all the lesions and conditions eventually turned into cancer, which is not true. In order to simplify this understanding and avoid the confusion between lesions and conditions, the World Health Organization in 2005 suggested the use of the term ‘potentially malignant disorders (PMDs)’. As per this recommendation, PMDs are the disorders in which the risk of malignancy is present in a lesion or condition either at the time of initial diagnosis or at a later stage. Examples of high-risk PMDs are erythroplakia, leukoplakia, oral submucous fibrosis and erosive lichen planus.

173

CHAPTER

7

Vesiculobullous Disorders Nagamani Narayana, Ravikiran Ongole

➧ Classification of Vesiculobullous Lesions ➧

Pemphigus Vulgaris Paraneoplastic Pemphigus (Paraneoplastic Autoimmune Multiorgan Syndrome) Bullous Pemphigoid Mucous Membrane Pemphigoid or Cicatricial Pemphigoid

Predominantly Vesicular Lesions Herpes Viruses

➧

Herpes Simplex Virus (HSV) infections

➧

Herpetic Whitlow and Herpes Gladiatorum

➧

Recurrent Herpes Infections Herpetic Labialis

➧

Varicella Zoster Infections

➧

Bullous Lichen Planus

➧

Erythema Multiforme Recurrent Erythema Multiforme

Complications Associated with Herpes Zoster ➧

Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis (Lyell’s Syndrome)

Dermatitis Herpetiformis

➧

Bullous Impetigo

Predominantly Bullous Lesions

➧

Epidermolysis Bullosa

Pemphigus

➧

Linear IgA Disease

➧

Hand, Foot and Mouth Disease

➧

Herpangina

➧ ➧

There are a variety of oral lesions which clinically present as vesiculobullous (VB) lesions. Although the lesions start as vesicles or bullae they rupture early and appear as ulcerated or erosive areas. As a result they are better called ulcerovesiculobullous diseases. In this chapter common oral VB lesions will be discussed. A vesicle is defined as a fluid-filled elevated lesion, less than 1 cm in diameter. A bulla is a fluid-filled elevated lesion greater than 1 cm in diameter.

CLASSIFICATION OF VESICULOBULLOUS LESIONS I. Acute and chronic vesiculobullous lesions (Table 1) II. Based on the clinical presentation 1.

174

Predominantly vesicular HSV infection Varicella infection Hand, foot and mouth disease

2.

Herpangina Dermatitis herpetiformis Predominantly bullous Pemphigus vulgaris Bullous pemphigoid Benign mucous membrane pemphigoid Bullous lichen planus Erythema multiforme Stevens–Johnson syndrome Bullous impetigo Epidermolysis bullosa Linear IgA disease

III. Histopathological classification Intraepithelial vesiculobullous lesions HSV infection Varicella infection Herpangina Hand, foot and mouth disease Pemphigus Familial benign chronic pemphigus

Chapter 7 – Vesiculobullous Disorders

Table 1 Comparison between acute and chronic vesiculobullous lesions

Table 2

Site of latency of viruses

Name of virus

Acute—VB lesions

Chronic—VB lesions

Duration

Short

Long

Age

Young

Middle aged—older

Etiology

Allergy, burns, viruses

Autoimmune

Examples

Herpes simplex infections

Pemphigus

Chicken pox

Bullous pemphigoid

Herpes zoster

Cicatricial pemphigoid

Herpangina

Bullous lichen planus

Hand, foot and mouth disease

Chronic herpes simplex

Erythema multiforme

Linear IgA disease

Site of latency

HSV 1 & 2, VZV

Sensory nerve ganglia

CMV

Lymphocytes, salivary gland tissue (rarely)

EBV

B lymphocytes and salivary gland tissue

HHV-6, HHV-7

CD4 lymphocytes

HHV-8

Still unknown but believed to be associated with B lymphocytes circulating in hematopoietic system

Epidermolysis bullosa Mucosal erythema multiforme Subepithelial vesiculobullous lesions Bullous pemphigoid Cicatricial pemphigoid Epidermolysis Bullosa Dermal Erythema multiforme Dermatitis herpetiformis Linear IgA disease

It is estimated that out of the 80 known herpes viruses, at least eight are known to infect human beings. The herpes viruses that are known to cause infection in humans are herpes simplex virus (HSV 1 and 2), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpes virus 6 (HHV-6), human herpes virus 7 (HHV-7) and human herpes virus 8 (HHV-8). These viruses are usually transmitted from host to host by direct contact or through saliva and genital secretions. Herpes viruses are shed in the saliva of asymptomatic hosts. When an individual comes in contact with the virus, primary infection is seen. Subsequently these viruses establish latency in the host. The site of latency for each form of herpes virus is different (Table 2).

IV. Based on whether the lesions are infectious or non-infectious

HERPES SIMPLEX VIRUS (HSV) INFECTIONS

Infectious VB lesions Herpes simplex infections Varicella infections Herpangina Hand, foot and mouth disease Non-infectious VB lesions Pemphigus Paraneoplastic pemphigus Bullous pemphigoid Cicatricial pemphigoid Erythema multiforme Dermatitis herpetiformis Epidermolysis bullosa acquisita Linear IgA disease

PREDOMINANTLY VESICULAR LESIONS Herpes Viruses The word herpes is derived from the Greek word ‘herpein’ which literally means to creep. The word signifies the creeping or spreading nature of the skin lesions caused by many of the herpes viruses.

Etiology and pathogenesis Herpes simplex virus infection is caused by two types of DNA viruses namely HSV 1 and HSV 2. Characteristically, HSV 1 is responsible for infections involving the oropharyngeal regions, dermatitis and meningoencephalitis (infections above the waist) and HSV 2 is responsible for anogenital infections (infections below the waist). However, changing sexual practices have shown that these viruses may not necessarily be responsible for infections of specific sites. In contrast to other viruses HSV needs physical contact to transfer infection. The incubation period ranges from 2 days to 3 weeks. After the primary infection the virus hides within the trigeminal ganglia and becomes activated when the environment is conducive for viral replication. Approximately 90% of USA population is seropositive for antibodies to HSV. Of this group only 1% exhibit primary herpetic infections and 30–40% demonstrate recurrent infections. Primary HSV infections are usually seen after 6 months of age and peak at about 2–3 years of age. Other specific HSV infections include herpetic whitlow, herpetic gladiatorum, herpetic meningoencephalitis, herpetic conjunctivitis, herpetic eczema (Kaposi’s varicelliform eruption) and disseminated herpes simplex of newborn. 175


Clinical features Primary HSV infection Only 1% of the population in USA exhibit all signs and symptoms of primary infection. It usually affects young children and adolescents, and occasionally young adults. The primary HSV infection seldom occurs in the first 6 months of life as the infant is protected by the maternal antibodies that are still circulating in the newborn. Primary herpetic gingivostomatitis is characterized by fever, malaise, anorexia, irritability and regional lymphadenopathy (especially, submandibular and superficial cervical group of nodes are involved). Subsequently the mouth becomes sore and the individual may complain of burning sensation in the mouth and difficulty in swallowing. Apart from the gingiva, the buccal mucosa, palate, tongue, tonsillar and pharyngeal region may be affected. The gingiva is erythematous, boggy and bleeds spontaneously or on the slightest of provocation. As the disease advances multiple tiny to moderately large (few mm to almost a centimeter in size) yellow colored vesicles develop that rupture to form shallow painful ulcers that are usually covered by a grayish colored membrane. These ulcers are bound by an erythematous halo. Generally in about 2 weeks the lesion heals without scarring. Immediately after the resolution of the primary lesion, the virus travels along the nerve pathway and lies dormant in the nerve ganglia regional to the site of the primary infection. Within the regional ganglion the virus incorporates its DNA into the host’s DNA thereby establishing the beginning of a life-long affliction. The trigeminal ganglion is usually the site for dormancy for HSV-1 and HSV-2.

HERPETIC WHITLOW AND HERPES GLADIATORUM Herpetic whitlow is an intense painful infection affecting the fingers or toes of children, adults and healthcare workers. It typically involves the terminal phalanx of the index and thumb fingers of children and healthcare workers. It is believed that HSV-1 is responsible for 60% of the known cases of herpetic whitlow and 40% are caused by HSV-2. In children, most cases can be attributed to autoinoculation of HSV-1 (infants suffering from acute herpetic gingivostomatitis who engage in thumb/finger sucking). In young adults and elderly, herpetic whitlow is caused by autoinoculation of HSV-2, usually due to digital-genital contact. Literature review reveals few reports describing herpetic whitlow affecting the toe. Ozawa et al (2004) reported an elderly patient who exhibited herpetic whitlow of the toe. The lesions of herpetic whitlow are usually preceded by prodromal symptoms of burning or tingling sensation and pruritus of the affected digit and sometimes the whole limb. 176

As the lesion progresses, the involved digit reveals multiple tiny vesicles which are extremely tender. The surrounding area appears edematous and erythematous. The lesion may rupture to form shallow ulcers and subsequently heal in about 10 days time. Similar vesicular lesions seen on the bodies of sportsmen (especially contact sports) and wrestlers is referred to as herpes gladiatorum. Investigations Typical clinical features will usually suffice to make a clinical diagnosis. However for definitive diagnosis cytological smears, antibody titers and viral isolation can be used. Cytological smear requires deroofing a fresh vesicle, followed by scraping of the base of the lesion and the smear made should be stained with Papanicolaou’s, Wright’s or Giemsa’s stain. The characteristic findings include the presence of multinucleated giant cells and intranuclear viral inclusion bodies such as Lipschütz bodies or Cowdry Type A (ovoid, amorphous, eosinophilic bodies that exhibit peri inclusion halo that is caused by the peripheral displacement of the nucleolus and the nuclear chromatin). The cells exhibit ballooning degeneration of the nucleus. On biopsy the microscopic features include an ulcerated epithelium with large keratinocytes showing glassy giant marginated nuclei (Tzanck cells) (Figures 1 and 2). Alternatively viral isolation can be done. It is one of the most definitive methods of identifying HSV. Serological tests can be used to detect antibodies in patient suffering from primary HSV. For the test, blood sample should be taken in the initial 3 days of an acute infection. Alternatively a convalescent blood sample can be obtained 4 weeks after the primary infection. It is believed that the antibody titer should increase by four times in convalescent serum sample for the diagnosis of the primary infection.

RECURRENT HERPES INFECTIONS Almost 30–40% of the individuals exposed to HSV infection will exhibit at least one episode of recurrent herpes infections. Recurrent infections can present either as recurrent herpes labialis or recurrent intraoral herpes. Various factors have been known to trigger these recurrent attacks such as stress, trauma, exposure to sunlight and menstruation. These recurrent infections usually have a milder course.

Herpetic Labialis This is the most common secondary herpetic lesion, usually following exposure to UV light or extreme cold.


Figure 1

Figure 3

Clusters of vesicles in a 26-year-old female, characteristic of herpes labialis. Courtesy: Dr Nagamani Narayana, Nebraska, USA

Photomicrograph of herpetic ulcer. H&E stain (10⫻). Arrow points to acantholytic cells and Tzanck cells. Courtesy: Dr Nagamani Narayana, Nebraska, USA

Figure 2

treatment. These are also present with prodromal symptoms such as paresthesia, swelling, burning and tingling. Secondary herpetic lesions recur, and the recurrence rate is ⬎ 6 times/year. Secondary intraoral herpetic lesions are seen in patients who are immunocompromised from HIV/AIDS, pre-transplant and post-transplantation surgery or post-chemotherapy. Intraorally ulcerations occur on bound and mobile mucosa. Yeo et al (2002) reported the presence of herpes labialis in musicians who play woodwind instruments and brass instruments such as the flute, saxophone, trumpet and horn. They suggest that the herpetic lesions are precipitated by mechanical trauma of the lips and stress suffered by the musicians preparing for a performance. It is commonly seen that the woodwind players tend to have lesions on the lower lip and brass instrument players have herpetic lesions on the upper lip. Differential diagnosis

Photomicrograph (40⫻). Arrow points to a Tzanck cell with large molded nucleus. Courtesy: Dr Nagamani Narayana, Nebraska, USA

Groups of vesicles appear at the vermillion border, and rupture may result in crusty lesions. The lesions are tingly and painful, normally healing within 2 weeks. The lesions are highly contagious at the weeping stage. Intraoral herpetic lesions are evident as clusters of vesicles (Figure 3). These vesicles rupture, leaving ulcerations on bound mucosa, usually within 3 days of recent dental

Acute herpetic infections Streptococcal pharyngitis, erythema multiforme and acute necrotizing ulcerative gingivostomatitis (ANUG) have to be considered. All these lesions will demonstrate systemic signs and symptoms. Erythema multiforme lesions occur commonly on the lip and less often on the gingiva. Lip lesions are bleeding and crusty. In ANUG the gingival lesions demonstrate punched-out interdental papilla with accompanying bleeding and halitosis. Secondary herpetic infections Consider aphthous ulcers in the differential diagnosis of intraoral recurrent lesions. Aphthous ulcers are found on mobile mucosa and do not go through a vesicular phase. The ulcers are painful and are difficult to differentiate from herpes simplex lesions. 177


Table 3

Treatment regimen for different kinds of HSV infection Immunocompetent

Immunosuppressed

Primary herpetic gingivostomatitis— children

Symptomatic—no aspirin or NSAIDs

Acyclovir capsules 200 mg or valacyclovir caplets 500 mg

Primary herpetic gingivostomatitis— adult

Symptomatic, aspirin and NSAIDs, magic mouthwash

Acyclovir capsules 200 mg, 5 times daily for 10 days or valacyclovir caplets 500 mg, 2 caplets twice daily for 5 days

Recurrent herpetic labialis

Abreva, Denavir 5%, valacyclovir 1,500 mg, single dose or valacyclovir 750 mg, twice daily for 1 day started within 1 hour of onset of prodromal signs

Valacyclovir caplets 500 mg, 4 caplets taken at prodromal symptoms and 4 caplets 12 hours later

Recurrent intraoral herpes

Acyclovir 200 mg 5 times a day for 10 days

Treatment The aims of managing HSV infections are to inhibit autoinoculation and transmission. The management is targeted at symptomatic relief. Topical and systemic antivirals like acyclovir can be used (Table 3). To be effective all treatment should be started within 72 hours of initial disease presentation. Patient compliance is shown to be better with fewer and shorter doses (Whitley, 2006). Prognosis The main question arises should you treat these patients when they have recurrent lesions. Universal precautions including use of gloves enable us to do proceed with treatment. If the lesions are oozing and will transfer virus to other sites and patient has no emergency it is advisable to postpone treatment. If in an emergency application of rubber dam may help in decreasing transmission of virus to other sites. Herpes simplex virus infections are described in detail in Chapter 4 on Bacterial, Viral and Fungal Infections.

VARICELLA ZOSTER INFECTIONS The primary and secondary infections are caused by VZV belonging to Herpedes family. Chicken pox is the primary infection and herpes zoster is caused by reactivation of the VZV. This infection occurs due to inhalation and primary infection occurs in children. Reactivation occurs when the patient is stressed or immunosuppressed. It usually affects dermatomes in the trunk, head or neck. Clinical features Primary infection (chicken pox) Primary varicella infection occurring in children is characterized by fever, chills, malaise and headache with a quick rash. The rash is pruritic 178

and may get secondarily infected. The common sites of involvement are the trunk, face and extremities. Intraorally, the buccal mucosa, tongue, palate, gingiva and pharyngeal mucosa are affected. Oral mucous membrane may show multiple shallow ulcers preceded by thin walled vesicles, which are usually not very painful. In adults varicella may result in complications like pneumonitis, encephalitis, and fetal abnormalities when seen in pregnancy. Secondary infection (herpes zoster) Herpes zoster is the reactivated form of the VZV. It is also referred to as shingles. The word shingles is reportedly derived from the Latin word ‘cingulum’ which means ‘girdle’. The term girdle is apt to describe the lesion of herpes zoster as it presents as a unilateral rash that can wrap around the waist or torso like a girdle. The word zoster is Greek word that refers to a belt like object that is used by warriors to hold the armor in place at the waist. Secondary varicella zoster infection occurs in adults with altered immune status or under stress and is unilateral. The main distinguishing feature of VZV is unilateral and involves one of the branches of the trigeminal nerve. Clinically tingling and vesiculation similar to herpes simplex are seen. Clinical appearance of these lesions is very similar to herpes simplex except for the unilateral location (Figures 4 and 5). Patients may complain of mild to severe pain that may exacerbate on the slightest of touch. The dermal lesions usually resolve in about a week forming a scab.

Complications Associated with Herpes Zoster The most common complication associated with HZ is the development of postherpetic neuralgia. In this condition the pain continues to persist even after the herpetic lesions have resolved. The pain is typically presented as sharp or burning pain. Postherpetic neuralgia is usually seen in individuals over the 5th decade of life.


Figure 4

present with painful inflammatory condition of the eye along with impaired vision or transient blindness. Some individuals exhibit only the prodromal symptoms of pain and paresthesia without the development of visible cutaneous rash. This phenomenon is referred to as ‘zoster sine herpete’. Ramsay Hunt syndrome is one of the rare manifestations of HZV infection where geniculate ganglion is involved. The facial and auditory nerves can be involved. The condition is characterized by facial paralysis, pain and vesicles in the external auditory canal and pinna of the ear and the oral cavity. Other associated findings are tinnitus, vertigo and ipsilateral hearing loss. Investigations Cytological smears derived from the vesicles reveal multinucleated giant cells along with intranuclear inclusion bodies. PCR and direct immunofluorescence assay are more effective in diagnosing HZV infections.

Herpes zoster seen in a 70-year-old male with papular lesions on the left half of his face. Courtesy: Dr Nagamani Narayana, Nebraska, USA

Figure 5

Differential diagnosis Recurrent herpetic lesions and aphthous ulcers should be considered in the differential diagnosis of intraoral lesions. Treatment and prognosis In healthy patients if the diagnosis occurs within 72 hours of initiation of the disease a course of acyclovir or valacyclovir can be administered. If the patient is seen later during the course of the disease symptomatic relief in the form of magic mouthwash can be prescribed. In immunosuppressed patients a prescription of acyclovir or valacyclovir can be administered. It is some belief that a prescription for antiviral and corticosteroid therapy prevents postherpetic neuralgia.

HAND, FOOT AND MOUTH DISEASE

Herpes zoster seen in a 70-year-old male with ulcerations in the palate, characteristically involving one half of the palate. Courtesy: Dr Nagamani Narayana, Nebraska, USA

The term hand, foot and mouth (HFM) disease was used for the first time in 1960 following an outbreak of a relatively mild febrile condition associated with papular and vesicular lesions on the dermis and the oral cavity in Birmingham, England. Etiology

Herpes zoster is generally unilateral. However in immunocompromised individuals or an associated malignancy, herpes zoster can exhibit a generalized involvement. Other relatively uncommon complications involve encephalitis, peripheral nerve palsies and myelitis. Zoster ophthalmicus is seen when herpes zoster involves the ophthalmic ganglion of the trigeminal nerve. Patients

Enteroviruses are known to cause HFM disease. The enteroviruses that have been implicated are Coxsackie virus serotype A 16, Coxsackie virus serotype A 4 to 7, 9, 10 and Coxsackie virus serotype B 1 to 3 and 5. Asia Pacific region including regions like Singapore, Japan, Indonesia, Malaysia and Taiwan in the 1970s reported severe forms of HFM disease resulting in a widespread epidemic. The cause for this 179


epidemic was Enterovirus-71 A, B, C (EV 71). The EV-71 apart from causing HFM disease can also cause flaccid paralysis, myocarditis, pulmonary hemorrhage, encephalitis and meningitis. Deshpande et al (2003) isolated a strain of EV-71 from the stool of a child suffering from acute flaccid paralysis following administration of oral polio vaccine. They termed this isolated strain as EV 71 D genotype. Sasidharan et al (2005) studied 81 children (age group of 7 months to 8 years) who presented with papulovesicular exanthems in Calicut, India. In their study 19 children showed a significant rise in the titers of IgM antibody against EV-71. Infection usually occurs by the fecal-oral route, leading to viremia and invasion of the skin and mucosa. The incubation period is approximately 3–7 days. Clinical features Patients usually present with prodromal symptoms such as low-grade fever, malaise, anorexia, myalgia, headache, cough, rhinorrhea and sore throat. The skin of the hands and feet along with the oral mucosa are involved. The oral mucosa and the hand are almost always affected. The skin lesions are characterized by the presence of numerous erythematous macules in the initial stage. As the disease progresses vesicles begin to appear in the macules which subsequently heal without crusts in about 10 to 14 days. The common sites of involvement are the palms and fingers of the hand, and soles and toes of the feet. Other sites that are less commonly affected are the trunk, external genitalia and the buttocks. Oral manifestations The oral lesions usually occur before the skin lesions. Multiple vesicles and ulcers may be seen affecting any part of the oral mucosa. However the common sites that are involved include the tongue, buccal mucosa and hard palate. Patients usually complain of pain, sore throat and dysphagia. Oral lesions usually heal without complications in about 7 days time. The oral manifestations of HFM disease mimic lesions of herpangina, acute herpetic gingivostomatitis, recurrent herpetiform and minor aphthous ulcerations and erythema multiforme. Management The disease is self-limiting and needs to be symptomatically managed. Systemic antipyretics (paracetamol suspension or tablet), topical analgesic mouthrinse (benzydamine hydrochloride) and topical anesthetic agents (2% lignocaine gel) are effective in the management of fever and sore mouth. 180

HERPANGINA Herpangina was first described by John Zahorsky in 1920. Herpangina is primarily caused by coxsackie virus A 1-10, 16, or 22. Other viruses that may cause herpangina are coxsackie virus B 1-5, enterovirus 71 and echovirus 3, 6, 9, 11, 16, 17, 22, 25, and 30. Herpangina occurs in epidemics and usually occurs in the summer months. It usually affects young children and adolescents. The mode of spread is the fecal-oral route. The incubation period varies from 1 to 10 days and usually lasts 4 days. Clinical features Compared to hand, foot and mouth disease the disease process is usually mild and patients may not exhibit overt prodromal symptoms. Patients may present with mild rise in temperature, malaise, anorexia, abdominal pain, sore throat and cervical lymphadenopathy. Oral manifestations Oral manifestations are very typical of this condition. Multiple minute vesicles and ulcers roughly measuring 1–2 mm in diameter are seen. The ulcers are surrounded by an erythematous halo. These lesions are typically confined to the posterior part of the oral cavity such as the faucial pillars, tonsillar region, posterior pharyngeal region, soft palate and uvula. Very rarely the posterior parts of the buccal mucosa and tongue are involved. Patients may complain of sore throat and difficulty in swallowing. Management Herpangina is a self-limiting disease. The fever associated with this condition usually subsides within 3–4 days. The oral ulcers heal within a week. The condition can be managed symptomatically with antipyretics and analgesic/ anesthetic mouthrinses.

DERMATITIS HERPETIFORMIS Dermatitis herpetiformis (DH) is a rare, chronic, pruritic immunobullous disorder of the skin that is associated with gluten hypersensitivity. The condition is characterized by the subepidermal deposition of IgA antibody against the tissue transglutaminase. Antibody deposition leads to the formation of dense neutrophilic abscesses, subepidermal vesicles and bullae. Spurkland et al (1997) described the genetic basis for DH. They showed that DH and celiac disease are associated with class II HLA alleles A1*0501 and B1*02, which encode the HLA-DQ2 heterodimer. Salmela et al (2001) showed that there was an upregulation of metalloelastase in both intestinal and lesional skin.


Clinical features Dermatitis herpetiformis usually affects individuals in the 2nd and 3rd decade of life. Dermal lesions are characterized by blisters over an erythematous or urticarial base. The lesions are pruritic. The common sites of involvement include the knees, elbows, scalp, back and buttocks. It is believed that about 10% of the patients present with symptoms of celiac disease. DH is believed to be associated with some of the autoimmune and connective tissue diseases such as Type I diabetes mellitus, pernicious anemia, autoimmune thyroiditis, Sjögren’s syndrome, lupus erythematosus, sarcoidosis, scleroderma and psoriasis. DH has also been frequently associated with hypopigmentation. Oral manifestations Dermatitis herpetiformis can involve any part of the oral mucosa. It manifests as multiple vesicles are bullae. These fragile vesicles rupture immediately to form shallow painful ulcers. Investigations Histopathologically, presence of microabscesses in the dermal papillae and subepithelial blister formation are some of the findings associated with DH. The characteristic finding in DH is the presence of eosinophilia. Direct immunofluorescence test reveals the presence of antibodies IgA, IgM and IgG at the junction of the dermis and epidermis. Dietrich et al (1999) demonstrated that the level of immunoglobulin A autoantibodies to endomysium in patients with DH was significantly elevated. Patients exhibit sensitivity to halogens. Management Dermatitis herpetiformis usually runs a prolonged course and sometimes persists for life. Patients are advised to avoid gluten in the diet. Dapsone is usually the drug of choice. In the initial stages 50 mg/day is given and later increased to about 300 mg/day as per the requirement.

PREDOMINANTLY BULLOUS LESIONS

Table 4

Antigens targeted by autoantibodies and corresponding forms of pemphigus

Antigens

Forms of pemphigus

Desmoglein 3

Predominantly mucosal pemphigus vulgaris

Desmoglein 3, desmoglein 1 and probably desmoglein 4

Mucocutaneous pemphigus vulgaris

Desmoglein 1

Pemphigus foliaceous

Desmoglein 3, Desmoglein 1 and plakin proteins

Paraneoplastic pemphigus

Adapted from Ettlin DA, Dent Clin North Am 2005;49:110.

short lived and easily break down resulting in ulcerations. The term ‘pemphigus’ is derived from the Greek word pemphix which literally means a blister or bubble. Chidgey (2002) in his update on desmosomes and disease described pemphigus as an autoimmune disorder that manifests with damage to the desmosomes of epithelial cells induced by the activity of antibodies against transmembrane desmosomal glycoproteins belonging to the cadherin supergene family of desmogleins (Dsg), resulting in intraepithelial immuno-deposits and breaking of intercellular bridges’. Table 4 summarizes the antigens targeted by autoantibodies in various forms of pemphigus. Types of pemphigus The three basic types of pemphigus depending upon the extent of epithelial involvement and clinical presentation include: 1.

2.

3.

Pemphigus vulgaris Pemphigus vegetans—variant of pemphigus vulgaris characterized by excessive granulation and crusting Pemphigus foliaceous Idiopathic pemphigus foliaceous Drug induced pemphigus foliaceous Pemphigus erythematosus Endemic pemphigus foliaceous/fogo selvagem Paraneoplastic pemphigus-associated with neoplasms Pemphigus vulgaris and vegetans—pemphigus foliaceous and erythematosus Affects entire epithelium Involves oral mucosa—affects upper prickle/spinous layer of epithelium of skin

Pemphigus Pemphigus is an autoimmune disease characterized by intraepithelial blister formation due to a breakdown in intercellular adhesion. This breakdown process is referred to as primary acantholysis. Prior to the advent of steroids, pemphigus was fatal due to fluid loss and electrolyte imbalance and bacterial infection. Pemphigus presents itself as clinically characterized vesicles and bullae. The lesions are

Pemphigus Vulgaris Epidemiology Pemphigus vulgaris occurs equally in both sexes during the 4th and 5th decades. Studies have shown a slight increased incidence in Ashkenazi Jews and individuals with HLA-DR, HLA-A10, HLA-DRB1 phenotypes. Other autoimmune 181


diseases such as myasthenia gravis, lupus eythematosus, rheumatoid arthritis, Sjögren’s syndrome and Hashimoto’s thyroiditis also may be present. Etiopathogenesis The underlying mechanism causing the characteristic intraepithelial lesion of pemphigus vulgaris is the binding of specific IgG antibodies to an antigen on the epithelial cell membrane. The stimulus that triggers the abnormal IgG production is unknown. However certain exogenous factors such as medications, dietary components and unknown environmental factors can induce or perpetuate pemphigus in a genetically predisposed individual. There is evidence that the binding of IgG antibody to the pemphigus antigen leads to epithelial cell separation by triggering either complement activity or the plasminogenplasmin system. IgG autoantibodies are said to target two structural proteins of the desmosomes namely desmoglein 1 and desmoglein 3. Recently a new pemphigus antigen desmoglein 4 has been discovered and implicated in the pathogenesis of pemphigus vulgaris. Immunogenetic aspects of etiology The increased incidence of pemphigus in Jews leads to the proposition that there is a genetic predisposition to the disease and initial studies examined the frequency of MHC class I antigens in affected individuals. The first evidence for genetically determined susceptibility was the demonstration by Krain et al (1973) of an increased frequency of HLA-A10 in Caucasian patients with pemphigus vulgaris, especially in those who were Jewish. A strong association with HLA-A10 was also noted in Japanese patients by Hashimoto et al (1977). Katz et al (1973) have reported an association between HLA-A13 and pemphigus vulgaris, but this has not been confirmed by others. Subsequent studies have shown that almost all pemphigus vulgaris patients have either HLA-DR4 or DRW6 haptotypes. Also the disease susceptibility has been linked to an HLA-DQB gene.

Oral manifestations ❍

❍

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Oral lesions usually appear first in this disease. Almost 80–90% of the patients with pemphigus vulgaris develop oral lesions sometime during the course of the disease and in 60% of the cases oral lesions occur first. The typical oral lesion begins as a bulla on a noninflamed base, which almost immediately ruptures to produce shallow ulcer. The margins of the ulcer show evidence of tissue tags. The commonly involved sites are the buccal mucosa (sites of trauma along the occlusal plane), gingiva and palate (Figure 6A, B). The edges of the shallow ulcers extend peripherally over a period of weeks until they involve large portions of the oral mucosa. Distal extension from the oral cavity causes involvement of the esophagus, pharynx and larynx, which causes hoarseness of voice and dysphagia.

Clinical features


❍

Various bullous diseases that pemphigus vulgaris must be differentiated are epidermolysis bullosa, erythema multiforme, bullous pemphigoid, cicatricial pemphigoid, bullous drug eruptions and other forms of pemphigus. The histological presence of suprabasal intraepidermal bulla with acantholysis is characteristic of pemphigus and usually differentiates it from other similar diseases.

❍ ❍ ❍

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182

nail folds may be involved first, together with the oral lesions. ❍ Dermal lesions are characterized by bullae over the skin. Fluid in the bullae appears clear at first but later it may become hemorrhagic or even seropurulent. Initially the bullae are tense, but soon become flaccid and rupture to form erosions which ooze and bleed easily. The denuded areas sometimes are partially covered with crusts with little or no tendency to heal and enlarge by confluence. The healed lesions usually leave hyperpigmented patches. However in some instances these solitary erosive areas may coalesce and involve extensive areas of the skin. ❍ Nikolsky’s sign (first described by Pyotr Vasiliyevich Nikolsky in 1896) is positive. The Nikolsky’s sign is positive if slight pressure or rubbing of the skin produces lateral movement of the upper layers of the epidermis. ❍ The Asboe-Hansen sign, or ‘bulla spread phenomenon’, is positive in pemphigus. Gentle pressure on an intact bulla will force the fluid to spread under the skin away from the site of pressure.

Occurs in the 5th and 6th decade of life. Rarely affects younger individuals. Men and women are equally affected. It most commonly occurs in Jews, Greeks, east Indians and individuals from the orient. Pemphigus vulgaris affects the mucosa and skin, resulting in superficial blisters and chronic ulceration. Various mucosal surfaces may be involved such as the oral, ocular, nasal, pharyngeal, laryngeal, upper respiratory and anogenital mucous membranes. The common sites of involvement are the groin, scalp, face, neck, axillae and genitals. However the

Investigations Cytology Smears taken from freshly opened vesicles are usually preferred. Tzanck cells can be seen. These are epithelial cells that are free in the vesicular space and are


Figure 6 A

B

(A) Shallow ulcers on the buccal mucosa in a patient with pemphigus vulgaris. (B) Shallow ulcers on the palate in a patient with pemphigus vulgaris. Courtesy: Dr Sumanth

characterized particularly by degenerative changes which include swelling of the nuclei and hyperchromatic staining. This is also referred to as Tzanck test. Shklar in 1971 reported that there is a marked increase in RNA in the cytoplasm of these acantholytic cells as well as in the epithelial cells at the floor of the vesicles. Histopathology Tissue specimen for biopsies is obtained from the active border of a denuded area, as intact blisters are rarely seen. The characteristic histological finding is an intraepidermal bulla resulting from a loss of cell-cell adhesion of keratinocytes. Although the basal cells lose lateral desmosomal contact with the adjacent cells, hemidesmosomes are intact. Therefore, attachment to the basement membrane is maintained, giving the appearance of a ‘row of tombstones’. Other pathologic changes seen are acantholysis, cleft and blister formation in the interdermal areas just above the basal cell layer and acantholytic cells. The separation of cells in the layers of the stratum spinosum is known as acantholysis. The loss of contact between the malphigian cells begins with the detachment of tonofilaments from the desmosomes, loss of intercellular cement substances and cellular degeneration with formation of the interepidermal cleft or bulla (Figure 7). Immunofluorescent studies In pemphigus vulgaris the antibody will bind the immunoglobulin deposits in the intercellular substance and exhibits a positive fluorescence under the fluorescent microscope. This is termed ‘fish-net’ pattern of binding. Management Pemphigus was traditionally considered a potentially fatal disease. Before the advent of effective therapies, mortality

Figure 7

Photomicrograph of the histological section of pemphigus vulgaris. Courtesy: Department of Oral Pathology, MCODS, Mangalore

approached 90%. However in the recent times the mortality rate is said to be approximately 10%. Topical therapy ❍ Eroded and crusted, painful skin lesions and the associated foul odor can be effectively managed by bathing the area with 0.01% potassium permanganate solution or 0.5% silver nitrate solution. ❍ Alternatively the raw surfaces can be sprayed with corticosteroids or 2% procaine hydrochloride. ❍ Chlorhexidine mouthrinses can be used to alleviate discomfort and malodor. 183


❍

Painful oral ulcerations can be managed by topical application of viscous xylocaine especially before food intake.

Systemic therapy Corticosteroids: Systemic administration of corticosteroids comprises three phases: – Control phase: Characterized by an initial high dose corticosteroid administration to the point of obvious clinical improvement. Therapy is initiated by giving 60–160 mg of prednisone daily. If there is no response even after a week, the dosage is doubled. When new lesions cease to form and old lesions heal, the dosage is decreased slowly. Lever (1977) suggests 180–360 mg of prednisone daily for 6–10 weeks. – Consolidation phase: In this phase the dosage of prednisone is reduced over a period of several weeks. According to Arnold, once the control over the disease is achieved, an attempt to decrease the steroid dose by transferring the patient to intramuscular injections of triamcinolone acetonide is highly advisable. – Maintenance phase: The corticosteroids are gradually tapered down to alternate day dose and ultimately stopped. However this reduction in dosage is made possible by replacing steroids with immunosuppressive drugs. The dosage of immunosuppressive drugs is reduced to zero in several months. ❍ Immunosuppressive agents: Azathioprine 100–200 mg per day in conjunction with prednisone 150–200 mg daily can be used. Fellner et al reported good results by combining 200 mg of prednisone with 100–200 mg cyclophosphamide. Other agents that have been used with mixed results are dapsone, gold sodium thiomalate and aurothioglucose. ❍ Plasmapheresis: It is particularly useful in patients who are refractory to corticosteroids. It involves removal of the circulating antibodies. ❍ Photopheresis: This modality of treatment was described by Rook et al. It involves administration of 8-methoxypsoralen followed by exposure of peripheral blood to ultraviolet radiation, causing photoinactivation of WBC. ❍ Immunomodulators: Chaffins et al in 1993 reported that drugs like levamisole (100 mg/week), combination of nicotinamide and tetracycline and oral prostaglandins are effective in the treatment of pemphigus. ❍

ulcerations and polymorphous skin lesions that progressed to blisters on the trunk and extremities. It was found that the autoantibodies from these patients reacted with an antigen complex composed of desmoplakin I and the 230-kd antigen of bullous pemphigoid. Paraneoplastic pemphigus is characterized by extensive mucocutaneous erosions associated with a neoplasm such as leukemia, lymphoma, sarcomas, thymomas, Castleman’s disease, Waldenström’s macroglobulinemia (high levels of macroglobulin [IgM], increased serum viscosity, and lymphoplasmacytic infiltrate in the bone marrow) pancreatic carcinoma, bronchogenic squamous cell carcinoma or intraductal breast carcinoma. It is believed that almost 80% of the patient’s suffer from either non-Hodgkin’s lymphoma, chronic lymphocytic leukemia or Castleman’s disease. Clinical features The predominant feature of paraneoplastic pemphigus is painful mucous membrane erosions, of which oral erosions are the first sign of disease in 22.2% of cases. The most common sites involved are the lips and oral mucosa, with multiple, severe, persistent erosions. Symptoms of oropharyngeal involvement may include sore throat and dysphagia. Bilateral conjunctival involvement has been noted in up to 72.2% of cases. The skin lesions vary in shape and size, with a confluent erythema of the trunk, on which blisters and erosions form. Erythematous maculopapular lesions with dusky centers or central vesicles may arise on the extremities, mimicking target lesions seen in erythema multiforme. Occasionally, the lesions may be pruritic. Paraneoplastic pemphigus is an extremely rare entity that has an onset at 60 years or older and is more common in women than men. Diagnostic criteria Anhalt in 2004 proposed a four-point minimal criteria for diagnosing paraneoplastic pemphigus: 1.

2. 3. 4.

Paraneoplastic Pemphigus (Paraneoplastic Autoimmune Multiorgan Syndrome) Anhalt and coworkers in 1990 were the first to suggest the term paraneoplastic pemphigus for a clinically and immunologically distinct condition. They reported five patients with underlying neoplasms associated with painful mucosal 184

Painful and progressive stomatitis which preferentially involves the tongue. This criterion is the most characteristic of this condition. Histologic findings of acantholysis or lichenoid or interface dermatitis. Demonstration of antiplakin autoantibodies, which are the key serological markers for this condition. Demonstration of an underlying lymphoproliferative neoplasm.

Histopathologic features and immunological studies On histopathologic examination, paraneoplastic pemphigus appears to be a combination of pemphigus vulgaris and erythema multiforme. There is suprabasilar acantholysis as


seen in pemphigus vulgaris, as well as basal cell vacuolation, lymphocytic exocytosis, and dyskeratotic keratinocytes typical of erythema multiforme. Paraneoplastic pemphigus is distinguished from the other forms of pemphigus as direct immunofluorescence reveals not only IgG and C3 deposits within the intercellular spaces but also along the basement membrane zone. In the classic forms of pemphigus, indirect immunofluorescence is positive only on stratified squamous epithelial substrates. However, in paraneoplastic pemphigus, there is staining of other tissues, including the bladder, heart, and liver. IgG autoantibodies are directed against desmoplakins I and II (components of the cytoplasmic plaque), which are present in stratified squamous epithelium and these other tissues. Management and prognosis There is little to offer in the treatment of paraneoplastic pemphigus. If a benign tumor is resected, some patients may go into remission. Unfortunately, the prognosis is generally poor, and treatment is usually unsuccessful. Immunosuppressive treatment and plasmapheresis have not been effective; however, immunophoresis may be a promising alternative. Paraneoplastic pemphigus is a rapidly progressive bullous disease that is invariably fatal when associated with a malignant tumor. When paraneoplastic pemphigus occurs in the context of a benign neoplasm, the mucocutaneous erosions will usually show gradual resolution after excision of the tumor. It is important to remember that paraneoplastic pemphigus may precede the clinical appearance of a neoplasm; therefore, it is mandatory that these patients receive screening for neoplasms and regular follow-up care. Other forms of pemphigus are described in Chapter 20, Autoimmune Disorders.

Bullous Pemphigoid Bullous pemphigoid (BP) was first described as a distinct clinical entity by Lever in 1953. It is an autoimmune condition characterized by subepidermal blistering resulting in large, tense bullae involving the skin and rarely the mucous membrane. Autoantibodies are targeted at the components of the basement membrane. Pathophysiology Kasperkiewicz et al (2007) reviewed the pathophysiology of BP. They described that the autoimmune response in BP is directed against two hemidesmosomal proteins within the dermal-epidermal junction, namely BP180 and BP230 (also known as BPAG1). BP230 localizes intracellularly and associates with the hemidesmosomal plaque. BP180 is a transmembrane glycoprotein with an extracellular domain. Most of the

patients have autoantibodies binding to an immunodominant region of BP180, the non-collagenous 16A domain (NC16A), which is located extracellularly close to the transmembrane domain of the protein. Autoreactive T and B cell responses to BP180 have also been found in patients with BP. Wohl and others (2008) studied the expression of vinculin in autoimmune cutaneous diseases. Vinculin is a cytoskeletal protein associated with cell to cell and cell to matrix junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane. On semiquantitative immunohistochemistry investigations they found that the expression and distribution of vinculin are accentuated in patients with various skin autoimmune diseases and appear to be stronger in diseases involving the basement membrane. Clinical features Three distinct clinical types BP have been reported: the commonly known adult form of BP and the relatively rare forms of BP occurring at infancy and childhood. The adult form of BP typically occurs between the 6th and 8th decades of life. Males and females can be equally affected. BP shows no ethnic or racial predilection. Dermal lesions of BP are polymorphous in nature. Literature is replete with reports of non-bullous forms of BP. They can present as urticarial papules, plaques, vegetating forms, nodular lesions, hyperkeratotic areas and erythematous and eczematous lesions. Initial lesions can usually present as urticarial eruptions that progress to bullae over weeks or months. The bullae are pruritic, large and tense. However they generally persist longer due to their thick wall. Over a few days the bullae rupture to form large and tender eroded regions. These bullae can occur in any part of the body such as the axillae, abdomen, legs, forearms and groin. The bullae may contain clear fluid or at occasions contain hemorrhagic content. The erosions heal without scar formation. Involvement of the mucous membrane is relatively uncommon in BP compared to pemphigus vulgaris. The oral cavity and genital and anal mucosa can be affected. Oral bullae tend to rupture and form erosions or ulcers due to the frequent micro trauma sustained during mastication. Childhood BP though rare, is the most common IgG mediated subepidermal bullous disease in children. It typically affects children below the age of 18 years and involves the skin. The mucous membrane involvement is relatively more common than the adult from of BP. The histopathologic picture is similar to the adult form consisting of subepidermal bullae with variable amount of eosinophils and direct immunofluorescent studies show linear deposition of IgG and/or C3 at the basement membrane zone. 185


The infantile form of BP is seen in infants in the first year of life. The mucous membrane involvement is slightly more common than the adult form of BP. However the characteristic feature is the involvement of hand and feet. Maria Isabel Martinez-De Pablo and others (2007) suggest that the IgA mediated autoimmune response predominates in children in contrast to the IgG response that is predominant in adults, due to immunological immaturity or frequent exposure to infectious agents and/or vaccines. Waisbourd-Zinman and others (2008) compared the features of infantile BP with childhood BP. They found that the number of infantile BP individuals is steadily increasing. The predisposition for acral (extremities like the hands and legs) involvement is significantly higher in infants. However the genital involvement is very rare in infantile BP compared to childhood BP. The deposition of IgM at the basement membrane zone was higher in the childhood variety of BP. Oral manifestations Bullous pemphigoid may or not affect the oral mucosa. The incidence of oral involvement varies from 8 to 45%. Some reports suggest that the oral lesions precede the skin lesions. ❍

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Oral lesions are characterized by small bullae, which form slowly and are less painful than those seen in pemphigus vulgaris. Buccal mucosal gingiva are relatively more commonly involved. Gingival lesions consist of generalized edema, inflammation and desquamation with localized area of vesicle formation. Oral lesions of bullous pemphigoid are clearly indistinguishable from oral lesions of cicatricial pemphigoid, but remission of bullous pemphigoid is more common. Bullous pemphigoid may coexist with lichen planus and referred to as lichen planus pemphigoides.

Histopathological and immunofluorescent studies Biopsy specimen from the perilesional area will show subepithelial separation. The epithelium is separated from the connective tissue at the level of the basement membrane. The typical finding in BP is the presence of eosinophils within the content of the bullae. Other inflammatory cells such as lymphocytes and histiocytes are seen. Electron microscopy reveals presence of the bullae within the lamina lucida of the basement membrane resulting in destruction of the anchoring filaments and desmosomes. Generally direct immunofluorescence will be sufficient to diagnose BP. However, some patients demonstrate circulating autoantibodies in the serum. Direct and indirect immunofluorescence reveals deposition of IgG and C3, along the basement membrane zone in a linear fashion. 186

Management and prognosis The clinical course of BP is limited, usually lasting from a few months to years. It is seldom fatal. Almost 50% of the patients exhibit remission in about 6 year duration. Mild cases of BP can effectively be managed with topical corticosteroids. Systemic steroids such as prednisolone is used for managing BP. Steroids can be tapered off with improvement of the condition. Steroids can be used in combination with immunomodulatory drugs such as dapsone, azathioprine and methotrexate.

Mucous Membrane Pemphigoid or Cicatricial Pemphigoid Mucous membrane pemphigoid is an autoimmune chronic inflammatory disorder characterized by subepithelial blistering. It affects the skin, oral mucosa and ocular mucosa. The name cicatricial pemphigoid is attributed to scarring of the conjunctival mucosa. Etiology and pathogenesis The etiology of mucous membrane pemphigoid is unknown. The pathogenesis is believed to be caused by the reaction of IgG antibody with BP protein 180 and laminin 5 which are present in lamina lucida of the basement membrane complex resulting in breakdown of the attachment between epithelium and connective tissue. The molecular players responsible for the pathogenesis in blister formation are still unknown. Clinical features Cicatricial pemphigoid is characterized by the presence of vesicles which heal by scarring. These vesicles generally tend to occur on the mucous membranes of the oral cavity and conjunctiva. It has been reported that 90% of the patients have oral involvement, 66% have conjunctival lesions and approximately 25% have skin involvement. Erosions and scarring may involve other mucous membranes, including those of the nasopharynx, oropharynx, esophagus, larynx, vagina, penis and rectum. Esophageal involvement can cause dysphagia secondary to fibrous adhesions and scarring. Laryngeal erosions, edema and scarring can be life threatening. Oral lesions ❍

Oral lesions can have two clinical presentations—erosions on the non-keratinized mucosa/keratinized gingiva or desquamative gingivitis. ❍ The common sites of involvement are the facial gingiva (64%), buccal mucosa (58%), palate (26%), edentulous alveolar ridge, especially under a prosthetic appliance (16%), tongue (15%) and lower lip (15%).


Figure 8

Figure 10

Oral erosions with distinct margins on the palate in cicatricial pemphigoid. Courtesy: Dr Sumanth

Figure 9

Symblepharon formation in cicatricial pemphigoid. Courtesy: Dr Sumanth, Department of Oral Medicine and Radiology, MCODS, Mangalore

Ocular findings ❍

Subconjunctival scarring leading to blindness in about 15% of the patients. ❍ Initial lesions may be limited to the upper tarsal conjunctiva, where they escape detection if the eyelid is not everted. ❍ Fibrous tracts fuse the scleral and palpebral conjunctiva resulting in symblepharon formation (Figure 10). Histopathology

Desquamative gingivitis in cicatricial pemphigoid, Courtesy: Dr Sumanth

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❍ ❍

Intact vesicles are rarely seen. However according to Martin (1998), it is much more likely to see an intact vesicle in cicatricial pemphigoid than in pemphigus as the lesions are thicker walled and they are subepithelial. The oral ulcers or erosions have a distinct margin. These ulcers generally may become secondarily infected and eventually heal in 3–4 weeks accompanied by scarring and fibrosis (Figure 8). Desquamative gingivitis can present as varying degree of erythematous gingiva either localized or generalized. Areas of erosion and denudation of the gingival surface may be noticed (Figure 9). Nikolsky’s sign is positive. Spontaneous gingival bleeding may be seen.

The classic histological feature of mucous membrane pemphigoid is separation of the epithelium from the underlying connective tissue due to subepithelial separation. A mixed inflammatory infiltrate is present in the underlying submucosa (Figure 11). Direct immunofluorescence demonstrates linear deposition of IgG and C3 at the basement membrane (Figures 12 and 13). Differential diagnosis Mucous membrane pemphigoid must be differentiated from pemphigus vulgaris, BP, lupus erythematosus, lichen planus and paraneoplastic pemphigus. Bullous pemphigoid is similar to mucous membrane pemphigoid, but BP is commonly seen in older women with circulating antibodies to BP protein 230 in addition to BP antigen 180. Treatment and prognosis There is no single treatment for mucous membrane pemphigoid, as it must be tailored to the individual patient similar to pemphigus vulgaris. If extensive lesions involving the oral cavity are present, systemic prednisone may be 187


Figure 11

Figure 13

Direct immunofluorescence pattern of benign mucous membrane pemphigoid with C3 deposited against the basement membrane. Courtesy: Dr Carol Stewart, Florida, USA Intact basal cells and sub-basal separation is seen in benign mucous membrane pemphigoid. H&E stained section (20⫻). Courtesy: Dr Nagamani Narayana, Nebraska, USA

Figure 12

If lesions are extensive, immunosuppressive medications such as azathioprine, mycophenolate and cyclophosphamide may be necessary to manage symptoms. Also, a combination of tetracycline and niacinamide (niacin flush free), 500 mg taken three or four times a day for 6 months with slow tapering, may be helpful in controlling the disease. This latter combination has no known serious side effects and is tolerated well by patients. It is important to educate patients about the disease process and inform them that treatment does not cure the condition, but only helps to control the disease. The disease may cycle through periods of exacerbations and remission over time. These patients should be instructed to undergo an annual eye examination to avoid complications such as blindness.

BULLOUS LICHEN PLANUS

Direct immunofluorescence pattern of benign mucous membrane pemphigoid with the autoantibody IgG-1 deposited against the basement membrane. Courtesy: Dr Carol Stewart, Florida, USA

indicated. Normally a short course of prednisone is prescribed (40 mg per day for 7 days without tapering). Topical steroids may be prescribed either alone or in addition to systemic steroids, as ointments or oral rinse solutions. 188

Hebra used the term ‘leichen ruber’ to describe lichen planus. However in 1869, Erasmus Wilson introduced the term lichen planus (LP). It is believed that almost 0.5 to 1% of the population is affected by lichen planus. Typically lichen planus affecting the skin presents as violaceous, polygonal flat topped papules, usually associated with white striae on their surface. Andreasen classified oral lichen planus into six types namely reticular, plaque-like, erosive, papular, atrophic and bullous lichen planus. It is believed that almost 25% of the individuals present with oral manifestations alone and about 50% of the patients with skin lesions have oral


lesions. Oral lesions are usually seen in women between the 4th and 7th decades of life. Bullous form of lichen planus is the rarest form of the various varieties of oral lichen planus. Bullous oral lichen planus manifests as small vesicles or bullae that rupture easily to form shallow erosions. The lesions of bullous oral lichen planus vary in size from few millimeters to several centimeters in diameter. Patients usually complain of burning sensation and pain when the bullae rupture to form erosive areas. These erosions mimic the clinical presentation of erosive lichen planus. Bullous lichen planus commonly affects the buccal mucosa (frequently seen adjacent to the second and third molar teeth) and lateral margins of tongue. The less commonly affected sites include the gingiva and labial mucosa. The exact etiology of bullous lichen planus is still unclear. However it has been suggested that there is an immunologically induced degeneration of the basal cell layer of the oral mucosa. Histopathological findings Histopathologic evaluation is required for identifying bullous lichen planus. The histopathologic features of dermal lichen planus and bullous lichen planus are the same such as hyperkeratosis and basal cell degeneration, a band of inflammatory cells at the epithelial connective tissue interface, and Civatte bodies may be seen in the epidermal or within the upper dermal cell layers. Gawkrodger et al (1989) stated that the characteristic feature of bullous lichen planus is the subepidermal clefting leading to separation of the epithelium from the basement membrane zone. However direct or indirect immunofluorescence labeling is negative. Lichen planus pemphigoides, bullous pemphigus and pemphigus vulgaris have to be differentiated from bullous lichen planus. Management Topical or systemic steroids, azathioprine, dapsone, cyclosporine, mycophenolate (Nousari et al, 1999) and retinoids have all been used to manage bullous lichen planus. AnneMoon van Tuyll van Serooskerken et al (2007) successfully treated bullous lichen planus on the lip with a combination of tretinoin 0.025% and triamcinolone 0.1%.

morphological appearances such as macule, papule, bullae and crust, hence the name ‘multiforme’. Previously, EM consisted of a disease spectrum that ranged from a mild or minor form, severe or major EM, Stevens–Johnson syndrome (SJS) and the most severe form of the disease, toxic epidermal necrosis (TEN) or Lyell’s syndrome. The present understanding of the disease process, groups EM minor and major into the EM spectrum and SJS and TEN into another group. EM shows very minimal mucosal involvement and less than 10% epidermal detachment. Etiopathogenesis It is estimated that almost 70 to 80% of the cases of EM are triggered by HSV 1 and 2 infections. Besides HSV other bacterial, viral and fungal infections have been reported to trigger EM attacks. Viruses such as CMV, VZV and HIV have been less frequently associated with EM. In children Mycoplasma pneumoniae is reportedly a common etiological agent. Other popular predisposing factors include drugs, chemicals and food coloring and flavoring agents. Medications that have been implicated in triggering EM include nonsteroidal anti-inflammatory drugs, penicillins, phenothiazines, sulfonamides, barbiturates, hydantoins, ciprofloxacin and metformin. EM has also been reported to occur after hepatitis B, smallpox and diphtheria-pertussis-tetanus (DPT) vaccinations. Aurelian et al (2003) and Kokuba et al (1999) studied the association of EM with HSV and drug intake respectively. They reported that the pathogenesis of herpes-associated erythema multiforme is akin to a delayed type hypersensitivity reaction. The disease begins with the transport of viral DNA fragments to distant skin sites by peripheral blood mononuclear cells. HSV genes within DNA fragments are expressed on keratinocytes, leading to the recruitment of HSV-specific CD4⫹ Th1 cells (helper T cells involved in cell-mediated immunity). The CD4⫹ cells respond to viral antigens with production of interferon-gamma, initiating an inflammatory cascade. However the drug-associated erythema multiforme lesions exhibit positivity for tumor necrosis factor-alpha and not interferon-gamma as in herpes-associated erythema multiforme lesions.

ERYTHEMA MULTIFORME

Clinical features

Erythema multiforme (EM) is an acute, reactive, self-limiting and recurring mucocutaneous disorder that causes blistering and ulceration of the skin and mucous membranes. Hebra in 1866 described EM as a benign condition characterized by skin lesions with concentric color changes, which were distributed symmetrically. EM has various

Erythema multiforme may affect individuals of any age. However, it is more common in young adults. Males and females are equally affected. EM lesions seldom present with prodromal symptoms. However mild and non-specific symptoms are reported by some patients such as low-grade fever, malaise, myalgia and diarrhea. The lesions of EM usually appear within 2–3 days of onset of the disease. 189


Figure 14

Photograph showing the characteristic target lesion on the patient’s back. Courtesy: Department of Oral Medicine and Radiology, KLE Society’s Institute of Dental Sciences, Bangalore

The lesions of EM seldom involve more than 10% of the surface area of the body. Though the lesions of EM may involve any part of the body, they are common in the sites of sun exposure, irritation or trauma. The face, oral mucosa, dorsal surface of the hands, feet, elbows and knees are the sites that are commonly affected. The lesions of EM are usually restricted to the oral mucosa unlike Stevens–Johnson syndrome. The typical dermal lesions of EM are target, iris or bull’s eye lesion. These are asymptomatic, discrete, erythematous macules or papules set in a concentric ring pattern usually comprising a central bulla. The iris lesion has three concentric zones: a central dusky or darker red area (central bulla or area of necrosis), a paler pink or edematous zone, and a peripheral erythematous zone (Figure 14). The size of the iris lesion varies from a few mm to about 2 cm in diameter. These lesions usually resolve in about 3 to 5 weeks. However recurrence is generally reported in EM.

Recurrent Erythema Multiforme Schofield et al (1993) studied 65 patients who had recurrent EM. They observed that the mean number of recurrences was 6 per year and the mean duration of the disease was 9.5 years. Sen and Chua (2004) described that the HSV associated EM, mycoplasma associated EM and drug associated EM (repeated readministration) usually present as recurrent EM. They state that infectious agents, commonly viruses (due to reactivation), are likely to be chiefly associated with recurrent EM. It is estimated that about 70% of cases have disease precipitated by HSV.

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Some authors propose that though HSV infection may not be readily apparent, subclinical attacks of HSV may play an important role in the pathogenesis of the disease. Aurelian and others (1998) suggest that most cases of recurrent EM may be herpes-related. Sen and Chua (2004) reported that the recurrent attack usually occurs even before the lesions from the previous attack have completely resolved. They suggest that the individuals suffering from recurrent EM report two or more attacks of erythema multiforme per year, with each episode lasting for about 2 weeks. However one should not use the diagnostic term of recurrent erythema multiforme for individuals with persistent skin lesions lasting weeks to months or a chronic non-episodic course of the disease. One should not consider recurrent erythema multiforme when an individual exhibits only acute mucosal inflammation without skin lesions. The presence of the typical skin lesion is indispensable for the diagnosis of the recurrent form of erythema multiforme. Oral manifestations Mucosal lesions of erythema multiforme are usually restricted to the oral mucosa. However in the major form of the condition mucosa of the eye and genitalia are frequently affected. It is estimated that approximately 40 to 60% of the individuals suffering from erythema multiforme major have oral manifestations. Lips and anterior parts of the oral cavity are frequently affected. The oral lesions of erythema multiforme are manifested as bullae, erosions or ulcers, which may or may not be covered by a pseudomembrane. Target lesions when seen are usually restricted to the lips. The vermillion border of the lip exhibits a characteristic ‘bloody crusted’ appearance (Figure 15). These lesions generally heal without scarring. Gingiva is typically uninvolved. Diagnosis The diagnosis of EM is usually by the typical clinical features. Histopathological features are not specific and hence not diagnostic. Perivascular infiltrate of CD4 and CD8 lymphocytes surrounding swollen blood vessels in the upper dermis with papillary dermal edema is seen. Vacuolar degeneration of the basal layer, subdermal blister formation and epidermal necrosis of keratinocytes can be appreciated. The severity of the keratinocyte necrosis increases with the advancing lesion. The individual necrotic keratinocytes are surrounded by CD8 cells termed ‘satellite cell necrosis’. An overproduction of interferon-gamma by CD4⫹ T helper-1 cells is seen in the epidermis.


Figure 15

STEVENS–JOHNSON SYNDROME AND TOXIC EPIDERMAL NECROLYSIS (Lyell’s Syndrome) Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are presently considered as a spectrum of the same disease process. They can be distinguished from erythema multiforme, varying only in the area of involvement of skin surface. The acute life-threatening conditions are characterized by epidermal sloughing and mucositis secondary to extensive keratinocyte apoptosis. Etiopathogenesis

Bloody crusted appearance of the lips in a patient with erythema multiforme. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Ng and others (2003) used nested PCR to detect HSVDNA in skin biopsies with histologically proven EM. Their findings showed that PCR was positive in 60% of the patients with HSV-related recurrent EM and PCR was positive in 50% of the patients with idiopathic recurrent EM. Differential diagnosis Dermal lesions may mimic lesions of hypersensitivity reactions, drug eruptions and urticarial lesions. Intraoral lesions may resemble recurrent aphthous stomatitis, contact stomatitis and ANUG when the gingiva is involved. Other conditions that can be considered are pemphigus and varicella infections. Management Patients with mild EM usually do not require any form of treatment as the condition is self-limiting. Since EM is usually associated with HSV, oral acyclovir will minimize the duration of the condition. Topical steroids will provide symptomatic relief. The incidence of recurrent EM drastically falls down following treatment with valacyclovir (500–1,000 mg/ day) or famciclovir (125–250 mg/day). Severe recurrent EM can be managed with immunosuppressive agents. Dapsone or antimalarials (hydroxychloroquine) are the primary drugs in the treatment of recurrent EM. Azathioprine also helps in suppressing the condition, however it has many side effects. Davis et al (2002) showed that mycophenolate mofetil can be used as an effective drug in managing recurrent EM.

Murata and Abe (2007) reported that the keratinocyte apoptosis is brought about by the interaction of the fas receptor and fas ligand. They also emphasize the need to evaluate other genetic factors that may predispose to TEN and SJS. Lerner et al (2000) used reverse transcriptase-PCR and immuniperoxidase staining to study the role of inducible form of nitric oxide synthetase in generating large amounts of nitric oxide. They proposed that a large burst of nitric oxide in TEN and SJS may cause the epidermal apoptosis and necrosis. In their study, inducible nitric oxide synthase was detected by reverse transcription polymerase chain reaction. Strong staining for inducible nitric oxide synthase was observed in inflammatory cells in the lower epidermis and upper dermis. Drugs are considered to be the most common cause of SJS/TEN. The drugs that commonly cause SJS/TEN are anticonvulsants, sulfonamides, non-steroidal anti-inflammatory drugs and antibiotics. SJS/TEN is considered as a cytotoxic immune reaction causing destruction of keratinocytes expressing drug-related antigens. TNF-alpha derived from macrophages and keratinocytes may play an important role in the pathogenesis by inducing apoptosis of epidermal cells or by attracting cytotoxic effector cells, or both. Drug metabolites such as hydroxylamines and arene oxides derived from sulfonamides and aromatic anticonvulsants respectively, bind to cell constituents if they are not rapidly detoxified by epoxide hydrolase. These metabolites act as haptens and render the keratinocytes antigenic by binding to them. A defect in the detoxification system may be the cause of the drug eruption. Clinical features Toxic epidermal necrolysis and Stevens–Johnson syndrome are usually seen in adults. Both the conditions occur as a single episode and associated with drug exposure. Literature review reveals various age groups being involved. The involvement of men and women also shows inconsistency. 191


Devi et al (2005) conducted a retrospective study of 41 patients diagnosed as SJS or TEN in India. The youngest patient in their study was 12 years old and the oldest was 72. Majority of the patients were in the 2nd to 5th decade of life. Kaur et al (1990) evaluated 30 patients with drug induced TEN in India. Their study revealed that the peak incidence of TEN was in the 4th to 6th decades of life. It is believed that the increased incidence in the elderly is due to their increased medicine intake and altered drug metabolism with advancing age. Kaur et al reported that males were slightly more commonly affected. Devi et al showed that males and females were equally affected. Most of the lesions of SJS or TEN are usually seen within 2 months of drug intake. However the recurrent lesions tend to appear within a week of a repeat episode of drug intake. The striking feature of SJS and TEN are that they do not recur if the offending drug is not taken, unlike in EM. Prodromal symptoms such as fever, nausea, vomiting, malaise, sore throat and rhinitis may been seen. This prodromal phase is followed by the appearance of macular rashes affecting almost all regions of the body. It is believed that TEN may be considered if the rash involves more than 30% of the surface area of the body. Severe sloughing of the skin and mucous membrane is evident. Some authors describe this finding as ‘scalded appearance’. Nikolsky’s sign and target lesions may be evident in some individuals. The oral, ocular and genital mucosae are affected in SJS. The ocular lesions present as corneal ulcerations, conjunctival scarring, uveitis and blindness. Genital lesions are characterized by genital ulcers and phimosis. Extensive sloughing may lead to secondary skin infection, sepsis, renal failure and death. Histopathological and laboratory studies Extensive epidermal necrosis is appreciated. Markedly lowered number of lymphocytes are seen around vessels. Macrophages and dendrocytes are typically found in large numbers in TEN. There is an elevated production of tumor necrosis factor-alpha in the epidermis, unlike EM (interferon-gamma is elevated in EM). Inflammatory cells are hardly found in TEN. Acute phases of TEN may show a temporary phase of reduced number of CD4⫹ T-lymphocytes. Erythrocyte sedimentation rate may be elevated. Management The offending drug should be immediately identified and discontinued. The following treatment guidelines followed by University of Florida can be practiced effectively. 192

University of Florida management guidelines for TEN and SJS 1. 2. 3. 4.

5. 6.

7.

8. 9.

10.

11.

12. 13. 14. 15.

16. 17. 18. 19.

Admit patient directly to the burn intensive care unit (BICU) or an intensive care setting Discontinue corticosteroids if they are being used to treat the eruption Discontinue unnecessary medications and suspect medications Obtain baseline laboratory tests, such as complete blood count, liver function tests, metabolic panel, chest radiographs, and any other appropriate imaging or serologic tests, including an immediate (stat) immunoglobulin A (IgA) serum level Look carefully for evidence of infection Obtain punch biopsies of skin for diagnosis confirmation. An alternative for rapid diagnosis is removal of a bulla roof for immediate frozen sections to differentiate between TEN and staphylococcal scalded skin syndrome (SSSS) Culture skin, blood, body orifices (as appropriate), and urine daily to monitor for early infection, and keep abreast of changing antibiotic sensitivities Use systemic antibiotics only for documented infections or signs of sepsis Place large-bore intravenous lines or a central venous line in an area of uninvolved skin to ensure adequate intravenous access If within 48–72 hours of bulla onset, use intravenous immunoglobulin (IVIG), sucrose depleted, 1 g/kg/day for 3 days infused over 4 hours. If 72 hours have passed, but the patient is still actively progressing with new lesions, IVIG may still be useful Monitor fluid and electrolytes closely and begin total parenteral nutrition (TPN) in patients unable to take nourishment. Fluid replacement need not be as aggressive as for burns of same extent Debridement of necrotic and desquamating areas may be performed Consult ophthalmologist to assess ocular involvement Consult otorhinolaryngologist to evaluate extent of upper respiratory tract involvement Further consultations driven by patient condition (i.e. internal medicine to manage comorbidities, pulmonary medicine for airway involvement, gastroenterology for alimentary involvement, and gynecology or urology for genitourinary involvement) Physical therapy daily to preserve limb mobility Pain relief measures, such as patient-controlled analgesia (PCA) pump Hydrotherapy (whirlpool) if needed Non-stick dressings to denuded areas, saturated with 0.5% silver nitrate impregnated every 3–8 hour as needed. Pre-impregnated dressings with silver nitrate are an alternative


20. Avoid sulfa-containing topical or systemic preparations 21. Oral care with chlorhexidine rinses and white petrolatum to lips 22. Air-fluidized bed to minimize shearing force 23. Keep room warm to prevent hypothermia 24. Foley catheter and nasogastric tube placement only when necessary 25. Avoid unnecessary manipulation of skin. Adhesive tape should not be applied directly to involved skin when possible 26. Baby shampoo for cleansing hairy areas daily 27. Mineral oil or petrolatum for dry skin 28. Skin substitute grafting (porcine xenografts or artificial skin) based on BICU protocol.

BULLOUS IMPETIGO Impetigo is a bacterial infection that affects the superficial areas of the skin. It commonly affects infants and young children in the age group of 2–5 years. However it has known to affect individuals of various age groups. It is believed that impetigo is the most common skin disease to affect children. Donovan et al (1992) in their study to evaluate whether bullous impetigo in homosexual men is a risk marker for HIV-1 infection, concluded that bullous impetigo if seen in an adult, it could prove to be a clinical indication that a person is either infected with HIV-1 or is in close (possibly sexual) contact with a person with HIV-1 infection. It is a highly contagious infection caused primarily by Staphylococcus aureus. However some cases have been reportedly caused by group A beta-hemolytic streptococcus (Streptococcus pyogenes) alone or in tandem with Staphylococcus aureus. The mode of transmission is generally by direct contact. Types There are two forms of impetigo, namely, bullous impetigo and non-bullous impetigo (impetigo contagiosa). The basic difference between the two is that the non-bullous variety represents the host response to the staphylococcal infection, whereas in bullous impetigo the staphylococcal toxin is responsible for the condition and not the host response. Clinical features Bullous impetigo is usually seen in infants. But it is seen to affect children and adults likewise. Unlike the nonbullous form which may be caused by a combination of staphylococcus and streptococcus. Bullous forms is always caused by the toxins produced by Staphylococcus aureus. Staphylococcus aureus, phage group II type 71 is the predominant causative organism. This strain of bacteria produces an exfoliatin toxin that causes subcorneal epidermal

cleavage. The exotoxin produced by staphylococci is directed against epidermal desmoglein 1. Itzhak Brook (1980) reported a case of bullous impetigo caused by Streptococcus salivarius. Bullous impetigo usually occurs in crowded places and unhygienic surroundings. Presence of large families in clusters will help the disease spread through direct contact. When the condition disseminates to affect various parts of the body, it is referred to as staphylococcal scalded skin syndrome. This is usually seen in immunocompromised patients. The toxin may disseminate hematogenously and lead to generalized staphylococcal scalded skin syndrome. Bullous impetigo can affect any part of the skin and mucosa. Literature review reveals few reports of buccal mucosa involvement. The initial lesion appears as small to large, superficial, fragile bullae. These bullae usually occur on the extremities, axille and the trunk. Some patients report history of trauma or infections. These bullae are generally painless. However some patients experience burning or itching sensation. The bullae measure about 2 to 5 cm in size and usually do not rupture easily. They contain a serous clear yellow fluid that subsequently turns cloudy and dark yellow. In about 3–4 days time the bullae rupture and produce a thin, light brown, varnish-like or honey like crust. A characteristic finding in bullous impetigo is a ‘collarette’ of scale surrounding the blister roof at the periphery of ruptured lesions. Management and prognosis Impetigo is a self-limiting condition and it usually resolves spontaneously in about 2 weeks without scar formation. The topical antibiotics mupirocin and fusidic acid are effective. Orally administered systemic antibiotics can be used in severe forms of the condition.

EPIDERMOLYSIS BULLOSA Epidermolysis bullosa (EB) comprises a group of inherited mucocutaneous disorders characterized by blister formation due to a defect in collagen metabolism. These blisters may arise spontaneously or as a result of mild trauma. These inherited forms of epidermolysis bullosa should be differentiated from epidermolysis bullosa acquisita which is an autoimmune disorder. Some authors prefer to use the term hereditary epidermolysis bullosa to refer to the forms that are generally inherited. EB is a genodermatosis. The pattern of inheritance may either be dominant or recessive. The recessive forms of EB are relatively more severe and aggressive. Types of EB based on ultrastructural features Jo-David Fine et al (2008) ‘The classification of inherited EB: Report of the Third International Consensus Meeting on Diagnosis and Classification of EB’ 193


Epidermolysis bullosa simplex—intraepidermal cleavage is seen (epidermolytic) Junctional epidermolysis bullosa—intralamina lucida cleavage (lamina lucidolytic) Dystrophic epidermolysis bullosa—sublamina densa cleavage (dermolytic) Kindler syndrome—mixed Epidermolysis bullosa simplex There are two basic types of EB simplex Suprabasal EB simplex Lethal acantholytic Plakophilin deficiency EBS superficialis Basal EB simplex Localized (previously called EBS, Weber-Cockayne) EBS, Dowling-Meara EBS, other generalized (the earlier term EBS, Koebner is no more used and presently included in generalized EBS) EBS with mottled pigmentation EBS with muscular dystrophy EBS with pyloric atresia EBS, autosomal recessive EBS, Ogna EBS, migratory circinate Junctional epidermolysis bullosa There are two basic types in JEB JEB, Herlitz no subtypes JEB, other JEB, non-Herlitz, generalized (was previously generalized atrophic benign EB) JEB, non-Herlitz, localized JEB with pyloric atresia JEB, inversa JEB, late onset (was previously known as EB progressiva) Laryngo-onycho-cutaneous (LOC) syndrome Dystrophic epidermolysis bullosa There are two subtypes Dominant dystrophic epidermolysis bullosa DDEB, generalized DDEB, acral DDEB, pretibial DDEB, pruriginosa DDEB, nails only DDEB, bullous dermolysis of the newborn Recessive dystrophic epidermolysis bullosa RDEB, severe generalized RDEB, generalized other RDEB, inversa

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RDEB, pretibial RDEB, pruriginosa RDEB, centripetalis RDEB, bullous dermolysis of the newborn General clinical features and oral manifestations Epidermolysis bullosa simplex The condition is characterized by the presence of the presence of multiple vesicles or bullae at birth or some time after birth. The common sites that are involved are the hand and feet. Oral mucosa is seldom affected. The condition is self-limiting. The vesicles heal in about a week to 10 days time without the formation of scars. Most of the children are free of this condition at puberty. Junctional epidermolysis bullosa The junctional variety of epidermolysis bullosa is a severe form that occurs at birth and usually death ensues in the first 3 months of life. In very severe forms the skin tends to shed increasing the risk for superinfection and septicemia. Children may present with hoarse cry, cough and breathing difficulty. Apart from the skin, oral, ocular, pharyngeal and genitor urinary mucosa may be affected. The oral lesions manifest as bullae and erosions affecting almost any part of the oral cavity. Infants may have difficulty in feeding. Dystrophic epidermolysis bullosa The dominant variety usually occurs at birth and occasionally at adolescence. At young age the condition has a generalized involvement. As the age advances the condition tends to be confined to a particular region. Bullae are seen on the feet, ankles, knees and elbows. Nails are typically dystrophic. Other features that may be seen are palmoplantar hyperkeratosis and hypertrichosis. The bullae rupture and heal with extensive scarring. Milia (tiny keratin filled cysts) may be seen on the face. Compared to the recessive form of the condition, the oral involvement is limited. Occasionally bullae may be seen in the oral cavity. Teeth are seldom affected. The recessive form of the condition is usually seen at birth or in neonates. Bullae are seen in the sites predisposed to pressure or mild trauma such as the buttocks, knees, elbows, feet and fingers. The bullae subsequently rupture to reveal raw erosive areas. These heal by extensive scarring. Scarring of the fingers may result in ‘club like fists’. Like the dystrophic variety, nail may be absent altogether or may be defective. Oral manifestations are commonly seen. Bullae may be seen affecting any part of the oral mucosa. With the rupture of the bullae, painful erosions are seen which heal by scarring. Extensive scarring of the oropharyngeal and esophageal tissues may lead to hoarseness of voice and difficulty in feeding and swallowing. Dental tissues are usually affected. Congenitally missing teeth, malformed or hypoplastic teeth are usually seen.


Linear IgA Disease Linear IgA disease has also been referred to as linear IgA bullous dermatosis (LABD) and linear immunoglobulin A dermatosis. It was considered to be a variant of DH or BP. However, it is presently considered as a separate disease entity. LABD is a chronic subepidermal bullous disease associated with linear deposition of IgA along the basement membrane. The disease can be idiopathic or drug-induced. Other provoking factors for LABD are viral infections, immunological disorders and malignancies. LABD affects both children and adults and the disease process is similar in both. However, when the disease occurs in children it has been referred to as chronic bullous dermatosis of childhood. Patients suffering from Linear IgA disease produce IgA antibodies against the BP-180 glycoprotein (type VII collagen) which is a component of the hemidesmosomes. Antibody deposition leads to complement activation and neutrophil chemotaxis, which results in loss of adhesion at the dermal-epidermal junction, thereby forming a bulla. Marinkovich et al (1996) reported that LAD-1 (a basement membrane component) is one of the targets of autoantibodies in patients with LABD. Clinical features Dermal lesions mimic lesions of DH or BP. Vesiculobullous rash may be appreciated over a normal or erythematous dermis. The bullae may contain serous sero-hemorrhagic content. The common sites of involvement include the extensor surfaces of the hand and feet, lower trunk, perioral region, genital region and buttocks. In adults, the trunk and the limbs are usually affected. Lesions may not be symmetric. The bullae may arrange in a herpetiform manner or clusters of discrete bullae, which has been popularly termed as ‘jewels sign’. Another characteristic finding is the presence of vesicles or bullae bordering the annular lesion which is termed ‘string of beads sign’. Dermal lesions usually heal without scarring. Mucosal manifestations It is estimated that approximately 80% of patients suffering from LABD exhibit mucosa involvement. Oral, nasal, ocular and/or genital mucosa can be involved. Mucosal lesions heal with significant scarring. About 60% of these patients show involvement of the oral mucosa. Any part of the oral mucosa can be affected. Gingival involvement can present as desquamative gingivitis. Oral

lesions are typically bullae which rupture to form tender erosions or ulcers. Patients complain of burning sensation and discharge from the eye when the ocular mucosa is affected. Common ophthalmic findings are subconjunctival fibrosis, symblepharon formation and cicatricial entropion with trichiasis. Drug-induced LABD The clinical and histological picture is the same as the idiopathic form of LABD. However, like the name suggests LABD develops after drug administration. Literature review reveals various drugs that have known to produce LABD, such as vancomycin, diclofenac, lithium, captopril, cyclosporine glibenclamide, interferon-gamma, iodine contrast agent, phenytoin sodium, somatostatin and sulfamethoxazole/ trimethoprim. Disease associations LABD has been reportedly associated with infections, malignancies and other autoimmune disorders. However many of the associations may simply be coincidental in nature. Few of the commonly associated infections with LABD are typhoid, tuberculosis, varicella, herpes zoster, and upper respiratory tract infections. It has been reported that almost 5% of the patients with LABD may have an associated malignancy such as Hodgkin’s disease and non-Hodgkin lymphoma, chronic lymphocytic leukemia, plasmacytoma, multiple myeloma and squamous cell carcinomas. LABD has also known to occur along with other autoimmune disorders such as Crohn’s disease, ulcerative colitis, multiple sclerosis, systemic lupus erythematosus and rheumatoid arthritis. Management and prognosis The lesions of LABD generally follow a chronic course with periods of acute exacerbations. Spontaneous remission may be seen in some patients. However almost all patients exhibit recurrence. Dermal lesions are managed with dapsone or sulfapyridine. However mucosal lesions are usually refractory to dapsone. Prednisolone along with dapsone will usually help in controlling the condition. Lewis et al (2007) successfully treated a patient suffering from LABD with oral mucosal involvement using mycophenolate, an antiproliferative immunosuppressive agent. They reported that mycophenolate can be used as a useful adjunct to manage oral lesions of LABD, when other immunosuppressants are contraindicated.

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CHAPTER

8

Oral Ulcerative Diseases Keerthilatha M Pai, Braz Campos Durso

➧ Classification of Oral Ulcers

➧

Stomatitis Medicamentosa Stomatitis Venenata

Traumatic Ulcers

➧

Ulcers Associated with Infections

➧

Herpes Simplex Infection

➧

Erythema Multiforme

➧

Varicella Zoster Infection

➧

Blood Disorders Causing Oral Ulcers RBC Disorders WBC Disorders

Chicken Pox Herpes Zoster ➧

Coxsackie Virus Infection

➧

Herpangina Hand, Foot and Mouth Disease

➧

➧

Acute Necrotizing Ulcerative Gingivitis

➧

Tuberculosis

➧

Syphilis

➧

Deep Fungal Infections Aspergillosis Histoplasmosis Mucormycosis Cryptococcosis North American Blastomycosis South American Blastomycosis

Immunologic Disorders Aphthous Ulcers

Dermatological Disorders Pemphigus Bullous Pemphigoid Cicatricial Pemphigoid

➧

Gastrointestinal Disorders Associated with Oral Ulcers Gastroesophageal Reflux Disease Crohn’s Disease Ulcerative Colitis Celiac Disease

➧

Neoplastic Ulcers

An ulcer may be described as breach in the continuity of the surface epithelium of the skin or mucous membrane to involve the underlying connective tissue as a result of micro molecular cell death of the surface epithelium or its traumatic removal.

❍ ❍ ❍ ❍ ❍ ❍

CLASSIFICATION OF ORAL ULCERS

Classification based on mode of onset and clinical presentation

Ulcerative lesions affecting the oral cavity can be categorized based on the etiology or based on the mode of onset and clinical presentation.

❍

Classification based on etiology ❍ ❍ ❍ 196

Drug-induced Oral Ulcers

➧

Traumatic Infectious (bacterial, viral and fungal infections) Drug induced

Ulcers associated with blood dyscrasias Immune mediated Oral ulcers associated with dermatological disorders Oral ulcers associated with GI disorders Neoplastic oral ulcers Ulcers of uncertain etiology.

Single ulcers – Traumatic ulcer – Tuberculous ulcer – Syphilitic ulcer – Histoplasmosis – Blastomycosis – Mucormycosis – Neoplastic ulcers

Chapter 8 – Oral Ulcerative Diseases

❍

Multiple ulcers – Acute multiple ulcers • Herpes virus infections • Primary herpes simplex virus infections • Coxsackievirus infections • Varicella zoster virus infection • Erythema multiforme • Contact allergic stomatitis • Oral ulcers secondary to cancer chemotherapy and/or radiotherapy • Acute necrotizing ulcerative gingivitis – Chronic multiple ulcers • Pemphigus • Subepithelial bullous dermatoses • Herpes simplex virus infection in immunosuppressed patients ❍ Recurring oral ulcers – Recurrent aphthous stomatitis – Behçet’s syndrome – Recurrent herpes simplex virus infection – Cyclic neutropenia – Chronic idiopathic neutropenia. Flowcharts 1 and 2 summarize acute ulcers that are recurring in nature and those that occur as an isolated episode.

TRAUMATIC ULCERS Traumatic injuries involving the oral cavity may lead to the formation of surface ulcerations. Although the exact incidence of these ulcerations is not known they are one of the most common ulcers seen affecting the oral cavity.

Types of Trauma ❍

❍

❍ ❍ ❍ ❍

Mechanical (sharp tooth, overextended denture, orthodontic brackets, toothbrush, ill-fitting dental prosthesis, etc.) Chemical (aspirin, concentrated clove oil, sodium hypochlorite, hydrogen peroxide, root canal medicaments, chemotherapy, etc.) Thermal (extremely hot or cold insults such as hot cheese, hot beverages, popsicle) (Figure 1) Radiation (used in treatment of head and neck cancer) Self-inflicted (self-harm) Iatrogenic (injuries caused by high speed rotary instruments, cotton rolls, etc.)

The oral cavity is prone to injuries from events such as accidentally biting oneself while talking, sleeping, mastication or as a result of an epileptic seizure. Fractured, malposed, or malformed teeth, as well as the premature eruption of teeth, can contribute to the formation of surface ulceration.

Flowchart 1 Recurrent episodes

Systemic symptoms

Absent

Trauma

Present IBD Location

Keratinized

Cyclic neutropenia

Nonkeratinized

Sprue Behcet’s

RAS

Culture + HSV

− Atypical RAS HIV Cyclic neutropenia

HIV FAPA Magic

Algorithm to evaluate acute oral ulcers that are recurrent in nature. (Reprinted with minor modifications from Bruce AJ (2003), ‘Acute oral ulcers’, Dermatologic Clinics, Vol. 21, p. 2, with permission from Elsevier)

Nocturnal parafunctional habits, such as bruxism may be associated with the development of traumatic ulcers of the buccal mucosa, the labial mucosa and the lateral borders of the tongue. Ulcerations may be the result of voluntary, selfinduced, and deliberate acts by patients with physical or psychological symptoms who suffer from attention seeking behavior. These ulcers are characteristically present over visible surfaces such as the lips, corner of mouth and facial aspects of gingiva (ulcers caused by gingival picking). Bulimic individuals may present with nail marks or minute pinpoint red spots and/or ulcerations over the palate which is brought about by the frequent efforts to vomit. Newborns and infants may present with sublingual ulcerations (Riga–Fede disease). These ulcers may occur as a result of chronic mucosal trauma due to adjacent anterior natal or neonatal teeth. The trauma is often associated with breast feeding. The lingual frenum may be ulcerated by repeated trauma because of the frenum rubbing against the mandibular incisors teeth in cunnilingus and in recurrent coughing episodes. Young children are commonly susceptible to electrical and/or thermal burns of the lips and commissure areas. 197


Flowchart 2 Single episodes

Infection

Drugs

Iatrogenic

Trauma Radiation

Bacterial

Viral Chemotherapy ANUG

HSV

Syphilis

VZV

Gonorrhea

Coxsackie

Tuberculosis

Rubeola

Rhinoscleroma

EBV

Algorithm to evaluate acute oral ulcers that occur as an isolated episode. (Reprinted with minor modifications from Bruce AJ (2003), ‘Acute oral ulcers’, Dermatologic Clinics, Vol. 21, p. 2, with permission from Elsevier)

Figure 1

A thermal burn on the hard palate secondary to intake of a hot bread sandwich. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Extensive ulcerations with necrosis may develop. Children in this age group have a tendency to chew their lips immediately after surgical removal of teeth under the influence of local anesthesia.

associated with areas of erythema. The ulcer may reveal the presence of a central yellowish purulent exudate. Occasionally the border of the ulcer is indurated. Ulcerations can occur throughout the oral cavity. Ulcers associated with mechanical trauma are often found on the buccal mucosa, the labial mucosa of the upper and lower lips, and the lateral border of the tongue (Figure 2). The mucobuccal folds, gingiva, and palatal mucosa may also be involved. Most lesions associated with electrical burns occur in children and involve the lips and commissural areas. Ulcers formed due to thermal injuries are generally seen to occur on the posterior regions of the buccal mucosa and the palate. Caustic chemical agents can damage any area of the oral mucous membrane. However, they are commonly seen on the gingival margins and buccal vestibular regions of the oral cavity. Very frequently these ulcers are covered by a whitish pseudomembrane which when peeled leaves behind a raw ulcerated surface (Figure 3). Some patients in the Indian subcontinent use cloves and topical pain balms meant for extraoral application over the gingiva to relieve tooth pain. Hence, most of the chemical burns are generally seen adjacent to carious teeth. Diagnosis

Clinical features In most cases, the source of the injury is identified. The patient’s usual complaint is pain or a painful ulceration. Individual lesions usually appear as shallow or deep ulcers 198

The diagnosis of traumatic ulcerations is based on the history of trauma or insult (hot/cold or radiation therapy) prior to onset of ulcer. Mechanical trauma induced ulcers often have linear configuration. The depth of ulcer depends on


Figure 2

Histologic features Histopathologically an area of surface ulceration covered by a fibrinopurulent membrane consisting of acute inflammatory cells intermixed with fibrin is seen. The stratified squamous epithelium from the adjacent surface may be hyperplastic and exhibit areas of reactive squamous atypia. The ulcer bed is composed of a proliferation of granulation tissue with areas of edema and an infiltrate of acute and chronic inflammatory cells. Management ❍ ❍

A traumatic ulcer on the left lateral aspect of the tongue due to sharp teeth. Courtesy: Department of Oral Medicine and Radiology, KLEDC, Bangalore

❍ ❍

Figure 3 ❍

❍

❍

A chemical burn on the right buccal mucosa extending into the vestibule in patient who had the habit of applying pain balm in the vestibule to manage periodontal pain. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

❍

Consumption of a soft and bland diet. Removal of traumatic factor (extraction of root stumps, supraerupted teeth and malposed third molars, sharp cuspal edges of teeth may be grounded, irritating dentures may be corrected, restoration of fractured teeth and orthodontic correction of malposed teeth) will cause the resolution of the ulcer in 10–14 days. Patient may be advised to rinse his/her mouth with warm saline. Topical application of antiseptic and analgesic/anesthetic medication (choline salicylate 8.7%, benzylkonium 0.01% and lignocaine hydrochloride 2%—patient can be asked to apply the agent over the ulcers 10 minutes prior to food intake, 3–4 times a day). In case of multiple ulcers—analgesic/antiseptic mouthwash (chlorhexidine gluconate 0.2% or benzydamine hydrochloride 0.15% mouthrinse—one teaspoon of the agent can be dissolved into 50 ml of water. This prepared solution is swished in the mouth for 1 minute. The patient is advised to rinse the mouth 3 times a day, 30 minutes after food intake). Application of topical corticosteroids (triamcinolone acetonide oral paste 0.1%). Patient can be advised to apply the paste 30 minutes prior to food intake, 3 times a day for 2 weeks. For extremely large and deep seated ulcers, penicillin may be administered (Capsule Amoxicillin, 500 mg, 3 times a day for 5 days) to prevent secondary infections. Patients presenting with ulcers secondary to selfinflicted injuries may be referred to a psychiatrist or psychologist after symptomatically managing the ulcer.

Complications nature of trauma. Generally the area surrounding the ulcer is inflamed. A traumatic factor will often be evident in the vicinity of the ulcer (e.g. sharp edge of tooth).

Most traumatic ulcers resolve with the removal of the etiological agent. However, some ulcers may be secondarily infected and subsequently heal with extensive scar formation.

Differential diagnosis Carcinomatous ulcer, recurrent aphthous ulcerations, ulcers associated with deep fungal infections can be considered in the differential diagnosis of traumatic ulcers.

Prognosis The outcome of traumatic ulcerations is excellent, provided the etiological factor is eliminated. Healing of the ulcerated 199


Table 1

Ulcers associated with infections Bacterial

Viral Specific

Non-specific

Herpes simplex virus • Primary herpetic gingivostomatitis • Recurrent herpes labialis • Recurrent intraoral herpes

Borrelia vincenti and Fusobaterium • ANUG • Cancrum oris/noma

Infected traumatic ulcer • Ruptured odontogenic abscess presenting as ulcer

Varicella zoster virus • Chicken pox • Herpes zoster

Mycobacterium tuberculosis • Tuberculous ulcer • Tuberculosis cutis orificialis

Coxsackie virus • Herpangina • Hand, foot and mouth disease

Treponema pallidum • Chancre • Snail track ulcer • Gumma

Epstein–Barr virus • Infectious mononucleosis

Gonococci • Gonococcal stomatitis

Fungal

• • • • •

Histoplasmosis Mucormycosis Blastomycosis Cryptococcosis Coccidiodomycosis

Human immunodeficiency virus • AIDS

mucosa is usually delayed when the lesions overlie the maxillary or mandibular alveolar process, hard palate and tip of the tongue. If the ulcer does not resolve within 2 weeks of removal of the etiological agent, biopsy of the ulcer may be considered to rule out malignancy.

❍

Ulcers associated with infections (bacterial, viral and fungal infections)

❍ ❍

Table 1 summarizes ulcers associated with infections.

❍

PRIMARY HERPETIC GINGIVOSTOMATITIS

❍ ❍ ❍

Prodromal systemic symptoms (fever, malaise, myalgia) precede oral lesions by 2–3 days. The skin, mucous membranes, eyes and central nervous system are the most commonly affected sites. Multiple oral ulcers affecting all parts of the mouth. Generalized erythema of gingiva usually associated with multiple vesicles or ulcers (Figure 4). Cervical lymphadenopathy occurs as a rule. Food intake becomes difficult and dehydration may ensue. Self-limiting condition in normal children. However, it may become disseminated in immunocompromised children or adults.

Diagnosis Primary herpetic gingivostomatitis is caused by herpes simplex virus (double-stranded DNA virus which is a member of the human herpes virus family). Most orofacial and ocular infections are caused by HSV-1. Infections involving the genitalia and the skin surface of the lower part of the body are caused by HSV-2. It has been reported that HSV-2 has a greater virulence. Almost 95% of the cases have a subclinical infection, only about 5% manifest symptoms. The infection confers resistance against another primary infection for lifetime.

Primary herpetic gingivostomatitis can be identified based on history and clinical findings. Cytological (PAP/Tzanck) smears of intact or recently broken vesicles may demonstrate epithelial giant cells containing intranuclear eosinophilic viral inclusions, that are typical of herpes viral infections. Differential diagnosis Leukemia, erythema multiforme and stomatitis medicamentosa can cause lesions that resemble primary herpetic gingivostomatitis.

Clinical features ❍ ❍

Primary herpetic gingivostomatitis has an acute onset. Typically affects children (generally below 6 years of age), but this infection also occurs in adults (immunocompromised). ❍ Males and females are equally affected. 200

Treatment Symptomatic management Ensure that the patient is adequately hydrated and electrolyte balance is maintained. Antipyretic and analgesic medication like acetaminophen, 500 mg given thrice daily is effective (3 times a day).


Figure 4

2.

Herpes labialis (occurs along external vermillion border of lips).

Precipitating Factors ❍ ❍ ❍ ❍ ❍ ❍

Exposure to UV light (sunlight) Menstruation Fever Stress Decreased immunity Traveling and change in climatic conditions.

Clinical presentation ❍ Gingival erythema, multiple small ulcers and vesicles in the attached gingiva in a 36-year-old man suffering from acute herpetic gingivostomatitis. Reproduced with permission from editor, JCDA. Ajar AH and Chauvin PJ. Acute herpetic gingivostomatitis in adults: a review of 13 cases, including diagnosis and management. J Can Dent Assoc 2002;68(4):247–51

Soothening oral rinses (anesthetic mouthwashes like dyclonine hydrochloride 0.5%, about 10 ml can be used 4 times a day as an oral rinse). Specific management Antiviral therapy can be instituted in children and adults. These medications will decrease the fever, pain, severity of the lesions and minimize viral shedding. In children antiviral medications like acyclovir can be given within first 72 hours in a dosage of 200 mg 5 times a day for 10 days. Acyclovir helps to decrease fever, pain, lesions and viral shedding. Newer drugs like valacyclovir (1 g orally times a day for 7 days) and famciclovir (500 mg times a day for 7 days) are more effective. Prognosis The outcome of primary herpetic gingivostomatitis is good in otherwise healthy individuals. Complications may occur in immunocompromised individuals. The virus remains dormant in nerve ganglion and may get reactivated later in life causing secondary infection.

❍ ❍

❍ ❍

Patients present with cluster of tiny fluid filled vesicles (Figure 5A–C) which rupture to form pinpoint ulcers. These ulcers may coalesce to form larger areas of ulceration. Lesions may be preceded by burning, itching, tingling sensation or pain in the region. The lesions last for 5–7 days and subside and subsequently recur. Now the frequency of recurrence may be varied. Occasionally associated with fever and pharyngitis. As a consequence to healing an area of pigmentation is noticed at the site of the lesion (however this pigmented area is readily visualized only in fair skinned individuals).

Diagnosis Recurrent herpes infection can be identified by their typical location and clinical presentation. In addition, biopsy and Tzanck smear can be performed. Treatment The management of recurrent lesions is generally symptomatic. Patients can be advised to stay indoors to minimize exposure to sunlight. Sunscreen lotion can be used when venturing out. However in individuals where there is an increased frequency of recurrence, acyclovir therapy can be instituted as a prophylactic measure (400 mg twice a day for 10 days).

VARICELLA ZOSTER INFECTION

RECURRENT HERPES INFECTION

Varicella zoster virus causes two distinct clinical entities. The primary infection by varicella zoster causes chicken pox, while the reactivated virus causes a secondary infection termed herpes zoster or shingles.

Recurrent infections of herpes can manifest in two forms:

Chicken Pox

1.

The primary infection by varicella zoster virus usually affects children. It is characterized by the sudden onset of

Intraoral herpes (occurs on highly keratinized mucosa of hard palate/gingiva)

201


Figure 5

Figure 6

A

B Vesicular lesions involving the face and neck in chicken pox. Courtesy: Dr Ceena Denny

generalized pruritic vesicular rashes affecting the skin. The incubation period of the virus varies from 10 to 21 days. Approximately 50% of the affected children present with prodromal symptoms of fever, malaise, headache, and abdominal pain, which last for about 1–2 days before the appearance of the dermal lesions. Dermal lesions C

❍

Typical lesions of chicken pox, clinically exhibit four phases. The maculopapular phase (erythematous macules are evident), vesicular phase (minute fluid filled vesicles are seen), ulcerative phase (commonly seen on mucous membranes of oropharynx, vagina and conjunctiva) and the phase of healing (Figure 6). ❍ In the maculopapular phase erythematous macules are seen. In some patients, vesicles develop within the maculopapular rash giving rise to ‘dewdrop on a rose petal’ appearance. ❍ The commonly involved sites are the scalp, face and trunk. ❍ The lesions are often pruritic.

(A) Vesicles on the upper lip in a patient with recurrent herpes labialis. (B) Ulcers formed subsequent to vesicle rupture in a patient with recurrent herpes labialis. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore. (C) Healing lesions of herpes labialis. Courtesy: Department of Oral Medicine and Radiology, KLEDC, Bangalore

202

On an average 100–300 new lesions are found at any given point of time. Lesions heal generally without scarring. Occasionally crusting of the lesions may be seen. However, an area of hypopigmentation may be appreciated at the site of the healed lesion. These hypopigmented areas fade away with time. Oral lesions The common intraoral sites affected are the hard and soft palate, labial and buccal mucosa. Oral lesions of chicken


pox are seen as small vesicles that subsequently rupture to form shallow round ulcers surrounded by an erythematous halo.

Figure 7

Management Vaccination against varicella zoster should be given to infants between 12th and 18th months of life. The management of the disease is mainly symptomatic. Acyclovir can be administered in the early phases of the disease.

Herpes Zoster Herpes zoster is caused by reactivation of varicella zoster virus that is inactive in dorsal root or cranial nerve ganglion, after primary infection. It is estimated that only in about 0.3–0.5% of the population, the virus is reactivated after the primary infection. Clinical features ❍ ❍ ❍ ❍

❍

❍

❍

❍

The clinical features depend on the dermatome involved. The nerves that are commonly affected are C-3, T-5, L-1 and L-2. Manifests in middle age. When the trigeminal nerve is involved, the ophthalmic division of the nerve is most commonly involved. About 15–20% of the affected individuals show involvement of the maxillary or mandibular division. Painful vesicles and/or ulcers seen both inside and outside the oral cavity, which stop abruptly at the midline (i.e. lesions do not cross midline) (Figure 7). Bilateral lesions may indicate severely immunocompromised state. Literature review reveals reports of necrosis of alveolar bone exfoliation of teeth in immunocompromised individuals. Occasionally pain may be present along the course of the affected nerve in the absence of vesicles. Such a manifestation is termed zoster sine herpete or zoster sine eruption. Ramsay Hunt syndrome is a symptom complex associated with herpes zoster. It is characterized by varicella zoster infection affecting the geniculate ganglion of the facial nerve, unilateral facial paralysis and unilateral vesicular eruptions involving the oral mucosa and external ear.

Post-herpetic neuralgia is one of the relatively common sequelae of varicella zoster infection that results from scarring of the involved nerve. Management Antiviral drugs like acyclovir, valacyclovir and famciclovir have been used successfully in shortening the course

Healed lesions of herpes zoster with scab formation. Characteristically, the lesions do not cross the midline and this patient had involvement of the ophthalmic, maxillary and mandibular divisions of the trigeminal nerve. Courtesy: Dr Sumanth

and healing time of the infection and reducing the pain associated with the disease. Acyclovir (800 mg) is given 5 times a day for a week or valacyclovir (1,000 mg) or famciclovir (500 mg) can be given 3 times a day for a week.

Herpangina Herpangina is caused by coxsackie virus (A 1-10, 16, or 22). It occurs generally in epidemics. It predominantly affects posterior parts of oral cavity. Clinical findings ❍

In the early stages erythematous macules are seen. As the disease progresses, vesicles with a central ulceration develop, which exhibit an erythematous halo. ❍ Generally around 2–10 lesions are seen which measure less than 5 mm in diameter. ❍ The common sites involved are the posterior pharyngeal region, uvula, anterior faucial pillars, tonsils and soft uvula. On occasions ulcers may be present on the tongue and buccal mucosa corresponding to the posterior regions of the oral cavity. ❍ The lesions are usually associated with mild fever which subsides within a week. 203


❍

It is a self-limiting condition and generally subsides within a week. ❍ Marginal gingiva is characteristically unaffected.

Hand, Foot and Mouth Disease Hand, foot and mouth disease is a viral disease caused by coxsackie viruses (members of the Picornaviridae family). It is characterized by oral lesions associated with lesions involving the extremities. Infections can occur in a sporadic form (coxsackie virus types A4–A7, A9, A10, B1–B3, and B5) or as epidemics (coxsackie virus A16 or enterovirus 71). The incubation period ranges from 3 to 6 days. Though the disease runs a mild course and is self-limiting, a severe form of the condition is seen in infants and children. Enteroviral infections may cause myocarditis, pneumonia, meningoencephalitis and even death. Infection occurring during the first trimester in pregnant women can result in spontaneous abortion and retarded development of the fetus. Clinical features Hand, foot and mouth disease typically affects young children below 10 years of age. Males and females are equally affected. Prodromal symptoms like low-grade fever, anorexia, malaise, abdominal pain, sore mouth and cough are evident which lasts for 12–36 hours. The condition is self-limiting. Mucosal and cutaneous lesions resolve spontaneously in 5–7 days. Literature review reveals that almost 22% of the patients may present with cervical or submandibular lymphadenopathy. Skin lesions ❍ ❍

❍

❍ ❍

Approximately 65% of the patients demonstrate skin involvement. The commonly affected sites are the hands (dorsal aspect of the hands and sides of the fingers are very commonly affected), feet and the buttocks. The characteristic skin lesion is seen as asymptomatic, erythematous macule characterized by a central grayish vesicle. The macule varies in size from 2 to 10 mm. These macules are elliptical with their long axis aligned parallel to the skin lines. The lesions subside in about a week’s time.

Oral lesions ❍

In the early stages, oral lesions begin as erythematous macules that evolve into 2–3 mm vesicles on an erythematous base. However, intact vesicles are rarely seen as they ulcerate instantaneously. ❍ The ulcers are painful and interfere with chewing and swallowing. 204

❍ ❍

Approximately five to ten ulcers are seen. Tongue may be involved in about 45% of the patients. Tongue may become swollen and tender. ❍ The other sites of involvement are the palate, buccal mucosa and gingiva. Management ❍

Topical application of anesthetics like viscous lidocaine and diphenhydramine may be used to manage painful oral ulcers. Sucralfate suspension can also be effectively used. ❍ Fever and arthralgias can be treated using antipyretics and analgesics. ❍ Literature review reveals that there is a reported quicker resolution of symptoms with the use of oral acyclovir. ❍ A low intensity laser ablation of the oral ulcers is said to shorten the duration of painful oral ulcers. Prognosis The prognosis of the condition is generally excellent owing to the self limiting nature of the disease. However, complications like meningoencephalitis, myocarditis, pulmonary edema, and death have been reported.

ACUTE NECROTIZING ULCERATIVE GINGIVITIS (Trench Mouth, Vincent’s Disease, Vincent’s Gingivostomatitis) Acute necrotizing ulcerative gingivitis (ANUG) is an acute bacterial infection affecting the gingiva. As per the 1999 American Academy of Periodontics classification system, ANUG is presently classified as necrotizing periodontal disease that is characterized by rapidly progressive ulceration typically starting at the crest of the interdental papilla, spreading along the marginal gingival and subsequently causing rapid and extensive destruction of the periodontal tissue. The anaerobic organisms that are said to cause ANUG are Fusobacterium necrophorum, Prevotella intermedia, Fusobacterium nucleatum, Porphyromonas gingivalis and Treponema species. Predisposing factors Suppressed immunity, malnutrition, stress, poor oral hygiene, smoking and local trauma predisposes to the development of ANUG. Literature review reveals that the prevalence of ANUG among HIV patients ranged from 4 to 16%. Clinical findings ❍

ANUG is generally seen in young and middle-aged adults. However, in the Indian subcontinent and


Figure 8

Necrosis of the interdental papillae in acute necrotizing ulcerative gingivitis. Reproduced with permission from editor, JCDA. Mirbod SM, Ahing SI. Tobacco-associated lesions of the oral cavity: part I. Non-malignant lesions. J Can Dent Assoc 2000;66:252–6

❍ ❍ ❍ ❍

❍ ❍

Africa, it occurs almost exclusively in children of age group between 3 and 10 years. These children characteristically belonged to the low socioeconomic groups. Hospital-based studies in Nigeria showed a prevalence rate of about 23% in children less than 10 years of age. Gingiva tends to bleed spontaneously or with the slightest of provocation. Marginal and interdental gingiva is erythematous and edematous. Crest of the interdental papillae is blunted. Minute punched-out crater like ulcers are seen in the interdental papillae. These ulcers are covered by a grayish white pseudomembrane. The ulcers are extremely painful (Figure 8). Foul odor. Patients may present with fever, malaise and regional lymphadenopathy.

Table 2 compares features of acute necrotizing ulcerative gingivitis and acute herpetic gingivostomatitis. Management of ANUG ❍ ❍ ❍ ❍

Manage underlying factors. Well balanced diet and regular meals. Gently remove necrotic material with swab. 3% hydrogen peroxide diluted with equal amount of water used to rinse mouth every 2 hours on first day; 3–4 times/day for next 4 days. ❍ Penicillin V (oral): 400,000 units/day for 5 days/amoxicillin 250–500 mg t.i.d. for 5–7 days. ❍ Metronidazole 400 mg t.i.d. for 5 days. ❍ Oral prophylaxis can be undertaken after acute symptoms subside.

Table 2

Comparison of acute necrotizing ulcerative gingivitis and acute herpetic gingivostomatitis

Acute necrotizing ulcerative gingivitis

Acute herpetic gingivostomatitis

Complex bacterial etiology

Viral etiology

Ulcers confined to gingiva

Ulcers all over mouth

Indefinite clinical course and duration

Self-limiting lasts for 7–10 days

Non-contagious

Contagious in those with depressed immunity

No viral antibodies

Convalescent sera shows viral antibodies

Treatment with antibacterial agent

No role for antibacterial agents

TUBERCULOSIS Tuberculosis is a chronic infectious granulomatous bacterial disease generally acquired by inhaling droplets contaminated by Mycobacterium tuberculosis. However, it can also be acquired by consuming unpasteurized cow’s milk that is infected by Mycobacterium bovis or by other atypical mycobacteria. Oral manifestations It is hypothesized that tubercle bacilli enter the oral mucosa through a break in the mucosal surface. Abbot et al in an independent study were able to isolate tubercle bacilli from the mouthwashings of 44.9% of the individuals suffering from pulmonary tuberculosis. This study underlines the importance of intact mucosal lining in providing protection against tuberculosis affecting the oral cavity. The oral manifestations of tuberculosis are rare. It is estimated that approximately 1.4% of the patients suffering from tuberculosis exhibit oral manifestations. The tuberculous lesions may present as ulcer, fissure, tuberculoma or as a generalized enlargement of the tongue. In the initial stages the lesion can be in the form of a nodule or opalescent vesicle which progresses to form an ulcer. The most common oral manifestation is ulcer (Figure 9). Oral tuberculous lesions typically present with severe, unremitting and progressive pain. Sites Soft tissues are more frequently affected than hard tissues. The sites of involvement include the tongue, soft palate, hard palate, gingiva, lips, floor of the mouth, vestibular and retromolar regions and recent tooth extraction sockets. Maxilla and the mandible have also been affected and referred to as tuberculous ostemyelitis. Mandible is more commonly involved. Tuberculous osteomyelitis generally 205


Figure 9

A solitary crateriform ulcer with slightly elevated and indurated borders on the lateral margin of the tongue in a patient with tuberculosis. Courtesy: Dr Velia Ramírez Amador, Universidad Autónoma Metropolitana-Xochimilco, Mexico

Figure 10

Caseation necrosis of a tubercular lymph node. Courtesy: Department of Oral Pathology, MCODS, Mangalore

Oral manifestations occurs due to a hematogeneous spread of the bacilli or through a direct extension through a fresh extraction socket. Typical lesion The ulcer is irregular with ragged, undermined edges, minimal induration and yellowish granular base. The ulcer is surrounded by sentinel tubercles. Primary oral tuberculous lesions are usually associated with caseation of the regional draining group of lymph nodes (Figure 10). Differential diagnosis Infected traumatic ulcer, major aphthous ulcer, syphilitic ulcer, sarcoidosis, lymphogranuloma venereum, foreign body granuloma, histoplasmosis and malignant ulcer can be considered as differential diagnosis for tuberculous ulcer. Management The pain associated with the ulcer can be treated symptomatically. Antitubercular therapy for 18 to 24 months should be instituted.

SYPHILIS Syphilis is a sexually transmitted disease that is caused by Treponema pallidum. 206

All stages of acquired syphilis can present as oral ulcers (chancre, mucous patch and gumma). Usually chancre and mucous patch are self-limiting and pass on to the next stage. Chancre The occurrence of primary syphilis in the oral cavity is extremely rare. Almost all chancres are seen in the genital region. However with the change in the sexual practices the oral cavity can also be a site for the presence of chancre. The lips, tongue, tonsillar regions and the palate are the common sites that are involved. In the initial stages a papule may be seen which subsequently erodes. The typical syphilitic ulcer is punched out, non-tender, indurated and associated with a yellowish serous discharge. The associated nodes are generally firm and non-tender on palpation. Chancres are self-limiting and last for a period of 2 weeks. They heal with minimal scar formation. Mucous patches Generally secondary syphilis appears after a latency period of 6 months after the primary lesions are noticed. Patients complain of fever, headache, bodyache and sore throat. Cutaneous maculopapular rashes associated with lymphadenopathy are seen. Oral lesions are characterized by the appearance of oval red macules (usually seen on the palate) or papules (usually seen on the buccal mucosa and commissures) and mucous patches. The oral commissures demonstrate split papules. Mucous patches are seen as raised erosive areas covered by a grayish white pseudomembrane and surrounded by an erythematous halo. They usually measure about 1 cm in


diameter and seen bilaterally on the movable surfaces in the oral cavity. These small lesions can join together to give rise to snail track ulcers (serpiginous pattern). A severe and generalized form of secondary syphilis can result in lues maligna, which is also termed ulceronodular disease. The oral mucosa reveals shallow crater like ulcers. The common sites involved are the palate, buccal mucosa, tongue, lower lip and gingiva.

Oral findings

Gumma Gumma is a highly destructive lesion that is typically seen in tertiary stage of acquired syphilis. The gummatous lesion may sometimes occur 8–10 years after the initial infection. The hard palate and tongue are common sites of involvement. However, literature review reveals sites like the parotid salivary gland, soft palate and the lower alveolar ridge being affected. Gumma of the hard palate will result in perforation, thereby producing an oronasal communication.

Histoplasmosis

Diagnosis and management

Mucormycosis

Sensitive tests like VDRL and specific tests like FTA-ABS test/TPI assay/ELISA can be used to diagnose syphilis. According to the 1993 Centers for Disease Control and Prevention (CDC) treatment guidelines for sexually transmitted diseases, parenteral penicillin G is the drug of choice for managing syphilis. Patients allergic to penicillin can be treated with doxycycline, tetracycline or erythromycin.

It is an opportunistic infection caused by a saprophytic fungus that is found in the soil, bread mold, animal manure and rotting vegetation. Mucoraceae are fungi that are commonly found in soil or in rotting vegetation. Rhizopus can be found in moldy bread. Mucormycosis can assume various clinical forms based on the site of involvement such as rhinocerebral form (spores deposited in nasal turbinates), pulmonary form (spores lodged in the lungs by inhalation), cutaneous form (spores introduced through wounds and cuts on the skin surface), gastrointestinal form (spores ingested) and a disseminated form. The rhinocerebral form of mucormycosis characteristically involves the paranasal sinuses. An extension of the disease process can result in ulceration of the palate. The typical lesion is seen as a large, painful ulcer of the palate filled with blackish necrotic slough. Ulcers have also been reported to occur on the gingiva, lip and alveolar ridge.

DEEP FUNGAL INFECTIONS Deep fungal infections are relatively uncommon in the oral cavity. These deep seated infections generally have systemic manifestations and rarely involve the oral cavity. The deep fungal infections that produce ulcerative lesions in the oral cavity include mucormycosis, blastomycosis, histoplasmosis, aspergillosis, cryptococcosis and paracoccidiodomycosis. Characteristically, these infections are seen in immunocompromised individuals suffering from HIV, AIDS or systemically debilitating conditions such as diabetes mellitus, malignancies and individuals on long-term immunosuppressive therapy.

Aspergillosis Aspergillosis is reportedly the second most commonly seen fungal infection affecting the oral cavity after Candida. Aspergillosis in humans is caused primarily by Aspergillus fumigatus and A. niger. The spore is found in rotting vegetation. The transmission of fungal spores to the human being is by inhalation. It primarily affects the lungs. Aspergillosis has a tendency for a hematogeneous invasion causing thrombosis and infarction of perivascular tissues.

Involvement of the maxillary sinus is rarely seen in aspergillosis. An extension of the infection from the sinus can result in involvement of the adjacent soft tissue and palate producing blackish or yellowish necrotic ulcerations.

Histoplasmosis is caused by Histoplasma capsulatum. Following inhalation of this dimorphic fungus it can cause an acute pulmonary histoplasmosis or can assume a disseminated form in immunocompromised individuals. The typical oral lesion, though very rare appears as an erosion or ulcer commonly involving the tongue, palate and buccal mucosa.

Cryptococcosis Cryptococcosis is an opportunistic fungal infection caused by Cryptococcus neoformans. It is usually present in bird droppings, rotting wood and soil. C. neoformans preferentially affects the meninges, basal ganglia and cortical gray matter. Oral mucosal lesions appear as superficial ulcers or as deep ulcers with indurated borders and rolled out edges.

North American Blastomycosis or Gilchrist’s Disease Gilchrist’s disease is caused by Blastomyces dermatidis. It is caused by inhalation of the spore which is predominantly found in the soil. Like most of the deep fungal infections, 207


blastomycosis has a localized form that affects the respiratory system and a disseminated form. However, unlike other fungal infections immunosuppression does not increase the risk of disseminated disease. Blastomycosis is endemic to the Mississippi and Ohio River basins in the United States and certain areas in Africa and India. Disseminated form of blastomycosis commonly involves the skin, CNS and the genitourinary tract. Papulopustular or verrucous, grayish lesions are seen on the skin surface. Oral mucosa may exhibit ulcerations.

Paracoccidiodomycosis or South American Blastomycosis Paracoccidiodomycosis is caused by Paracoccidioides brasiliensis. This disease is commonly seen in Latin American and South American regions (Brazil, Colombia, Argentina and Venezuela). Clinical features It usually affects men older than 30 years of age. Farmers are at a greater risk of acquiring this disease. After inhalation, the fungus usually remains dormant and the individual is asymptomatic. In an immunocompromised host, the fungus exhibits the clinically active state. Lung is the first site of involvement. It leads to productive cough, chest pain and shortness of breath. Other symptoms include joint pains and body aches. Cervical and axillary lymphadenopathy is seen. Painful ulcers involve the mucosa of the oral cavity; gastrointestinal (GI) tract and upper respiratory tract are common. Oral ulcers are typically seen on the lips, gingiva, and tongue.

Paracoccidioidomycosis The paracoccidioidomycosis is one of the most prevalent deep systemic mycoses. It is more frequently observed in patients from South America or Central America and is an important expression of the spectrum of pathology in Latin America. Brazil accounts for approximately 70% of the cases reported in the literature. Immigrants from these regions may carry it elsewhere or people visiting these endemic areas may acquire the infection. Knowing paracoccidioidomycosis is important to the dentist, since the oral mucosa provides an important substrate to the saprophytic life of the fungus, and the disease has frequent oral and dermatological manifestations, usually the first to be detected. In spite of that, few cases have been reported in the English language literature. Although a primarily lung infection,

208

paracoccidioidomycosis is frequently diagnosed because of mouth lesions. In this sense, the dentist plays a fundamental role in the diagnosis of this pathology. Oral lesions are usually extensive, can be found on up to 78.9% of the cases investigated, and frequently affect more than one area of the oral mucosa. The mucous and mucocutaneous lesions of paracoccidioidomycosis have a significant clinical diagnostic value, since they provide direct observation of the lesion and easy access to the anatomopathological and mycological examination, in addition to their high prevalence. The main clinical feature in the oral lesions is a granulomatous mulberry-like surface and ulceration. Because of the chronic character and progressive extension of the ulcerated oral lesions, they may resemble other infections and neoplastic diseases. In the clinical routine, the patients are mistakenly diagnosed as having mainly squamous cell carcinoma, tuberculosis, sarcoidosis, leishmaniasis, Wegener’s granulomatosis, histoplasmosis, actinomycosis, lupus erythematosus, lymphoma, or syphilis. The predilection for male patients, in what seems to be a result of a protective effect of female hormones such as ␤-estradiol, which inhibits transformation of the hyphal form of the organism to the pathogenic yeast form as well as is a consequence of the professional outdoor activities of males. It is postulated that after menopause, women are more susceptible to the disease. However, possible genetic factors associated to the HLA antigen may facilitate the appearance of mycosis. The fungus Paracoccidioides brasiliensis is easily recognized under hematoxylin and eosin (H&E) staining, inside or outside of giant cells, as birefringent, double-contoured cyst-like structures with a diameter ranging from 1 to 30 ␮m. Typically, H&E stained slides reveal epithelial pseudoepitheliomatous hyperplasia, granulomatous response and microabscesses. The underlying connective tissue displays a chronic granulomatous reaction, with epithelioid cells and giant cells. The number and organization of granulomas are variable. Disorganized granulomas tend to predominate in the oral lesions. The periodic acid-Schiff (PAS) and GrocottGomori methenamine silver are particularly useful to highlight the yeast-like structures with multiple budding that resemble a pilot’s wheel or Mickey Mouse ear. Eosinophilic inflammatory infiltrate is a common finding, however it is not directly related to the amount of fungus or granulomas. Immunocytochemical techniques may provide new information on the microscopic aspects of this disease and should be encouraged. The treatment scheme will depend on the severity of the disease, and long-term follow-up is mandatory. Even with supposedly adequate treatment, death is not uncommon in both acute and chronic cases.


DRUG-INDUCED ORAL ULCERS The oral mucosa is susceptible to insult from both systemically administered drugs and locally applied drugs in the oral cavity. The term ‘stomatitis medicamentosa’ is reserved for the effects of systemically administered drugs and ‘stomatitis venenata’ is the term used for the effects induced by topical application of drugs or due to contact (contact stomatitis). Pathogenic basis of drug-induced stomatitis/ oral ulceration Drug-induced stomatitis or ulcerations are said to be caused either by immune mediated or non-immune mediated pathways. These changes in the oral cavity depend on the potential toxicity of the drug, frequency of intake, route of drug administration and the inherent immunity of the individual receiving the medication. Immune-mediated pathway The medicament or one of its components is thought to trigger an immune response. This immune response is targeted at the surface epithelium, thereby forming ulcers. Non-immune mediated pathway In this form of reaction there is no evidence of an immune response and it is not dependent on antibodies. The medication administered will directly stimulate mast cells and lymphocytes to release cytotoxic chemical mediators that cause stomatitis and oral ulcerations.

Stomatitis Medicamentosa Adverse effects of drugs are generally manifested over the skin surface. However, literature review reveals that the oral cavity can sometimes be the only site of involvement. It is a known fact that no medication is safe and that every drug has the potential to cause damage to the body including the oral cavity. These drug reactions affecting the oral mucosa can be in the form of stomatitis, lichenoid reactions, erosions and ulcers.

ulcers are resistant to all treatment modalities and persist for months. Management The suspected medication should be replaced by an alternative drug wherever possible. Patients can be advised to apply topical anesthetic agents over the ulcer. Tetracycline mouthwashes and topical steroids are effective in managing drug-induced oral ulcers.

Stomatitis Venenata (Contact Stomatitis) Contact stomatitis is relatively rare when compared to contact dermatitis. The inherent qualities of the oral mucosa and the oral environment make it more resistant to potentially allergic agents than the keratinized skin. Saliva dilutes and digests or washes away allergic agents. It also contains a high concentration of epidermal growth factor which aids in healing of mucosal injuries if any. The oral epithelium, which is non-keratinized in nature, has fewer proteins; as a result there are fewer targets for the allergens. Allergens in contact with the oral mucosa are removed very rapidly because of the higher epithelial turnover rates of the oral epithelium. However, in spite of the inherent protective mechanism of the oral mucosa, topical application of medicaments can elicit a localized mucosal reaction in some individuals. Types of contact stomatitis Allergic contact stomatitis and irritant contact stomatitis are subtypes of contact stomatitis (Table 3). The agents causing stomatitis are usually dentifrices, mouthwashes, dental materials, cosmetic agents, food coloring and flavoring agents and preservative agents. The agents causing contact stomatitis are summarized in the Box 1. Management The first step in managing contact stomatitis is by avoiding contact with the identified or suspected irritant or allergen.

Medications causing oral ulcers Non-steroidal anti-inflammatory drugs (indomethacin, piroxicam and ibuprofen), anti-depressant (sertraline), COX-2 inhibitors (celecoxib, rofecoxib), anticancer chemotherapeutic agents such (cyclosporine, methotrexate, doxorubicin), anti-hypertensives (calcium channel blockers) and miscellaneous agents like gold salts can cause stomatitis and/or oral ulcerations. Antidepressants cause xerostomia, which in turn results in stomatitis or ulceration. Drug-induced oral ulcers are generally solitary and typically seen over the lateral margins of the tongue. These ulcers are often surrounded by a white halo. Most of the

Table 3

Contact stomatitis: types

Irritant contact stomatitis

Allergic contact stomatitis

No previous history regarding exposure to suspected irritant

Previous history regarding exposure to allergen is required

Clinical signs are seen within minutes to hours of exposure to irritant

Clinical manifestations usually seen after 48 hours of subsequent exposure (a type IV hypersensitivity reaction)

Activation of immunologic Activation of memory T-cells mediators without involvement of memory T-cell function

209


Box 1

Common agents causing contact stomatitis

Oral cleansing aids • Dentifrices (contain peppermint, cinnamon) • Mouthrinses (chlorhexidine) • Dental floss (contains colophony or rosin) Dental materials • Free monomer (in acrylic appliances) • Nickel (content of orthodontic wires) • Mercury (dental amalgam fillings) • Gold (constituent of crowns, fillings) • Denture adhesives (contains rosin which is resin obtained from conifers) • Eugenol (in periodontal packs, cements) • Phenol Cosmetics (contain rosin derivatives, propolis and ricinoleic acid) • Lipsticks • Lip balms • Sunscreens Latex

Table 4

Blood disorders causing oral ulcers

RBC disorders

WBC disorders

Anemia

Quantitative disorders

Qualitative disorders

• • • •

• • • •

Lazy leukocyte syndrome

Iron deficiency Pernicious Sickle cell anemia Thalassemia

Leukemia Agranulocytosis Cyclic neutropenia Multiple myeloma

WBC Disorders WBC disorders can cause oral ulcerations and necrotizing lesions which are commonly seen on the gingiva, floor of the mouth, buccal mucosa and pharynx. These ulcers are characterized by the lack of the inflammatory halo and generally associated with necrosis and foul smell. Cyclic neutropenia is associated with recurring oral ulcers. The treatment is directed at the cause of the ulceration.

Food substances (containing preservatives, coloring and flavoring agents, sea food, fruits such as apples, pears, etc.)

IMMUNOLOGIC DISORDERS Patients are instructed to avoid smoking. Toothpaste and mouthwashes with strong flavoring agents are best avoided (baking soda can be an effective alternative to tooth pastes). Topical triamcinolone acetonide or flucinonide 0.05% gel can be used.

ERYTHEMA MULTIFORME Described in Chapter 7 on Vesiculobullous Disorders.

BLOOD DISORDERS CAUSING ORAL ULCERS Blood disorders are associated with increased risk of oral ulcers. Necrosis is generally a prominent feature of these ulcers. Other clinical signs and symptoms and a hemogram will help the diagnosis. The red blood cell (RBC) and white blood cell (WBC) disorders that cause oral ulcers are summarized in Table 4.

RBC Disorders Iron deficiency anemia is characterized by the presence of glossitis and glossodynia, angular cheilitis and atrophic areas on the tongue due to papillary atrophy. Patients with pernicious anemia exhibit glossitis, burning tongue, angular cheilitis, papillary atrophy, and recurrent oral ulcerations. Sickle cell anemia and thalassemia exhibit oral ulcerations. These patients are relatively more likely to develop osteomyelitis. 210

Aphthous Ulcers (Recurrent Aphthous Stomatitis, Aphthae, Canker Sores) Recurrent aphthous stomatitis (RAS) is a common condition characterized by recurring ulcers confined to oral mucosa in patients with no other signs of disease. Patient presents with multiple round or ovoid ulcers generally with well-defined borders and erythematous halo surrounding the periphery of the ulcer. Literature review reveals that approximately 25% of the population is affected with this condition. Etiopathogenesis Although many theories were proposed to explain the etiology of RAS, there appears to be no single causative factor. Various etiological factors have been proposed, such as hereditary, trauma, deficiency states, psychological factors, endocrine disorders, allergic conditions, infections, blood dyscrasias, drugs, GI diseases, urological disorders, dermatological disorders and immunologic origin, etc. Lehner (1964) and Dolly (1969) were of the opinion that RAS belonged to the group of autoimmune diseases. Lehner in 1969, found elevated levels of IgG and IgA in the sera of patients with RAS. A fluorescent antibody technique showed both IgG and IgM were binding by epithelial cells of the spinous layer of oral mucosa in RAS patients. Greenspan et al (1981) implicated antibody dependent cellular cytotoxicity as a pathogenic mechanism in RAS. Thomas and coworkers (1990) showed that T lymphocytes from RAS patients had increased cytotoxicity to oral epithelial cells.


Clinical features

❍

❍

Individuals may experience burning sensation which may appear 2–48 hours before the ulcer appears. During the initial periods, a localized area of erythema develops within hours, a small white papule forms, ulcerates and gradually enlarges over the next 48–72 hours. ❍ The ulcers are usually regular and well defined. They are rimmed by an erythematous halo (Figure 11) and the ulcer is covered with a yellowish-gray fibrinous pseudomembrane. ❍ The number and size of the ulcers vary based on the type of RAS.

Figure 11

Ulcers are usually seen on the non-keratinized oral mucosa (commonly on the buccal and labial mucosa). Ulcers are rarely seen in the heavily keratinized palate or gingiva.

Types of recurrent aphthous stomatitis Three forms of RAS are clinically recognized, namely, minor, major, and herpetiform. Minor aphthous ulcers (Mikulicz ulcer) The minor RAS are tiny round to ovoid ulcers that mainly involve the nonkeratinized oral mucosa (such as the buccal mucosa, labial mucosa, floor of mouth, ventral surface of the tongue). In most individuals one to six ulcers measuring about 2–4 mm in diameter are present at any given point of time. The ulcers are surrounded by an erythematous halo (Figure 12A, B). These ulcers heal in about a week’s time without scarring. Major aphthous ulcers (Sutton’s ulcers; periadenitis mucosa necrotica recurrents) Like the name suggests these ulcers are larger in size (almost up to 1 cm in size) when compared to minor RAS. Major RAS involve even the keratinized areas of the oral mucosa (such as the palate and dorsum of tongue). These ulcers usually occur in very few numbers ranging from one to six at a time. They persist for a longer duration and heal in about 2–6 weeks with scarring.

Aphthous ulcer on the upper labial mucosa. The ulcer is surrounded by an erythematous halo. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Herpetiform ulcers These are present as crops of tiny pin head sized ulcers which coalesce together. These may be present both on the keratinized as well as the nonkeratinized mucosa. These ulcers typically begin as tiny vesicles that subsequently ulcerate. These are extremely painful and tend to heal in about 10 days and almost immediately recur.

Figure 12 A

B

(A) A minor aphthous ulcer on the lower labial mucosa. (B) A minor aphthous ulcer on the lateral margin of the tongue. The ulcer is surrounded by the characteristic erythematous halo. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

211


Table 5

Comparison of recurrent aphthous ulcer and recurrent intraoral herpes

Recurrent aphthous stomatitis (RAS)

Recurrent intraoral herpes (RIHS)

Non-specific etiology

Viral etiology

Wide range of age group

Middle age

Freely movable mucosa involved

Attached mucosa

Single or 2–3 ulcers at a time except in herpetiform where crops of pinpoint ulcers occur

Multiple pinpoint ulcers

Non-specific findings on H/P

Tzanck cells on smear

No antibody titers

Convalescent sera show viral antibodies

Corticosteroids used

Corticosteroids contraindicated

Table 5 compares clinical features of recurrent aphthous stomatitis and recurrent intraoral herpes. Diagnosis The diagnosis of RAS is done by exclusion. Hematological examination can be performed to rule out blood dyscrasias. Ocular, genital, skin, or rectal lesions should not be present to make a diagnosis of aphthous stomatitis. Management The primary goals of therapy for RAS are relief of pain, reduction of ulcer duration, and restoration of normal oral function. Secondary goals include reduction in the frequency and severity of recurrences and maintenance of remission. Topical medications, such as antimicrobial mouthwashes and topical corticosteroids, can achieve the primary goals but have not been shown to alter recurrence or remission rates. Systemic medications can be tried if topical therapy is ineffective. Levamisole has shown variable efficacy in reducing ulcer frequency and duration in patients with minor recurrent aphthous ulcer (RAU). Dose: 150 mg per day for 3 consecutive days followed by a gap of 2 weeks. Then repeat for 3 days. This is to be done 6 times (total therapy time is 3 months and total number of tablets is 18). Thalidomide is effective but, because of its toxicity and cost, should be used only as an alternative to oral corticosteroids.

DERMATOLOGICAL DISORDERS Pemphigus Pemphigus is a chronic, autoimmune skin disorder which is considered to be the most dreaded, dramatic and devastating of all dermatologic disorders. Pemphigus vulgaris, vegetans, 212

foliaceous and erythematoses are the four histopathological variants of the disease. Pemphigus vulgaris is the most severe form. Clinical features It is commonly seen in Jews and predominantly affects adults with no sex predilection. Bullae of varying sizes are seen on skin and mucosal surfaces. The bullae on the skin are tense; however in the oral cavity they rupture almost immediately to form ulcers or erosions (Figure 13A, B). These ulcers typically have peripheral tissue tags. Nikolsky’s sign (lateral pressure applied over apparently normal skin or mucosa causes sliding of the skin) is positive. Ashboe– Hansen sign, also known as bulla spreading sign (pressure applied over a bulla makes it spread) is positive. Desquamative gingivitis is commonly seen in pemphigus vulgaris (Figure 14). Diagnosis The diagnosis of pemphigus vulgaris is made based on the typical clinical signs. Histopathologically, the presence of intraepithelial bulla is characteristic of pemphigus vulgaris. Immunofluorescent studies exhibit a positive fluorescence under the fluorescent microscope with the antibody binding to the immunoglobulin deposits in the intercellular substance. Other non-specific findings associated with pemphigus vulgaris are a raised ESR and hypoalbuminemia. Management The mortality associated with untreated pemphigus vulgaris is about 10%. Systemic corticosteroids are effective in managing the condition. Prednisolone 0.5–1 mg/kg/day or about 40–80 mg/day is administered. Cyclophosphamide is given at an initial dose of 50 mg/day and the dose escalated to 100 mg/day. Mouthwashes like benzydamine hydrochloride 0.15% will help in managing pain. Antiseptic oral rinses such as chlorhexidine gluconate 0.2% can be used.

PEMPHIGOID Bullous pemphigoid and benign mucous membrane pemphigoid cicatricial pemphigoid are the two variants of pemphigoid.

Bullous Pemphigoid Bullous pemphigoid is commonly seen in women in the 6th and 7th decades of life. It is characterized by the appearance of bullae over the skin, which rupture to give rise to erosive areas, which heal spontaneously. Not all cases of bullous pemphigoid involve the oral cavity. Intraorally small bullae are seen especially on the


Figure 13 A

B

(A) Ulcers in the vestibular region in pemphigus vulgaris. (B) Erosions on the hard palate in pemphigus vulgaris. Courtesy: Dr Sumanth

Figure 14

Ultrastructural studies reveal the loss of attachment of the epithelium and basement membrane to the underlying connective tissue or lamina propria.

GASTROINTESTINAL DISORDERS ASSOCIATED WITH ORAL ULCERS

Desquamative gingivitis in pemphigus vulgaris. Courtesy: Dr Francisco Sánchez, Morelia City, Mexico

gingiva and buccal mucosa. Patients may complain of mild pain. These bullae rupture over a period of time to form erosions or ulcers. Histopathologically subepidermal bullae formation is seen. Bullous pemphigoid is treated with systemic steroids. Azathioprine and cyclophosphamide have also been used successfully.

Cicatricial Pemphigoid Cicatricial pemphigoid is a chronic subepidermal blistering autoimmune disease. It is characterized by the presence of vesicles involving the oral, genital, and conjunctival mucosa. The oral lesions are generally erosions or shallow ulcers on the facial gingiva, buccal mucosa, palate, tongue, and lower lip. The ulcers exhibit a distinct outline and heal with scarring in about one month.

Gastrointestinal diseases that may be associated with oral ulcers include gastroesophageal reflux disease (GERD), inflammatory bowel diseases (Crohn’s disease, ulcerative colitis) and celiac disease. These patients have symptoms of gastrointestinal discomfort along with oral ulcers. Generally barium meal and gastroscopic examination will confirm involvement of the GI tract.

Gastroesophageal Reflux Disease Gastroesophageal reflux disease arises out of the passage of gastric contents into the esophagus. GERD is considered the most common upper GI tract disorder with the prevalence ranging from 6 to 10% of the population. However, heartburn which is the most common symptom of GERD is reported by 59% of the population. Gastroparesis, increased abdominal distention, hiatal hernia, and myopathy causing defective GI motility are the common causes for GERD. Clinical features ❍

Patients complain of pain burning sensation extending from epigastrium to the neck (heart burn) which is commonly felt after a meal. ❍ Chest pain that mimics anginal pain. 213


❍ ❍

Esophagitis, esophageal ulceration and stricture. Patients may complain of chronic coughing episodes.

Clinical features ❍


Erosion of palatal surfaces of teeth leading to dentinal hypersensitivity and occasional pulpal involvement. ❍ Mucosal atrophy, erythema and ulceration. ❍ Dysgeusia.

Crohn’s Disease Crohn’s disease is a chronic inflammatory bowel disease that can affect any part of the GI tract. It causes fissures, transmural inflammation, and non-caseating granulomas of the GI tract. It generally affects males and females equally, however it affects white males more frequently. Clinical features ❍

It has a bimodal peak of incidence. Crohn’s disease affects individuals in the 2nd and 3rd decades of life and in the 6th and 7th decades of life. ❍ Individuals may complain of diarrhea or constipation, abdominal pain, and intermittent fever. ❍ Some patients may present with extra intestinal manifestations characterized by arthritis and erythema nodosum.

❍ ❍ ❍

Oral findings Oral mucosal involvement is characterized by the presence of ulcers, angular stomatitis and superficial hemorrhagic ulcers. It is estimated that approximately 5–10% of the patients with ulcerative colitis exhibit oral manifestations.

Celiac Disease Celiac disease is an autoimmune gluten-dependent enteropathy characterized by intestinal malabsorption and subtotal or total atrophy of intestinal villi which improves after gluten-free diet.

Oral findings

Clinical features

Many patients present with oral manifestations before any systemic manifestations are evident. Halme in 1993 reported that the severity of oral lesions may be used as a marker to judge the severity of the intestinal impairment. On an average approximately 8–9% of the patients may exhibit oral manifestations prior to intestinal involvement. Patients may present with:

1.

❍ ❍ ❍ ❍ ❍

Diffuse painful swelling of the lips, gingiva and other areas of the oral mucosa. Oral ulcers and angular cheilitis. The characteristic feature of Crohn’s disease is the cobblestone appearance of the buccal mucosa. Histopathological finding of non-caseating granulomas is typical of Crohn’s disease. Difficulty in eating and swallowing due to the presence of ulcers and fissures.

Ulcerative Colitis Ulcerative colitis is a chronic inflammatory bowel disorder sharing the similar clinical features of Crohn’s disease except that the involvement is restricted to the mucosa and submucosa of the colon. 214

❍ ❍

Ulcerative colitis may occur at any age. However, it most commonly affects individuals between the 2nd and 4th decades of life. Males and females are equally affected. Patients may complain of abdominal pain and diarrhea associated with blood and mucus. Loss of appetite, dehydration, fatigue and loss of weight. Some patients may complain of severe abdominal cramps and the constant desire to empty bowels. Handlers in 1999 reported extra intestinal manifestations such as ulcerations on the buttocks, abdomen, thighs and face.

2.

3. 4. 5.

Infants present with growth retardation, diarrhea, vomiting and abdominal distention. Patients who are not treated in time may present with short stature, pubertal delay, iron and folate deficiency with anemia, and rickets. Young children may be depressed and irritable. Adults may report of episodic or nocturnal diarrhea and weight loss. Other extra intestinal manifestations reported in literature include infertility, peripheral neuropathy, convulsions, psychiatric disturbances and increased incidence of bone fractures.

Oral findings Patients may present with oral ulceration that may mimic ulceration of recurrent aphthous stomatitis.

NEOPLASTIC ULCERS Neoplastic lesions that exhibit oral ulcerations are squamous cell carcinoma, adenocarcinoma, mucoepidermoid carcinoma and metastatic carcinoma.


Clinically, these ulcers exist for long periods of time, and induration is a prominent feature. However, biopsy will help in diagnosing the nature of the ulcers. The treatment for most of these ulcers is surgery/radiation or combination of both. The prognosis depends upon the stage of diagnosis.

ULCERS OF UNKNOWN ETIOLOGY Necrotizing Sialometaplasia Necrotizing sialometaplasia is a non-neoplastic, self-limiting, inflammatory condition of the salivary glands. Abrams et al in 1973 described this condition for the first time. The clinical and histopathological picture of necrotizing sialometaplasia resembles those of a malignancy, which often leads to its misdiagnosis. It is proposed that necrotizing metaplasia occurs due to vascular ischemia.

❍ ❍ ❍ ❍ ❍

PFAPA Syndrome (Marshall’s Syndrome) In 1987, Marshall et al reported a condition with periodic fever. This was termed Marshall’s syndrome. However, this condition was later referred to as PFAPA which included periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis. Diagnostic criteria for PFAPA syndrome (proposed by Thomas et al) 1.


❍

❍ ❍ ❍ ❍

Literature review reveals that it affects individuals from an early age of 8 months to 70 years. However, it is commonly seen to affect individuals in the 4th and 5th decades of life. The minor salivary glands of the palate (75% involvement) are very frequently involved followed by other minor salivary glands in the retromolar pad area, buccal mucosa, tongue, incisive canal, and labial mucosa. Involvement of the parotid and submandibular salivary glands are also reported. Lesions of necrotizing sialometaplasia can present as ulcers or well-defined submucosal swellings. The typical ulcer has a crater like form, usually measuring 1–3 cm in diameter. Erosion of the palatal bone may be appreciated in some cases.

Diagnosis Based on clinical appearance alone necrotizing sialometaplasia cannot be diagnosed. Generally, a histopathological evaluation of the lesion is necessary to establish the correct diagnosis. Malignant ulcers, Wegener’s granulomatosis, and extranodal lymphoma can be considered in the differential diagnosis.

MAGIC syndrome (mouth aphthae, genital lesions and interstitial chondritis) Behçet’s syndrome Reiter’s syndrome Stevens–Johnson syndrome Ramsay Hunt syndrome

2.

3. 4. 5.

Regularly recurring fevers with an early age of onset (⬍ 5 years of age) Symptoms in the absence of upper respiratory tract infection with at least one of the following clinical signs: a. aphthous stomatitis b. cervical lymphadenitis c. pharyngitis Exclusion of cyclic neutropenia Completely asymptomatic interval between episodes Normal growth and development.

MAGIC Syndrome Literature review reveals that the symptom complex of mouth and genital ulcerations associated with inflamed cartilage (polychondritis) was first described in 1995. Apart from the typical ulcers involving the oral cavity and the genital regions, polychondritis is present. It involves the auricles, lungs, heart, and the vascular system. Patients may also complain of associated symptoms such as fatigue, malaise, and fever. Use of immunosuppressive agents such as azathioprine, methotrexate, or cyclophosphamide is the modality of choice to manage symptoms and signs associated with MAGIC syndrome.

Reiter’s Syndrome

SYNDROMES ASSOCIATED WITH ORAL ULCERS The syndromes that are associated with ulcerative lesions affecting the oral cavity are: ❍

PFAPA syndrome (periodic fever, aphthae, pharyngitis, adenopathy)

Reiter’s syndrome is named after Hans Reiter who described a classical triad of arthritis, non-gonococcal urethritis, and conjunctivitis, in 1916. However, in the recent years the term ‘Reiter’s syndrome’ is used to refer to peripheral arthritis lasting longer than one month, associated with urethritis, cervicitis, or diarrhea. It is usually seen following a gastrointestinal or genitourinary infection. Reiter’s syndrome secondary to gastrointestinal infection is seen in 215


children whereas Reiter’s syndrome secondary to genitourinary infection is seen in adults. It is generally seen in individuals in the second and third decades. Peripheral arthritis is the most characteristic feature. It usually affects the lower limbs. Mucocutaneous lesions of Reiter’s syndrome are seen in adults. Balanitis and vulvitis are typical of Reiter’s syndrome. Oral ulcers and erosions are seen in some patients. Histopathologically it is difficult to distinguish these lesions from psoriasis.

Behçet’s Syndrome Behçet’s syndrome is named after Hulusi Behçet, a Turkish dermatologist who described a triad of RAUs, genital ulcerations, and uveitis leading to blindness, in 1937. There are two widely used diagnostic criteria for Behçet’s disease, namely, the International Study Group Criteria for diagnosis of Behçet’s syndrome and O’Duffy criteria. International Study Group Criteria for diagnosis of Behçet’s syndrome Oral ulcers (major/minor/herpetiform RAUs) occurring at least thrice in a year and the presence of at least two of the following: ❍ ❍

Recurrent genital ulcerations Recurrent eye lesions (uveitis, retinal vasculitis and cells in the vitreous) ❍ Skin lesions (erythema nodosum/papulopustular lesions/ acneiform nodules) ❍ Positive pathergy test. O’Duffy criteria The O’Duffy criteria require the presence of oral ulcers (recurrent aphthous ulcerations) and the presence of any two of following: ❍ ❍ ❍ ❍ ❍

Genital ulcers Uveitis Cutaneous pustular vasculitis Synovitis Meningoencephalitis.

The diagnosis requires the exclusion of inflammatory bowel disease, systemic lupus erythematosus (SLE), Reiter’s syndrome, and herpetic infections. Oral ulcers Oral ulcers are characteristic of this disease. Usually, oral ulcerations are the first clinical finding. For diagnostic

216

purposes the presence of at least three episodes of ulcers in a year is required. Painful crops of ulcers are seen which typically heal without scarring. Genital ulcers Vulva and vagina in females and scrotum and penis in males are the common sites for ulcers. These ulcers are painful and usually heal with scar formation. Ocular involvement Patients complain of increased lacrimation, conjunctival erythema, blurring of vision, eye pain and photophobia. Other clinical findings Patients can present with non-specific pustular skin rashes, erythema nodosum and folliculitis. Arthralgias and arthritis can be seen. Patients may frequently complain of abdominal pain, diarrhea, and melena. Involvement of the central nervous system is the most dreaded manifestation of Behçet’s disease. Patients are also susceptible to deep vein thrombosis and arterial disease as a result of vessel involvement.

Stevens–Johnson Syndrome Stevens–Johnson syndrome is characterized by the presence of minute blisters on the skin. Detachment of the skin is limited to about 10% of the body surface area. Skin detachment involving 30% or more of the body surface area associated with epidermal necrosis is referred to as toxic epidermal necrolysis. Clinically another variant is considered which is characterized by skin detachment between 10 and 29% of the body surface area and is termed Stevens–Johnson syndrome—toxic epidermal necrolysis overlap. Clinical findings Patients complain of fever and myalgia. The initial presentation of the condition is an erythematous rash on the face and trunk that rapidly spreads to involve other parts of the body. Occasionally blisters are seen within the rash. Stevens–Johnson syndrome and toxic epidermal necrolysis usually begin with fever, headache, cough, and body aches, which may last from 1 to 14 days. This is followed by the appearance of a flat red rash on the face and trunk, that often spreading later to the rest of the body in an irregular pattern. The areas of rash enlarge and spread, often forming painful blisters in the center. The skin over the blisters can be easily slided off. Blisters are seen on oral, ocular and genital mucosa that subsequently ruptures to form ulcers. Patients will complain


Table 6 Diagnostic protocols Acute

Chronic

Single

Multiple

Single

Multiple

Recurrent

• Traumatic ulcer • Aphthous ulcer

• • • • • • • • • • • • • • •

• • • • • • • •

• • • • • • • •

• • • • • • •

Herpetic gingivostomatitis Recurrent intraoral herpes Herpangina Hand, foot and mouth disease Chicken pox Herpes zoster Infectious mononucleosis HIV infection ANUG Stomatitis medicamentosa Stomatitis venenata Herpetiform aphthous ulcers Minor aphthous ulcers Leukemia Cyclic neutropenia

Infected traumatic ulcer Major aphthous ulcer Necrotizing sialometaplasia Tuberculous ulcer Syphilitic ulcer Cancrum oris Fungal ulcer Malignant ulcer

Multiple major aphthous ulcers Behçet’s syndrome Reiter’s syndrome Pemphigus vulgaris Benign mucous membrane Pemphigoid Erosive lichen planus Lichenoid reactions

Aphthous ulcers Cyclic neutropenia Behçet’s syndrome Reiter’s syndrome Lichen planus Pemphigus Pemphigoid

Table 7 Diagnostic protocols: investigations Acute

Chronic

Single

Multiple

Single

Multiple

Recurrent

• Generally no need of investigations • Routine hemogram may be performed

• Hemogram to rule out hematological malignancies • Tzanck smear • Antibody titers in recurrent viral infection • Paul Bunnell test for infectious mononucleosis • Bone marrow study for leukemia

• Biopsy • In case of TB, Mantoux test, ESR, lymphocyte count, chest X-ray, PCR • In case of syphilis, VDRL test, FTA-ABS test or TPI assay • Special stains in case of suspected fungal infections

• Biopsy for histopathologic examination and DIF • Indirect IF • Routine hemogram with ESR • Serum protein level • Patch test in case of suspected lichenoid reactions

• For cyclic neutropenia, TC and DC thrice in a week for 6–8 weeks • Hemogram • Pathergy test in Behçet’s syndrome

difficulty in eating and swallowing. Increased salivation may be an associated complaint.

Step 3: Correlate the history and clinical findings and draw a differential diagnosis Step 4: Investigations to establish the diagnosis (Table 7).

DIAGNOSTIC PROTOCOL Step 1: Determine whether ulcers are acute or chronic, single or multiple or recurrent (by history) (Table 6). Step 2: Note the features of the ulcer(s) and associated symptoms: 1. Size, shape, location, surrounding area, tissue tags at periphery, tenderness, foul smell, bleeding, induration of base, edges, margins, floor 2. Presence of skin lesions (e.g. lichen planus, pemphigus, pemphigoid, erythema multiforme, Stevens–Johnson syndrome, etc.) 3. Systemic symptoms (fever, malaise, etc.) seen in viral infections, ANUG, TB, erythema multiforme, etc.

Step 5: General guidelines for managing oral ulcers: 1. Patient is advised to discontinue oral habits such as smoking/pan chewing/alcohol. 2. In viral ulcers, rest is important and adequate hydration to be ensured. 3. The treatment should be directed at the cause. 4. Symptomatic relief with topical anesthetic/analgesic preparations. 5. Antiseptic ointments/gels to prevent secondary infection. 6. Topical steroids in ulcers taking longer time to heal (triamcinolone acetonide in Orabase). 7. Systemic steroids in case of erythema multiforme, pemphigus, pemphigoid, erosive or vesiculobullous lichen planus and allergic stomatitis.

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CHAPTER

9

Dermatological Diseases K Srinivas, Sarita Dimri, Ravikiran Ongole

➧ Lichen Planus

➧

Hailey–Hailey Disease (Familial Benign Chronic Pemphigus)

Psoriasis

➧

Darier’s Disease (Keratosis Follicularis)

Ectodermal Dysplasia

➧

Reiter’s Syndrome

➧

Ehlers–Danlos Syndrome

➧

➧

Pachyonychia Congenita

Incontinentia Pigmenti (Bloch–Sulzberger Syndrome)

➧

Dyskeratosis Congenita

➧

➧

Pityriasis Rosea

Kawasaki Disease (Mucocutaneous Lymph Node Syndrome)

➧

Xeroderma Pigmentosum

➧

➧

Acanthosis Nigricans

Tuberous Sclerosis Complex (Epiloia, Bourneville’s Disease)

➧

Goltz–Gorlin Syndrome

➧

Graft-versus-host disease

➧

Acrodermatitis Enteropathica

➧

Diagnostic Signs in Dermatology

➧

Epidermolysis Bullosa

➧ ➧

LICHEN PLANUS Lichen planus (LP) has also been known as lichen ruber planus. It is one of the most common dermatologic, immunopathological diseases to affect the oral mucous membrane. The management of oral lichen planus continues to challenge even the most experienced oral physician. The term ‘lichen planus’ is derived from a Greek word lichen which means tree moss and a Latin word planus which means flat. The strange name of the condition was provided by the British physician Erasmus Wilson, who first described the lesion in 1869. Thibierge first described the oral lesions systematically in 1885. Fitzpatrick et al (1993) described LP as a unique cutaneous entity consisting of an eruption of papules distinct in color and configuration, in patterns and location of appearance and in microscopic as well as gross structure. Andreasen categorized oral LP into six types, namely, reticular, papular, plaque-like, atrophic, erosive, and bullous. Lichen planus has been associated with various diseases such as hepatitis C, oral cancer, and diabetes mellitus. 218

Etiopathogenesis An interplay of host, lifestyle, and environmental factors has been implicated in the etiopathogenesis of LP. It is believed that LP is caused due to cell-mediated immunity initiated by endogenous or exogenous factors. Clinical features The onset of LP occurs most commonly during the 5th or 6th decade. No sexual predilection is evident. The typical cutaneous lesions of LP present as flat topped, purple, polygonal, pruritic papules and plaques most commonly occurring on the flexor surfaces of the arms, wrists, ankles, and legs. Oral lesions may be observed in up to 75% of patients with cutaneous LP and in approximately 25% of cases it can be the only manifestation of the disease. Conversely, only 10–20% of patients whose initial presentation is oral LP will develop cutaneous LP. The oral lesions have been observed in up to 1–4% of the population. Oral LP almost invariably occurs as a bilateral disease and it involves the posterior buccal mucosa followed less commonly by the tongue, gingiva, hard palate, and the

Chapter 9 – Dermatological Diseases

Unknown antigenic change in oral mucous membrane

Figure 1

Focal accumulation of Langerhans cells within the epithelium

Activated helper/inducer T lymphocyte in the lamina propria

Expression of ICAM and HLA-DR on the surface of keratinocytes

Influx of cytotoxic/suppressor T-cells within the epithelium

Keratinocyte damage

Basal cell degeneration

Pyknotic and shrunken basal cells (Civatte bodies)

Apoptosis of keratinocytes

Linear lesions of LP occurring as a result of scratching characteristic of Koebner’s phenomenon. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Atrophic and erosive lesions involving the gingiva results in desquamative gingivitis which is characterized by bright red areas involving the full width of attached gingiva.

Failure of phagocytosis of apoptotic cells

Investigations Colloid bodies (underlying dermis)

labial mucosa. Although any site can be involved, palatal and sublingual lesions are very uncommon. Clinically oral LP appears as radiating white or gray velvety thread like lesion, which consists of papules in linear, annular or retiform arrangement. A tiny white elevated dot is present at the intersection of the white lines known as ‘Wickham’s striae’ or ‘Honiton lace’. An isomorphic response (Koebner’s phenomenon) is common occurrence in LP, and develops in areas previously subjected to some type of trauma (Figure 1). Reticular is the most common type, consisting of slightly raised fine whitish lines in an interlocking lace like keratotic pattern. Papular lesions are small (0.5–1.0 mm) white raised papules. Plaque type closely resembles leukoplakia with a reticular surrounding. Atrophic type appears as inflamed areas of mucosa covered by thin red appearing epithelium. Erosive type presents with atrophic mucosa with ulcers. Bullous form is very rare and is characterized by formation of large thin walled bullae. Papular, plaque like, atrophic and erosive lesions are very frequently accompanied by reticular lesions. All forms of oral LP are generally asymptomatic, but atrophic, erosive and bullous forms are associated with pain and burning sensation.

Biopsy of the lesion should be done to confirm the diagnosis. In situations where histopathology does not confirm the diagnosis then immunofluorescence studies of biopsy specimens should be done. Direct immunofluorescence demonstrates a shaggy band of fibrinogen in the basement membrane zone in 90–100% of cases. Specimens for immunofluorescence should be stored in Michel’s/Bouin’s solution or normal saline and then sent to histopathology. Differential diagnosis Reticular form Plaque form

– Lichenoid reactions – Leukoplakia, hyperplastic candidiasis, traumatic keratosis Atrophic form – Speckled leukoplakia, anemic stomatitis, systematic lupus erythematosus and discord lupus erythematosus Erosive and bullous form – Vesiculobullous lesions Annular form – Erythema circinata migrans. Management The lesions of oral LP appear, regress and reappear in some what unpredictable fashion. Asymptomatic LP need not be treated. The treatment of symptomatic LP is necessary. The role of Candida in the causation of oral LP has been debated, therefore a smear for candida needs to be made and 219


if positive, a topical antifungal—clotrimazole (available as Candid gum paint in India) should be given for 14 days. Steroid-resistant cases can be treated using topical tacrolimus 0.1% (available as Tacroz and Tacrovate), cyclosporine rinse and systemic hydroxychloroquine sulfate 200 mg o.d. for 3–6 months (available as tablet HCQS). Other modes of treating oral LP are topical and systemic retinoids, psoralen ultraviolet A (PUVA) therapy, dapsone, mesalazine and levamisole. Erosive LP is a premalignant condition with a malignant transformation rate of 0.1–0.3%. It has to be supplemented with systemic vitamin A preparations for chemoprevention. However most lesions of erosive LP do not respond to conventional steroid therapy unless supplemented by intralesional steroids and especially so if ulcerations are present. Treatment of oral lichen planus is given in Flowchart 2 on page no 153.

EPIDERMOLYSIS BULLOSA Epidermolysis bullosa (EB) is a diverse group of disorders that have as a common feature blister formation with tissue separation occurring at variable depths in the skin and/or mucosa depending on the specific EB type. There may be marked oral involvement, potentially creating devastating alterations in the soft and hard tissues. Oral tissue fragility and blistering is common to all EB types. Classification ❍ ❍ ❍ ❍

Epidermolysis bullosa simplex Epidermolysis bullosa simplex with muscular dystrophy Epidermolysis bullosa atrophicans genaralisata graves Epidermolysis bullosa dominant dystrophic/hypertrophic form ❍ Scarring epidermolysis bullosa with dermolytic vesicles. The current classification proposed for epidermolysis bullosa is mentioned in Chapter 7 on Vesiculobullous Disorders. Etiopathogenesis Pertaining to hereditary forms pathogenesis appears to be related to genetic defects in basal cells, hemidesmosomes or anchoring connective tissue filaments depending on the disease subtype. The acquired non-hereditary type is often precipitated by exposure to specific drugs, and type VII collagen antibodies located below the lamina densa are found. Clinical features Epidermolysis bullosa simplex Epidermolysis simplex is seen in neonates and infants. Nails, feet, hand and neck 220

develop vesicles and bulla in response to friction. Oral vesicles are mild and small and heal without scarring. Epidermolysis bullosa simplex with muscular dystrophy An autosomal recessive disorder that appears at birth. Multiple bullae are seen frequently involving the oral mucosa. Extremities develop more bullae which result in scarring that eventually leads to muscular dystrophy and deformity. Epidermolysis bullosa atrophicans generalisata graves An autosomal recessive disorder that develops in neonates within hours after birth. Nail beds are usually the first area of involvement with shedding of nails, remaining skin surface progressively develops bullae. Many infants die within a few months and survivors have nail distortion, growth retardation, anemia, scarring and skin lesions. Large fragile vesicles and bullae are frequently seen in the oral cavity, especially in the posterior hard palate and soft palate. Enamel hypoplasia and enamel pits leading to dental caries are usually seen. Another routinely encountered feature is perioral crusting. Epidermolysis bullosa dominant dystrophic/hypertrophic form An autosomal dominant form, which is very mild; 20% of patients develop lesions before 1 year of age. Vesicles and bullae begin to develop and gradually lessen with age. Dystrophic nails and scarring is prominent. White mucosal epithelial inclusion cysts may be seen on the tongue, buccal mucosa and palatal mucosa. Scarring epidermolysis bullosa with dermolytic vesicles An autosomal recessive disorder that appears shortly after birth. Bullae are seen on the feet, fingers, buttocks, back and the occiput. Oral vesicles prone to scar formation are seen. Hypoplastic enamel and enamel pits are commonly found. Differential diagnosis Lesions of pemphigus vulgaris, erythema multiforme and dermatitis herpetiformis mimic epidermolysis bullosa. Histopathological and immunofluorescent studies will help in differentiating these conditions. Management Treatment is often frustrating because conventional therapy with corticosteroids and immunosuppressive agents frequently does not result in significant clinical improvement. Various therapeutic modalities have recently been used which include cyclosporine, colchicine, plasmapheresis, extracorporeal photochemotherapy and intravenous gamma globulins. Although the data are preliminary, they suggest that intravenous immunoglobulins may be a promising treatment modality for resistant, non-responsive or refractory EB acquisita.


Dental management

Etiopathogenesis

The majority of individuals with mild EB subtypes may receive dental treatment with only minor modifications in approach. Individuals with EB can retain their dentition using conventional restorative techniques. With aggressive preventive interventions and management of developing malocclusions using serial extraction, it is also possible to reduce the likelihood of rampant caries, achieve an acceptable occlusion without the need for active tooth movement or appliance therapy, and allow these individuals to benefit from maintaining a natural healthy dentition.

Although the cause of psoriasis is unknown, it is now widely accepted that psoriasis involves an increase in the rate of epithelial cell proliferation. It is proposed that the increased epithelial turnover rate of psoriasis is associated with cell damage. There also appears to be a strong genetic component to the pathogenesis of psoriasis. Thirty-five percent of patients with psoriasis have a positive family history. Studies on the major histocompatibility complex (MHC) have shown a strong association between B13, Bwl7, Bw37, and Cw6 antigens and development of psoriasis. Clinical features

PSORIASIS Psoriasis is a non-contagious skin disorder that most commonly appears as inflamed, edematous skin lesions covered with a silvery white scale. Types ❍ ❍ ❍ ❍

Guttate psoriasis Pustular psoriasis Inverse psoriasis Erythrodermic psoriasis.

Psoriasis is more common in whites and in women. Approximately 10–15% of new cases begin in children younger than 10 years. The median age at onset is 28 years. Typical skin lesions of psoriasis appear as well-circumscribed erythematous patches with overlying thick silvery scales (Figure 2A, B). Lesions may occur in any location, but most commonly involve the scalp and the anterior hairline, torso, bony prominences of the extremities, nails, perianal and perineal areas. The course of the disease is unpredictable and characterized by spontaneous episodes and relapses. If the deep scales are removed, one or more tiny bleeding points are disclosed, which is popularly referred to as Auspitz’s sign.

Figure 2 A

B

Erythematous patches on the forearms along with silvery scales in psoriasis. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

221


The oral counterpart of psoriasis is rare. The first descriptions of oral lesions of psoriasis have been attributed to Oppenheim and Thimm (1903). Van der Waal and Pindborg described four types of oral psoriatic lesions. ❍

Well-defined, gray to yellowish white, tiny, round to oval lesions. ❍ Lacy, circinate, white elevated lesions on the oral mucosa and the tongue paralleling skin lesions. ❍ Fiery red erythema of the oral mucosa including the tongue seen primarily in the acute form of psoriasis. ❍ A geographic tongue that occurs more frequently among patients with psoriasis than without.

Clinical features The condition is characterized by hypodontia, hypotrichosis, and hypohidrosis. Neonates exhibit excessive scaling of the skin and unexplained pyrexia. Patients present with sparse hair and eyebrows (Figure 3A, B). As the age progresses frontal bossing, saddle nose, sunken cheeks, thick/everted lips wrinkled and hyperpigmented

Figure 3 A

Histopathology Histopathologically, intraepithelial microabscesses (Munro’s abscesses) are common. However, these are not specific for the disease. Management Oral lesions should be treated with topical corticosteroids. The topical steroids that are available in India are triamcinolone acetonide—0.1% with orabase (Kenacort oral paste, TESS cream), clobetasol propionate—0.05% (Clobetamil cream, Tenovate skin cream). Psoriatic arthritis Psoriatic arthritis is a systemic disorder and inflammatory condition and this disease may be the major contributing factor to temporomandibular dysfunction (TMD) symptoms and signs. TMD signs and symptoms are found more frequent and more severe in the patients with psoriatic arthritis of other joints than in the patients with psoriasis without arthritis. TMD signs and symptoms in psoriasis are mainly caused by the related joint involvement that directly affects the masticatory system.

B

ECTODERMAL DYSPLASIA The ectodermal dysplasias comprise a large and heterogeneous group of disorders (about 170) characterized by a variety of congenital defects in structures of ectodermal origin including skin, hair, teeth, nails, and sweat glands. Out of these the most common and best studied disease is anhidrotic or hypohidrotic ectodermal dysplasia (Christ– Siemens–Touraine syndrome). Etiopathogenesis It is an inherited X-linked recessive trait associated with the repressed expression of a gene on the X-chromosome in the positions from q13 to q21. 222

(A) A boy with sparse scalp hair in ectodermal dysplasia. Courtesy: Dr Sumanth KN. (B) Photograph showing hair loss of the eyebrows and scalp hair. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore


Figure 4

Hypoplastic and conical primary maxillary central incisors in ectodermal dysplasia. Courtesy: Dr Sumanth KN

Figure 5

Figure 6

Hypoplastic and malformed maxillary second primary molars as well as underdeveloped alveolar ridges in ectodermal dysplasia. Courtesy: Dr Sumanth KN

malformed (Figure 6). Orthopantomograph will help to confirm the absence of teeth (Figure 7). Differential diagnosis Distinct condition if all the three components are present. However, for single component of disease the differential diagnosis is isolated oligodontia, Witkop tooth nail syndrome and trichodental syndrome. Management There is no treatment available and the treatment is symptom related. For xerostomia, pilocarpine 5 mg one tab is given three times a day. Salivary substitutes can be used. Crowns for malformed teeth and dental implants for edentulous areas can be recommended.

Hypoplastic and malformed mandibular second primary molars as well as underdeveloped alveolar ridges in ectodermal dysplasia. Courtesy: Dr Sumanth KN

skin around the eyes are seen. Patients may present with fever of unknown origin because of the inability to sweat. Oral manifestations Anodontia/oligodontia is often seen. The remaining teeth are usually malformed. Both deciduous and permanent teeth are affected. Most common missing teeth are molars. Malformed teeth have truncated and conical crowns and shortened roots (Figures 4 and 5). Dry mouth, high palatal arch and cleft palate may be seen in some individuals. The alveolar ridges are usually

EHLERS–DANLOS SYNDROME The term Ehlers–Danlos syndrome (EDS) was coined after the names of a Danish dermatologist, Edvard Ehlers (1901) and a French dermatologist, Henri Alexandre Danlos (1908) who reported patients exhibiting thin, hyperplastic skin, loose jointedness, and hemorrhagic tendencies. It is a group of inherited disorders characterized by excessive looseness (laxity) of the joints, hyperelastic skin that is fragile and bruises easily, and/or easily damaged blood vessels. The diagnosis of EDS encompasses any of six types of connective tissue disorders that are hereditary in nature and exhibit a characteristic defect in collagen metabolism. There are six major types of EDS that are characterized by distinctive features. 223


Figure 7

Orthopantomograph showing multiple missing teeth in ectodermal dysplasia. Courtesy: Dr Sumanth KN

EDS was initially subdivided into seven types following a meeting of various authors in Berlin, Germany. However owing to its complex nature, another widely accepted classification consisting of six types of EDS was proposed in Villefranche, France in 1997. Villefranche classification of EDS ❍ ❍ ❍ ❍ ❍

❍

Classical EDS (similar to Berlin Type I [gravis] and Berlin Type II [mitis])—Type V collagen defects. Hypermobility EDS (similar to Berlin Type III [hypermobile])—unknown collagen defects. Vascular EDS (similar to Berlin Type IV [arterialecchymotic])—Type III collagen defects. Kyphoscoliosis EDS (similar to Berlin Type VI [ocularscoliotic])—defect in lysyl hydroxylase. Arthrochalasia EDS (similar to Berlin Type VIIa and VIIb [arthrochalasis multiplex congenita])—defect in Type I collagen. Dermatosparaxis EDS (similar to Berlin Type VIIc [human dermatosparaxis])—defect in procollagen N-peptidase.

Etiopathogenesis Different forms of EDS have different modes of inheritance. Family history is a risk factor in some cases. Various subtypes are inherited as autosomal dominant/recessive and X-linked traits. A variety of genetic mutations cause abnormality in collagen that will result in the disease. Clinical features Symptoms Joint dislocation/subluxation/joint pain, increased joint mobility, joints popping, early arthritis, doublejointedness and flat feet ❍ Easily damaged, bruised, and stretchy skin which is very soft and velvety ❍

224

❍ ❍ ❍

Easy scarring and poor wound healing Premature rupture of membranes at birth Visual difficulties.

Signs ❍ Excessive joint laxity and hypermobility ❍ Soft, thin, or hyperextensible skin ❍ Mitral valve prolapse ❍ Signs of platelet aggregation failure ❍ Rupture of intestines, uterus, or eyeball (seen only in vascular EDS, which is rare) ❍ Deformed cornea. Oral manifestations Scarring on the chin and forehead, a history of repeated luxations of the TMJ, epicanthus, hypertelorism, a narrow curved nose, sparse hair and hyperelasticity of the skin. Fragile mucosa and gingiva—early-onset generalized periodontitis leading to premature loss of deciduous and permanent teeth. Tooth mobility is often encountered. Hypoplasia of the enamel is commonly seen. Premolar and molar teeth can present with deep fissures and long cusps. Microdontia is sometimes present. Irregularities in the dentin structure and dentinal tubules may also be seen. Radiographic examination often reveals pulp stones and roots that are short and deformed. The tongue is very supple. Approximately, 50% of those with the syndrome can touch the end of their nose with their tongue (Gorlin’s sign), compared to 8–10% of the normal population and the palate is commonly vaulted. Investigations ❍ ❍ ❍ ❍

Collagen typing performed on a skin biopsy sample Collagen gene mutation testing Lysyl hydroxylase or oxidase activity Echocardiograph (heart ultrasound).


Differential diagnosis Marfan’s syndrome, generalized familial joint hypermobility syndrome, cutis laxa, pseudoxanthoma elasticum and Larsen’s syndrome. Management There is no specific cure for EDS, so individual problems and symptoms must be evaluated and cared for appropriately. Genetic counseling is recommended for prospective parents with a family history of EDS. Dental considerations ❍

Mitral valve prolapse indicates prophylactic antibiotics are for relevant procedures. ❍ Inferior alveolar nerve blocks should be given with great care to avoid causing hematoma. ❍ Forces used in orthodontic treatment should be lighter than usual, given the fragility of the periodontal ligament and relapses are common dictating a longer period of retention. ❍ Ideally, oral surgery should be avoided. It is imperative to test blood coagulation values before proceeding with surgery. Since sutures do not hold well wounds should be covered with acrylic dressings.

PACHYONYCHIA CONGENITA Pachyonychia congenita (PC) is a rare autosomal dominant keratin disorder that typically affects the nails and palmoplantar skin, and often the oral mucosa, tongue, larynx, teeth, and hair. Müller made the first documented observation in 1904. Jadassohn and Lewandowsky published the next reports in 1906. In the dermatologic literature, PC is better known as Jadassohn–Lewandowsky syndrome. PC is also known as Touraine’s polykeratosis congenita, palmoplantar keratoderma. Etiopathogenesis The disease results from mutations in the genes encoding epidermal keratinocyte keratins. The mutation is likely to have a deleterious effect on protein structure as it interferes with the assembly of polypeptides forming the keratin skeleton of epidermal cells (Bowden, 1995). Clinical features Onychodystrophy, palmoplantar keratoderma and follicular keratosis in areas of friction are characteristic features. Epidermal inclusion cysts and pilosebaceous cysts are often seen in PC. Thickened or coarse curly hair is usually seen. Laryngeal involvement is usually present

as hoarseness and occasionally as a life-threatening respiratory stridor. Oral manifestations Oral findings present soon after the birth and may be the earliest sign of the disease. Focal or generalized white opaque thickening of oral mucosa (oral leukokeratosis) is commonly seen on the buccal mucosa, tongue and lips. Intermittent angular cheilitis is also seen in some cases. Patients sometimes present with natal and prenatal teeth. Investigations Molecular DNA analysis will help in identifying the condition. Biopsy may be performed to differentiate oral leukokeratosis from leukoplakia. Though no specific treatment exists for the condition, it is believed that the clinical manifestations of the condition become less severe with advancing age.

DYSKERATOSIS CONGENITA Dyskeratosis congenita, also known as Zinsser–Engman– Cole syndrome and Hoyeraal–Hreidarsson syndrome, is a rare, progressive bone marrow failure syndrome characterized by the triad of reticulated skin hyperpigmentation, nail dystrophy, and oral leukoplakia. It is a pre-malignant condition. It is genetically heterogeneous, with X-linked recessive, autosomal dominant and autosomal recessive subtypes. It is related to telomerase dysfunction. Telomeres are repeat structures found at the ends of chromosomes that function to stabilize chromosomes. With each round of cell division, the length of telomeres is shortened and the enzyme telomerase compensates by maintaining telomere length in germline and stem cells. Because telomeres function to maintain chromosomal stability, telomerase has a critical role in preventing cellular senescence and cancer progression. Rapidly proliferating tissues with the greatest need for telomere maintenance (e.g. bone marrow) are at greatest risk for failure. Clinical features Mucocutaneous features The mucocutaneous features are the most consistent features of the disease. Reticulated skin hyperpigmentation affecting the neck, face, chest, and arms is the most common finding occurring in approximately 90% of patients. Telangiectasia, atrophy (poïkilodermia) dystrophic nails and palmoplantar keratoderma, hyperhidrosis, blepharitis, conjunctivitis, epiphora include other signs which are less frequently seen. Leukoplakia, which is the third feature of the classic clinical triad, has been reported in 80% of the affected 225


patients. This can occur on any mucosal surface, but has been most frequently reported affecting the oral mucosa. The specific intraoral sites affected include lingual mucosa, buccal, mucosa and the palate, with the tongue being the most frequently affected. The other sites reported include the urethra, glans penis, vagina and anorectal region. Patients have a recognized increased risk of malignancy from pre-existing mucosal leukoplakia, reaching an incidence of approximately 35% with a peak in the third decade of life. Non-mucocutaneous features The non-mucocutaneous features include bone marrow failure, pulmonary disease, ophthalmic, skeletal, dental, genitourinary, gastrointestinal and neurological abnormalities. One of the most common features of this disease is bone marrow failure resulting in peripheral cytopenias. Bone marrow failure is reported as the principal cause of death in 70% of patients as a consequence of bleeding or opportunistic infections. Oral manifestations Manifestations in the oral cavity other than leukoplakia include hyperpigmentation of the buccal mucosa, severe periodontal disease, hypocalcified teeth and taurodontism. Crops of vesicles with patches of white necrotic mucosa infected with Candida are another commonly encountered feature. The oral lesions can be histopathologically evaluated for assessing the degree of dysplasia. Management Pancytopenia responds to androgen therapy in about 50% of patients. Supportive care is important. Bone marrow transplant has cured about 25% of a small number of patients. Oral leukoplakia should be treated conventionally. Dental considerations It is imperative to test blood coagulation values before proceeding with surgery in patients with aplastic anemia and pancytopenia.

PITYRIASIS ROSEA Pityriasis rosea (PR) is an acute self-limiting disease, probably infective in origin, affecting mainly children and young adults, and characterized by a distinctive skin eruption and minimal constitutional symptoms. Etiology The cause of PR is uncertain, but many epidemiological and clinical features suggest that an infective agent may be 226

implicated. Recently herpes like particles have been found in 71% of PR lesions. Involvement of two herpes viruses, HHV-6 and HHV-7 has been suggested as a cause of eruption. There are various reports associating PR like eruptions with drugs like metronidazole, barbiturates, captopril, clonidine, gold and ketotifen. However, reported epidemiological evidence for infectivity includes occasional family history or household outbreaks, seasonal and year to year to fluctuations. Clinical features The first manifestation of the disease is usually the appearance of the herald patch which is sharply defined, bright red, round or oval plaque of 2–5 cm covered with fine scales usually seen on the thigh or upper arm, trunk or the neck in 50–90% of cases. After an interval of 5–15 days, the general eruptions begin to appear in crops at 2–3 days interval as dull pink colored oval small plaques covered by fine, dry, silvery scales in Christmas tree pattern (long axis of the lesion characteristically follow the lines of cleavage parallel to the ribs) on the upper chest and back. Involvement of oral mucous membrane is unusual but ill-defined red patches with some desquamation or with punctuate hemorrhages, or bullae may be observed. The lesion of PR can be large (PR gigantea), urticarial (PR urticata), vesicular, pustular, purpuric and erythema multiforme like. Differential diagnosis ❍ ❍ ❍ ❍

Seborrheic dermatitis Guttate psoriasis Secondary syphilis Pityriasis lichenoides.

Treatment and prognosis Since the disease is asymptomatic and self-limiting, no treatment is required. Oral erythromycin in a dose of 200 mg four times a day has been shown in a study by Sharma et al to hasten the clearance of the lesions. If the itch is troublesome or the appearance is distressing, a topical steroid or UVB irradiation can be helpful. The skin lesion commonly fades after 3–6 weeks and may leave temporary hypo- or hyperpigmentation. Second attack of PR occurs in about 2% of cases after an interval of few months or many years.

XERODERMA PIGMENTOSUM Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by photosensitivity, pigmentary changes, premature skin aging, neoplasia and abnormal


DNA repair. Some patients with XP also have neurological complaints. Etiology Hebra and Kaposi first reported this disorder in 1874 and the term ‘xeroderma pigmentosum’ meaning pigmented dry skin was introduced in 1882. Inheritance is autosomal recessive and there are at least eight different subtypes that are recognized, designated complementation groups A–G and XP variant. Cleaver first reported in 1968 that fibroblast from most patients with typical XP lack the normal capacity to repair UV radiation damage to DNA. Epstein et al in 1970 showed that DNA repair was defective in vivo. Approximately, 80% of patients with XP show a defect in the initiation of DNA excision repair of UV photoproducts in all cell types: epidermal cells, dermal fibroblasts, lymphocytes, conjunctival cells, corneal cells and amniotic fluid cells. Clinical features Skin is normal at birth and first symptoms are noted between the 6th month and the 3rd year in 75% of cases as freckling and increasing dryness on light exposed surfaces followed by acute sunburn or more persistent erythema telangiectasia and angiomas on unexposed skin and on the lingual and buccal mucosa. Superficial ulcers, healing with difficulty leave disfiguring scars and contractures may produce ectropion. Keratoacanthomas, actinic keratoses, small round white atrophic spots and crusted vesiculobullous lesions are also seen. Malignant tumors like basal cell carcinoma, squamous cell carcinoma may develop as early as the 3rd or 4th year. The disease is often fatal before the age of 10 years and worldwide two-thirds die before 20 years of age. Ocular symptoms The eyes are affected in 80% of cases and presents as photophobia and conjunctivitis as early symptoms and ectropion, symblepharon, ulceration, vascular pterygium, corneal opacities and epitheliomas of lid conjunctiva and cornea may develop later. Neurological symptoms Neurological symptoms occur in 20% of XP patients with one or more of the following: mental retardation, areflexia or hyporeflexia, spasticity, ataxia, sensorineural deafness, dysphasia and abnormal electroencephalographic findings. Oral manifestations Oral manifestations which often occur before 20 years of age, include development of squamous cell carcinoma of the lower lip and tip of the tongue.

Diagnosis The unscheduled DNA synthesis assay (following UV irradiation of the cells in culture) is the standard laboratory method for diagnosis of XP. Prenatal diagnosis by amniocentesis and molecular genetic techniques allow for earlier and more reliable results. Treatment Patients must be protected from sunlight by every possible means—by using sunblock creams, sunglasses with side shields, two layers of clothing and broad brimmed hat. Early and adequate excision of all tumors is essential. Topical 5-fluorouracil may be useful for early or premalignant lesions. A recent clinical trial by Yarosh et al used the microbial enzyme T4 endonuclease V applied regularly as a topical liposome lotion for over a period of 1 year, significantly reduced the onset of both new basal cell carcinoma and actinic keratoses. The prognosis is poor. Most patients die 30 years earlier than the normal population, either directly from cutaneous malignancy or from complications associated with the treatment of the cancer.

ACANTHOSIS NIGRICANS Acanthosis nigricans (AN) is an acquired dermatologic condition characterized by the development of a velvety, brownish alteration of the skin. The cutaneous lesions itself is benign, yet it is significant because it represents a cutaneous marker for internal malignancy. Etiology Acanthosis nigricans has a variety of known causes whose common mechanism is likely to be stimulation of tyrosine kinase growth factor receptor signaling pathway in epidermis. In insulin resistance syndrome, high levels of circulating insulin directly or indirectly activate the insulin-like growth factor 1 receptor (IGF1R), which is a transmembrane protein related to the insulin receptor. Tumor-derived growth factors are preserved to be involved in malignant AN. Clinical features Earliest changes are pigmentation, dryness and roughness of the skin which in the affected areas is grayish brown or black, palpably thickened and covered by small papillomatous elevations, which give it a velvety texture. As the thickening increases, the skin lines are further accentuated and the surface becomes mammillated or rugose and larger warty excrescences develop. Most common sites are axillae, 227


the back and sides of neck, anogenital region and the groin and flexures. Oral lesions of AN have also been reported and may occur in 25–50% of affected patients, especially those with malignant forms. The lesions appear as diffuse, finely papillary areas of mucosal alteration that most often involve the tongue or lips, and rarely buccal mucosa. Types of AN 1. 2. 3. 4. 5. 6. 7. 8.

Inherited forms of acanthosis nigricans Benign acquired acanthosis nigricans HAIR-AN syndrome—hyperandrogenism, insulin resistance and acanthosis nigricans Autoimmune acanthosis nigricans Drug-induced acanthosis nigricans Malignancy-associated acanthosis nigricans Tripe palms Nevoid acanthosis nigricans.

Management Treatment is of the underlying cause or is otherwise symptomatic and of little help. Removal of the tumor in the malignant form may allow some improvement. A case of hereditary benign AN improved dramatically with etretinate. Although AN itself is a harmless process, the patients should be evaluated to ascertain which form of disease is present.

GOLTZ–GORLIN SYNDROME Goltz–Gorlin syndrome is also referred to as focal dermal hypoplasia syndrome or Goltz syndrome. We should be aware that this syndrome is not the same as Gorlin syndrome or Gorlin–Goltz syndrome, which is basal cell nevus syndrome. This uncommon genetic condition is transmitted as an autosomal dominant trait. It is characterized by typical skin defects and widespread involvement of various organ systems. It affects the eyes, skeletal system, urinary system, cardiovascular and central nervous system and the gastrointestinal system. Clinical features Almost 90% of the individuals who present with this syndrome are females. When it occurs in males the condition is lethal. The clinical features are usually evident at birth and the signs and symptoms progress with advancing age. Patients are usually short statured with sparse hair over the scalp, pubic region, eyebrows and eyelashes. Patients may complain of hypohidrosis. Other features include nail dystrophy and syndactyly, polydactyly and lobster-claw deformity of the hands. Diffuse cortical cerebellar atrophy and recurrent respiratory infections may be seen. 228

Skin manifestations As the name suggests there is a focal loss of the dermis characterized by the outpouching or herniation of the subcutaneous fat. Based on the degree of melanin pigmentation, the lesion has varied appearances. Erythematous macules are evident in fair skinned individuals whereas areas of hypo- or hyperpigmentation are seen in darker individuals. The lesions are typically confined to the lines of Blaschko. The common sites that are affected are the forearms, thighs and cheeks. Some authors describe the presence of raspberry like papillomas. Papillomas are usually present at the skin and mucosal junction such as the perioral, periocular, perianal and perivulvar regions. Facial features Patients may have an asymmetrical face with a pointed chin. The eyes are usually sunken and ears may appear to be protruded and asymmetric. Colobomas of the iris, choroid, retina, or optic disk are seen in almost 35% of the patients. Occasionally, hypertelorism and blue sclera may be seen. Oral features Occasionally, cleft lip and palate associated with this syndrome have been reported. Both the deciduous and permanent dentition may be affected. Teeth are usually hypoplastic and microdontic. Oral papillomas may be seen in any part of the oral mucosa. However, the lips, gingiva, tongue and buccal mucosa are the common sites. Other relatively rare findings include split/double lingual frenum, high palatal vault and cleft lip/palate. Radiographic findings The characteristic finding is the presence of osteopathia striata (longitudinal striations) in the metaphysis of the long bones and the sacral bone. Orthopantomograph may reveal the presence of multiple taurodonts. Treatment and prognosis No definitive treatment is possible for the condition. The prognosis and severity of the condition depends on the organ system that is involved.

ACRODERMATITIS ENTEROPATHICA Acrodermatitis enteropathica (AE) is a rare disease transmitted as an autosomal recessive trait. It was first recognized in 1936 by Thore Brandt and further investigated by Danboly and Closs. Although deficiency dermatitis caused by low dietary zinc has the exact clinical and histological features but the term should be reserved only for genetic causes of zinc deficiency.


Etiology

Clinical features

The gene defect appears to involve SLC 39 A4 on 8q24 which encodes a ZIP protein responsible for the zinc transport in enterocytes. Zinc absorption in patients of AE is low about 2–3% compared with 27–67% in normal adults.

The condition usually presents in the third or fourth decade as flaccid vesicopustules, crusted erosions or expanding circinate plaques appearing in areas exposed to friction. Flexural disease may be hypertrophic and malodorous with soft, flat, moist vegetations and fissures. Asymptomatic longitudinal white bands are present in the nails of some patients and fine palmar pits have been documented. Herpes simplex virus and contact dermatitis, both irritant and allergic, may exacerbate Hailey–Hailey disease.

Clinical features The disease typically starts after weaning or earlier if the infant is not given breast milk. The child turns peevish, withdrawn and photophobic and develops a vesicobullous dermatitis on the hands, feet and periorificial areas. The scalp hair is lost. Diarrhea is often present. Growth is stunted and there is a decreased resistance to infection. Wound healing is poor and skin lesions do not heal. Differential diagnosis ❍ ❍ ❍ ❍

Atopic dermatitis Cutaneous candidiasis Epidermolysis bullosa Seborrheic dermatitis.

Diagnosis Low serum of zinc and alkaline phosphatase (a zinc dependent enzyme) may aid in the diagnosis of zinc deficiency. Treatment and prognosis Zinc sulfate for AE was introduced between 1973 and 1974. Oral zinc in a dose of about 2 mg/kg per day was found to clear all clinical manifestations. Prolonged therapy up to adult age is necessary.

HAILEY–HAILEY DISEASE (Familial Benign Chronic Pemphigus) Hailey–Hailey disease is a rare autosomal dominant intraepidermal blistering disease which is characterized by recurrent vesicles and erosions usually affecting the neck, axilla and groin. The condition was described by Hailey brothers in 1939.

Differential diagnosis ❍ ❍ ❍ ❍

Pemphigus vegetans Darier’s disease Impetiginized eczema Candidal intertrigo.

Treatment and prognosis Loose, cool clothing will reduce friction and sweating. Topical steroids with antibacterial agents may be effective. Rarely systemic corticosteroids may be required for widespread disease. Oral treatment of herpes simplex should be considered in patients with unresponsive painful disease. Long remissions are common and many patients may improve in old age.

DARIER’S DISEASE (Keratosis Follicularis) Darier’s disease, described independently by White and Darier in 1889, is an autosomal dominant condition characterized by a persistent eruption of hyperkeratotic papules, histological examination with a distinctive overlying dyskeratosis. Etiology It is caused by mutations in ATP2A2 gene at chromosome 12q24.1, which encodes the sarco and endoplasmic reticulum calcium ATPase type 2 (SERCA2) which is a member of a family of ion pumps that maintain high calcium concentration in endoplasmic reticulum. Clinical features

Etiology Hailey–Hailey disease is caused by mutations in ATP2C1, a gene on chromosome 3q21 that encodes a P-type calcium transport adenosine triphosphate (ATPase). The cellular process that may be affected by mutation includes gene transcription, post-translational modifications and trafficking of adhesion proteins and the assembly of adhesion junctions.

Characteristic lesion of Darier’s disease is a firm rough papule, which is skin colored, yellow brown or brown seen on seborrheic areas which exacerbate on sun exposure, coalescent papules form irregular warty fissured plaques or papillomatous plaque masses which, in the flexures, become vegetating and malodorous. On the scalp, heavy crusting has a characteristic spiny feel on palpation with loss of hair. The external auditory meatus may be 229


blocked by keratotic debris. Palms and soles show minute pits or, in older subjects, punctuate or filliform keratosis. Frequency of oral lesions ranges from 15 to 50% but is usually asymptomatic and is discovered on routine examination. They consist of multiple, normal to white colored flat topped papules that if numerous enough to be confluent, result in cobblestone mucosal appearance. The lesion primarily affects the hard palate and alveolar mucosa. If palate lesions are prominent, the condition may resemble inflammatory papillary hyperplasia or nicotine stomatitis. Nail changes include red or white longitudinal bands of varying width, often ending in a pathognomonic notch at the free margin of the nail. The nails are brittle. Treatment Many patients with mild disease require no treatment other than emollients, simple hygiene and advice to avoid excessive sun exposure. In severe disease oral and topical retinoids are usually effective.

REITER’S SYNDROME Reiter’s syndrome is characterized by the presence of a non-suppurative polyarthritis exceeding a duration of 1 month associated or preceded closely by a lower urogenital or enteric infection in young men who carry the HLA-27 antigen. It was named after Professor Hans Reiter, who in 1916 reported a German officer who developed urethritis conjunctivitis and arthritis following an episode of bloody diarrhea. Inflammatory eye involvement and mucocutaneous manifestations are common. The classical triad of arthritis, conjunctivitis, and urethritis is observed only in 33% of the cases. The less stringent criteria of American College of Rheumatology, comprising of peripheral arthritis of more than 1 month duration, occurring in association with urethritis or cervicitis exhibit a sensitivity of 84.3% and specificity of 98.2% when compared with other arthropathies. Etiology The etiopathogenesis of Reiter’s disease centers on the determination of the role of probable infective triggering agents and the proneness of certain individuals to develop the condition due to genetic susceptibility (Table 1). Clinical features The earliest features of Reiter’s disease usually presents within 1–4 weeks of exposure. Fever, constitutional complaints and features of urethritis or enteritis usually precede arthritis. 230

Table 1

Infectious organisms associated with the onset of Reiter’s disease

Urogenital pathogens

Enteric pathogens

Chlamydia trachomatis C. psittaci C. pneumoniae Ureaplasma urealyticum Neisseria gonorrhoeae

Shigella flexneri, serotype 2a, 1b Salmonella typhimurium S. enteritidis S. paratyphi Yersinia enterocolitica Campylobacter jejuni

Genitourinary tract involvement Urethritis is the most common presentation and manifests as dysuria with mucoid or mucopurulent discharge. Acute abacterial cystitis with increased micturitional frequency and chronic prostatitis may occur. In females, persistent urogenital involvement may manifest as cervicitis, urethritis and vaginitis. Arthritis The arthropathy is typically an acute asymmetric additive and ascending inflammatory oligoarthritis of weight bearing joints. Symptoms may range from slight arthralgia with no visible signs to marked erythema, edema, tenderness and exquisite joint pains with complete immobility. Characteristic features of the arthropathy of reactive arthritis and Reiter’s syndrome are oligoarticular, predominantly lower limbs, asymmetrical dactylitis, enthesitis and lower back/buttock pain. Cutaneous lesions The classic skin lesions of keratoderma blenorrhagica manifests as thickened, heaped up, crusted and yellowish scaly lesions on an erythematous base affecting the acral lesion. Circinate balanitis affects about 20–40% and occurs in up to 85% of men with sexually acquired Reiter’s disease has been shown in a study by Martin et al. In uncircumcised males, it appears as painless, serpiginous, erosive, geographic lesions on the glans penis and in circumcised males as hyperkeratotic papules. Nail involvement is seen in 15% of cases as yellowish discoloration, subungual hyperkeratosis and onycholysis. Ocular involvement Conjunctivitis is the only presentation and is mild, transient and recurrent. Keratitis and uveitis can occur. Musculoskeletal features Plantar fasciitis, the classical ‘lover’s heel’ occurs in 25% of patients. It is often associated with calcaneal spur; both are highly suggestive of Reiter’s disease. Oral manifestations The oral lesions which occur in slightly less than 20% of the patients are described in various ways. Some reports


mention painless erythematous papules distributed on the buccal mucosa and palate while other reports describe shallow, painless ulcers that affect the tongue, buccal mucosa, palate and gingiva. Some authors have even described that geographic tongue may be a component of Reiter’s syndrome, probably because geographic tongue bears a superficial resemblance to the lesion of circinate balanitis. Treatment and prognosis Therapeutic intervention in Reiter’s disease should aim at suppression of inflammation, optimum joint protection, relief of pain, patient education, and when appropriate, eradication of infection; NSAIDs is the mainstay of treatment. Indomethacin (75–150 mg/day), phenylbutazone (200–600 mg/day), naproxen (375–750 mg/day) and diclofenac sodium (100–200 mg/day) can be used. Systemic corticosteroids (40–60 mg) prednisolone are indicated for the patients with florid disease, severe pain, wasting, fever, high ESR, posterior uveitis, pericarditis and in those who have failed to respond to NSAIDs. Conjunctivitis is self-limiting and requires no treatment. One percent atropine and steroid drops for iritis and systemic steroids for posterior uveitis can be given. Keratoderma blenorrhagica and circinate balanitis require hygiene and topical steroids. Methotrexate and azathioprine should be considered as second line of therapy. The prognosis and course of individual patient is varied and unpredictable. Severe disability occurs in less than 15% of cases and is usually secondary to debilitating lower extremity disease, aggressive axial involvement or blindness. Death is rare and is usually attributable to cardiac complications.

Teeth and jaw changes are seen in 65–95% of cases and are of considerable diagnostic importance because, in contrast to many dermatologic features, they persist through life. The changes are delayed eruption, changes in dental contour, hypodontia/microdontia, micrognathia/ prognathia. Hair are sparse and thin and partial baldness is seen in 35–70%. Central nervous system changes are seen in 10–40% of cases as microcephaly, mental retardation, spastic paralysis, convulsions and epilepsy. Structural anomalies are most frequently related to neurological system and is seen in 14% of the cases as body asymmetry, scoliosis, spina bifida, syndactylia, ear anomalies, additional ribs and skull malformations. Breast anomalies are seen in 1% of the cases as hypoplasia or additional nipples. Dental defects are frequent—delayed dentition, partial anodontia, and cone-or peg-shaped teeth are the most usual. Diagnostic criteria No evidence of IP in a first degree female relative. Major criteria Typical neonatal rash ❍ Erythema ❍ Vesicles ❍ Eosinophilia Typical hyperpigmentation ❍ Mainly trunk ❍ Blaschko’s line ❍ Fading in adolescence Linear atrophic hairless lesions

INCONTINENTIA PIGMENTI (Bloch–Sulzberger Syndrome) Incontinentia pigmenti (IP) is a rare X-linked dominant disease that affect skin, eyes, hair, teeth and central nervous system and manifest itself during early neonatal period. The disease was first described by Garrod in 1903, its pathogenesis in 1926 by Sulzberger and localization of rash in 1985 by Happel. Clinical features Four stages are differentiated according to the changes in the skin are shown in (Table 2). Nail dysplasia is found in 40–60% of cases. Eye changes are seen in one-third of the cases as speckled diffuse hypopigmentation in the retina (a pathognomonic feature), microphthalmia, lenticular hemorrhage, retrolental fibroplasia, cataract and atrophy of the optic nerve.

Minor criteria (supportive evidence) ❍ Dental involvement ❍ Alopecia ❍ Woolly hair/abnormal nails ❍ Retinal disease. At least one major criterion is necessary to make a firm diagnosis of sporadic IP. The minor criteria, if present, will support the diagnosis. Evidence of IP in a first degree female relative The evidence of IP is likely in a primary female relative of an affected female if any of the following features are demonstrable, alone or in combination. ❍ ❍

Suggestive history or evidence of typical rash Skin manifestation of IP – Hyperpigmentation – Scarring 231


Table 2

Four stages are differentiated according to the changes in the skin

Stages

Clinical features

Stage 1 vesicular

Linear vesicles, pustules, or blisters with erythema along Blaschko’s line

During infancy, possible in childhood

Stage 2 verruciform

Keratotic papules and plaques

At the age of 2–8 weeks

Stage 3 pigmented

Hyperpigmented macules along the Blaschko’s line in the mastoid, axillary, and inguinal sites; the localization of secondary rash may not coincide with that of the primary rash

At the age of 12–40 weeks

Stage 4 depigmented

Brownish macules begin to disappear; hyperpigmentation becomes more apparent during examination under Wood’s lamp; in the site of lower limbs there remains linear hypopigmentation and skin atrophy

Continues from infancy to childhood

– Hairless streaks – Alopecia at vertex – Anomalous dentition ❍ Woolly hair ❍ Retinal disease ❍ Multiple male miscarriages. Differential diagnosis In acute stage of disease, herpes simplex infection, impetigo, candidosis, epidermolysis bullosa congenita. In later stage, differentiated from post-inflammatory pigmentation and hypomelanosis of Ito. Treatment and prognosis The vesicles should not be touched and the skin must be kept clean to avoid infection. Local anti-inflammatory treatment with steroids may be applied. Timely diagnosis of IP prior to pregnancy and early genetic consultation of pregnant women with IP to evaluate the risk of damage for the children of such women are essential.

KAWASAKI DISEASE (Mucocutaneous Lymph Node Syndrome) This condition is usually seen in children, often affecting those below 2 years of age, characterized by fever and generalized exanthem with lymphadenitis. The disease was first described in 1967 by Kawasaki from Japan.

Time of manifestation

Clinical features The onset is acute, with a high fever, which lasts for at least 5–7 days. The mucosa and conjunctiva are injected. In the mouth, the lips are dry and fissured, the tongue appears red with prominent papillae (strawberry tongue) and the throat is injected. After 3–4 days there is generalized exanthema. The area affected on the limbs becomes edematous followed by scaling. There is accompanying cervical lymphadenitis, although not always present and may only involve one node. Fever resolves in 1–2 weeks. Complications In about one-fourth of cases there is accompanying myocarditis which may be followed by symptomatic coronary artery disease and in 1–2% by myocardial infarction. Other complications include arthralgia, arthritis, severe erythema multiforme, iritis, proteinuria, hepatitis and aseptic meningitis. Diagnosis Abnormalities on investigation includes leukocytosis and thrombocytosis with a raise ESR. The raised platelet count is most often seen in the post-acute phase. Treatment Intravenous gammaglobulin in high doses (2 g/kg in a single effusion over 10 hours) is very helpful in reducing the overall mortality and complication of the disease. Shortterm use of aspirin is also helpful in reducing the risk of platelet aggregation.

Etiology Various hypotheses have been advanced to account for its symptoms. These include rickettsial illness, exposure to house-dust mite. It has been suggested that bacterial superantigens cause disease through wide scale activation of immune mechanism with cytokine release bringing other cell types, including vascular endothelium, into an uncontrolled immunological reaction. 232

TUBEROUS SCLEROSIS COMPLEX (Epiloia, Bourneville’s Disease) Tuberous sclerosis (TSC) is a genetic disorder of hamartoma formation in many organs, particularly the skin, brain, eye, kidney and heart. The characteristic skin lesions are angiofibroma, shagreen patch, periungual fibroma and


ash leaf white macules classically, although not invariably seen in combination with epilepsy and mental retardation. Sherlock coined the term ‘epiloia’ indicating the diagnostic clinical triad of epilepsy, low intelligence and adenoma sebaceum. Etiopathogenesis The inheritance of tuberous sclerosis is determined by single autosomal dominant gene, with variable expression. It is recognized that about half the TSC families are linked to 9q34 (TSC1) and other half to 16p13 (TSC2). TSC1 gene has not yet been coded but TSC2 gene encodes a protein named ‘tuberin’ which shows homology to the catalytic domain of the GTPase activating protein Rap1 which is involved in the regulation of cell proliferation and differentiation. Approximately, 60–70% of TSC cases are thought to be the result of new mutations, but before genetic counseling of the normal parent of an affected child, both parents should be fully investigated. A study by Flinter et al showed that about 30% of normal parents had TSC. Clinical features Onset before the age of 5 years with cutaneous changes or with epilepsy is usual, although the disease may remain latent until adolescence. Diagnostic criteria determined by a committee of the US National Tuberous Sclerosis Association have been modified. A definitive diagnosis of TSC requires two major features. Major features Facial angiofibroma or forehead plaque Non-traumatic ungular or periungual fibroma Shagreen patch (connective tissue nevus) Multiple retinal nodular hamartoma Cortical tuber Subependymal nodule Subependymal giant cell astrocytoma Cardiac rhabdomyoma, single or multiple Lymphangioleiomyomatosis and/or renal angiomyolipoma ❍ Hypomelanotic macules (⬎3) ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍

Suggestive features requiring further investigation Multiple randomly distributed pits in dental enamel Hamartomatous rectal polyps Bone cyst Cerebral white matter radial migration lines Gingival fibromas Non-renal hamartomas Retinal achromic patch Confetti skin lesions Multiple renal cysts Skin tags Positive family history in first degree relatives.

❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍

Skin lesions Skin lesions are found in 60–70% cases. Lesions of four types are pathognomonic: ❍

Angiofibromas usually appear between the ages of 3–10 years and often become more extensive at puberty and then remain unchanged. Firm, discrete, red brown, telangiectatic papules 1–10 mm in diameter, extend from the nasolabial furrows to the cheeks and chin. ❍ Periungual fibromas (Koenen’s tumors) appear at or after puberty as smooth, firm 5–10 mm in length, flesh colored excrescences emerging from nail fold. ❍ Shagreen patch is an irregularly thickened, slightly elevated, soft skin colored plaque, usually in the lumbosacral region. ❍ Ash leaf macules are present at birth or in infancy and are 3 cm in length, most easily detectable by examination under Wood’s light, are frequently present on the trunk or limbs.

Mental deficiency Mental deficiency is present in 60–70% of cases and may be progressive, but if mental development has been normal throughout the childhood subsequent deterioration is uncommon. Epilepsy is seen in almost all mentally retarded patients and in some 70% of those with average intelligence. It usually begins in infancy or early childhood, thus often preceding the skin lesions by many years. Ocular signs Ocular signs occur in 50% of the cases but are hard to detect. Retinal phacomas, pigmentary and other retinal abnormalities and hypopigmented spots on iris can occur. Cardiac and renal tumors, pulmonary changes, gastrointestinal tumors and endocrine and other metabolic disturbances can occur. Oral manifestations Oral manifestations of tuberous sclerosis include developmental enamel pitting on the facial aspect of the anterior permanent dentition in 50–100% of patients. These pits are readily appreciated after applying a dental plaque–disclosing solution to the teeth. Multiple fibrous papules affect 11–56% of patients seen predominately on the anterior gingival mucosa. Diffuse gingival enlargement and radiolucencies of the jaws that represents dense fibrous tissue proliferation is also seen. Treatment and prognosis The cosmetic appearance may be improved by removing angiofibromas with pulsed dye vascular laser (585 nm). 233


Neurosurgery should be considered when epilepsy is controlled by drugs and there is fixed, circumscribed, electroencephalographic focus. The treatment of lesions in other organs is unsatisfactory and surgical procedure may be required for relief of symptoms. Patients affected by this condition have a slightly reduce life span compared with the general population, with deaths usually related to CNS or kidney disease.

GRAFT-VERSUS-HOST DISEASE Graft-versus-host disease (GVHD) occurs when immunocompetent cells from a donor recognize and react against ‘foreign’ tissue antigen in an immunocompromised host. Moderate to severe acute GVHD affects 9–35% of patients undergoing standard allogenic bone marrow transplantation, despite using HLA matched sibling donors and immunosuppression after grafting.

followed by a faint red maculopapular rash leading to desquamation or even toxic epidermal necrolysis. Chronic GVHD occurs 3–14 months after the transplant. When the condition is localized it occurs as hypopigmented nodular areas which eventually soften and atrophy. Generalized GVHD starts as erythematous rash and becomes lichenoid. With advancing time scleroderma like changes appear. The oral mucosal manifestations of GVHD depend on the duration and severity of the attack and the target oral tissue. Sometimes the oral lesions of GVHD are the only signs of disorder. It is estimated that 33–75% of patients suffering from acute GVHD and about 80% of patients suffering from chronic GVHD will have oral involvement. Patients will present with fine reticular network of white striae that resembles oral lichen planus involving tongue, labial mucosa and the buccal mucosa. Atrophy, ulceration and xerostomia of the oral mucosa can be present. Treatment and prognosis

Etiology Billingham described the original criteria for development of a GVHD in 1966: ❍

Genetically determined histocompatibility difference between donor and recipient. ❍ Immunocompetent cells in the grafted tissue able to recognize foreign histocompatibility antigens in the host and to react against them. ❍ Inability of the host to recognize and react against the grafted tissue. Clinical features Acute GVHD occurs within 60 days of bone marrow transplantation and most often after 7–10 days. Mild fever is

Diagnostic Signs in Dermatology Antenna sign: This sign is seen in keratosis pilaris. Individual follicles show a long strand of keratin glinting when examined in side light resembles like antenna is known as antenna sign. Asbo-Hansen’s phenomenon (bulla spread phenomenon): Refers to the ability to induce peripheral extension of a blister as a consequence of applying lateral pressure to the border of intact blister. This is seen in pemphigus. Auspitz’s sign: This sign is seen in plaque type of psoriasis. When the surface of the typical plaque is lifted from the base, punctuate bleeding points occur at the sites of scale removal. Café-au–lait spots: These are light to dark brown wellcircumscribed round to oval cutaneous macules, which vary in size from 1 to 20 cm. These are usually present at birth or appear during infancy. Isolated lesions are found in 10–33% of 234

Prophylactic use of cyclosporine, methotrexate, prednisolone combination therapy has reduced incidence of acute GVHD. T-cell depletion by using anti-T cell receptor antibodies is successful. Granulocyte colony stimulating factor, used to enhance engraftment may reduce the incidence of GVHD. Once the disease is established, treatment with high dose steroids or cyclosporine is of value symptomatically and antilymphocyte globulin may be of additional benefit. The prognosis depends on the extent to which the disease progresses and whether it can be controlled. Mortality is caused by the disease itself and severe superinfection due to immunosuppressive therapy. It is believed that about 55% of the patients with mild GVHD survive compared to the 15% survival rate in severe GVHD.

normal population. Multiple café-au-lait spots especially more than six in number and exceeding 1.5 cm in diameter are seen then underlying systemic disease is suspected. It is seen in neurofibromatosis (outline is like the coast of California), Albright’s syndrome (outline is like coast of Maine), Fanconi’s anemia, Bloom’s syndrome and Cowden’s syndrome. Carpet tacks sign: Usually seen in discoid lupus erythematosus. Removal of the scale shows its undersurface to be covered with the horny plugs which filled the follicles, resembling ‘carpet tacks’. ‘Cerebriform tongue’ sign: The sign is originally described by Premalatha and coworkers (1981). Oral lesions in pemphigus vegetans are hyperplastic masses which on the tongue can give rise to cerebriform appearance. Crowe’s sign: The sign is seen in neurofibromatosis. Axillary freckling seen in neurofibromatosis is known as Crowe’s sign.


Darier’s sign: This sign is observed in mastocytosis. Gentle rubbing of the urticaria pigmentosa skin lesion causes local itching, redness and whealing and is known as Darier’s sign. This sign is due to the local histamine release in the lesional skin.

Id reaction: It is an allergic manifestation of candidiasis, the dermatophytoses, and other mycoses characterized by itching and vesicular lesions that appear in response to circulating antigens at sites that are often far distant from the primary fungal lesion itself.

Deck-chair sign: This sign is noted in papuloerythroderma of Ofuji. Papuloerythroderma of Ofuji is a rare, intensely pruritic eruption of unknown etiology, consisting of wide spread coalescing sheets of uniform erythematous papules. The lesion characteristically spares the compressed abdominal body folds, and this is known as deck-chair sign.

Koebner’s phenomenon: Linear lesions occurring as a result of external trauma such as scratching is called Koebner’s phenomenon. This phenomenon can be seen in psoriasis and lichen planus.

Dimple sign: This sign is usually seen in dermatofibroma. If the overlying epidermis is squeezed the dimple will be seen, indicating the tethering of the overlying epidermis to the underlying lesion. Dubois sign: Usually seen in congenital syphilis. Very short little finger seen occasionally as late stigmata in congenital syphilis is known as Dubois sign. Flag sign: Commonly seen in kwashiorkor and rarely in severe ulcerative colitis and after extensive bowel resection. Alternating white and dark bands occur along individual hair is known as flag sign. Intermittent protein malnutrition leads to this sign. Forschheimer’s sign: Originally described by Forschheimer, is observed in rubella. An enanthema is present in up to 20% of patients during the prodromal period or on the first day of the rash, and are confined to the soft palate. This presence of enanthema is known as Forschheimer’s sign. Gorlin’s sign: Ability to touch the tip of the nose with the tongue in patients with Ehlers–Danlos syndrome. Groove sign: Originally described by Greenblatt in lymphogranuloma venereum (LGV). Enlargement of lymph nodes above and below the inguinal ligament may give to bubo a grooved appearance known as groove sign. Headlight sign: Vascular stigmata associated with atopic dermatitis. Perinasal and periorbital pallor is termed as headlight sign. Hertoghe’s sign: Cutaneous stigmata associated with atopic dermatitis. Thinning of the lateral eyebrows is known as Hertoghe’s sign. Higoumenakis’ sign: This sign is commonly seen in congenital syphilis. Irregular thickening and enlargement of the sternoclavicular portion of the clavicle is known as Higoumenakis’ sign. It is the result of periostitis and usually is unilateral than bilateral. Hutchinson’s sign: This sign is observed in subungual malignant melanoma as well as herpes zoster ophthalmicus. A longitudinal melanotic streak accompanied by periungual pigmentation in subungual malignant melanoma is known as Hutchinson’s sign. In ophthalmic nerve zoster, appearance of vesicles on the side of the nose indicates the involvement of the nasociliary nerve, and this is known as Hutchinson’s sign.

Koebner effect: In patients with psoriatic arthritis of TMJ, who have disabling movements of the mandible, surgery is indicated and surgery may be complicated by psoriasis forming on the surgical scar, which is referred to as Koebner effect. Leser–Trélat sign: This sign often occurs as a manifestation of visceral malignancy. Internal malignancy associated with sudden development of numerous seborrheic keratoses, in an eruptive fashion with or without pruritus, is generally accepted as the sign of Leser–Trelat. Nikolsky’s sign: It was named after Pytor Vasilyenich Nikolsky who was the first to describe this finding. On applying gentle mechanical pressure (e.g. blowing air or applying pressure with a mirror handle) on affected tissue will result in the formation of a lesion. Nikolsky’s sign is seen both in the skin and oral mucosa. It is seen in pemphigus, paraneoplastic pemphigus, mucous membrane pemphigoid, epidermolysis bullosa, linear IgA bullous disease, lupus erythematosus, graft-versus-host disease and toxic epidermal necrolysis. Nose sign: This sign is evident in exfoliative dermatitis. Nose and perinasal area is characteristically spared in exfoliative dermatitis involving the other parts of the face and body is known as nose sign. Oil drop sign: This sign is usually seen in psoriasis. Circular areas of discoloration of the nail bed and hyponychium may resemble oil drop below the nail. Histologically there are areas of psoriatic change below the nail bed and hyponychium. Ollendorf’s sign: This sign is observed in secondary syphilis. In secondary syphilis, the papule is exquisitely tender to the touch of a blunt probe, which is termed positive Ollendorf’s sign. Osler’s sign: This sign is seen in alkaptonuria. By the third decade of life, the deposition of pigment in alkaptonuria becomes apparent. In the early stages, the sclera is pigmented which is termed Osler’s sign. Psoriasiform lesions: Lesions that have histopathological similarities to psoriasis are termed as psoriasiform lesions. Examples of such lesions are Reiter’s syndrome, geographic tongue and erythema circinata migrans (ectopic geographic tongue). Romana’s sign: This sign is observed in American trypanosomiasis also known as Chagas disease. Unilateral edema of the eyelids, inflammation of the lacrimal gland associated with the

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preauricular lymphadenopathy is known as Romana’s sign. This sign is due to portal of Trypanosoma cruzi in the conjunctiva. Sailor’s skin: Skin damage (dry, wrinkled skin) due to prolonged exposure to the sun and wind. Some authors use the term ‘farmer’s skin’. Actinic elastosis or solar elastosis is one such dermal condition where sailor’s skin can be appreciated.

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(1886–1954). It is basically a type of exfoliative cytology. In pemphigus, acantholytic cells are seen and in herpes multinucleated giant cells with Lipschutz bodies are seen.

Thumb sign: This sign is positive in Marfan’s syndrome. Completely opposed thumb in the clenched hand projects beyond the ulnar border, known as thumb sign. It is simple screening test for Marfan’s syndrome.

Wickham’s striae: It is seen in lichen planus. On skin, there are flat-topped papules with violaceous hue and the surface of these papules is covered by characteristic very fine grayish white lines called Wickham’s striae. In the oral cavity the disease appears as radiating white lines. At the intersection of these white lines a tiny white elevated dot is present known as striae of Wickham or Honiton lace.

Tzanck’s test: The examination of fluid from a bulla (a blister) in search of Tzanck cells characteristic of varicella (chicken pox), herpes zoster, herpes simplex, and pemphigus vulgaris. It was named after a Russian dermatologist Arnault Tzanck

Wimberger’s sign: This sign is observed in early congenital syphilis. Radiological examination shows loss of density on the medial side of the upper end of the tibia is known as Wimberger’s sign.

SECTION

IV

Diseases of Specific Structures

10 Temporomandibular Disorders 11 Diseases of Salivary Glands

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CHAPTER

Temporomandibular Disorders

10

Shibu Thomas, Joanna Baptist, Ravikiran Ongole, Thomas Zachariah

➧ Components of Temporomandibular Joint ➧

Clinical Evaluation of Temporomandibular Joint

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Clinical Evaluation of Muscles of Mastication and Accessory/Cervical Muscles

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Disorders Associated with Deviation/ Alteration in the Form of Articular Surfaces

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Articular Disk Defects Disk Thinning and Perforation Adherence and Adhesions Disk Displacement Disk Displacement with Reduction Disk Displacement without Reduction Displacement of Disk–Condyle Complex (Hypermobility and Dislocation)

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Osteoarthrosis Osteoarthritis Juvenile Idiopathic Arthritis Polyarthritides Traumatic Arthritis Infectious Arthritis/Septic Arthritis Rheumatoid Arthritis Psoriatic Arthritis Hyperuricemia ➧

TMJ Ankylosis

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Masticatory Muscle Disorders Acute Disorders Chronic Conditions

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Congenital, Developmental and Acquired Disorders of the TMJ

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Neoplasms Affecting the TMJ

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Condylar Fractures

Inflammatory Joint Disorders Synovitis or Capsulitis Retrodiscitis

The temporomandibular joints (TMJs) are two joints between the mobile mandible and the fixed temporal bone. Each joint contains two joint spaces which are separated by a fibrocartilaginous articular disk. The TMJ is a compound joint. It can also be considered as ginglymodiarthroidal joint (capability of both hinge type and sliding/gliding movement). The use of the term ‘compound joint’ is justified based on the fact that the TMJ is composed of three bones, namely, the mandibular condyle, squamous portion of temporal bone and the non-ossified articular disk. The TMJ is the articulation between the condyle of the mandible and the squamous portion of the temporal bone.

COMPONENTS OF TEMPOROMANDIBULAR JOINT Glenoid Fossa and Articular Eminence/ Protuberance The glenoid fossa or mandibular fossa is a well-defined hollow area on the inferior portion of the squamous temporal

Degenerative Joint Diseases

bone. The convex articular eminence forms the anterior limit of the joint. The glenoid fossa is covered by a thin layer of fibrocartilage.

Mandibular Condyle The condyle is elliptically shaped with its long axis oriented mediolaterally. The dimension of the condyle is roughly 20 mm in the mediolateral direction and approximately 8–10 mm in the anteroposterior direction. The articulating surface of the condylar head is covered by fibrocartilage (Figure 1).

Articular Capsule and Articular Disk The articular capsule is a fibrous membrane that surrounds the joint and incorporates into the articular eminence. It attaches to the articular eminence, the articular disk and the neck of the mandibular condyle. Superiorly, it is attached to the temporal bone and inferiorly to the neck of the condyle. The anatomical and functional boundaries of the 239

Section IV – Diseases of Specific Structures

Figure 1

Figure 2

The biconcave articular disk. Courtesy: Dr Arturo Mann Skeletal components of TMJ (condylar head and the glenoid fossa). Courtesy: Dr Arturo Mann

TMJ are defined by the articular capsule. The inner surface of the capsule is covered by the synovial membrane that aids in the secretion of the synovial fluid. The articular capsule confines the synovial fluid to the articulating surfaces. Temporomandibular ligaments provide additional reinforcement to the capsule on its lateral wall. Articular disk is a biconcave oval structure with a thin intermediate zone and a thick posterior and anterior border. These thick posterior and anterior bands act as wedges, giving the disk a self-seating capacity with the condyle functioning against the intermediate zone. The importance of this feature cannot be overemphasized; the contour of the disk with the thick bands helps prevent the displacement of the disk from the condyle during translation. An absence of blood vessels and nerves in the intermediate zone of the disk enables this part of the disk to act as a pressure-bearing area (Figure 2). The disk is a fibrous, saddle-shaped structure that separates the condyle and the temporal bone. The meniscus varies in thickness—the thinner, central intermediate zone separates thicker portions called the anterior band and the posterior band. Posteriorly, the meniscus is contiguous with the posterior attachment tissues called the bilaminar zone. The bilaminar zone is a vascular, innervated tissue that plays an important role in allowing the condyle to move forward. The meniscus and its attachments divide the joint into superior and inferior spaces. The superior joint space is bounded above by the articular fossa and the articular eminence. The inferior joint space is bounded below by the

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condyle. Both joint spaces have small capacities (passive volume of the upper joint space is 1.2 ml and the passive volume of the lower joint space is 0.9 ml). The condyle articulates with the inferior surface of the disk to form the lower joint, the disk–condyle complex, where only hinge or rotatory movement occurs. Translation or sliding movements occur in the upper joint, composed of the disk–condyle complex articulating with the mandibular fossa of the temporal bone. During functional movements of the mandible, stability within the TMJ is achieved by maintaining the thin intermediate zone of the disk between the condyle and the eminence. The disk also serves as a shock absorber to counteract the many forces acting on the joint during both function and parafunctional activity.

Synovial Fluid The main functions of the synovial fluid are to nourish the avascular articulating cartilage and provide lubrication between the articulating surfaces during function. Synovial fluid is a clear straw-colored thixotropic fluid which is composed of mucin with some albumin, fat, epithelium, and leukocytes. Synovial fluid also contains lubricin secreted by synovial cells. It is mainly responsible for socalled boundary layer lubrication, which reduces friction between opposing surfaces of cartilage. Synovial fluid is made of hyaluronic acid and lubricin, proteinases and collagenases. During movement, the synovial fluid held within the cartilage is squeezed out mechanically to maintain a layer

Chapter 10 – Temporomandibular Disorders

of fluid on the cartilage surface (so-called weeping lubrication). Boundary lubrication is a function of water physically bound to the cartilaginous surface by a glycoprotein.

Discal Ligaments The medial and lateral portions of the articular disk are attached to the corresponding poles of the condyles via nonelastic, short discal ligaments. These ligaments are vascularized and innervated. These ligaments restrict the movement in the lower joint to hinge or rotatory action when viewed in a sagittal plane. Discal ligaments cause the disk to move passively with the condyle in an anterior and posterior direction during condylar translation. These ligaments permit very little lateral excursion.

Posterior Attachment or Retrodiscal Tissue or Bilaminar Zone The retrodiscal tissue is confined to the space between the articular disk and the posterior wall of the articular capsule. It is richly vascularized and well innervated. It is attached anteriorly to the posterior band of the articular disk and posteriorly to the tympanic plate and posterior aspect of the condyle. The retrodiscal tissue contains loosely associated collagen fibers and a meshwork of elastic fibers. The upper retrodiscal lamina is elastic in nature and exerts a posterior traction on the disk. The inferior retrodiscal lamina is non-elastic and restricts forward rotation of the disk on the condyle.

Ligaments Associated with Temporomandibular Joint The ligaments associated with the TMJ have three major functions: stabilization, guidance of movement, and movement limitation. The ligaments that have been associated with the TMJ include lateral ligament (temporomandibular ligament), stylomandibular ligament, sphenomandibular ligament, discomalleolar ligament (Pinto’s ligament) and Tanaka’s ligament. The lateral ligament is comprised of two parts: a deep part (horizontally oriented) and a superficial part (vertically oriented). The horizontally oriented portion of the lateral ligament limits retrusion and laterotrusion. In this manner, the sensitive retrodiscal tissue is protected from injury. The vertically oriented portion of the ligament limits opening of the jaw. The vertically oriented superficial part of the temporomandibular ligament contains nerve endings

(Golgi tendon organs) which play an important role as static mechanoreceptors for protection of these ligaments around the TMJ. Accessory ligaments of TMJ include the stylomandibular and sphenomandibular ligaments. The stylomandibular ligament runs from the styloid process downward and forward to the medial surface and border of the angle of the mandible. The stylomandibular ligament functions by limiting excessive mandibular protrusion. The sphenomandibular ligament arises from the spine of the sphenoid bone and extends downward and forward to insert on the lingula of the mandible along the lower border of the mandibular foramen. The sphenomandibular ligament restricts protrusive, mediotrusive as well as passive jaw opening. Discomalleolar ligament was described by Pinto in 1962. This ligamentous structure connects the malleus in the tympanic cavity and the articular disk and capsule of the TMJ. It is estimated that only 29% of the TMJs reveal the presence of this ligament. This anatomical relationship between the middle ear and the TMJ is believed to be one of the explanations for the aural symptoms associated with TMJ dysfunction. Tanaka’s ligament was described in 1986. This ligament provides a cord like reinforcement to the medial wall of the articular capsule.

Muscles of Mastication Various mandibular movements such as opening, closing, protrusion and retrusion occur under the coordinated movements of the muscles of mastication, namely, the masseter, temporalis, medial pterygoid and lateral pterygoid. Masseter muscle Masseter muscle arises from the lower border and inner surface of the anterior two-thirds of the zygomatic arch, passes inferiorly and posteriorly, and inserts on the outer surface of the mandibular ramus (Figure 3). The deep fibers of the masseter muscle (pars profunda) are vertically oriented whereas the superficial fibers (pars superficialis) are more oblique. This muscle is responsible for elevating the mandible to aid in jaw closure and for clenching and crushing action. Temporalis muscle The temporalis is a broad, fan-shaped muscle that arises from the temporal fossa (superior and inferior lines of the temporal bone). Via a strong tendon it inserts into the upper anterior border and the medial aspect of the coronoid

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process, and into the anterior border and adjacent medial surface of the mandibular ramus. The anterior fibers run obliquely downward and posteriorly (serve as elevators and also maintain the postural (resting) position of the mandible, with the teeth slightly apart), the middle part of the temporalis muscle helps in closure of the jaws and the posterior fibers which are oriented in a horizontal direction help in retrusion of the mandible and gentle finer movements to achieve a position of intercuspation. Medial pterygoid muscle The medial pterygoid muscle originates from the pterygoid fossa (medial surface of the lateral pterygoid plate). Some of the fibers also originate from the maxillary tuberosity.

Figure 3

Temporal muscle

Masseter muscle

Schematic diagram showing the location of the temporalis and masseter muscle

The muscle fibers extend inferiorly, posteriorly and laterally to insert into the medial surface of the ramus, approximating the angle of the mandible. Here it joins with the masseter to form a muscle sling (Figure 4A, B). The medial pterygoid primarily aids in jaw closure. It also participates in protrusion of the mandible. Lateral pterygoid muscle The lateral pterygoid muscle comprises two functionally distinct entities: (i) the smaller, superior head arises from the infratemporal surface of the greater wing of the sphenoid and runs backward in a nearly horizontal direction; (ii) the larger, inferior head arises from the lateral surface of the lateral pterygoid plate and runs backward in a somewhat oblique upward direction. Both heads merge posteriorly into a tendon that inserts in the following way: the upper fibers, which correspond more to the superior head, insert into the anterior surface of the capsule and disk; the inferior fibers, which correspond mainly to the inferior head, attach mostly to a depression (pterygoid fovea) on the inner side of the anterior surface of the mandible (Figure 5). Studies on the run and the attachment of the lateral pterygoid muscle on 41 cadavers by Abe et al (1993) showed the presence of a third intermediate belly of the lateral pterygoid muscle. Both the heads of the lateral pterygoid muscle function as independent antagonistic muscles. Contraction of the inferior head pulls the condyle forward down the slope of the articular eminence (opening of the mandible and protrusion); whereas the superior head is active during mandibular closure and contracts in conjunction with the mandibular elevation muscles. It also exerts a holding or bracing action on the condyle when the teeth are held together and during power strokes. The superior head also acts to rotate the disk anteriorly on the condyle

Figure 4 A

B

Lateral pterygoid muscle (upper head) Lateral pterygoid muscle (lower head) Temporal muscle Medial pterygoid muscle

Schematic diagram showing the medial pterygoid muscle

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Figure 5

Schematic diagram showing the lateral pterygoid muscle

when the disk–condyle complex is moving upward and backward against the eminence. By keeping the disk between the condyle and eminence, the superior head of the lateral pterygoid muscle aids in maintaining joint stability. Suprahyoid muscles The digastric, mylohyoid, geniohyoid, stylohyoid muscles are grouped under suprahyoid musculature owing to their anatomic location. These muscles are considered accessory muscles of mastication and help in jaw opening along with the lateral pterygoid muscle. Mandibular movements Forward movement or protraction The articular disk glides forward over the upper articular surface, the head of the mandible moves along with it. The movement in the opposite direction is referred to as retraction. Slight mouth opening The mandible moves on the undersurface of the disk like a hinge. Wide mouth opening The hinge like movement is followed by gliding of the disk and the head of the mandible, as in protraction. At the end of this movement the articular disk comes and rests against the articular eminence. Chewing movements/lateral excursions In these movements the condylar head of one side glides forward along the disk but the head of opposite side merely rotates on a vertical axis. This moves the chin forward and to one side.

Arterial Supply, Venous Drainage and Sensory Innervation of TMJ The TMJ and the muscles of mastication are primarily fed by the maxillary artery and superficial temporal artery. The blood supply to the condylar head is also derived from the inferior alveolar artery via the bone marrow. The venous drainage is via the superficial temporal vein, maxillary plexus and the pterygoid plexus. The mandibular branch of the trigeminal nerve is the motor supply to the muscles of mastication. The TMJ is innervated predominantly by the articulotemporal nerve, masseter and the temporal nerves. Four types of receptors aid in proprioception: Ruffini mechanoreceptors (type I), pacinian corpuscles (type II), Golgi tendon organs (type III) and free nerve endings (type IV). The joint capsule, lateral ligaments and genu vasculosum in the bilaminar zone typically contain these receptors. Comparatively, the anteromedial portion of the capsule contains very few type IV receptors.

CLINICAL EVALUATION OF TEMPOROMANDIBULAR JOINT Temporomandibular joints are located about 1.5 cm anterior to the tragus of the ear. The two TMJs, considered together, compromise only one part of the total articulation between the lower jaw and the skull–facial skeleton complex. The other important contribution is made by the interdigitations of the mandibular and maxillary dentition, and function and health of the joint is directly related to condition of the teeth. The history of presenting illness should include the onset and course of signs and symptoms. Past history should include the details regarding arthritis, infections, degenerating diseases, parotitis, ear disorders, muscular disorders, trauma, past dental treatment, diet/nutritional adequacy and habits like clenching, gum chewing, etc. and the individual lifestyle.

Examination of Temporomandibular Joint The TMJ is examined by a thorough inspection, palpation, and auscultation. The face is inspected for any obvious asymmetry, scars (may be indicative of previous surgeries, trauma), swelling/ ulceration/sinus openings in the pre-auricular region. Observe for deviation/deflection (Figure 6) of mandible on mouth opening. The TMJs can be palpated by extra-auricular and intraauricular methods. Palpation can be done standing at 10 o’clock or 11 o’clock positions by the clinician. Intraauricular palpation can be achieved by placing the little 243


Figure 6

supra-orbital ridge to above the ear. The patient is asked to report any discomfort or pain. Masseter Masseter is palpated bilaterally in the area overlying the anterior border of the mandibular ramus. The area of palpation is directly above the attachment of the body of the mandible. Pterygoids Palpation of the pterygoid muscle is difficult because of the inaccessibility of the muscle. Medial pterygoid

Deflection of the mandible to the left side. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

finger inside the external auditory meatus. During mandibular movement the posterior poles of the condylar head can be palpated with the pulp of the little finger. Intraauricular palpation may also be used to elicit capsular tenderness. Extra-auricular examination of the TMJ is achieved by placing the index fingers in the pre-auricular region about 1.5 cm medial to the tragus of the ear. The lateral pole of the condyle is accessible during this examination. Palpatory examination of the TMJ should include the assessment of mouth opening, range of mandibular movements, joint tenderness, detection of clicks and/or crepitus.

CLINICAL EVALUATION OF MUSCLES OF MASTICATION AND ACCESSORY/CERVICAL MUSCLES Tenderness of the muscles of mastication results from stress and fatigue which are characteristics of temporomandibular dysfunction. The muscles to be examined should include the temporalis, masseter, medial and lateral pterygoids, digastric, cervical and sternocleidomastoid muscles. Temporalis Temporalis is palpated simultaneously with the fingertips aligned in a row from the hairline just above the

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Medial pterygoid can only be palpated near its insertion by placement of the index finger laterally and posteriorly into the floor of the mouth toward the medial surface of the angle of the mandible. Lateral pterygoid Tenderness of the lateral pterygoid can occasionally be detected by indirect application of pressure. The index finger or back end of the handle of an instrument is positioned distal and posterior to the maxillary tuberosity and posterior pressure is exerted to compress tissue against the muscle (Figure 7). Alternatively, the medial and lateral pterygoid muscles can be assessed by functional evaluation. These can be achieved by asking the patient to perform simple tasks like opening the mouth against resistance (Figure 8) and closing the mouth against resistance. Digastric muscle Digastric muscles are palpated with the fingertips aligned roughly parallel to the inferior border of the mandible in the submental and submandibular region.

Cervical Examination Temporomandibular disorders/myofascial pain disorders often have musculoskeletal problems in other regions that are particularly associated with neck. Check for mobility of the neck and examine for range and symptoms. Patient is first asked to look to the right and then to the left. There should be at least 70⬚ rotation in each direction. Next patient is asked to look upward as far as possible (extension) and then downward (flexion). Any pain is recorded and any limitation of the movement determines muscular or vertebral problem. Sternocleidomastoid/trapezius/posterior cervical muscles are often part of neck disorder and may refer pain to face and head.


Figure 7

length of the muscle is palpated down to its origin near the clavicle. Posterior cervical muscles

Use of the back end of a mouth mirror to elicit tenderness at the site of the attachment of the lateral pterygoid muscle

Trapezius, longissimus (capitis and cervices) splenius (capitis and cervices) and levator scapulae. The posterior cervical muscles do not directly affect mandibular movements; however, they do become symptomatic during temporomandibular disorders and therefore are routinely palpated. They originate at the posterior occipital area and extend inferiorly along the cervicospinal region. Because they are layered over each other, sometimes it is difficult to identify them individually. These muscles can be examined by slipping fingers behind the patient’s head. Those of the right hand palpate the right occipital area and those of the left hand palpate the left occipital area, both at the origins of the muscle (the patient is questioned regarding any discomfort). The fingers then move down the length of the neck muscles through the cervical area and any patient discomfort is recorded. Trapezius

Figure 8

Trapezius, an extremely large muscle of the back, shoulder and neck, does not directly affect jaw function but is a common source of headache and is easily palpated. It commonly has trigger points (TrPs) that refer pain to the face and hence the purpose of its palpation is to search for active TrP. The upper part is palpated from behind sternocleidomastoid, inferolaterally to the shoulder and any TrP are recorded. Splenus capitis Splenus capitis is palpated for general pain, tenderness, and TrP. Its attachment to the skull is a small depression just posterior to the attachment of the sternocleidomastoid. Palpation is begun at this point and moves inferiorly as the muscle blends into the other muscles.

Occlusal Evaluation

Functional evaluation of lateral pterygoid muscle (opening mouth against resistance)

Sternocleidomastoid Palpation is done bilaterally near its insertion on the outer surface of the mastoid fossa behind the ear. The entire

Examining the dentition and occlusion is an important part of the physical examination of a TMJ disorder or orofacial pain patient. It may provide very useful information about the existence of bruxism or other oral habits and their possible effects on the dentition, periodontium or other oral structures. Such an examination can also determine whether there has been a progressive change in the occlusal relationship (midline shift, anterior open bite, unilateral posterior open bite, etc.) that may indicate the presence of such conditions as unilateral condylar hyperplasia, rheumatoid arthritis, or neoplasm. Noting the number of missing teeth particularly loss of posterior occlusal

245


support is important since this situation may predispose the TMJs to degenerative joint disease (osteoarthrosis) especially in the presence of bruxism.

DISORDERS ASSOCIATED WITH DEVIATION/ ALTERATION IN THE FORM OF ARTICULAR SURFACES

Imaging Protocol

Changes associated with the articular surfaces include those of the mandibular condyle and glenoid fossa. The changes that can be appreciated are condylar head flattening (Figure 9), flattening of the glenoid fossa or bony irregularities over the condylar head. Thinning of the articular disk borders and perforations are common changes associated with change in form of the disk.

Decision should be taken considering the following: ❍ ❍ ❍

Clinical situation Cost Radiation dose.

These depict the osseous structures of the joint with varying degrees of bony detail. ❍

Plain films, panoramic radiographs, conventional and computed tomography

CT can be reserved for the evaluation of: ❍ ❍ ❍ ❍

Foreign body giant cell reaction to implants Suspected tumors Ankylosis Complex facial fractures – MRI is indicated for soft tissues, including disk position and contour – MRI when contraindicated, arthrography is recommended.

Disorders of TMJ Dimitroulis in 1998 described ‘temporomandibular disorders’ as a collective term used to describe a number of related disorders involving the TMJ, masticatory muscles and occlusion with common symptoms such as pain, restricted movement, muscle tenderness and intermittent joint sounds. The disorders of the TMJ may exhibit a wide variety of symptoms and signs. The symptoms and signs that are frequently associated with temporomandibular disorders include: pain on mouth opening, limitation of mouth opening, pain on chewing, joint noises (clicking and/or popping, grating), pain in the region of the joint and/or muscles, pain around the region of the ear, temporal region and cheeks, subjective hearing loss, occlusal irregularities, attrition of teeth, headache (frontal, temporal, suboccipital), tinnitus, muscle hypertonicity and hypertrophy of jaw muscles, neck pain and difficulty in swallowing. TMJ disorders may arise from macro trauma such as in road traffic accident (RTA), excessive mouth opening (yawning, biting onto a large chunk of food) or from repeated micro trauma such as in parafunctional habits (bruxism), uneven occlusal loading (malocclusion, high points in restorations, poorly contoured crowns). Other causes include stress, underlying systemic diseases, arthritis and developmental abnormalities. See Box 1 for classification of TMJ disorders. 246

Clinical features Patient is usually asymptomatic. Over a period of time the patient is accustomed to a new pattern of mouth opening, thereby avoiding pain during mandibular movements. Occasionally, a click may be evident during the opening and closing movements. What is interesting about the clicks associated with condition is that the click is evident at the same point both during opening and closing. Whereas in click associated with disk displacement, the opening click is usually evident after 20 mm of mouth opening and the closing click is felt just short of occlusion of teeth. This condition can be managed by instructing the patient to develop a path of mandibular movement that avoids the interference and to chew on the affected side. This will minimize the intra-articular pressure in the ipsilateral joint.

ARTICULAR DISK DEFECTS Disk Thinning and Perforation It is believed that the disk wears out over a period of time. Hence, elderly individuals may generally present with thinning of the disk which may ultimately perforate. The other causes include excessive occlusal loads from parafunctional habits such as bruxism, clenching and trauma. The thinnest intermediate portion of the disk may show a circular hole with irregular or fragmented border. A perforated disk will expose the articular surface of the joint leading to degenerative changes. Clinical features On auscultation of the TMJ, crepitus or grating noises may be heard. In the early phases of the process pain may be a presenting complaint. Once the disk is perforated occlusion may be altered when teeth are in maximum intercuspation. Disk changes are readily evident on MRI and arthrography. Degenerative changes can be appreciated on traditional imaging modalities and CT.


Box 1

Classification of temporomandibular disorders

I. Disorders of the TMJ Deviation in form Articular surface defects Disk thinning and perforation Adherence and adhesions Disk displacement Disk displacement with reduction Disk displacement without reduction Displacement of disk–condyle complex Hypermobility Dislocation Inflammatory conditions Capsulitis and synovitis Retrodiscitis Degenerative diseases Osteoarthrosis Osteoarthritis Juvenile idiopathic arthritis Polyarthritides Ankylosis II. Masticatory muscle disorders Acute conditions Reflex muscle splinting Myositis Muscle spasm Chronic conditions Myofascial pain Hypertrophy Fibromyalgia III. Congenital, developmental and acquired disorders of condylar process Congenital and developmental disorders Condylar hyperplasia Condylar hypoplasia Aplasia Acquired disorders Neoplasms Fractures

Figure 9

Orthopantomograph (OPG) showing flattening of the condylar head on the right side

Cholitgul et al (1990) evaluated 15 patients who were reported to have disk perforation at arthrography. Eleven patients reported pain. Clicking and crepitation was common. Deviation of the mandible at maximum mouth opening toward the affected side was seen in nine patients. The muscles of the affected side were tender on palpation. The disk perforation was located in the posterior attachment in most joints. An anterior disk displacement was found in almost all patients. They concluded that most joints with disk perforations were osteoarthrotic and the most severe clinical and radiological findings are associated with an anterior disk displacement without reduction.

Adherence and Adhesions Adherence refers to a transient phase in which the condylar head and the articular disk (inferior joint space) or the articular disk and the glenoid fossa (superior joint space) may adhere together. However, prolonged periods of adhesion may result in a permanent state of adhesion (true adhesions). The causes for adhesion are long periods of static loading of the joint (e.g. jaw clenching during sleep) and hemarthrosis caused by macro trauma or surgery. Normally, when the joint is loaded, weeping lubrication is exhausted and boundary lubrication takes over to prevent adhesions. But when the jaw is subjected to long periods of static loading, the boundary lubrication is not sufficient to compensate for the exhaustion of weeping lubrication, resulting in adherence of the disk either with the upper or lower joint compartment. Clinical features Patients may complain of a stiff jaw, dull aching pain and limited mouth opening, especially if they habitually clench their teeth. However, the limitation in mouth opening characteristically corrects following a ‘single click’ when the patient makes attempts to open the mouth. True adhesions may cause elongation of the collateral discal ligaments and anterior capsular ligaments. Hence, during translatory movements the condyle is ahead of the articular disk thereby appearing that the disk is posteriorly dislocated. It is thus hypothesized that posterior disk displacements may result from disk adhesions. Clinically, restriction of the condylar movements to rotation alone, is typical of adhesions between disk and superior joint space (mouth opening may be restricted to about 25 mm). However, when the adhesion occurs between the disk and the inferior joint compartment, rotational movement is inhibited and the translatory cycle is normal (patient can open the mouth to a normal interincisal distance but experience a jerk or limitation when attempting to open the mouth to its full extent). 247


Disk Displacement Disk displacements are also termed as internal derangement. The internal derangements could include disk displacement with reduction and disk displacement without reduction. Anterior disk displacement is common and it usually occurs when there is elongation of the disk attachment and deformation or thinning of the posterior border of the disk, which in turn permits the articular disk to get displaced in an anterior direction on the surface of the condyle. In normal conditions, when the teeth are in occlusion, the posterior band of the disk ends at the apex of the condyle. In anterior disk displacement, the posterior band of the articular disk terminates ahead of the condylar apex. The most common causes for internal derangement include trauma, clenching and biting on hard substances.

Disk Displacement with Reduction It is characterized by an anterior or anteromedial displacement of the disk upon mouth opening. However, on closing the mouth the disk returns to a more normal position relative to the condyle on opening (Figure 10). Clinical features Clicking sound may be heard during mandibular opening and closing. The opening click may be heard during any phase of the translatory cycle and the closing click may be felt as the disk again becomes displaced. Mandible may be deviated to the affected side. Muscle splinting may result in joint tenderness and limitation of mouth opening.

Disk Displacement without Reduction In this condition the condylar head is unable to pass under the displaced disk. The reasons for the condyle to be trapped include: thickening of posterior band, change in shape of disk from biconcave to biconvex and decrease in tension in the posterior attachment. Such a trapping of the disk in

front of the condyle, limiting the condylar translation in the affected joint results in a ‘closed lock’ (Figure 11). Clinical features It is generally a painful condition as the articular capsule, discal ligaments and posterior attachment are inflamed. Patient may present with pain and severe limitation in mouth opening (maximum of 25–30 mm). Mandible is deflected to the ipsilateral side on mouth opening. There is limitation in protrusive movements. Chronic cases may present with joint crepitus. Lateral excursions are limited.

Displacement of Disk–Condyle Complex (Hypermobility and Dislocation) Occasionally during the terminal phases of the translatory cycle, as the condyle moves past the articular eminence it may suddenly move forward to facilitate a wide mouth opening referred to as subluxation (hypermobility, partial dislocation). Hypermobility may occur due to joint laxity seen as a genetic predisposition (Ehlers–Danlos syndrome), following dental procedures that require prolonged mouth opening (endodontic procedures, third molar extraction), excessive yawning and during endotracheal incubation for general anesthesia. Clinical features Many patients describe the sudden forward movement as a feeling of a ‘thud’ sound. This condition is usually painless unless it becomes chronic. Patients may exhibit a tapered/ elongated face. Hypermobility may be distinguished from anterior disk displacements in which the click is associated only with wide opening and absence of closing click.

Dislocation (Open Lock) Dislocation of the condyle is a common condition that may occur in an acute or chronic form. It is characterized

Figure 10 Resting phase

Early translatory phase

Late translatory phase

Open click

Phases of anterior disk displacement with reduction

248


by inability to close the mouth with or without pain. Dislocation has to be differentiated from subluxation which is a self-reducible condition. When the mouth is opened, the head of the condyle should not pass beyond the apex of articular eminence. In case of laxity of capsular structures, a wide open position allows the condyle to move pass the articular eminence which cannot be reduced by the patient. Dislocation can occur in any direction with anterior dislocation being the most common one. Various predisposing factors have been associated with dislocation like muscle fatigue and spasm, the defect in the bony surface like shallow articular eminence, and laxity of the capsular ligament. People with defect in collagen synthesis like Ehlers–Danlos syndrome, Marfan syndrome are said to be genetically predisposed to this condition. Clinical features

Lateral dislocation has been described by Allen and Young in 1969 in two subgroups: type 1 is the lateral subluxation and type 2 is a complete dislocation where the condyle if forced laterally and superiorly to the temporal fossa. It is accompanied by the fracture of body of mandible at symphysis. Superior dislocation as described by Zecha in 1977 is the dislocation of condyle in the middle cranial fossa and associated with fracture of glenoid fossa. It is said to be most probably due to the small rounded shape of the condyle which fails to impinge in the margins which is stronger than the central area.

INFLAMMATORY JOINT DISORDERS Synovitis or Capsulitis

The condition is characterized by inability to close the mouth after wide opening. Bilateral dislocation is more common than unilateral dislocation. However, when the dislocation is unilateral, the chin is deviated to the contralateral side. Palpation in the preauricular region reveals an empty joint fossa and may reveal the condyle anterior to the joint. The inability to close the mouth is due to the spasm of the masticatory muscles. A typical facial expression (elongated face) is due to anxiety related to the thought of not being able to close the mouth (Figures 12A, B and 13A, B).

Synovitis and capsulitis are clinically considered as a single disorder. Synovitis refers to inflammation of the synovial tissues and inflammation of the capsular ligaments is referred to as capsulitis. Various causes have been attributed to these inflammatory conditions such as trauma, opening the mouth excessively, chronic condylar displacement in a posterior direction and sometimes from a direct spread of inflammatory products from the surrounding structures. Clinical features

Types of dislocation Depending upon the position the condyle occupies, Heslop in 1956, described the anterior dislocation in which the condyle moves anterior to the articulating eminence. It is one of the most common type of dislocation. It represents the pathological forward extension of normal translatory movement of head of condyle. The anterolateral variant was described by Morris and Hutton in 1957. Helmy in 1957 described the posterior variant in which the head of condyle is displaced posterior to its usual position. It is usually associated with a fracture of base of skull or the anterior wall of bony meatus.

Continuous pain that exacerbates during function is characteristic of this condition. Limitation in jaw movements is another common finding. In some individuals malocclusion in the posterior teeth is seen due to inferior displacement of the condyle resulting from the edema.

Retrodiscitis Inflammation of the retrodiscal tissues (retrodiscitis) results from a traumatic injury which may indirectly cause the condylar head to impinge on the retrodiscal tissues.

Figure 11 Resting phase

Early translatory phase

Late translatory

Phases of anterior disk displacement without reduction

249


Figure 12 A

B

(A) ‘Elongated face’ in bilateral condylar dislocation. (B) OPG showing bilateral condylar dislocation. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Figure 13 A

B

(A) Normal facial appearance following reduction of the dislocated condyles. (B) Normal positions of the condyle in the glenoid fossa after reduction. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Chronic disk displacement and dislocation may also result in insults to the retrodiscal tissues.

However, patient should be instructed to chew on the affected side as this will relieve occlusal load on the side affected thereby hastening the healing process.

Clinical features Inflammation of the retrodiscal tissues may lead to a forward and downward placement of the condyle thereby producing a same-sided malocclusion of posterior teeth and heavy contact in the anterior teeth of the opposite side. Continuous pain is felt in the TMJ region, which exacerbates on clenching. 250

DEGENERATIVE JOINT DISEASES Osteoarthrosis Osteoarthrosis is a non-inflammatory degenerative disorder of a joint affecting articular tissues and subchondral bone.


Figure 14

Ely cyst in the mandibular condyle. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

It is believed that excessive load on the TMJ leads to degeneration of the fibrous articular tissue covering the condyle. Osteoarthrosis occurs secondary to displacement of the disk. Clinical and radiographic features Patients will exhibit restricted movement of the mandible. Mouth opening may be associated with deflection toward the affected side. Auscultation may reveal crepitus during opening and closing the mouth. The condition is painless. Long-standing osteoarthrosis leads to the formation of multiple cystic areas in the medullary region of the condyle which in turn may collapse to form erosive areas altering the condylar morphology. Some authors suggest that osteoarthrosis is a ‘burned out’ or resolved phase of osteoarthritis. Management Occlusal irregularities, if any, may be corrected to prevent TMJ overloading.

Osteoarthritis Osteoarthritis is characterized by pain secondary to TMJ synovial inflammation. It is usually seen in elderly and relatively more frequently in women. Clinical features Almost all the patients report of a gradual onset of symptoms. The condition is self-limiting and even in the absence of active treatment the symptoms subside over a period of time, and the TMJ movements revert back to an acceptable level.

In the early stages of osteoarthritis patient may complain of pain that exacerbates after function and relieved by rest. However, as the condition worsens pain may be present even at rest. TMJs are usually stiff in the early morning hours and cold climatic conditions may exacerbate the pain. On clinical examination, the TMJ may exhibit very limited range of movement. Mouth opening will result in deviation of the mandible to the same side. Some patients may present with an anterior open bite. Crepitus, myositis and masticatory muscle spasm are other characteristic features of osteoarthritis. Radiographic features Various radiographic findings may be seen based on the extent and severity of the degeneration and the simultaneous remodeling. Radiographs may reveal a reduction in the size of the joint compartments or a total lack of space, flattened condylar head, erosion on the articulating surface, subchondral sclerosis and osteophytes. These osteophytes may eventually break off to lie on the joint space and may be detected on MRI and arthrography as joint mice or loose bodies. Another characteristic finding is the presence of subchondral bone cysts (Ely cyst). These pseudo cysts (Figure 14) are areas of degeneration, containing fibrous tissue, granulation tissue and osteoid. In severe cases, as the posterior slope of the articular eminence erodes, the glenoid fossa enlarges in size.

Juvenile Idiopathic Arthritis The juvenile idiopathic form of arthritis is a chronic, inflammatory, systemic disease typically beginning before 16 years of age. It may affect one or more joints of the body. 251


Clinical features

Figure 15

The condition is characterized by peripheral arthritis. An immunoinflammatory pathogenesis is considered as the etiology. Based on the clinical expression at the onset and the first 6 months of the disease, three types have been described: oligoarticular (four or fewer involved joints), polyarticular (five or more involved joints), and systemic (presence of arthritis and severe systemic involvement). Patients present with chronic synovitis, arthralgia, and impaired joint mobility. Chronic inflammation in the joint results in degenerative changes thereby causing pain, joint sounds, and limited movement. Alterations in facial growth, such as micrognathia, retrognathia, facial asymmetry, and anterior open bite, also occur due to condylar involvement. Other extra-articular manifestations of disease include fever, rheumatoid rash, cardiac disease and chronic uveitis.

Polyarthritides Polyarthritides represent a group of disorders characterized by inflammation of the articular surfaces of the joint. It resembles osteoarthritis as it exhibits degenerative changes in the articular cartilage and underlying bone along with inflammation of the capsule and synovial tissues. Clinically, tenderness may be elicited on TMJ palpation. The TMJ area may exhibit swelling and erythema. The patients may have limited function. Crepitus is a characteristic finding. Patient’s symptoms may aggravate with parafunctional habits. Radiographs reveal surface changes in the glenoid fossa and flattening of the articular eminence.

Traumatic Arthritis Occasionally a major traumatic episode can result in inflammatory changes that ultimately lead to articular surface changes. Patients may complain of restricted mouth opening and pain. On palpation a soft end feel is typically evident.

Limitation in mouth opening and deviation of the jaw in septic arthritis. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Swelling, tenderness and rise in local temperature are characteristic of septic arthritis. Limitation in mouth opening and deviation of the jaw to the affected side are other findings (Figure 15). Affected side may reveal tender cervical lymphadenopathy. Synovial fluid and blood studies will aid in the diagnosis. The commonly isolated organisms from a previously normal TMJ are gonococcal species and from TMJ with previous history of arthritis, Staphylococcus aureus has been isolated. Untreated cases of septic arthritis can lead to brain abscess, ankylosis and osteomyelitis of temporal bone. Ankylosis and facial asymmetry may be a common complication in children.

Rheumatoid Arthritis Infectious Arthritis/Septic Arthritis This form of arthritis is generally seen in patients with previously existing joint disease or with underlying systemic illness. The highest incidence of septic arthritis is seen in individuals on long-term immunosuppressive drugs or corticosteroids. Otherwise sterile articular surfaces and joint spaces may become infected secondary to blood borne bacterial infection or extension of infection from adjacent sites such as the molar teeth, middle ear and parotid gland. Clinically patient gives a history of constant pain in the TMJ region which typically aggravates with function. 252

Rheumatoid arthritis (RA) is a chronic inflammatory, autoimmune disorder, which may involve many of the diarthrodial joints (usually in a symmetrical fashion) in the body characterized by persistent synovitis. Women are three to four times more affected than men. The age of onset varies between 25 and 55 years. Though the exact nature of RA is still unknown, it is believed that the inflammation of the synovial membranes extends into the surrounding connective tissues and articular surfaces (this reactive macrophage laden fibroblastic proliferation from the synovium that extends to the joint surface is called pannus), which then become thickened and tender. The cells of the synovial membrane express


enzymes that cause destruction of the articular surface, eventually leading to a fibrous ankylosis.

Figure 16

Clinical features TMJ afflicted with RA may produce pain, joint stiffness, limited mouth opening, joint sounds and open bite. The reported prevalence of TMJ involvement by RA varies widely from 4.7 to 88%. The American Rheumatism Association (1987) laid down guidelines for diagnosis of RA. According to these guidelines, the patient must present three or four of the following symptoms for more than 6 months: morning stiffness for more than 1 hour; arthritis in three or more joints; arthritis in the hands; symmetrical arthritis; rheumatoid nodes; presence of rheumatoid factor; radiographic alterations. Laboratory investigations The level of rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein, thrombocyte count and plasma tumor necrosis factor-␣ will aid in the diagnosis. Radiographic features The characteristic radiographic findings include generalized decreased density of bone, severe erosion of the condylar head (occasionally only the neck of the condyle may be remaining), subchondral sclerosis, flattening of the condylar head, subchondral cysts and osteophyte formation. In some individuals, the condyle may assume a sharpened pencil shape owing to the erosion of the anterior and posterior condylar surfaces (Figure 16). A modified grading system for the evaluation of TMJ abnormalities based on the degree of bony destruction of the mandibular condyle can be summarized as: ❍

Grade 0 (normal): well-defined cortical outline of the condyle ❍ Grade I (mild): presence of cortical destruction and irregular margin of the condyle ❍ Grade II (moderate): bony destruction or erosion of the condyle or evident flattening, with deviation from normal joint morphology ❍ Grade III (severe): complete or almost complete destruction of the condyle.

Psoriatic Arthritis Psoriatic arthritis (PA) is present in about 5–7% of the patients suffering from psoriasis. The diagnosis can be made when patients present with erosive polyarthritis with negative rheumatoid factor and psoriatic skin lesions are seen long before TMJ is affected. The skin lesions are seen long. This condition affects the fingers and spine along with the TMJ. Eighty-five percent of the patients present with pitting of the nails.

Pencil-shaped condyle on the right side and condylar head flattening of the left side. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Clinical features Unlike rheumatoid arthritis, the TMJ symptoms associated with PA are unilateral. Patients present with pain over the TMJ, limited mandibular movement and deviation of the mandible to the affected side. Radiographically, the TMJ changes are generally similar to those that are seen in rheumatoid arthritis, however in some patients extensive sclerotic changes may be evident.

Hyperuricemia Gout is considered a true crystal deposition disease. Gout may be described as a pathological response of the periarticular tissues to the presence of monosodium urate monohydrate crystals. Though a chronic state of hyperuricemia is required for the development of gout, it alone is not sufficient to predispose to gout. It is estimated that 95% of hyperuricemic individuals may not develop gout. Gout commonly affects the first metatarsophalangeal joint (50%) and other joints such as the ankle, knee, wrist, elbow and the TMJ. Clinical features Crystal deposition may be seen in tissues adjacent to the TMJ. Occasionally, monosodium urate crystals may be evident in the synovial fluid aspirate.

TMJ ANKYLOSIS Ankylosis is an intra-articular condition where there is fusion between the bony surfaces of the joint, the condyle and the glenoid fossa. The term ‘ankylosis’ is derived from 253


a Greek word which means stiffening of a joint as a result of a disease process. Ankylosis of the mandible with immobility of the joint may be of an osseous, fibro-osseous, or cartilaginous variety. Ankylosis must be distinguished from its counterpart pseudoankylosis. Hypomobility of the joint due to coronoid hyperplasia or due to fibrous adhesions between the coronoid and tuberosity of the maxilla or zygoma (e.g. as in ‘V-shaped’ fracture of the zygomatic arch impinging on coronoid leading to fibrous or bony union) are also examples of pseudoankylosis. Even though jaw movement is restricted as in bony ankylosis, the pathology is extraarticular in these cases. Etiopathology Trauma Most cases of ankylosis result from condylar injuries sustained before 10 years of age. A unique pattern of condylar fractures is seen in children. Condylar cortical bone in children is thin with a broad condylar neck and rich subarticular interconnecting vascular plexus. An intracapsular fracture leads comminution and hemarthrosis of the condylar head. This sort of intracapsular burst fracture is called ‘mushroom fracture’. This results in the organization of a fibro-osseous mass in a highly osteogenic environment. Moreover, immobility leads to ossification and consolidation of the mass, resulting in ankylosis. Ankylosis may also occur in trauma sustained during forceps delivery. Laskin (1978) had outlined various factors that may be implicated in the etiology of ankylosis following trauma: ❍

Age of patient: Younger patients have significantly higher osteogenic potential and rapidity of repair. Moreover, the articular capsule is not as well developed in younger patients, thus permitting easier condylar displacement out of the fossa and thereby damage to the disk. Finally, there is a greater tendency for prolonged self-imposed immobilization of the mandible post-traumatically in children. ❍ Type of fracture: The condyle in children has a thinner cortex along with a thick neck, which predisposes them to a higher proportion of intracapsular comminuted fracture. In contrast, adults have a thinner condylar neck which usually fractures at the neck, thus sparing the head of the condyle within the capsule. ❍ Damage to articular disk: The direct contact between a comminuted condyle and the glenoid fossa either from a displaced or torn meniscus is the key factor in the development of ankylosis. ❍ Period of immobilization: Prolonged mechanical immobilization or muscle splinting can promote osteogenesis and consolidation to set in an injured condyle. Total immobility between articular surfaces after condylar injury leads to a bony type of fusion, whereas some movement leads to a fibrous type of union. 254

Local infections Otitis media, mastoiditis, osteomyelitis of temporal bone, parotid abscess, infratemporal or submasseteric space or parapharyngeal infections, furuncle, actinomycosis (the source of infection is contiguous, from adjacent structures). Systemic conditions Tuberculosis, meningitis, pharyngitis, tonsillitis, rubella, varicella, scarlet fever, gonococcal arthritis, ankylosing spondylitis (the route of spread is hematogeneous). The local and systemic infections may pass along as septic arthritis which may not always cause ankylosis. Staphylococcus species, Streptococcus species, Hemophilus influenzae, Neisseria gonorrhoeae are the most likely causes of septic arthritis. The infection may take either the hematogeneous, contiguous, or by direct inoculation. The synovium with its high vascularity and lack of a limiting basement membrane is vulnerable to infection. Arthritis/inflammatory conditions About 50% cases in juvenile RA (Still’s disease) also have TMJ involvement along with polyarthritis. Osteoarthritis may also lead to ankylosis. Neoplasms Sarcoma, osteoma and condroma may also result in ankylosed joint. The pathogenesis of ankylosis is generally the same in all the non-traumatic conditions— degenerative, destructive, and inflammatory changes in disk followed by repair leading to ankylosis. Destruction of the disk leads to bony contact between the condyle and glenoid fossa. Classification of ankylosis according to tissues involved and extent ❍ ❍ ❍ ❍ ❍

‘True’ ankylosis or pseudoankylosis Extra-articular or intra-articular Fibrous, bony, or fibro-osseous Unilateral or bilateral Partial or complete.

Classification of ankylosis by Topazian (1966) ❍

Type I: Fibrous adhesions in or around the jointrestricted condylar gliding. ❍ Type II: Formation of a bony bridge between the condyle and glenoid fossa. ❍ Type III: Condylar neck is ankylosed to the fossa completely. Grading of TMJ ankylosis Sawhney (1986) graded TMJ ankylosis into four types: ❍

Type I: Flattening or deformity of condyle with little joint space on radiograph. There is minimal bony fusion, but extensive fibrous adhesions around joint. Some movement is possible.


❍

Type II: Bony fusion on the outer edge of articular surface, but no fusion on the deeper aspect of the joint. ❍ Type III: A bridge of bone exists between the ramus and zygomatic arch. The upper articular surface and the articular disk on the deeper aspect are still intact. Medially, a displaced atrophic condyle still exists and which is functional. Type III ankylosis results from a fracture-displaced condyle, compared to the crushing types of condylar injuries as in types I and II. ❍ Type IV: Total TMJ obliteration between ramus and skull by large bony mass. It is the most common type.

Figure 17

Clinical features The clinical features of ankylosis depends on: ❍

Type of ankylosis: Unilateral versus bilateral, bony versus fibrous, extent of joint involvement. ❍ Age of onset and duration of ankylosis: The deformity will be severe if it occurs before the age of 5 years. Clinical features of unilateral ankylosis Facial features ❍ ❍

❍ ❍

❍ ❍

❍

Obvious facial asymmetry. Chin receded with hypoplastic mandible on affected side, resulting in deviation of chin and mandible toward affected side. Unilateral vertical deficiency on the affected side. Roundness/fullness on affected side; foreshortened mandible, flatness and elongation on normal side as it grows toward the affected side. Loss of the normal bilateral symmetrical divergence from the mental region toward the angle. The lower border of the mandible on the affected side has a concavity that ends in a well-defined antegonial notch. Markedly elongated coronoid process.

Intraoral features ❍

Occlusal cant with deviation of maxillary and mandibular midlines toward affected side. ❍ Class II Angle malocclusion present on the affected side with unilateral crossbite on the opposite side. ❍ The mouth opening is restricted: amount of opening depends upon degree of ankylosis. Clinical features of bilateral ankylosis Facial features ❍ ❍

Symmetrical defect. Retrognathic mandible with a short ramus and a small body. ❍ Often microgenia, small chin. ❍ ‘Bird-face deformity’ (Figure 17) or ‘Andy Gump’ facies. ❍ Convex profile.

Bird face deformity. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

❍

Relatively short hyomental distance with tight suprahyoid musculature. ❍ Cervicomental angle may be reduced or completely absent. ❍ Obstructive sleep apnea may be present due to oropharyngeal airway narrowing in cephalocaudal, anteroposterior, and transverse directions.

Intraoral features ❍ ❍ ❍ ❍

❍

Mouth opening would be less than 5 mm (Figure 18) or may be nil at times. Generally a class II malocclusion, although class I occlusion may also be seen. Incompetent lips and proclined lower anteriors. Open bite with protrusion of both upper and lower anteriors resulting from the protrusive action of tongue because of decreased tongue space. Severe crowding, multiple impacted teeth with oral health maintenance problems, leading to caries and periodontal problems.

The key clinical difference between intra-articular and extra-articular ankylosis is the ability or limited ability to translate the mandible. If the ankylosis has an extraarticular origin, translation and anteroposterior movement may not be as limited as rotational movement. Radiographic features In fibrous ankylosis, joint may appear normal or the articulating surfaces may be irregular. The joint space is 255


Figure 18

Management The goals of management should include restoration of mouth opening and joint function, facilitation of condylar growth, correction of facial profile and to relieve upper airway obstruction. Surgical correction of ankylosis is best achieved by condylectomy, gap arthroplasty, coronoidectomy, interpositional arthroplasty (with autogenous or alloplastic grafts) and secondary procedures such as orthognathic surgery and distraction osteogenesis. Surgical correction should be followed by active physiotherapy. When ankylosis is left untreated it may result in abnormal facial growth and development, speech defects, nutritional impairment, respiratory distress syndrome, conditions related to poor oral hygiene and psychological impact on the patient.

Restricted mouth opening. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

MASTICATORY MUSCLE DISORDERS Acute Disorders Reflex Muscle Splinting

Figure 19

Muscle splinting or protective co-contraction is a CNS response to actual tissue injury/a threat of injury. Like the name suggests, in the event of an injury or threat of potential injury the sequence of muscle activity is modified such that the tissue is protected from any further insult. High points in a newly fabricated crown, biting on hard food substance, etc. may lead to a reflex muscle splinting. Clinical features Patient may report of muscle weakness following the tissue injury. Pain is experienced only during function and is not evident at rest. Limited mouth opening which can improve when the patient attempts to open the mouth gently is another characteristic feature. The affected muscle may feel tight/stretched on palpation. Management and prognosis

Orthopantomograph showing bony ankylosis in the right side and elongated coronoid process. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

markedly decreased. In bony ankylosis, the joint space may be obliterated, completely or partly by an osseous bridge (Figure 19). Other features include deepening of the antegonial notch and compensatory elongation of the coronoid process on the affected side. 256

Usually removal of the cause and resting the affected muscle is sufficient. Moist heat fomentation will aid in hastening the recovery process. Patient should be advised not to overuse the affected the muscle. Muscle relaxants can be used for a short period of time.

Myositis Inflammation of the muscle that results from a local cause is referred to as myositis. The causes of myositis include traumatic injuries, muscular strain and orodental infections.


However, myositis usually arises out of a long standing, severe and neglected muscle splinting and myospasm. Clinical features The involved muscle is painful and usually associated with a swelling. Like all muscular disorders, the pain exacerbates when the muscle is under function. Muscular dysfunction occurs secondary to muscle pain and inflammatory exudate as opposed to muscle contraction. Untreated myositis results in a myofibrotic contracture.

Muscle Spasm (Myospasm) Myospasms of the muscles of mastication are uncommon. It is a CNS-induced tonic muscle contraction. In this condition, all the motor units of the affected muscle contract resulting in shortening of the muscle length resulting in an acute spasm. Certain local muscle conditions have known to predispose to myospasms such as muscle fatigue, alteration in the local electrolyte balances and deep pain. Muscles that have already been overused or those that have been weakened because of protective splinting more likely undergo a spasm. Certain tranquilizers may also cause masticatory muscle spasm. Clinical features Patient usually presents with limited mouth opening. Pain is usually dull and continuous with occasional periods of acute pain. The pain may be referred to the face, temple region and the ear. Malocclusion is another characteristic feature. Analgesics can be prescribed. Moist heat fomentation will help in relaxing the muscle. Local anesthetic without vasoconstrictor can be injected into the affected muscle to relieve pain and facilitate speedy recovery. Occlusal bite guards may be given to counteract the effects of parafunctional habits if any.

in spasm, with increased tension and decreased flexibility. It usually presents with regional muscle pain distributed in one or two quadrants of the body. Taut bands are groups of muscle fibers that are hard and tender on palpation. Tender spots are specific sites of localized pain. Predisposing factors Acute muscular injury sustained as a result of macro trauma or sudden wide mouth opening or a sustained state of muscular contraction such as injuries due to bad posture, muscular tension and clenching/bruxism can predispose to MFP. Pathophysiology Precipitating factors of MFP may cause the facilitated release of acetylcholine at motor end plates, sustained muscle fiber contractions and local ischemia with release of vascular and neuroactive substances, and muscle pain. More acetylcholine may then be released, thus perpetuating the muscle pain and spasm. Local muscle fibrosis may occur after a prolonged period of time. Clinical features Laskin included the following signs and symptoms for the diagnosis of MFP: ❍

Unilateral, dull pain in the ear or preauricular region, that is worse on awakening ❍ Tenderness in muscle of mastication on palpation (localized TrP) ❍ Limitation/deviation of mandible on opening. A more comprehensive description of the clinical features are described below. Primary finding ❍

Chronic Conditions

❍

Myofascial Pain

❍

Costen (1934) first described a symptom complex, ‘TMJ pain dysfunction syndrome’, which included facial and head pain and TMJ dysfunction. Laskin (1969) was the first to coin the term ‘myofascial pain dysfunction syndrome’. Myofascial pain (MFP) can arise in any skeletal muscle such as those in the head (commonly the muscles of mastication), neck, lower back and shoulders. Traditionally, MFP is believed to arise from TrP (trigger point) in a muscle. TrPs are minute sensitive areas in a muscle that spontaneously or upon compression cause pain to a distant region, known as the referred pain zone. In recent times, MFP includes muscle pain from ‘taut bands’ (TB) with TrP or ‘tender spots’ (TS). The muscles are

❍ ❍

Patient complains of pain in one or more masticatory muscle Tenderness or pain upon manipulation/palpation of masticatory muscle with replication of chief complaint Tender site pain can be referred to other orofacial areas (TrP) Pain aggravated by mandibular function Acute malocclusion.

Secondary findings ❍ ❍ ❍ ❍ ❍ ❍

Restricted range of motion (ROM) Maximum assisted opening ⬎ maximum unassisted opening ⬎ pain free opening ROM increases by use of vapocoolants Limited function Clinical or behavioral indications of hyperfunction/ parafunction Acute malocclusion. 257


Possible findings ❍ ❍ ❍ ❍

TMJ pain Joint sounds Inflammation Restricted range of motion unmodified by assisted opening/vapocoolant ❍ Hypertrophy ❍ Myalgia secondary to systemic disease. Other reported symptoms include: musculoskeletal symptoms (fatigue, stiff joints and swelling), neurological symptoms (tingling, numbness, blurred vision, muscle twitching and excessive lacrimation), and otologic symptoms (ear pain, tinnitus, diminished hearing, dizziness and vertigo). Other symptoms that patients report of include: dentinal hypersensitivity and cutaneous hypersensitivity. Referral pattern for myofascial pain 1. 2.

3. 4.

Medial pterygoid muscle: Pain referred to posterior part of mouth and throat, TMJ and infra-auricular area. Lateral pterygoid muscle: Inferior head refers pain to the TMJ area and the superior head refers to the zygomatic area. Masseter muscle: Pain is referred to the posterior mandibular and maxillary teeth, ear and TMJ. Temporalis muscle: Pain is referred to all maxillary teeth and upper portion of face.

Management The management of MFP requires a multi-pronged approach. In the short term, the aim is to abolish the TB, TrP and TS for pain relief. In the long-term, achieving muscle flexibility and eliminating associated precipitating factors is the objective. Counseling Patient should be counseled about the nature of the condition and encouraged to discontinue parafunctional habits and consume soft diet. Physiotherapy Physical modalities are useful supplementary treatments that help in controlling muscle pain and spasm. Moist heat application to the affected site increases blood flow and increases vascularity, resolution of inflammation and fibrosis. It also increases flexibility of connective tissue and decreases muscle spasm and pain. However moist heat fomentation provides superficial heat with limited subcutaneous penetration. Ultrasound, on the other hand, provides deep heat with higher subcutaneous penetration. Trigger point therapy Spray and stretch technique and local injections are used. Refrigerant spray such as ethyl chloride or fluoromethane can be sprayed onto the skin surface from a distance of about 18 inches at an angle of 30⬚. The skin surface should be stretched manually during the spray. The spray anesthetizes the site and facilitates the patient to stretch the 258

muscle in spasm. Alternatively, 0.5% procaine without epinephrine can be injected into the trigger point. Medication NSAIDs and skeletal muscle relaxants (chlorzoxazone, methocarbamol) can be used. Patients who are anxious can be prescribed 2 mg of diazepam three times a day and 5 mg at bed time for a 2-week period. This will help in controlling the anxiety and relaxing the muscles. Such individuals should be counseled not to drive and to avoid using heavy machinery. Occlusal splint therapy The occlusal splint helps in maintaining a harmonious relation between the TMJ and muscles. It also aids in re-establishing a coordinated pattern of activity in the absence of tooth influence. The most important function of the splint is that it helps in the resolution of micro trauma to muscle. Other treatment modalities include isokinetic jaw exercises, biofeedback, acupuncture and hypnotherapy. Transcutaneous electric nerve stimulation (TENS) The TENS temporarily activates afferent nerves, thereby modulating pain. The electrical impulses are produced in a handheld battery-operated device. TENS has been proven to be useful in controlling masticatory muscle and neurogenic pains. The impulses generated have a duration of 2 millisecond with an interval of 0.5–1.5 second. The operating voltage is about 4 volts. TENS is believed to have physiological (rhythmic contractions of muscles increase blood supply), neurological (electrical stimulation inhibits pain conduction), pharmacological (releases endorphins) and psychological (placebo) effects.

Muscular Hypertrophy Enlargement or hypertrophy of the masticatory muscles is a relatively rare condition. The hypertrophy is clinically evident as a localized firm non-tender swelling along the body of the affected muscle. Legg was the first to describe bilateral enlargement of the masseter and temporalis muscles. However, literature review reveals the description of muscular hypertrophy of the masseter, temporalis and the pterygoid. Masticatory muscle enlargement can be either congenital or acquired. Usually, the acquired form is a result of parafunctional jaw habits such as bruxism or masticatory hyperfunction (chewing hard food, chewing gum). Some authors believe that emotional stress may result in chronic forceful clenching of the jaws and bruxism, resulting in hypertrophy of the muscle (Figure 20). Muscular hypertrophy should be differentiated from conditions such as lipomatosis, vascular tumors, liposarcoma, rhabdomyosarcoma and infiltrative leukemia and lymphoma. MRI and ultrasound will help in revealing the homogeneous enlargement of the muscles.


Figure 20

However, one should be careful to distinguish tender points associated with myofascial pain from those seen in fibromyalgia. Only tender points associated with myofascial pain refer pain, produce a ‘jump response’ on palpation and cause central excitatory response. Clinical features Fibromyalgia is more common in women compared to men (9:1). The peak onset of disease is between 45 and 60 years of age. Patients have also reported of paresthesia, symptoms of irritable bowel syndrome, dysmenorrhea and Raynaud’s phenomenon. Official diagnostic criteria for fibromyalgia

Masseteric hypertrophy. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Orthopantomographs may reveal enlarged ramal region and a prominent antigonial notch in masseteric hypertrophy. Anteroposterior radiographs show bone spurs at the mandible angle (it is estimated that 20% of normal population may also show bone spurs). Guggenheim and Cohen reported that bone spurs are caused by periosteal irritation and new bone deposition responding to increased forces exerted by the muscle bundles. Management In normal circumstances muscular hypertrophy needs no specific treatment. However, when cosmetic compulsions are paramount, various non-surgical and surgical treatment modalities may be considered. It has been suggested that cessation of the parafunctional habit such as bruxism may result in muscular atrophy. Premature contacts, poorly contoured restorations and malocclusions should be corrected. Minute doses of botulinum toxin type A may be injected into the affected muscle. Surgical options include partial or complete resection of the enlarged muscle and reduction of bone prominence from the mandibular angle.

Fibromyalgia Fibromyalgia is a syndrome characterized by chronic widespread musculoskeletal pain, stiffness, non-restorative sleep, and fatigue. Occasionally, many of the patients may mimic patients of chronic fatigue syndrome. The characteristic feature of fibromyalgia (FM) is the presence of non-inflammatory muscle and connective tissue ‘tender’ points that are widespread, involving all four quadrants of the body.

The diagnostic criteria were developed by the American College of Rheumatology in 1990. ❍

History of widespread pain: Pain is considered widespread when all of the following are present: pain in the left side of the body, pain in the right side of the body, pain above the waist, and pain below the waist. In addition, axial skeletal pain (cervical spine or anterior chest or thoracic spine or low back) must be present. In this definition, shoulder and buttock pain is considered as pain for each involved side. Low back pain is considered lower segment pain. ❍ Pain in 11 of 18 tender point sites on digital palpation: Digital palpation should be performed with an approximate force of 4 kg/cm2. For a tender point to be considered ‘positive’, the subject must state that the palpation was painful. ‘Tender’ is not to be considered ‘painful’. Note: For classification purposes, patients will be said to have fibromyalgia if both criteria are satisfied. Widespread pain must have been present for at least 3 months. The presence of a second clinical disorder does not exclude the diagnosis of fibromyalgia. The 18 tender points are depicted in Figure 21: 1, 2 (Occiput): bilateral, at the suboccipital muscle insertions. 3, 4 (Low cervical): bilateral, at the anterior aspects of the intertransverse spaces at C5–C7. 5, 6 (Trapezius): bilateral, at the midpoint of the upper border. 7, 8 (Supraspinatus): bilateral, at origins, above the scapula spine near the medial border. 9, 10 (Second rib): bilateral, at the second costochondral junctions, just lateral to the junctions on upper surfaces. 11, 12 (Lateral epicondyle): bilateral, 2 cm distal to the epicondyles. 13, 14 (Gluteal): bilateral, in upper outer quadrants of buttocks in anterior fold of muscle. 15, 16 (Greater trochanter): bilateral, posterior to the trochanteric prominence. 259


Figure 21

Figure 22 Back

Front

Occiput Trapezius

Lower cervical

Supraspinatus

2nd rib

Gluteal

Lateral epicondyle

Greater trochanter

Knee

Unilateral posterior open bite. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Schematic diagram showing tender points in fibromyalgia

17, 18 (Knee): bilateral, at the medial fat pad proximal to the joint line. Management Fibromyalgia can be treated effectively with amitriptyline (tricyclic antidepressant). Amitriptyline improves the sleep quality and minimizing pain. NSAIDs and muscle relaxants have also been tried successfully.

CONGENITAL, DEVELOPMENTAL AND ACQUIRED DISORDERS OF THE TMJ Developmental disturbances affecting the condyle such as aplasia, hypoplasia and hyperplasia have been described in Chapter 2 on Developmental Disturbances.

Malignant tumors such as chondrosarcoma, synovial sarcoma, fibrosarcoma, osteogenic sarcoma and multiple myeloma have been reported to affect the TMJ structures. Distant metastasis to the TMJ have been reported to occur from primaries in the breast, lungs, prostate, liver, uterus, pancreas and rectum. The clinician needs to be aware of these uncommon neoplasms as they tend to mimic the clinical features of other common temporomandibular disorders such as limited jaw movements, restricted mouth opening, deviation or deflection during mouth opening and joint sounds. As the condition advances it may result in extension of the tumor mass into the middle cranial fossa or invade posteriorly through the glenoid fossa and present as a lesion of the middle ear or external auditory canal. When the tumor mass extends laterally it can produce a preauricular swelling mimicking a parotid gland tumor. Cranial nerves may be involved if the tumor mass extends into the infratemporal and pterygopalatine fossae. Clinical features

NEOPLASMS AFFECTING THE TMJ Both benign and malignant tumors can affect the TMJ structures that include the articular disk, synovial membrane, articular capsule, glenoid fossa and most importantly the condyle. Malignant tumors are rare and reports of metastasis to the TMJ from distant sites are very few in number. Despite this fact, one should also look out for locally invasive lesions originating from the middle ear and parotid. The common benign tumors that affect the TMJ include: osteoma, chondroma, osteochondroma and osteoblastoma. 260

Benign tumors All the benign tumors share the similar features of slow growth of the tumor mass, gradually developing malocclusion (generally unilateral posterior open bite, Figure 22), deflection of the mandible to the unaffected side, facial asymmetry (Figure 23A, B), joint noises and restriction in jaw movements. Benign tumors are usually painless. The tumors are usually seen in the 2nd and 3rd decades of life. They may radiographically present as a welldefined nodular mass extending from the condylar head, unlike hyperplasia where there is uniform enlargement of the condylar head (Figure 24). Another distinguishing


Figure 23 A

B

Facial asymmetry in patient with osteochondroma of the condyle. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Figure 24

Orthopantomograph showing uniform enlargement of the condylar head on the right side. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

feature between the two is that the hyperplasia occurs usually as a reactive lesion to trauma, whereas benign tumors arise spontaneously. The most common benign tumor to affect the TMJ is osteoma followed by osteochondroma. Osteomas may occur as single isolated lesion or as a part of Gardner’s syndrome. Benign osteoblastomas though frequently seen in the 2nd decade of life, may occur anywhere in the 1st to 8th decades of life. These benign tumors often produce a tender swelling and patients usually give a history of trauma. Malignant tumors Chondrosarcomas account for about 1–3% of the sarcomas affecting the facial bones and jaws. It is usually seen in women in the 5th decade of life. Low-grade tumors have excellent prognosis (however high

recurrence rates are common), whereas high-grade tumors may metastasize through the lymphatics. Many of the patients complain of a rapidly growing swelling (in the preauricular region) and pain, diminished hearing and restricted mouth opening. Synovial chondrosarcoma (SC) may usually originate as a primary from the synovium or secondarily in an already existing synovial chondromatosis. These tumors generally occur in women in the 5th and 7th decades of life. SC presents as a soft tissue mass resulting in TMJ dysfunction and pain. Radiographs reveal clumps of calcifications occurring in a soft tissue mass. The articulating surfaces may show erosion. Joint space may occasionally exhibit freely lying cartilaginous nodules. Synovial sarcomas arise from the pluripotential mesenchyme. These tumors originate in close proximity to tendons, tendon sheaths and joint capsule. They are said to represent about 5% of all soft tissue sarcomas. These tumors are relatively slow growing and painless and usually present as mass in the pre-auricular region. Synovial sarcomas are usually present in the 2nd and 4th decades of life. Strikingly 50% of these tumors show calcifications radiographically. Recurrences are common and the lung is the most preferred site for metastasis. Synovial sarcoma is unique in the sense that it is one sarcoma that metastasizes (20% of the cases) to the lymph nodes. Osteosarcomas may be seen in any age group ranging from the 2nd to the 6th decade of life. The clinical features include mild pain, malocclusion and restricted mouth opening and other mandibular movements. Radiographs reveal extensive destruction of bone. Metastasis to the lungs is common. 261


Multiple myeloma and occasionally a solitary plasmacytoma may affect the TMJ in males over the 6th decade of life. Patients usually present with pain and limited mouth opening. Large tumors may exhibit pre-auricular swelling. Radiographs reveal well-defined punched-out radiolucent areas without a sclerotic rim. Occasionally pathological fractures may be seen. Metastatic tumors Metastasis to the jaws is rare and the condyle is almost never a location. However, isolated reports have described TMJ dysfunction and pathologic fracture as the presentation features. There have been various theories suggested to explain the cause for very less chances of metastasis to the condyle. Some of these include lack of abundant red marrow, relatively sluggish pace of blood flow, separate vascular supply from the circular penetrating branches of the maxillary and superficial temporal arteries and an osseous plate that cuts off the condylar marrow cavity from the spongiosa of the rest of the mandible. Synovial chondromatosis is an idiopathic condition, which has been one of the more commonly reported conditions associated with loose joint bodies. It is thought to represent a cartilaginous metaplasia associated with an abnormal synovium, rather than a true neoplasia. It presents with multiple cartilaginous nodules located within the joint space. Symptoms include joint swelling, pain, limited movement and joint noise.

CONDYLAR FRACTURES Condylar fractures are the most common among fractures involving the mandible. It is estimated that of all the mandibular fractures approximately 25–52% involve the condyle (Figure 25). Lindhal in 1977 described three major sources of condylar injuries: 1.

2.

3.

262

When kinetic injury is imparted to a static individual (such as in interpersonal violence i.e. a blow to the chin). Usually in such cases, fracture of the parasymphysis may be seen on the side of trauma along with condylar neck fracture on the contralateral side. When kinetic injury is imparted to a moving individual against a static surface (such as in a ‘parade ground’ fracture, or injury sustained when an individual falls on the floor like in an epileptic fit). In these instances symphyseal fracture is usually associated with bilateral condylar neck fractures. When a moving individual strikes against another moving object, a summation of the kinetic energies of the first two varieties occurs leading to a severe form of injury (such as in road traffic accidents). Such injuries may cause bilateral parasymphyseal along with bilateral condylar neck fractures.

Classification of Condylar Fractures I. Lindhal’s classification of condylar fractures A detailed and comprehensive classification of mandibular condylar fractures was proposed by Lindhal in 1977. In order to categorize the condylar fractures it is mandatory that radiographs be taken in two planes at right angles to each other. This classification takes into consideration three parameters, namely, the level of fracture, relationship of the fractured condylar segment to the mandible and the relationship of the condylar head to the glenoid fossa. 1. Level of fracture (Figure 26) a. Intracapsular head or condylar head fracture: Vertical fractures (anteroposterior sagittal split), compression fractures (results in a mushroom-shaped expansion of the condylar head) and comminuted fractures are the subtypes of the fractures of the condylar head. b. Condylar neck fractures: These fractures are seen at the inferior attachment of the capsule. c. Subcondylar fractures: These fractures occur inferior to the condylar neck. The subcondylar region corresponds to the area extending anteriorly from the inferior-most point of the sigmoid notch to the point of maximum curvature of the posterior border of the mandible. 2. Relationship of the fractured condylar segment to the mandible The relationship of the fractured condylar segment with the remainder of the mandible is categorized into: undisplaced (fissure fracture), deviated (angulated fractured segment without overlap), displaced with medial overlap of the fractured segment, displaced with lateral overlap, anterior and posterior overlap and fractured fragment with no contact with the remainder of the mandible.

Figure 25

Condylar fracture marked on a dry skull specimen


Figure 26

Intracapsular fracture

Extracapsular fracture

Subcondylar fracture

Schematic diagrams showing various levels of condylar fractures

3. Relationship of the condylar head to the glenoid fossa There are three subtypes under this category, namely, no displacement (radiographically the joint space appears normal), displacement (increased joint space but the mandibular condyle is related to the glenoid fossa and dislocation (condylar fragment is totally out of the glenoid fossa, usually dislocated in an anteromedial direction). II. MacLennan’s classification MacLennan considered the relationship of the fractured condylar fragment to the mandible for his classification. Four broad categories have been described: (i) no displacement, (ii) fracture deviation (simple angulation of the condylar fragment in relation of the remainder of the mandible as seen in greenstick fractures), (iii) fracture displacement (overlap of the condyle and the remainder of the mandible) and (iv) fracture dislocation (complete disruption of the condylar head from the glenoid fossa). III. Classification of condylar neck fractures Spiessl and Schroll classified condylar neck fractures into six different types: 1. 2. 3. 4. 5. 6.

Type I: Condylar neck fracture without serious dislocation Type II: Deep seated condylar neck fracture with dislocation Type III: High condylar neck fracture with dislocation Type IV: Synovial deep seated condylar neck fracture with luxation Type V: High condylar neck fracture with luxation Type VI: Head or intracapsular fracture.

Clinical signs and symptoms of condylar fractures Unilateral condylar fractures may present with a distinct swelling over the TMJ region. Occasionally, bleeding from

the ear on the side of fracture (laceration of anterior wall of the external auditory meatus) may be evident. Ecchymosis of the skin just below the mastoid process on the side of fracture may be seen. This is due to the downward tracking of the hematoma around the fractured condyle to an area beneath the external auditory canal. This clinical appearance should not be misunderstood as the Battle’s sign which is a similar sign seen in the base of skull fractures. Traumatic injuries to the condyle (involvement of the condylar growth center) during the period of mandibular growth may result in stunted and inhibited growth producing a hypoplastic mandible. Occasionally, limited joint function may be seen secondary to hemorrhage and subsequent bone formation within the joint spaces. The higher the fracture is located and greater the degree of displacement of the fragments, the less favorable are the expected functional results. When the fracture fragments are displaced at least by 5 mm and displaced by a minimum of 30⬚, a severely dislocated fracture can be considered. The condylar neck is usually very slender (about 4.9 mm) and hence very amenable to fractures (Figure 27). The condylar neck usually fractures secondary to a blow to the chin or parasymphyseal region. When the fracture line runs above the level of insertion of the lateral pterygoid muscle within the capsule of the joint, then very minimal bony displacement is evident. However, when the fracture occurs below the level of muscle insertion, condylar displacement is usually seen in the direction of the pull of the muscle (anteriorly, inferiorly and medially directed forces) (Figure 28). In severe cases the mandibular condyle may be impacted through the glenoid fossa and the patient may not be able to open the mouth. On palpation, following trauma, the patient may experience severe tenderness over the temporomandibular region. Paresthesia of the lower lip may be seen when the bleeding from the condylar region trickles down across the base of the skull to exert pressure over the mandibular 263


Figure 27

Figure 28

Posteroanterior (PA) view showing medial displacement of condylar neck fracture Cropped orthopantomograph showing condylar neck fracture

division of the trigeminal nerve as it exits from the foramen ovale. Patient may not be able to protrude the mandible and may have a limited ability to exhibit lateral excursion of the mandible to the opposite side. Unilateral fracture causes shortening of the ramus and molar occlusal gagging on the same side. Bilateral condylar fractures usually present with all the clinical signs and symptoms of the unilateral fractures occurring on both the sides. Bilateral displacement of the condylar fragments may result in an anterior open bite. Condylar fractures usually

264

occur in association with symphyseal or parasymphyseal fractures. Long-standing condylar fractures may present with a hollow over the condylar head region. However, this hollowing due the medial displacement of the condylar fragment may not be appreciated due to the edema following immediate injuries. Routine CT studies of suspected closed head injury encompass the calvaria to the cranial base. It is at the cranial base that the glenoid fossa appears. An ‘empty glenoid fossa’ sign is when there is no condyle associated within the fossa. This is suggestive of a condylar neck fracture.

Diseases of Salivary Glands Carol M Stewart, Indraneel Bhattacharyya, Madhu K Nair, James C Pettigrew, Seunghee Cha, Joseph Katz

➧ Developmental Disturbances

➧

Aplasia/Agenesis and Related Aberrancy of Salivary Glands Hyperplasia of Minor Salivary Glands ➧

➧

➧

Non-inflammatory Conditions of Salivary Glands

➧

Salivary Gland Tumors

➧

Benign Tumors Pleomorphic Adenoma (Benign Mixed Tumor) Canalicular Adenoma Basal Cell Adenoma Papillary Cystadenoma Lymphomatosum (Warthin’s Tumor) Oncocytoma (Oxyphilic Adenoma)

Inflammatory Conditions of Salivary Glands Mucocele Ranula Sialolithiasis, Salivary Duct Stone, Salivary Calculi Sialadenitis Non-specific Sialadenitis Bacterial Sialadenitis Subacute Necrotizing Sialadenitis Cheilitis Glandularis Necrotizing Sialometaplasia Chronic Sclerosing Sialadenitis (Kuttner Tumor)

11

Sialadenosis Anorexia/Bulimia-related Sialadenosis Sialadenosis Associated with Alcoholic Cirrhosis Diabetes Mellitus Medication-induced Sialadenosis Orofacial Granulomatosis Sarcoidosis

Saliva, Xerostomia, Hyposalivation, and Sialorrhea Saliva Hypofunction and Xerostomia Xerostomia and Salivary Gland Hypofunction due to Medications Xerostomia and Salivary Gland Hypofunction due to Radiation Therapy Sjögren’s Syndrome Benign Lymphoepithelial Lesion (Mikulicz’s Disease) Sialorrhea

CHAPTER

➧

Malignant Tumors Mucoepidermoid Carcinoma Intraosseous Mucoepidermoid Carcinoma Acinic Cell Adenocarcinoma Malignant Mixed Tumor (Carcinoma Ex Pleomorphic Adenoma) Metastasizing Mixed Tumor Adenoid Cystic Carcinoma Polymorphous Low-Grade Adenocarcinoma

Viral-induced Salivary Gland Pathology Mumps Human Immunodeficiency Virus (HIV)

Salivary glands and saliva play a critical role in maintenance of oral and systemic health. Salivary glands are frequently involved in a wide array of conditions which result in glandular dysfunction. These may be subdivided into five categories which include: 1. 2. 3.

Developmental disturbances Saliva and salivary flow alterations Inflammatory conditions

4. 5.

Non-inflammatory conditions Tumors.

Many of these conditions result in salivary gland hypofunction, enlargement, pain and facial nerve paresthesia that will prompt the patient to seek evaluation and treatment from the dentist. This chapter will address each of these five subgroups focusing on the etiology, clinical features, diagnosis and treatment of these conditions. 265


DEVELOPMENTAL DISTURBANCES Aplasia/Agenesis and Related Aberrancy of Salivary Glands Congenital aplasia or agenesis of the major salivary glands is an uncommon finding, characterized by partial or total lack of development of the gland. Agenesis may involve one gland, pairs, or multiple glands, and be unilateral or bilateral. It may be a single independent finding or be associated with other developmental anomalies. Congenital agenesis of major salivary glands was first reported by Gruber in 1985. A recent search of the world literature reported 30 documented cases. Three cases of unilateral aplasia of the parotid have been reported. As it may be asymptomatic and go unnoticed, the true incidence is unknown. Bilateral agenesis is more common, with 10 cases reported in the English literature. Sometimes congenital absence of one parotid or submandibular gland is associated with hypertrophy of the contralateral gland. Aplasia may occur as a single event or with autosomal dominant inherited developmental conditions such as first branchial arch anomalies, hemifacial microsomia and mandibulofacial dysostosis. Parotid gland aplasia may be associated with malformations of the lacrimal apparatus as well. A combination of multiple developmental anomalies is found in the lacrimo-auriculo-dento-digital (LADD) syndrome (Levy–Hollister syndrome). This is an autosomaldominant multiple congenital anomaly disorder characterized by hypoplasia, aplasia or atresia of the lacrimal and salivary systems, ear anomalies, hearing loss, digital malformations and dental alterations. As the parotid gland develops during the 4th week of uterine life, and the submandibular and sublingual, and minor glands develop between 6th and 12th weeks, association of salivary gland aplasia with other congenital abnormalities is easily understood. Bilateral aplasia of the parotid gland has also been reported in a patient with Down’s syndrome. In ectodermal dysplasia, aplasia of the submandibular glands and alterations in salivary gland function have been reported as well. Clinical features and diagnosis Salivary gland agenesis may be asymptomatic if only partial agenesis occurs or if the condition is isolated to one gland. If more extensive involvement occurs, agenesis can produce profound hyposalivation in children resulting in advanced dental caries, candidiasis, ascending sialadenitis, and even laryngitis and pharyngitis. A child with subjective xerostomia and functional hyposalivation should be carefully examined for salivary gland dysfunction to include partial or complete salivary gland agenesis. Familial parotid gland aplasia has been reported, hence examination of the siblings of a child with agenesis, might be 266

prudent. Sometimes, congenital absence of salivary glands is not noticed until adulthood resulting in unfortunate sequelae. However, clinical suspicion of salivary gland agenesis should be heightened in the setting of the ‘nondrooling baby’. Lack of complete development of the submandibular gland duct has been reported in two infants which presented as unilateral cystic swellings in the floor of the mouth. Both cases responded to simple incision and decompression of the fluid-filled ducts. Early treatment is important to avoid feeding difficulties and possible later complications such as ranula or sialadenitis. Diagnostic imaging When a unilateral glandular anomaly is observed clinically, bilateral imaging should be considered to examine for possible lesions on the contralateral side. Computed tomography (CT) can be used to demonstrate congenital total or partial absence of salivary glands. Management Salivary gland aplasia has been associated with rampant dental decay in children. Treatment for potential hyposalivation resulting from salivary gland agenesis would include frequent dental examinations, salivary stimulants for glands that might remain, meticulous home care and a customized fluoride program.

Hyperplasia of Minor Salivary Glands Clinical features Adenomatoid hyperplasia of the minor salivary glands is a rare lesion characterized by localized swelling that clinically mimics a neoplasm. The lesion most often develops on the hard or soft palate, although it has been reported in other oral minor salivary gland sites. The most common presentation is during the 4th to 6th decades of life. The typical presentation is a painless, indolent palatal swelling which may be soft or firm to palpation. The overlying mucosa is usually normal in color, although some lesions are red or bluish in color. The etiology is uncertain. In one report, the occurrence of adenomatoid hyperplasia on the palate occurred in patients who were tobacco smokers or denture wearers or both. The authors, Barrett and Speight suggested that chronic, local trauma could be a factor in the development of the condition. Histopathology Histopathologic examination demonstrates lobular aggregates of normal appearing mucous acini that are greater in number (hyperplasia) than normally would be found in the area. These glands may appear to be increased in size (hypertrophy). Chronic inflammation, if present, is usually mild and localized. Shimoyama et al reported that Ki-67

Chapter 11 – Diseases of Salivary Glands

staining for cell proliferative activity demonstrated no statistically significant differences among adenomatoid hyperplasia and a matched group of normal palatal salivary glands. The conclusion was that adenomatoid hyperplasia had limited growth potential. Treatment To determine the true nature of a clinical enlargement, a biopsy is necessary. After the diagnosis of adenomatoid hyperplasia has been established via histopathologic examination, no further treatment is indicated.

SALIVA, XEROSTOMIA, HYPOSALIVATION AND SIALORRHEA Saliva Saliva is an essential fluid for maintaining oral and systemic health and a satisfactory quality of life. While saliva is sometimes considered bothersome during restorative procedures, the alteration in quality and/or quantity of saliva has serious sequelae for the patient. Saliva is the product of three paired major salivary glands (the parotid, submandibular, and sublingual), and minor glands found in the hard and soft palate, lips, tongue, and buccal mucosa (Figure 1). Major salivary glands are composed of ductal and acinar structures. The acinar cells are the secretory components and ductal cells are the branching network that transports saliva into the oral cavity. The acinar cells of the parotid gland are purely serous elements and upon

Figure 1

stimulation, parotid secretions account for at least half of the volume of whole saliva. Serous secretions are ‘watery’ and contain digestive enzymes, water, salts, and ions. They aid in mastication, clearing agents from the oral cavity, and facilitate swallowing and speech. Fluid from the parotid gland enters the oral cavity through the main excretory duct, Stensen’s duct, located in the buccal mucosa next to the maxillary second molars. In the submandibular gland, the acinar components are mixed mucous–serous, but predominantly serous. At rest, the submandibular gland secretions account for approximately two-thirds of the unstimulated saliva production. Wharton’s duct is the main duct of the submandibular gland and enters the floor of the mouth on either side of the lingual frenum. The sublingual gland, the smallest of the three major glands, is located above the mylohyoid muscle. Acinar elements are mixed, but predominantly mucous. The mucin produced facilitates lubrication and swallowing. The main excretory duct of the sublingual gland, Bartholin’s duct, may join Wharton’s duct resulting in a blending of secretions, or open into the oral cavity with a separate sublingual papilla. Numerous sublingual ducts may join the submandibular gland duct or open separately into the floor of the mouth. Minor salivary glands are named according to their location—lingual (anterior and posterior), labial, buccal, palatine and glossopalatine. Table 1 summarizes the nomenclature for the major and minor salivary glands and their acinar components. In health, approximately 750 ml of saliva is produced in a day. The principal control of salivary secretion is mediated by sympathetic and parasympathetic innervation. The adrenergic (␣ and ␤) receptors are regulated by the sympathetic nervous system and the muscarinic receptors by the parasympathetic nervous system. At least five muscarinic-cholinergic receptor subtypes exist and it has been determined that the muscarinic receptor that medicates secretion of saliva is the M3 subtype. The parasympathetic

Table 1

Parotid gland Sublingual gland Submandibular gland

Major salivary glands. Courtesy: Roger Hoover

Major and minor salivary glands and secretion

Glands

Type of secretion

Parotid

Purely serous

Submandibular

Mixed, however predominantly serous

Sublingual

Mixed, however predominantly mucous

Lingual minor salivary glands Anterior lingual (glands of Blandin and Nuhn) Posterior lingual (glands of von Ebner)

Primarily mucous Purely serous

Labial and buccal minor salivary glands

Mixed

Glossopalatine and palatine minor salivary glands (Weber’s glands)

Purely mucous

267


nerve stimulation leads to an increased volume of saliva, whereas the sympathetic stimulation has an effect on protein content and salivary composition. Saliva plays a major role in the local and systemic protection of the oral cavity, oropharyngeal region, and the upper gastrointestinal tract. Normal quantity and protein composition is essential for buffering the acidity of the oral cavity, lubrication of tissues, maintaining the integrity of the oral tissues, providing antimicrobial proteins and digestive enzymes, and remineralization of the teeth. Lack of saliva, hyposalivation, may increase a patient’s susceptibility to dental decay, oral ulcers, fungal infections, and dysphagia or difficulty in swallowing. Saliva contains many antimicrobial proteins that help maintain a normal oral flora. The histatins provide antifungal properties, and proline-rich proteins help reduce bacterial colonization by modifying the ability of organisms to attach to tissues. Mucins are salivary glycoproteins that play a role in mucosal lubrication and assist in aggregation of oral microorganisms. Statherin and proline-rich proteins have calcium-binding properties to assist remineralization. These proteins combined with the cleansing and flushing ability of saliva constitute significant protective mechanisms for the oral cavity and upper gastrointestinal system. Of special importance to the dentition is the presence of buffers to help maintain a neutral pH and the remineralizing capacity. The pH range of saliva will vary from 6.7 to 7.4 in health. Of concern is pH below 5.5, which will promote enamel dissolution and increase caries susceptibility.

Hypofunction and Xerostomia Altered saliva production, both qualitatively and quantitatively, creates significant oral health concerns for the patient and challenges the dentist to provide appropriate patient education and treatment. Patients frequently present with the complaint of a ‘dry mouth’. Xerostomia is the subjective sensation of dry mouth and may be determined by questioning individuals about their perceptions of oral dryness. The need to sip water while eating dry foods, difficulty in swallowing food without liquids, and a feeling of ‘too little’ saliva in the mouth have been correlated with salivary gland hypofunction. Hyposalivation is the production of inadequate or less than normal amount of saliva, usually from gland hypofunction. A few simple chairside assessments could be performed to quickly assess oral dryness. The lack of salivary pooling in the floor of the mouth is a basic clinical indicator of hyposalivation. Another indicator is the ‘cracker sign’. If a patient states that they cannot eat a cracker without drinking fluids, xerostomia and hyposalivation should be suspected. Another indicator is the ‘lipstick sign’. Patients with hyposalivation may have lipstick adhere to the incisal edges of the anterior teeth because they lack saliva that would normally prevent adherence. Another clinical clue to hypofunction is 268

the ‘mouth mirror test’. The clinician places the mirrored surface of the mouth mirror over the buccal mucosa and attempts to move it. If the mirror glides effortlessly over the tissue, one can deduce that salivation is adequate. The prevalence of xerostomia in the population varies widely due to the lack of a clear definition for xerostomia. Some clinicians use the terms ‘xerostomia’ and ‘hyposalivation’ interchangeably. Hyposalivation or salivary gland hypofunction results when the salivary gland flow rate is lower than normal. Defining ‘normal’ is problematic due to variations in the literature on collection methods, time of day collections were performed, and the inability to control for medications. Unstimulated whole salivary flow rates of less than 0.15 ml/min might provide a good reference for hyposalivation. The determination of hyposalivation and xerostomia do not consistently correlate as one might expect. Patients with salivary gland hypofunction are sometimes without complaints of oral dryness, or xerostomia. Conversely, patients with complaints of ‘dry mouth’ may not have reduced salivary flow rates. Xerostomia and salivary hypofunction affect the oral health-related quality of life. Reported reasons include the negative impact of oral dryness on speaking, eating, and wearing dental prostheses. Both xerostomia and salivary gland hypofunction require a careful systematic evaluation to determine causative factors. Dry mouth has a variety of causes as indicated in Box 1. Common causes of salivary gland dysfunction leading to hyposalivation include medications, irradiation to the head and neck, and autoimmune diseases such as systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS). Other systemic conditions affecting salivary glands include sarcoidosis, sialadenosis, and viral infections such as HIV and hepatitis C. Mouth-breathing, tobacco smoking, alcohol use, and consumption of beverages containing caffeine can contribute to oral dryness as well. Age-related hyposalivation has been reported due to structural changes in salivary glands with increasing age. Other studies have reported no agedependent decrease in saliva flow rate in healthy elderly populations. The incidence of xerostomia will increase and

Box 1

Possible causes of salivary gland hypofunction

Medications Radiation to head and neck Systemic diseases Sjögren’s syndrome Sarcoidosis Systemic lupus erythematosus Primary biliary cirrhosis Viral infections HIV Hepatitis C


the oral manifestations will continue to be a challenge for the clinician. Treatment of xerostomia is symptomatic and supportive, but should be aggressively proactive in prevention of dental decay associated with salivary hypofunction. Patient education and patient empowerment so they become participants in their oral healthcare are key to successful outcomes. Hydration, dietary modifications and meticulous oral hygiene are especially helpful. Symptomatic treatment is aimed at minimizing the subjective complaints, and includes drinking water or finely crushed ice chips and sugar-free fluids. Patients should be advised that caffeine can contribute to the feeling of oral dryness and consequently, caffeine-free and sugar-free drinks should be strongly encouraged. Avoiding alcohol, including alcoholbased mouthrinses, spicy foods, and strong flavorings, such as cinnamon and mint, should also minimize oral discomfort. Artificial saliva is helpful for many patients due to the coating action, but does not provide long-lasting relief. Some patients find relief by chewing sugar-free gum or sucking on sugar-free candies. Lip balms and moisturizers may be helpful as well. Because patients with hyposalivation are at increased risk for dental decay, oral applications of topical fluorides should be initiated. The fluoride is incorporated into the enamel of the teeth to increase resistance to demineralization and decay. Fluoride products are available over-thecounter as rinses and as more highly concentrated brush-on gels (0.4% stannous fluoride gel). Prescription products are available which provide 1.1% neutral sodium fluoride treatment in convenient brush-on gels or rinses. These should be used after regular toothbrushing in the evening just before retiring. Patients should be reminded to avoid rinsing, eating or drinking for 30 minutes following the fluoride application. Stannous fluoride or neutral sodium fluoride treatments can be provided using fluoride carriers, or custom trays fabricated from a cast of the patient’s mouth. The carriers are particularly helpful in treating severe hyposalivation resulting from head and neck radiation therapy. Preventive fluoride programs should be customized by the dentist to meet the specific needs and conditions of the patient.

cause subjective complaints of dry mouth and many induce hyposalivation. The drugs most frequently implicated in dry mouth include the tricyclic antidepressants, antipsychotics, atropinics, beta blockers and antihistamines. In another study as reported by Thomson, the unstimulated (resting) salivary flow rate was reduced among individuals who were older, female, or taking antidepressants, and higher among smokers or people who were taking hypolipidemic drugs. Other studies have correlated dry mouth with the number of medications taken, rather than specific types of medications. Field et al have demonstrated that medication is a better predictor of risk status for dry mouth than either age or gender. Medications that induce salivary hypofunction are a concern among the elderly, but xerostomia can also be a concern for young adults. Thomson et al in his study involving a large cohort of 32-year-old subjects, reported that the prevalence of xerostomia was found to be 10%, with no apparent gender difference. There was a strong association between xerostomia and diminished oral health-related quality of life. Xerostomia was significantly higher among those taking antidepressants, iron supplements, or narcotic analgesics, and those subjects taking antidepressants at both 26 and 32 years of age demonstrated 22 times the odds of reporting xerostomia. A study of medications and caries among older individuals by Thomson et al revealed that an adjusted coronal caries increment (AdjCI) was higher among males and those taking a beta blocker or an anti-asthma drug for the previous 5 years. Several classes of drugs have been associated with dry mouth (Box 2). The most common groups include those with: (i) anticholinergic effects such as tricyclic antidepressants, drugs for urinary retention and overactive bladder, antipsychotics, diuretics, and antihistamines; (ii) sympathomimetic drugs such as antihypertensives, antidepressants, decongestants, and bronchodilators; (iii) skeletal muscle relaxants; (iv) benzodiazepines; (v) proton pump inhibitors; and (vi) anti-migraine agents. Dry mouth has

Box 2

Drugs associated with xerostomia and hyposalivation

Tricyclic antidepressants

Xerostomia and Salivary Gland Hypofunction due to Medications Jacobsen and Chavez in their article describe that individual above 65 years of age comprise 13% of the population, but consume approximately one-third of all drugs prescribed. Loesche et al and Foc have reported many studies that have demonstrated a link between dry mouth in the elderly and polypharmacy. Shinkai et al reported that in a group of 1,163 adults (age range 32–81 years), 57% reported dry mouth to be the most frequent side effect of their medications. Hundreds of medications can

Antipsychotic medications such as phenothiazines Diuretics Antihistamines Anti-migraine agents Proton pump inhibitors and H2 antagonists Anti-HIV drugs such as dideoxyinosine and protease inhibitors Opioids Benzodiazepines Decongestants Selective serotonin reuptake inhibitors (SSRIs)

269


been reported to be a consequence of cytotoxic drugs such as 5-fluorouracil. Medications used for treatment of HIV have also been associated with dry mouth. These include didanosine and protease inhibitors. It is important for the dentist to inquire about all medications, both prescription and over-the-counter agents, during the health history review. Sometimes the dentist can provide assistance by sharing concerns of medicationinduced hyposalivation with the primary care physician. In some situations, the dentist might suggest medications such as pilocarpine or cevimeline to promote salivation. These medications will be discussed in the section on Sjögren’s syndrome.

Xerostomia and Salivary Gland Hypofunction due to Radiation Therapy The role of saliva in oral health and function relates both to its fluid characteristics and to its specific components. The water (fluid) phase accounts for 99% of the volume and the remainder is salts and proteins. Essential functions of these components include flushing, buffering the acidity, and mucosal coating to maintain tissue integrity. Mucosal coating and tissue lubrication are essential for speech, taste perception, mastication, and swallowing. Cancer patients undergoing treatment for head and neck disease often experience severe difficulties maintaining such functions. Salivary function can also be diminished by radioiodine therapy for thyroid carcinoma, especially if multiple doses are administered. Deterioration of oral health and radiationinduced oral dryness has a significant influence on patients’ overall quality of life during and after treatment. Together with surgery, radiation therapy is the main treatment for head and neck tumors. All or part of the major and minor salivary glands may be included within the radiation field due to the site and extension of the tumor and the lymphatic spread. Exposing the glands to radiation often results in severe salivary gland hypofunction and changes in saliva composition. A profound decrease in salivary flow occurs during the 1st week of radiation therapy and continues throughout the course of therapy. In general, fully irradiated parotid glands exposed to doses exceeding 60 Gy sustain permanent damage resulting in severe hypofunction, and there is no recovery of gland function over time. Partial salivary flow recovery may occur at lower doses. Radiation mucositis may begin during the 2nd week of therapy. Primary sites are intraoral mucosal surfaces within the direct portals of radiation. A whitish discoloration will appear from keratin accumulation, which is followed by sloughing, revealing atrophic erythematous, and friable mucosa. Ulceration then develops producing burning and pain which is exacerbated by eating and oral hygiene. Symptomatic support for radiation mucositis is important to assist the patient in maintaining adequate nutrition. 270

The mucositis will slowly resolve 2–3 weeks after cessation of the treatment. A loss of taste has been reported which generally is recovered after 6 months. Minimizing the probability of osteoradionecrosis (ORN) includes a dental examination at least 2 weeks prior to the initiation of radiation therapy to address or remove teeth that have a hopeless long-term prognosis. Daily fluoride treatments in custom carriers and close follow-up aid in reducing the incidence of xerostomia-induced dental caries. Due in part to more efficient radiation techniques, the incidence of ORN has been declining in radiation patients over the last two decades. Advances in radiation techniques, including the use of fractionated radiation doses, have minimized the incidental damage to adjacent tissues. Furthermore, use of three-dimensional dosimetric intensitymodulated radiation therapy (IMRT) has been shown to reduce late salivary toxicity, since the portion of tissue exposed to low radiation doses has a potential for repair. Based on recent publications, the prevention of ORN remains controversial. A recent report compiled by Chang et al after reviewing a large series of ORN studies stated that extraction of teeth with poor prognosis before radiation therapy did not appear to reduce the risk of ORN. The investigation of IMRT by Wu et al to achieve sparing of the parotids and yet achieve higher tumor control appears to show promise. Until additional evidence is available to define guidelines, a pre-radiation referral for a dental evaluation is necessary. To facilitate prevention of ORN, irradiated dental patients should maintain a high level of oral health. Pre- and posttherapy close collaboration by a multidisciplinary team can be invaluable for patients receiving head and neck radiation therapy.

Sjögren’s Syndrome Sjögren’s syndrome (SS) is a chronic autoimmune disease affecting the exocrine glands, primarily the salivary and lacrimal glands. Patients most commonly complain of a subjective persistent feeling of dry mouth (xerostomia) and of dry eyes (keratoconjunctivitis sicca). This is due to lymphocytic infiltrates and destruction of salivary and lacrimal glands and systemic production of autoantibodies. In 1933, Henrik Sjögren, a Swedish ophthalmologist, presented his doctoral thesis entitled ‘Zur Kenntnis der Keratoconjunctivitis Sicca’, and described the clinical and histopathological aspects of the disease. Sjögren’s syndrome occurs worldwide and while it may occur at any age, the peak incidence is between 40 and 50 years. Sjögren’s syndrome has one of the highest female-to-male ratio (9:1) of any autoimmune rheumatic disease. In addition to ocular and oral dryness, a wide spectrum of extraglandular manifestations may occur as well. The musculoskeletal, hematological, vascular, pulmonary, gastrointestinal, dermatological, renal and nervous systems may be involved. Patients with SS have an increased


risk of developing lymphoma. Early reports estimated that patients with SS had up to 44 times increased risk of developing lymphoma compared with the general population. Chronic fatigue, depression, and a diminished quality of life are also common components of SS. Classification Two forms of the disease are recognized. Primary SS is the presence of sicca syndrome, xerostomia, or ‘dry mouth’, and xerophthalmia, or ‘dry eyes’ together, with no other autoimmune disease. Secondary SS is sicca syndrome plus another associated autoimmune disease such as rheumatoid arthritis (RA), SLE, or scleroderma. Based upon the classification criteria applied, the prevalence of SS may range from 0.5 to 3.0% of the population. All classification systems use a combination of both subjective and objective findings in the diagnostic process. The most recent 2002 criteria include subjective symptoms of dry mouth and dry eyes, and the following objective tests: ocular signs by Schirmer’s test and/or Rose Bengal score; focal sialadenitis by histopathology; salivary gland involvement by either salivary scintigraphy, parotid sialography or unstimulated salivary flow rate; and autoantibodies of SS-A/Ro and/or SS-B/La specificity. Box 3 presents the 2002 AmericanEuropean Consensus Group Criteria for SS. Etiopathogenesis Currently, the etiology of SS is not clearly understood, but appears to be multifactorial. It has been suggested that environmental agents may trigger SS in genetically predisposed individuals. Experimental and clinical evidence suggest that immune reactivity is modulated by gender. Immune reactivity is higher in females than males, and lymphocytes and monocytes from female subjects show higher antigen presenting activity and mitogenic responses. Taiym et al have found higher prolactin levels in SS patients than controls. Estrogens might be pro- or antiinflammatory, based on dose-related metabolite conversions. The role of sex hormones in rheumatic autoimmune diseases has yet to be clarified. Potential mechanisms underlying SS include disturbances in apoptosis, circulating autoantibodies against the ribonucleoproteins Ro and La or cholinergic muscarinic receptors in salivary and lacrimal glands or cytokines. These processes interfere with normal glandular function; and as the mucosal surfaces become sites of chronic inflammation, the disease appears to enter a self-perpetuating inflammatory cycle. While a genetic predisposition to SS appears to exist, no simple Mendelian inheritance pattern has been demonstrated. Cases of two or more individuals with SS per family and SS in twins have been described. However, the level of genetic contribution is not known. Because large twin studies in SS are lacking, the twin concordance rate cannot be estimated. Familial clustering of different autoimmune

Box 3

European American Consensus Group criteria for Sjögren’s syndrome

Ocular symptoms (must have 1 of 3) 1. Daily dry eyes ⬎ 3 months 2. Recurrent sand or gravel sensation in the eyes 3. Use of tear substitutes more than 3 times per day Oral symptoms (must have 1 of 3) 1. Feeling of dry mouth for more than 3 months 2. Recurrent or persistently swollen salivary glands as an adult 3. Need frequent liquids to aid in swallowing dry food Ocular signs (1 of 2) 1. Schirmer’s test, performed without anesthesia (ⱕ 5 mm in 5 minutes) 2. Rose Bengal score or other ocular dye score (ⱖ 4 according to van Blijsterveld’s scoring system) Histopathology in minor salivary gland biopsy Focal lymphocytic sialoadenitis, with focus score ⱖ 1 (focus is ⱖ 50 lymphocytes per 4 mm2 tissue adjacent to normal appearing mucous acini) Salivary gland involvement (1 of 3) 1. Unstimulated whole salivary flow (ⱕ 1.5 ml/15 minutes) 2. Parotid sialography showing the presence of diffuse sialectasis (punctuate, cavitary of destructive pattern) without evidence of obstruction in the major ducts 3. Salivary scintigraphy, showing delayed uptake, reduced concentration and/or delayed excretion of tracer Autoantibodies Antibodies to SS-A/Ro or SS-B/La or both For primary SS a. Any 4 of the 6, as long as either item 4 (histopathology) or item 6 (serology) is positive b. Presence of any 3 of the 4 objective criteria items (items 3, 4, 5, 6) For secondary SS In the presence of another connective tissue disease, the presence of item 1 or 2 plus any 2 from 3, 4, and 5 Exclusion criteria Past head and neck radiation Hepatitis C infection Acquired immunodeficiency syndrome (AIDS) Pre-existing lymphoma Sarcoidosis Graft-vs-host disease Use of anticholinergic drugs (since a time shorter than four-fold half-life of the drug) Source: Vitali et al. Annals of Rheumatic Diseases 2002;61:554–58.

diseases and co-association of multiple autoimmune diseases has been reported by Becker et al. Reports have also indicated that a SS proband may have relatives with other autoimmune diseases in approximately 30–35% of the cases. Assessing human leukocyte antigen (HLA)-DR and HLA-DQ gene segments in patients with SS reveals an increased use of haplotypes B, Drw52 and DR3. Correlations 271


have been found between presence of HLA-DR haplotype and the presence of Ro/LA in SS. Gene polymorphisms have been analyzed, but no clear-cut relationship between these and primary SS have been identified. Clustering of non-major histocompatibility complex (MHC) susceptibility candidate loci in human autoimmune diseases supports a hypothesis that, in some cases, clinically distinct autoimmune diseases may be controlled by a common set of susceptibility genes.

Figure 2

Clinical features and diagnosis Dry mouth and dry eyes are the most common complaints of patients with SS. Patients’ ocular concerns may include a history of dry eyes, a sensation of sand or gravel in the eyes, and/or frequent (⬎ 3 times per day) use of tear substitutes. Objective ocular tests for dry eyes include a Schirmer’s test for tear production. Using sterile strips of filter paper placed just inside the lower lid, tear production can be assessed by measuring the length of wetness on the filter paper. Less than 5 mm of wetness in 5 minutes, without local anesthesia is considered a positive test, meeting the 2002 Sjögren’s consensus criteria. A second ocular test utilizes Rose Bengal staining of the cornea, and measures areas of increased dye intensity. With the use of a slitlamp, the stain will detect devitalized tissue. The ocular dryness is sufficient to produce disruption in the integrity of corneal and conjunctival epithelium and dye will accumulate in these areas. The total areas identified are used to determine the extent of ocular damage. Patients with complaints of ocular dryness, especially if combined with other symptoms of SS, should be referred to the ophthalmologist for evaluation. Untreated keratoconjunctivitis sicca can progress to corneal ulcerations and even blindness. The most frequent oral signs and symptoms a dentist will encounter are xerostomia, a subjective sensation of oral dryness, and hyposalivation, or a diminished salivary flow rate. These will vary between patients, and the subjective dryness may not directly correlate with objective measures of hyposalivation. Initial indications of a diminished salivary output would be a lack of pooling in the floor of the mouth, thick or frothy saliva, and observing examination gloves sticking to the tongue or buccal mucosa. Patients may complain of difficulty chewing and swallowing, difficulty wearing their dentures, and altered taste. They will relate the necessity for drinking liquids to aid in swallowing food or to enhance their ability to speak. They may admit to keeping water by their bedside at night or frequently waking with a dry mouth. Patients with SS frequently carry water with them and often need to sip every 10–15 minutes during a consultation appointment. Upon intraoral examination, the tongue may appear fissured, slightly erythematous, and sometimes depapillated. If the patient complains of a ‘burning tongue’ and dysgeusia, oral candidiasis should be suspected (Figure 2). Salivary 272

Xerostomia and fissured tongue. Courtesy: Dr Carol Stewart

Figure 3

Oral cavity of Sjögren’s syndrome patient showing dental caries and fissured tongue. Courtesy: Dr Carol Stewart

flow rate is diminished in primary SS patients compared with controls. In addition to quantitative changes, the protein content of the saliva is altered as well. Proteins necessary for buffering the oral acidity, countering fungal and microbial organisms may be altered. The lack of adequate salivary flow and qualitative changes in protein content may predispose the patient to dental decay, particularly in the cervical area, tooth loss, candidiasis and oral ulcerations (Figure 3). The change in saliva is linked to the lymphocytic infiltrate in the glands and subsequent damage to the functional units. From one-fourth to two-thirds of patients with primary SS will have a diffuse enlargement of the major salivary glands during the course of their disease (Figure 4).


Figure 4

Figure 5

Sjögren’s syndrome patient with enlarged parotid gland. Courtesy: Dr Carol Stewart

This swelling may be unilateral or bilateral, intermittent or constant in nature. If the parotid swelling initially is unilateral, it often becomes bilateral with time. It commonly produces mild to no discomfort. However, diminished flow will enhance a patient’s susceptibility to bacterial infection in the glands and recurrent sialadenitis, which will produce pain. Although SS is considered primarily a disease of middle-aged females, it has also been reported in children and adolescents. Recurrent bilateral parotitis in children and adolescents should include the possibility of SS in the differential diagnosis. Conventional sialography renders useful information about the gland architecture and changes within it. Waterbased radiopaque dye is injected into the major gland ducts followed by conventional imaging. Peripheral ducts within the glands are usually affected first with the inner ductal structure relatively well preserved. However, punctuate collections of the contrast material may be visible in the early stages of the disease followed by globular or larger collections as the condition progresses as shown in Figures 5–7. Once extensive intraglandular destruction has taken place and infection has become established, dilatation of central ducts is noted. Abscesses within the gland may be noted with a uniform distribution, unlike focal abscesses caused by other types of infections. However, sialography is an invasive procedure and other imaging modalities may be considered. Imaging with CT and MRI is common. The glands enlarge with time, assuming a denser appearance on CT. A honeycomb appearance is not infrequent but this is also seen with granulomatous conditions. Bilateral enlargement with cystic and solid lesions is noted (Figure 8A, B). In the early stage, the parotids appear normal. Multiple cysts appear during the intermediate stage. These eventually grow with time. If the mass assumes an invasive

Sialograph of Sjögren’s syndrome. Courtesy: Dr James Pettigrew

Figure 6

Sialograph of Sjögren’s syndrome of the submandibular salivary gland. Courtesy: Dr Ajit Auluck and Dr Chandrakant Shetty

appearance, malignant transformation may be suspected. Foci of calcification within the glands are not uncommon. Heterogeneous enhancement may therefore be expected (Figure 9A, B). The glands could eventually appear smaller in size. In MRI, numerous punctuate areas appear within the glands with low signal intensity on T1 and T2 weighted images as the disease progresses. This is considered diagnostic of the condition. But, a lymphoma arising in a benign lymphoepithelial lesion (BLEL) does not have characteristic features that would help differentiate it from other tumors. However, it may be considered in patients who present with a parotid mass. Function of the glands is 273


directly correlated with the amount of fat deposition, thereby indicating that a monitoring of this feature may be useful in diagnosing the condition. Another imaging technique that is useful is magnetic resonance sialography. It has been shown to be highly accurate with excellent sensitivity and specificity. Globular, punctuate or a lytic appearance is typical of the condition. If cysts develop within BLEL, these are detected using CT or MR. The absence Figure 7

Sialograph of Sjögren’s syndrome showing atelectasia. Courtesy: Dr James Pettigrew

of lymphadenopathy helps exclude HIV-related lymphoepithelial cyst formation. Another test to confirm altered salivary gland function is whole unstimulated sialometry. Sialometry is the measurement of salivary flow rate. It is instrumental in reaching a diagnosis of hyposalivation (below normal salivary flow rate), a common finding in patients with SS. In an ideal situation, patients should not eat, drink, smoke, or brush their teeth for 90 minutes before the sialometric assessment. The patient is asked to expectorate into a preweighed container, while sitting upright for 15 minutes. After reweighing the tube post-collection, dividing by 15 and applying the conversion factor (1 g ⫽ 1 ml), a flow rate can be determined. Unstimulated salivary flow ⱕ 1.5 ml/15 min or ⬍ 0.1 ml/min is considered consistent with Sjögren’s diagnosis. After an SS diagnosis has been established, periodic flow rates (every 3–6 months) may provide meaningful information to assess disease progression. Subsequent salivary assessments should be collected at the same time each sampling, preferably either 9:00 AM–noon or 1:00 PM–3:00 PM, to avoid fluctuations due to circadian rhythm of salivary secretion and composition. Often, an SS patient will be prescribed a sialogogue to enhance salivary flow. Periodic flow rates are helpful to track medication efficacy as well. Lymphocytic infiltration in the lacrimal and salivary glands is a major feature of SS. One of the criteria for classification of SS includes the biopsy of the labial salivary glands. A 1.5-cm incision is made on normal appearing mucosa of the lower lip lateral to the midline (Figure 10).

Figure 8 A

B

Sjögren’s syndrome. CT images showing diffuse sialadenitis affecting the submandibular and parotid glands bilaterally. Courtesy: Dr Madhu Nair

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Figure 9 A

B

Chronic Sjögren’s syndrome. Contrast CT demonstrating a granular appearance of parotid glands that have been reduced in size. Courtesy: Dr Madhu Nair

Figure 10

Sjögren’s labial salivary gland biopsy procedure. Courtesy: Dr Carol Stewart

Five or more accessory salivary gland lobules are examined histopathologically for the presence of focal chronic inflammatory aggregates. A focus is 50 or more lymphocytes and some plasma cells within a 4 mm2 field in the salivary gland biopsy specimen. As noted in Figure 11A, B, these aggregates are adjacent to normal-appearing acini

and are found throughout the glands. A finding of more than one focus within a 4 mm2 area of glandular tissue is supportive of a SS diagnosis. Manthorpe et al have reported an interesting fact that the focus scores are lower in SS patients who are cigarette smokers. While the labial salivary gland biopsy is widely considered one of the best diagnostic tools for SS, it is not 100% reliable. Personal experience has shown that minor salivary gland histopathology may not present the classic picture, yet be supportive of an SS diagnosis. Some SS patients may show areas of classic patchy lymphocytic foci with other areas more consistent with chronic sclerosing sialadenitis in confirmed primary SS patients. In addition, salivary gland biopsies of patients with long-standing SS demonstrate areas of fibrosis more prominently than the classic criteria allow. In more chronic cases, repeated biopsy attempts reveal only fibrosis and no viable labial salivary gland lobules. Sampling and timing of the biopsy may be more critical than previously considered. Laboratory diagnosis values Patients presenting with signs and symptoms of SS should have an appropriate laboratory assessment. Common findings include a positive rheumatoid factor (RF). RFs are autoantibodies against antigenic determinants that are present on the Fc portion of human IgG, and are found in sera and saliva of 60–80% of patients with primary SS. A positive RF does not confirm that the patient has rheumatoid arthritis. Positive antinuclear antibodies (ANA) are 275


Figure 11 A

B

Sjögren’s labial salivary gland histopathology (5⫻ and 40⫻). Courtesy: Dr Carol Stewart. (A) Magnification 5⫻; (B) magnification 40⫻

found in most patients, particularly anti-SS-A/anti-Ro and anti-SS-B/anti-La. Reports have demonstrated that precipitating autoantibodies to Ro and La occur in patients with SLE, but are more prevalent in primary SS, occurring in 60–80% (anti-Ro) and 40–60% (anti-La) of SS patients. Management The patient with SS must be treated by a multi-specialty team for an optimal outcome. The rheumatologist will monitor the inflammatory components related to core disease and any extraglandular manifestations. The ophthalmologist will manage the ocular health of the patient on a routine basis. A variety of treatment modalities might be appropriate to help maintain ocular secretions, such as lachymal duct plugs and laser occlusion. Prescription eye drops containing 0.05% cyclosporine emulsion may help some patients with ocular moisture. Many patients use overthe-counter artificial tears as well. As many SS patients seem to be sensitive to agents in cosmetics and preservatives in over-the-counter products, hypoallergenic products may be preferred. The dental management for patients with SS is critical to their long-term oral health. Patients demonstrating hyposalivation may also demonstrate increased susceptibility to dental decay. Follow-up visits every 4 months may assist in monitoring and treating active dental caries. Patients should be educated and empowered to assist in the management of their own oral health. Artificial saliva substitutes and oral hygiene products that contain lactoperoxidase and lysozyme (e.g. Biotene® toothpaste and mouthrinse) may be helpful. Meticulous home care with a home fluoride program customized for the patient is essential. Nutritional counseling might be helpful, which 276

includes minimizing carbonated drinks and avoiding snacking on sticky sugary processed foods. Salivary stimulants such as sugar-free gums and lozenges will assist in enhancing the salivary flow. If available, xylitol sweetened gums and lozenges are beneficial due to their reported anticariogenic effects. Prescription sialogogues, such as pilocarpine and cevimeline can be very helpful as long as functional salivary gland tissue remains. However, prescription sialogogues are not recommended for all SS patients. These should not be used in patients with uncontrolled asthma or narrow-angle glaucoma, and should be used with caution with certain types of cardiovascular disease, eye, lung, and liver conditions. Consultation with the patient’s rheumatologist before prescribing these medications is prudent to confirm the lack of contraindications. Not only are SS patients more susceptible to dental decay and candida, their periodontal status should be monitored as well. While some reports indicate no significant difference between the periodontal status of SS patients and controls, others report more severe periodontitis in SS patients. Patients should be given all assistance possible to maintain their dentition in the optimal condition. As many of these patients are taking bisphosphonates for osteoporosis, the option of implant replacements for lost teeth, or implant supported dentures is one that should be approached with utmost care and patient’s informed consent. The potential of bisphosphonate-associated osteonecrosis should be reviewed with the patient prior to extractions, implants, or any oral surgical procedures. While SS often follows an indolent course, of critical importance is the concern for development of lymphoma. Kassan et al reported that SS patients have 40 times higher risk of development of lymphoma than the normal population. Lymphoma has been reported by Voulgarelis et al


Figure 12

immunosuppressives are reserved for treatment of severe extraglandular manifestations of SS. Anti-B-cell therapy is a new potential therapy for the glandular and extraglandular manifestations in addition to the management of lymphoma associated with SS. Gene-transfer modalities used in animal models continue to show future promise. The dentist should be an integral part of the medical management team, along with the rheumatologist and ophthalmologist, for optimal patient care.

Benign Lymphoepithelial Lesion (Mikulicz’s Disease)

Palatal MALT lymphoma and carious roots in Sjögren’s syndrome patient. Courtesy: Dr Carol Stewart

in 4.3% of patients with SS. These tumors may arise in the salivary gland or within lymph nodes. What was considered a BLEL in the past might currently be diagnosed as a low-grade non-Hodgkin’s B-cell lymphoma of the mucosaassociated lymphoid tissue (MALT) lymphoma. Figure 12 demonstrates a patient with SS demonstrating a bluish area in the hard palate, which was diagnosed as BLEL. In addition, SS patients may develop caries that involve root surfaces. MALT is normally found in Peyer’s patches in the ileum of the lower gastrointestinal tract, where it plays a role in normal humoral immune response. Mononuclear cell lymphocytic infiltrates in the exocrine glands can develop into marginal zone B cell lesions or acquired MALT. A recent enlargement or persistent parotid enlargement could be a lymphoma. MALT lymphomas have even been discovered though SS labial salivary gland biopsies. Patients with SS have an increased risk of developing monoclonal B-cell MALT lymphoma due to perhaps prolonged autoimmune inflammation or persistent antigenic stimulation to virus or bacteria. Occasionally, high-grade lymphomas develop which can demonstrate aggressive behavior. A patient demonstrating a persistent swelling of the major salivary glands or lymph nodes, or sudden parotid gland enlargement or pain should be evaluated to rule out possible lymphoma. Currently, SS patients suffer from diminution in quality of life resulting from the sicca complex, extraglandular manifestations, and the depression from disease chronicity and anxiety associated with development of lymphomas. Educating patients and helping them to understand their disease and empowering them with knowledge is an important management strategy. The prognosis for SS patients may improve as greater understanding of the pathogenesis is achieved through continued research. Currently, systemic

In the late 1800s, Johann von Mikulicz-Radecki described a patient with an unusual bilateral painless swelling of the lacrimal glands and all the major and minor salivary glands. Histopathologic examination showed an intense lymphocytic infiltrate, with features that were recognized as the BLEL. The clinical presentation became known as Mikulicz’s disease and the term was used to describe cases of bilateral parotid and lacrimal enlargement. With time, the histopathological diagnosis of these cases proved to be inconsistent with Mikulicz’s disease. The clinical picture of symmetrical lacrimal and salivary gland enlargement was attributed to other diseases such as tuberculosis, sarcoidosis and lymphoma. Consequently, these cases were later described as Mikulicz’s syndrome, restricting the term Mikulicz’s disease for use with a histopathologic diagnosis of BLELs. Over the years, the use of these terms became interchanged and confusing, so their use has been discouraged. Clinical features Mikulicz’s disease is reportedly characterized by symmetric and persistent swelling of the lacrimal glands and either or both of the major salivary glands (parotid and submandibular) and the exclusion of other diseases that may mimic this presentation, such as sarcoidosis, viral infection or lymphoproliferative disorders. Many cases of BLELs were a component of SS. The lymphoepithelial lesion was commonly found in adults, primarily women, and usually in the parotid gland. The affected gland was diffusely enlarged, asymptomatic or mildly painful. Diagnosis Microscopic examination demonstrates a heavy lymphocytic infiltrate associated with the destruction of the salivary acini. The ductal epithelial cells and surrounding myoepithelial cells become hyperplastic, and form groups of cells known as ‘epimyoepithelial islands’. These islands, once considered benign, are currently recognized to be indicative of low-grade salivary lymphoma of the MALT. A review of Mikulicz’s initial case report concluded that 277


Mikulicz actually reported the first case of MALT lymphoma, based on the published histopathology. The authors, Ihrler and Harrison further urged that the terms Mikulicz’s disease and Mikulicz’s syndrome should no longer be used. Conversely, a recent report by Yamamoto et al concluded that Mikulicz’s disease is a distinct entity and different from SS both clinically and histopathologically. Additionally, the authors reported that Mikulicz’s disease was an IgG4-related systemic disease. Treatment The affected gland must be surgically removed. Fortunately, most MALT lymphomas are low-grade tumors that tend to remain localized with good survival rates. Occasionally, tumors transform to high-grade lymphomas with aggressive behavior.

Sialorrhea Clinical features Sialorrhea or ptyalism is a condition characterized by increased salivary flow. Sialorrhea can occur with various neurologic disorders, infections, the secretory phase of the menstrual cycle, heavy metal poisoning, Wilson disease, paroxysmal sialorrhea, and rabies. Older aged individuals in chronic care facilities and chronically debilitated with cerebrovascular accident may demonstrate chronic drooling. Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and cerebral palsy are neurodegenerative diseases associated with sialorrhea. The appearance of excess saliva in neuropathologic conditions may be due to excessive saliva, but is usually related to impaired cerebral control of orofacial function. Weakness of the facial and perioral muscle tone inhibits the normal retention, movement, and/or swallowing of saliva. Excessive salivation has been reported in familial dysautonomia (FD) due to submandibular and sublingual salivary gland hyperactivity. These changes may be the result of ongoing parasympathetic denervation characteristic in FD. The consequences of ‘drooling’ are not restricted to medical issues, but can cause major social handicaps. Severe psychosocial consequences and social stigmatization may be emotionally devastating for patients and families. Drug-induced sialorrhea has been reported as well. Major medication groups associated with drooling are anti-psychotics, particularly clozapine, and direct and indirect cholinergic agonists that are used to treat dementia of the Alzheimer’s type and myasthenia gravis. Other drugs cited include risperidone, lithium and digoxin. Heavy metal toxins, such as mercury and thallium produce sialorrhea as does exposure to irreversible acetylcholinesterase inhibitors such as insecticides and nerve agents. 278

Patients reporting to the dental office will present due to concern about the unknown condition which carries significant social stigmas. The patient may bring their ‘spit cup’ with them and describe their saliva as ‘foamy’. Several conditions should be considered. Minor sialorrhea may be associated with minor oral irritations and ill-fitting or new dentures. Episodic sialorrhea may be a subtle manifestation of gastroesophageal reflex disease (GERD). Excessive saliva is produced as a protective buffering mechanism in patients with GERD. This is called ‘water brash’. A similar condition of sialorrhea with unknown etiology termed ‘idiopathic paroxysmal sialorrhea’ is reported to consist of episodes of increased salivary flow occurring 1 or 2 times per week at 2–5 minutes in duration. The episodes are preceded by a prodrome consisting of nausea or epigastric pain, but without progression to vomiting. These may be variants of the same condition. Sialorrhea may be associated with esophageal obstruction (foreign body, cancer, or stricture formation), infection, and nasogastric intubation with symptomatic sequelae of sialorrhea. Treatment Treatment of sialorrhea depends on its etiology. Some causes of mild or transitory sialorrhea may need no treatment. If the salivation is believed to be due to GERD, referral to their physician for evaluation and treatment would be appropriate. If the condition is due to inadequate motor control, speech therapy might improve the situation, if the patient is able to cooperate. Botulism toxin injected into the parotid gland has been reported to have efficacy for ALS and PD as reported by Lagalla et al and Contarino et al. Surgical techniques might be needed to modify the salivary glands or ductal structures. A recent report by McAloney et al showed efficacy and safety from bilateral submandibular duct relocation and bilateral sublingual gland excision. The prognosis of sialorrhea will vary with the degree to which the causal factors can be managed.

INFLAMMATORY CONDITIONS OF SALIVARY GLANDS Inflammatory conditions are the most common pathology affecting the salivary glands. Dentists should be familiar with their clinical manifestations and recommended treatment.

Mucocele The mucocele is a common lesion that results from rupture of a salivary gland duct and spillage of mucin into the


surrounding tissues. For that reason, the term ‘mucus extravacation’ phenomenon is used to describe this lesion. The rupture of the gland or duct may be due to local trauma, but many cases develop without a history of trauma. These will be found most frequently in the lower lip. Clinical features Mucoceles typically present as fluctuant, non-ulcerated dome-shaped mucosal swellings that range from 2 mm to several centimeters in size. Mucoceles have been reported in patients of all ages. The lesions typically have a bluish translucent hue due to the spilled mucin under the tissue surface (Figure 13). Deep mucoceles may appear normal in color, and may feel firmer to palpation than superficial ones. Duration may be days to years. Patients will often report that the lesion intermittently gets larger, and then shrinks. This history is consistent with the nature of the lesion which will enlarge, sometimes during eating, and then spill contents into the surrounding tissue, and eventually shrink in size. The most common location is the lower lip, but mucoceles may also be found in the buccal mucosa, anterior ventral tongue and floor of the mouth (ranula).

and plasma cells. The lumen is filled with an eosinophilic coagulum containing inflammatory cells. Treatment Treatment of the mucous retention phenomenon is excision. If only incised, the contents will be released, but the lesion may recur when the area has healed.

Ranula Clinical features ‘Ranula’ is the term used for mucoceles that occur in the floor of the mouth in association with ducts from the submandibular or the sublingual gland. Generally these are larger than mucoceles occurring in other locations and can elevate the tongue. The ranula is usually located lateral to the midline and appears as a dome-shaped fluctuant swelling in the floor of the mouth as seen in Figure 14. The color may be translucent blue or normal in color if deep seated. A rare plunging type that has herniated through the mylohyoid muscle has been described by Davison et al.

Histopathology

Histopathology

They consist of a circumscribed cavity in the connective tissue, producing an elevation of the mucosa with thinning of the epithelium. The cavity wall is made up of a lining of compressed fibrous connective tissue and fibroblasts. The connective tissue wall may demonstrate granulation tissue infiltrated by polymorphonuclear leukocytes, lymphocytes

The histopathology of a mucocele and ranula are similar, however, the ranula may be a true cyst with an epithelial lining. Spilled mucin may elicit a granulation tissue response that contains foamy histiocytes.

Figure 13

Treatment Treatment of a ranula includes unroofing the lesion, excision of the lesion, or removal of the sublingual gland. Figure 14

Mucocele of the lower lip. Bluish dome-shaped lesion of short duration on the mucosal aspect of lower lip. Courtesy: Dr Indraneel Bhattacharyya

Ranula. Courtesy: Dr Praveen, Department of Oral Medicine, KLE Institute of Dental Sciences, Bangalore

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Sialolithiasis, Salivary Duct Stone, Salivary Calculi

Figure 15

Clinical features Sialoliths are calcified bodies that develop within the salivary gland or ductal system. These are one of the most common salivary gland conditions. These are believed to develop from deposition of calcium salts around a focus of material within the duct lumen. Solitary or multiple sialoliths can form. The initiating focus may consist of desquamated epithelial cells, bacteria, foreign bodies, or mucus. Sialoliths most commonly occur in the submandibular gland (80–90%), but may develop in the parotid and sublingual gland as well. Multiple stones are more common in the parotid glands than other major glands. Minor gland calculi are occasionally seen in labial glands and buccal mucosa. These usually form in young and middle-aged adults, but may develop at any age. The classic presentation is an intermittent postprandial salivary gland swelling that gradually subsides over the next 2–3 hours. Patients report moderately severe pain, just before, during and after meals due to stimulation of salivary flow and the pressure produced against the occluded duct. Recurrent and chronic obstruction causes stasis, inflammation, and infection, which can result in persistent enlargement. Sialoliths may be round or elongated and measure from 2 mm to 2 or more centimeters in diameter. The involved duct may contain a single stone or multiple stones. Upon excision and gross examination, these appear yellow in color. The cause is uncertain, but sialolith formation can be promoted by chronic sialadenitis and partial duct obstruction.

Occlusal radiograph of sialolith in submandibular gland. Courtesy: Dr Carol Stewart

Figure 16

Diagnostic procedures Conventional radiographs can successfully image most sialoliths as they appear as radiopaque masses. Smaller sialoliths that are not fully calcified pose a diagnostic challenge. Underexposed radiographs can sometimes demonstrate the presence of the sialolith. Occlusal films help identify stones in the submandibular gland as shown in Figures 15 and 16. If a panoramic film is generated, multiple calcifications may be identified as shown in Figure 17. It is possible for multiple calcifications to appear superimposed on the mandible and mimic a bony lesion. A sialograph of Wharton’s duct depicts ductal enlargement proximal to the sialolith in Figure 18. However, Rabinov and Weber report that up to 20% of salivary calculi are radiolucent. If not calcified, the stones may not be evident on these films. Non-contrast CT is often considered the best single modality for the diagnosis of calculi. Most stones not seen on conventional radiographs can be detected by CT. Sialographs are useful in detecting non-calcified sialoliths, but sialography is an invasive procedure with potential to dislodge the stone deeper into the gland, as well as 280

Occlusal radiograph of sialolith in submandibular gland. Courtesy: Dr James Pettigrew

facilitate retrograde spread of any existing bacterial infection as a result of stasis. In addition, sialography can cause increased pain when acute sialadenitis exists. Dormant infections can get worse after sialography; thus necessitating the use of antibiotics. Contrast CT examination, on the other hand, can image non-calcified sialoliths if these are larger. In Asia and Europe, ultrasound imaging is the mainstay of imaging.


Figure 17

invasive treatment modality that does not require removal of the gland for sialolithiasis. Commonly associated with sialolithiasis is acute or chronic sialadenitis, which is described in the next section.

Sialadenitis

Panoramic film of multiple sialoliths in parotid gland. Courtesy: Dr James Pettigrew

Sialadenitis or an inflammation of the salivary glands may arise from a variety of infectious and non-infectious conditions. Non-infectious causes of salivary gland dysfunction include disorders such as SS, sarcoidosis, radiation therapy, medications, and congenital anomalies were discussed in the previous sections. The infectious causes, which will be discussed in the following sections, commonly include bacterial and viral infections. Salivary stones or sialoliths are also associated with salivary gland dysfunction of the major and minor glands. Conditions that predominately affect the minor salivary glands, such as cheilitis glandularis and necrotizing sialometaplasia will be reviewed as well.

Figure 18

Non-specific Sialadenitis

Sialograph of submandibular gland showing dilatation of Wharton’s duct proximal to sialolith. Courtesy: Dr Ajit Auluck and Dr Chandrakant Shetty

Histopathology The histopathologic features include a calcified mass that exhibits concentric laminations surrounding a central focus of amorphous debris. The associated duct will demonstrate squamous, oncocytic or mucous cell metaplasia. Treatment Small stones may be removed by massaging and manipulation to move the stones toward the duct orifice or peripheral/ transoral ductotomy. Large stones may require excison of gland and/or associated duct. Lithotripsy has been tried with limited success. Sialoendoscopy provides a new minimally

Non-specific sialadenitis may manifest as chronic parotitis, also called chronic recurrent parotitis. The cause of the parotid gland enlargement may be multifactorial and include decreased salivation either from decreased production or decreased secretion, stasis and an ascending retrograde infection. Sometimes, no predisposing factor is identified. This entity is usually unilateral, painful (mild to severe), and characterized by intermittent exacerbations of swelling and remission. Massaging or milking the gland will reveal cloudy or purulent secretions. In a large series, Bhatty et al reported that the mean age was 46 years, with mean duration of symptoms of 4.6 years. The swelling may last for several hours or several weeks. The condition establishes a cycle of blockage and infection, which becomes self-perpetuating. Fever and malaise may be present. Remissions last from weeks to years. The extent of the gland destruction may increase over time with each episode as does the pain intensity. The disease tends to progress and may lead to the formation of a fibrous mass in the affected gland. Diagnostic imaging Sialography will demonstrate the parotid duct system. A ‘sausage-like’ pattern reflects areas of duct wall dilatations and stricturing that result from the effects of the ascending bacterial infection. Because sialography may result in retrograde spread of infection into the gland, other imaging modalities are preferred. CT scan may show increased density due to the normal parotid gland fat being replaced by inflammation and fibrosis. Contrast CT will show enlargement of the gland and its duct in the absence of 281


a causative agent such as a sialolith. Figure 19 shows unilateral gland and duct enlargement of the right submandibular gland. Figure 20A–C show non-specific sialadenitis in the right parotid and submandibular glands. Histopathology The histopathology is consistent with non-specific sialadenitis with marked infiltrate of inflammatory cells. The histology may show mild chronic sialadenitis or widespread

involvement of the gland with areas of destruction. Acinar loss and fibrosis will be present in varying amounts. Treatment Treatments include antibiotic therapy during an acute attack, sialogogues, increased fluid intake and parotid gland massage. When surgical intervention is appropriate, a superficial parotidectomy has a high success rate with minimal long-term complications.

Bacterial Sialadenitis

Figure 19

Bacterial sialadenitis may arise from a bacterial infection involving any of the salivary glands. Acute bacterial sialadenitis most commonly occurs in children younger than 2 months and in elderly persons who are debilitated by systemic illness, or who have had surgical procedures. However, persons of all ages may be affected. The most common pathogens are Staphylococcus aureus and anaerobic bacteria. Clinical features

Unilateral enlargement of the right submandibular gland and duct, consistent with low-grade sialadenitis. Courtesy: Dr Madhu Nair

Acute sialadenitis is seen in the parotid gland and is bilateral in 10–25% of case. The affected gland is swollen and painful, and the overlying skin may be erythematous. The patient may present with a low-grade fever and trismus. Milking the gland may reveal a purulent discharge. Acute suppurative sialadenitis is most frequently due to S. aureus, but also may arise from streptococci, including Streptococcus pneumoniae and Streptococcus pyogenes and gram-negative aerobic bacilli including Escherichia coli. A study of acute sialadenitis from all three major glands

Figure 20 A

B

C

Non-specific sialadenitis noted in the right parotid and submandibular glands. Courtesy: Dr Madhu Nair

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with 47 specimens as reported by Brook revealed a broad spectrum of microbes present in the purulent fluid. The predominant aerobes were S. aureus and Hemophilus influenzae, while anaerobes were gram-negative bacilli, including Prevotella, Porphyromonas, Fusobacterium and Peptostreptococcus species.

necrosis. The ducts tend to be atrophic and do not show squamous metaplasia characteristic of necrotizing sialometaplasia. Based on the clinical and histopathologic features, some prefer to consider SANS a separate non-specific inflammatory condition of the minor salivary glands with unknown etiology.

Histopathology

Treatment

The diagnostic features of acute sialadenitis will include neutrophils within the ductal system and acini.

Subacute necrotizing sialadenitis is self-limiting and heals within 2–3 weeks. It generally requires no treatment.

Diagnosis A history of preceding events may aid in making the diagnosis. Predisposing factors can include dehydration, malnutrition, immunosuppression, dental infection, anticholinergic medications, tracheotomy, sialectasis, ductal obstruction, neurosurgical, and abdominal surgical procedures. Treatment Treatment for acute sialadenitis includes appropriate antibiotic therapy based on culture and sensitivity findings. Rehydration is important to improve salivary flow. If an abscess has formed, surgical drainage may be required. If the condition is severe, surgical removal of the gland may be necessary. In debilitated patients, the condition may be fatal due to spread of infection and sepsis. Prompt recognition by the dentist with appropriate referral otorhinolaryngologist for definitive treatment is essential for a good outcome.

Subacute Necrotizing Sialadenitis Clinical features Subacute necrotizing sialadenitis (SANS) is a form of salivary inflammation that occurs most commonly in young adults and teens. The lesion involves minor salivary glands of the hard and soft palate, and presents as a localized palatal swelling covered by erythematous, intact mucosa. The nodule may be accompanied by abrupt onset of pain. An infectious or allergic origin has been suggested. Some diagnosticians have questioned whether SANS represents a separate entity or part of the spectrum of necrotizing sialometaplasia. Unlike necrotizing sialometaplasia, SANS does not ulcerate or slough necrotic tissue. Histopathology Subacute necrotizing sialadenitis is characterized by a heavy mixed inflammatory infiltrate consisting of neutrophils, lymphocytes, histiocytes, and eosinophils. There is an absence of acinar cells and those present may exhibit

Cheilitis Glandularis The term ‘cheilitis glandularis’ was first used by Volkmann in 1870 to describe a disorder that presented with a chronic, suppurative inflammation of the lower lip characterized by swelling of the mucous glands, dilated openings, and mucopurulent discharge. Cheilitis glandularis is an uncommon inflammatory condition of the minor salivary glands, and most commonly affects the lower lip of adult males. The etiology is unknown, however associated factors have been suggested. These factors include tobacco, poor oral hygiene, bacterial infections, possibly heredity, and actinic damage. Clinical features Cheilitis glandularis most commonly affects the lower lip, but it has been reported in the upper lip, palate, and buccal mucosa. Affected individuals experience swelling and eversion of the lower lip as a result of hypertrophy and inflammation of the glands as seen in Figure 21. The openings of the minor salivary ducts are inflamed and dilated, and pressure on the glands may produce mucopurulent secretions emanating from the ductal openings. The condition most frequently occurs in middle-aged men, but women and children have been reported as well. Historically, cheilitis glandularis has been classified into three types, based on the severity of the disease. These are (i) simple, (ii) superficial suppurative (Baelz’s disease), and (iii) deep suppurative (cheilitis glandularis apostematosa). The superficial suppurative type demonstrates painless crusting, swelling, and induration of the lip with superficial and deep ulceration. This type seems to be the result of secondary infection of the simple type. The deep suppurative type, also known as cheilitis glandularis apostematosa, myxadenitis labialis, or cheilitis glandularis suppuritiva profunda, is a deep-seated infection associated with abscess formation and spontaneous expression of suppurative material from the ducts. The latter two types represent progressive stages of the diseases with bacterial involvement and demonstrate increased inflammation, suppuration, and ulceration of the lip.

283


Figure 21

Cheilitis glandularis. Courtesy: Department of Oral Medicine, MCODS, Mangalore

Histopathology Histopathologic features consist of non-specific chronic inflammation, dilated secretory ducts, dilated ducts containing mucin, areas of fibrosis, and areas of chronic sclerosing sialadenitis. The ductal lining may show oncocytic metaplasia and atrophy of the acini. Concomitant dysplastic changes may be seen in the surface epithelium. Diagnosis The differential diagnosis for cheilitis glandularis would include orofacial granulomatosis and multiple mucoceles. Orofacial granulomatosis, which will be described in the next section, is a non-tender, persistent swelling of the lips usually with oral ulcerations. Histologic findings would include non-caseating giant cell granulomas. Definitive diagnosis of cheilitis glandularis requires a biopsy along with the clinical picture. Treatment The treatment for cheilitis glandularis may vary depending on the severity of the condition. It may be treated with lip balms, sunscreens, topical steroids, intralesional steroids, systemic antihistamines, and/or antibiotics. If conservative therapy fails, surgical resection or vermillionectomy may be indicated. A significant percentage of cases of deep suppurative type have been associated with the development of squamous cell carcinoma of the overlying epithelium. Because actinic damage has been implicated in many cases of cheilitis glandularis, malignant degeneration could be associated with susceptibility to environmental factors, especially sun damage versus considering cheilitis glandularis 284

Figure 22

Necrotizing sialometaplasia of the palate. A well-defined ulcer that began after 1 week of seating porcelain fused to metal (PFM) crown on tooth number 3. Patient reported mild discomfort and that the lesion was progressively getting larger. Courtesy: Dr Indraneel Bhattacharyya

as a true malignant condition. Radiation therapy was used in the past, but is no longer recommended due to associated complications.

Necrotizing Sialometaplasia Clinical features Necrotizing sialometaplasia is an uncommon, benign, but locally aggressive inflammatory lesion of salivary gland tissue which both clinically and histologically may mimic a salivary gland malignancy. In 1973, it was described by Abrams and colleagues as a reactive necrotizing inflammatory process of the minor salivary glands of the hard palate. While the etiology is unknown, the prevailing theory is that local ischemia of the salivary tissue leads to local infarction. Most patients are in the 4th or 5th decade, but the lesion has been reported in all ages, except children. In a large series as reported by Brannon et al, males were affected more often than females, and whites were affected more commonly than African-Americans by a ratio of 5:1. Most lesions occur in the posterior hard palate, usually unilateral (Figure 22). Bilateral and midline lesions may occur as well. Other intraoral sites such as the retromolar pad, buccal mucosa, lower lip, and tongue have been affected. Early lesions may present as a non-ulcerated swelling in the posterior palate with or without pain. Within 2–3 weeks, the necrotic tissue sloughs and leaves a crater-like ulcer ranging from 1 cm to more than 5 cm. Commonly, patients do not seek treatment until the ulcer occurs. They may report a feeling of fullness in the area, prior to the ulceration. Pain may or may not be a complaint even though the ulcer may be quite large.


Diagnostic imaging

Diagnostic imaging

A palatal soft tissue attenuation focus with no characteristic appearance may be noted on CT and MRI. Osseous changes are not noted. Lesions in the parotid are also sometimes seen. Ultrasonography may detect multiple foci of hypoechoic nature within the parotids. Contrast CT demonstrates high attenuation areas within the parotids while MRI can clearly show well-delineated masses that are hypointense on T1 and isointense on T2 weighted contrasted images. Findings could resemble those of benign tumors such as pleomorphic adenomas. Alternatively, a more diffuse margin on CT can be misconstrued for a malignant tumor. The condition can also appear in other locations within the sinonasal and upper aerodigestive tracts.

Ultrasound imaging results in the gland appearing enlarged and lobular with a cirrhotic pattern of numerous hypoechoic regions against a heterogeneous background. The presence of lymph node enlargement is sometimes noted on CT/MRI. Diffuse enlargement of the gland with enhancement may be noted on CT.

Histopathology Biopsy is necessary to confirm the diagnosis and rule out malignant disease. The histopathology includes ulcerated mucosa, pseudoepitheliomatous hyperplasia of the epithelium, acinar necrosis, and squamous metaplasia of salivary ducts. Coagulation necrosis has been seen in early lesions. Inflammatory cells may be found with fibrosis and granulation tissue. While mucous cells are necrotic, the lobular architecture of involved glands is preserved. The lesion can be misdiagnosed as squamous cell carcinoma or mucoepidermoid carcinoma in the absence of an adequate representative section of the lesion.

Treatment The treatment is surgical removal.

VIRAL-INDUCED SALIVARY GLAND PATHOLOGY Mumps Clinical features

Chronic Sclerosing Sialadenitis (Kuttner Tumor)

Epidemic parotitis or mumps is a moderately infectious disease caused by a virus of the paramyxovirus group. Generally, mumps is a disease of childhood with an incubation period of 2–3 weeks. The virus may be in the saliva of affected persons and dissemination through droplets is common. The patient will complain of fever, fatigue, and present with a painful unilateral, or more commonly, bilateral parotid enlargement. The infection may also involve the submandibular gland. Clinical features include a flulike illness with fever, headache, vomiting, and pain below the ear. This is followed by firm, somewhat rubbery swelling of the salivary glands, sometimes elevating the ears. The glands are extremely tender to palpation and milking them may produce a thick white secretion from Stensen’s ducts. The swelling may last approximately 1 week. Other organs may be involved which include the testes, ovaries, pancreas, and mammary glands.

Clinical features

Prognosis and treatment

The Kuttner tumor, a chronic inflammatory condition of the salivary glands, was first described by Kuttner in 1896. Clinically, the condition cannot be distinguished from a true neoplasm. The submandibular gland is affected more commonly than any other salivary gland. It is usually localized to the superficial aspect of the submandibular gland, but may involve the deep aspect. It manifests as a firm, enlarged gland. Etiology may be sialolithiasis (about one-third of all cases), autoimmune sialadenitis or idiopathic. Recent reports suggest that pathogenesis probably has an immunologic background.

When the disease affects the adult male, orchitis, inflammation of the testicles, is a complication approximately 20% of the time. The orchitis is usually unilateral, but can occur bilaterally. Even with involvement of both testicles, sterility is only a rare complication of orchitis. In adults, dyspnea secondary to severe swelling of the salivary gland which required a tracheostomy, has been reported by Ishida et al. The mumps vaccine has been available since 1968, which has resulted in a marked decline in the incidence of the disease.

Treatment Once the diagnosis has been established, no specific treatment is indicated. The lesion will heal by secondary intention with no intervention within 4–10 weeks.

Histopathology The histolopathologic features consist of chronic sclerosing sialadenitis, specifically chronic inflammation and fibrosis. It may be seen with sialolithiasis.

Human Immunodeficiency Virus (HIV) Clinical features Benign lymphoepithelial lesions (BLEL) in AIDS or AIDSrelated parotid cysts (ARPC) are frequently reported in HIV 285


infected patients, and may develop later in the course of the disease. The term ‘ARPC’ is preferred to help differentiate between AIDS-related lesions and BLELs. HIV-positive status alone is needed to manifest with BLEL and therefore, the term ‘BLEL-HIV’ is most appropriate. Approximately 5% of patients with HIV-1 develop parotid enlargement. These cysts can be single or multiple and usually involve the superficial lobe of the parotid gland. These are usually bilateral, often cystic, and sometimes accompanied by cervical lymphadenopathy. These may be soft or firm to palpation and can produce significant cosmetic deformities. Symptoms of dry mouth, ocular dryness, and arthralgia can occur, along with normal or reduced salivary flow rates. The pathogenesis of HIV-associated salivary gland disease may include hyperplasia of intra-parotid lymphoid tissue.

to the increased use of medications to control AIDS-related infections. Bilateral enlargement in imaging studies is more common even in the absence of such clinical findings. On T1 weighted images, cysts may appear with low signal intensities. Inhomogeneity of lesions is noted sometimes, primarily with solid lesions. On T2 weighted images, the cysts appear hyperintense and well-defined, as do reactive lymph nodes. T1 coronal and axial fast fluid-attenuated inversionrecovery (FLAIR) MRI images depict bilateral cysts within the parotids quite well (Figure 23A, B). On ultrasonographic studies, the cystic lesions appear with some internal septations, generating little echo. On the other hand, solid lesions appear with the same characteristics of solid tumors.

Histopathology

Treatment

The AIDS-related swellings reflect the lymphoid hyperplasia or lymphoepithelial cyst formation. The cyst wall may contain germinal centers and a dense infiltrate of lymphoid cells.

Sometimes, patients seek treatment only when the cosmetic deformity from the enlarged glands becomes very prominent. Highly active antiretroviral therapy is an effective treatment approach. Because HIV-associated salivary gland disease can clinically resemble SS, the differential diagnosis of bilateral parotid enlargement should include HIV infection. While the parotid manifestation is considered to have a benign course, progression to lymphoma is possible. Consequently, periodic monitoring is indicated. Any change in growth pattern would require biopsy. Rosso et al suggest that annual ultrasonography evaluation should be done to identify possible malignant transformation of BLELs in vertically infected children.

Diagnostic imaging Contrast enhanced CT or MRI is advised to help delineate the internal architectural details. Cystic and solid tumors can appear within the parotids. Bilateral enlargement is noted on advanced imaging modalities with associated cervical and nasopharyngeal lymphadenopathy. Adenoids and tonsils may appear enlarged as well. However, reactive adenopathy may not be seen on these studies, owing

Figure 23 A

B

Axial and coronal T1 FLAIR MRI images showing cysts in the parotids bilaterally in an HIV-positive individual. Courtesy: Dr Madhu Nair

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NON-INFLAMMATORY CONDITIONS OF SALIVARY GLANDS

Figure 24

Sialadenosis Sialadenosis (sialosis) is a non-inflammatory, non-neoplastic, often recurrent condition which most commonly manifests as a bilateral enlargement of the parotid and/or submandibular glands. In a recent report of 65 cases of sialadenosis as described by Satoh and Yoshirara, age ranged from 19 to 71 years and the male:female ratio was 5:3. The salivary gland enlargements are usually slow growing, may be unilateral or bilateral, and are sometimes associated with pain. The condition is usually associated with an underlying systemic disorder. These disorders include diabetes, hypothyroidism, pregnancy, alcoholism, malnutrition, obesity, anorexia nervosa, bulimia, and medications that affect the autonomic nervous system. Treatment depends upon identification of the underlying cause. As patients with these conditions will commonly present to the dental office, an understanding of the causes and effective management strategies is essential for optimal patient care.

Anorexia/Bulimia-related Sialadenosis Clinical features Eating disorders are not uncommon in young women who seek to be thin or have a more ideal figure. These disorders include anorexia nervosa and bulimia nervosa. Anorexia involves deliberate lack of food intake and bulimia includes binge eating with self-induced purging. It has been estimated that up to 19% of college-going women have bulimia. Only 5–10% of people with bulimia are male. Sometimes the frequent purging of acidic gastric fluids will produce a characteristic enamel erosion on the lingual surfaces of the maxillary anterior teeth (Figure 24). However, if measures are taken to neutralize the oral pH and maintain oral hygiene, these signs may not be present. Parotid sialadenosis has been reported to occur in 10–66% of people with bulimia. Bilateral parotid gland enlargement has been the presenting sign in some cases and one report by Mignogna et al also included bilateral palatal minor gland enlargements in addition to the parotid gland involvement. Schlienger et al reported a case where a 24-year-old female consulted physicians for 3 years for treatment of a painless parotid swelling which was initially confused with SS. Eventually, bulimia was confirmed. Unilateral parotid gland and submandibular gland swelling may also occur in sialadenosis associated with bulimia, but less frequently. Bulimics may purge several times per day. Emetics, diuretics, and laxatives frequently are used as adjunctive agents for weight reduction, but may not be revealed during a routine medical history review.

Perimyolysis. Characteristic pattern of dental erosion of the lingual enamel resulting from purging and vomiting associated with bulimia. Courtesy: Dr Carol Stewart

Pathogenesis While the specific pathogenesis has not been determined, it is generally accepted that multiple emetic episodes cause an autonomic neuropathy. The enlargement is believed to affect the autonomic innervation of the salivary acini, causing disruption of the intracellular secretory cycle. This may lead to excessive accumulation of secretory granules, with marked enlargement of the acinar cells. Due to sympathetic nerve dysfunction, zymogen (a precursor of amylase) production and storage may increase. Individual acinar cells enlarge because of zymogen granule engorgement. Diagnosis Because patients with bulimia and anorexia do not frequently disclose their condition, a broad medical evaluation will be required. The diagnostic assessment would include tests to rule out SS (ANA, anti-SS-A/Ro, anti-SSB/La, rheumatoid factor, hepatitis C virus, complete blood count [CBC], serum angiotensin-converting enzyme, immunoglobulin disorder [IgA, IgM, albumin, urine Bence Jones protein], hepatic disorder [glutamic oxaloacetic transaminase and glutamic pyruvic transaminase], diabetes [fasting blood glucose], and hypokalemia [serum electrolytes]). Salivary secretion may be decreased or normal. Sialography may be helpful in establishing the diagnosis. Sialography may demonstrate a ‘leafless tree’ pattern which is thought to be caused by compression of the finer ducts by the hypertrophic acinar cells. Splaying of the ducts within the enlarged gland may be seen, with the ducts appearing normal. In early stages of the disease however, there may be no sialographic changes. CT scan of the parotids may show a bilateral enlargement of the parotid glandular parenchyma with increased glandular density, fibrosis or fatty infiltration that are characteristic of advanced 287


changes. CT is non-specific. The changes could be misconstrued for a lipoma; however, the absence of a fibrous capsule is helpful in differentiating between these conditions; ultrasound and MRI are useful and non-invasive approaches. Histopathology The histopathological report of a salivary gland biopsy will reveal hypertrophy of the acinar cells, sometime 2–3 times greater than normal size. The nuclei are displaced to the cell base, and the cytoplasm is engorged with zymogen granules. Significant inflammation is not observed. Treatment Therapy will include psychological counseling with an eventual goal of cessation of vomiting. This may result in a gradual reduction of the salivary gland enlargement. Pilocarpine hydrochloride drops have shown efficacy in reducing parotid gland enlargement in bulimic patients. In cases refractory to treatment, parotidectomy may be considered to improve unacceptable esthetics in patients with bulimia.

Sialadenosis Associated with Alcoholic Cirrhosis Clinical features Salivary gland enlargement, usually the parotid glands, may occur in some patients who ingest large quantities of alcohol on a long-term basis with resultant liver damage. The enlargement results from an ethanol-produced peripheral autonomic neuropathy that causes disordered salivary metabolism and secretion. Increased intracytoplasmic zymogen granules within the acinar cells are believed the cause of parotid enlargement. Diagnosis In alcohol associated sialadenosis, 40–60% of the adult patients with hepatic damage presented with parotid enlargement. The histopathology of parotid glands reveals an increase in fatty infiltration, edema and fibrosis without inflammation. Diagnosis would be assisted by the patient’s history of alcohol intake. The dentist could request liver enzymes and bilirubin tests to aid in making the diagnosis. Elevated levels would prompt the dentist to refer the patient to an internal medicine specialist for evaluation and a radiologist for imaging. Diagnostic imaging On CT, the parotid will demonstrate increased density with time, as the fat is replaced with increased acinar hypertrophy.

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Treatment Treatment should focus on the underlying liver disease as well as the oral complications. When the liver disease is managed, the parotid glands may reduce somewhat in size. In addition to sialadenosis, the dentist should also be aware of salivary changes that increase caries risk susceptibility. The parotid gland flow rate in patients with alcoholic cirrhosis has been reported to be less than flow rates in healthy controls. Diminished buffer capacity and less attention to oral hygiene will put the patient at increased risk for dental decay. In addition, patients who consume large quantities of wine will have increased risk for dental erosion due to the erosive potential of wines due to their acidity. The pH of wine is reported to range from 3.0 to 3.8 and the pH at which enamel dissolves is reported to be pH of 5.0 to 5.7. Treatment will include patient education and complete dental evaluation.

Diabetes Mellitus Clinical features Diabetes mellitus is a disorder of carbohydrate metabolism mediated through decreased production of insulin or tissue insensitivity to the effects of insulin, resulting in hyperglycemia. Two types of presentations are recognized, although overlap is seen. Type I is characterized by a lack of insulin production and is commonly diagnosed during childhood, and Type II may present in obese children and adults, due to decreased sensitivity to insulin. The complications include kidney failure, blindness, neuropathies, and atherosclerosis. Oral symptoms may include dry or burning mouth, gingival inflammation. Sialadenosis has been reported in diabetes mellitus. The sialadenosis is believed due to an autonomic neuropathy, as in alcoholism and nutrition-induced sialosis. With autonomic disturbances in sympathetic innervation, alteration in protein synthesis occurs. Cytoplasmic swelling develops from engorgement by intracytoplasmic zymogen granules. As a result, the parotid acini may double in size (hypertrophy) resulting in clinically obvious parotid gland enlargement. Diagnosis Long-standing, bilateral, painless enlargement of the parotid glands may be observed. These are soft in consistency and follow the outline of the parotid glands, without nodularity. Milking the parotid glands may reveal fluid of normal volume and consistency. Lower resting and stimulated saliva flow rates in diabetics versus normal controls have been reported as well. Levels of calcium are increased and salivary magnesium, zinc and potassium are reduced.


Diagnostic imaging CT scan may show enlarged parotid glands without masses, but demonstrating decrease in density due to significant fat infiltration of the gland. Histopathology The histopathology associated with parotid gland biopsies of diabetic patients when compared with those from alcohol associated sialadenosis is characterized by an increased number of lipid intracytoplasmic droplets in the acinar and ductal cells, and abundant adipose infiltration in the stroma. Treatment While proper glycemic control should be the treatment goal, this does not result in a significant reduction in the parotid enlargement. Cosmetic improvement may be obtained with gland removal, but the risk–benefit ratio must be considered.

Medication-induced Sialadenosis Medication-induced sialadenosis has been reported for a number of medications that affect the autonomic nervous system. Antihypertensive agents, psychotropic drugs, ␤-adrenergic agents, and bronchodilators have been implicated. Mauz et al reported a case were valproic acid was associated with bilateral parotid and submandibular gland sialadenosis.

Orofacial Granulomatosis Clinical features Orofacial granulomatosis was first introduced in 1985 by Wiesenfeld and encompass a spectrum of clinical presentations that share common histopathologic findings of non-caseating giant cell granulomas. The conditions included in this category are Melkersson–Rosenthal syndrome, cheilitis granulomatosa, Crohn’s disease, sarcoidosis, and tuberculosis. Clinical presentation will vary, but the most frequent site affected is the lips. Patients present with a non-tender, persistent enlargement of the upper or upper and lower lips. When this presentation is combined with fissured tongue and facial paralysis, the clinical condition is called Melkersson–Rosenthal syndrome. Involvement of the lips alone is called cheilitis granulomatosa. Signs and symptoms include edema, erosions, paresthesia or taste alterations. Histopathology and diagnosis The diagnosis is confirmed upon characteristic histopathologic findings. Scattered aggregates of non-caseating

granulomatous inflammation are found, often surrounding vessels. Granulomas contain histiocytes and multinucleated giant cells. Special stains for fungal organisms and acid-fast bacteria are negative. No foreign bodies or inclusions are identified in the tissue. Treatment and prognosis Upon receiving the histopathologic findings, the clinician must determine the initiating cause. Treatments have included intralesional corticosteroids, radiotherapy, sulfasalazine, hydroxychloroquine sulfate, azathioprine, cyclosporine A, methotrexate, metronidazole, and other antibiotics. Most clinicians treat the lips with intralesional corticosteroids with variable success. Spontaneous remissions occur as well. The prognosis is variable as there is no clearly effective treatment to date.

Sarcoidosis Sarcoidosis is an immune-mediated multisystem disease of unknown origin, characterized by the presence of epithelioid non-caseating granulomas in the involved organs. Sarcoid granulomas are commonly encountered in the lungs, with lymph node involvement, but may be seen in many other sites. Sarcoidosis may also affect the heart, liver, spleen, bones, skin, eyes, lymph nodes, parotid glands and the oral cavity and may first manifest in the oral and maxillofacial region. The disease occurs worldwide and may affect either gender. Geographically, there appears to be a higher incidence among central and northern Europeans. It usually arises in the 2nd to 4th decades of life, with a slight female predominance. In the United States, sarcoidosis primarily affects African Americans, who tend to have more acute symptoms, extrapulmonary manifestations and higher mortality rate at an earlier age compared to whites. The most prominent manifestation of the disease involves the lungs with acute dyspnea, cough, and chest pain being common symptoms. Chest radiographs reveal bilateral hilar lymphadenopathy, diffuse parenchymal infiltrates or both. Less commonly, sarcoidosis develops slowly over months or years, especially among whites. In some cases, patients have no symptoms, and the disease is discovered on routine chest radiographs. Mortality rates are similar among races. Approximately, one-fourth of those with chronic sarcoidosis die of respiratory failure as reported by Keller. Skin lesions occur nearly 25% of the time. These often appear as chronic, violaceous indurated lesions that are termed ‘lupus pernio’ and frequent the nose, ears, lips and face. Symmetric elevated indurated purplish plaques are also commonly seen on the limbs, back and buttocks. Scattered, non-specific, tender erythematous nodules known as ‘erythema nodosum’, frequently occur on the lower legs.

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Enlargement of the major salivary glands may be the first sign of the condition. Diagnosis can be difficult and prolonged due to the non-specific symptoms. Examination may reveal bilateral parotid and submandibular gland enlargement of recent onset, asymptomatic or mildly symptomatic, and firm and sometimes nodular upon palpation. Facial nerve involvement at presentation may be mistaken for malignancy. Glandular size does not fluctuate upon eating. Milking the parotid glands may demonstrate delayed flow and sialometry may be below normal. The infiltration of major salivary glands and subsequent xerostomia predispose patients to dental decay and fungal infections. An analysis of 45 published cases as reported by Blinder et al revealed an age range between 5 and 69 years, with highest prevalence between 30 and 40 years. The study reported lesions in the jaws, buccal mucosa, palate, lips, gingiva, and floor of the mouth. Sarcoid lesions in the buccal mucosa and tongue present as submucosal nodules and indurations or superficial ulcerations. In gingival lesions, erythematous swelling is generally seen with some superficial ulcerations in the anterior labial gingiva. Lesions in the floor of the mouth may present as ranulas. In many cases, the lesions in the buccal mucosa, gingiva and tongue were the first clinical manifestation of the disease. Bony jaw lesions appear as diffuse, poorly defined radiolucencies which may be associated with tooth mobility. Lesions in maxilla, mandible and condyle have also been reported. Histopathology and laboratory investigations Because the differential diagnosis of oral dryness and bilateral parotid enlargement would include sarcoidosis, SS, MALT lymphoma, sialadenosis, Warthin’s tumor, and HIV-associated salivary gland disease, biopsy of the enlarged glands is sometimes required. The histopathologic findings from salivary gland biopsy usually demonstrate non-caseating granulomas. Tightly clustered aggregates of epithelioid histiocytes are present with a surrounding rim of lymphocytes, mixed with Langhans giant cells. The granulomas often contain laminated basophilic calcifications known as Schaumann bodies or stellate inclusions known as asteroid bodies. However, neither is specific for sarcoidosis. The differential diagnosis for granulomatous diseases would include infectious agents such as mycobacteria, fungi, bacterial and parasitic organisms, hypersensitivity to environmental agents, and other autoimmune disorders such as Wegener’s granulomatosis. Referral to appropriate physicians to evaluate the lungs, heart, central nervous system, eyes, skin and lymph nodes would be required for a comprehensive diagnostic evaluation and management. The serum angiotensinconverting enzyme (sACE) is considered a diagnostic tool

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for sarcoidosis. Secretion of angiotensin-converting enzyme by granuloma-forming epithelioid cells results in elevated serum levels in 80–90% of cases. However, this is supportive and non-diagnostic for sarcoidosis. When bone lesions occur, hypercalcemia may be observed. Other laboratory findings in sarcoidosis might include anemia, leucopenia, thrombocytopenia, and an elevated erythrocyte sedimentation rate. Treatment Treatment will be determined by the onset and course of the disease. Spontaneous regression is common. In approximately 60% of patients, the symptoms resolve spontaneously within 2 years without treatment. Of those affected, one-fifth can be treated with corticosteroids. Those with refractory disease may be treated with methotrexate, azathioprine, and cyclophosphamide which will impact dental care. A recent refractory case was successfully treated with infliximab. A small percentage of patients die of pulmonary, cardiac or CNS complications. Consultation with the physician is essential for quality dental care.

SALIVARY GLAND TUMORS Salivary gland tumors represent 2–3% of all head and neck neoplasms. Salivary gland neoplasms may be either benign or malignant. Almost 80% of salivary gland neoplasms occur in parotid glands; and two-thirds to fourfifths of the parotid tumors are benign. Nearly half of the submandibular gland tumors are malignant and up to 80% of tumors of the minor salivary glands are malignant. In general, the smaller the salivary gland, the greater is the probability of malignancy. Tumors of the sublingual gland are rare and comprise approximately 1% of all salivary gland neoplasms; however, the majority of sublingual gland tumors, 70–90%, are malignant. Minor glands are a common site for salivary tumors, and may involve the palate, buccal mucosa, and labial mucosal glands. These tumors comprise approximately 10–20% of salivary gland tumors, with nearly half being malignant. Clinical presentation and behavior will vary with each specific type of tumor. Diagnosis will depend on clinical presentation, imaging, and the distinctive histopathology. Fine-needle aspiration (FNA) technique has been used to identify salivary gland neoplasms, but with mixed performance. A retrospective analysis as reported by Hughes et al found false-positive rates with benign lesions and malignant cases with false-negative rates. These were most commonly associated with lymphoma, actinic cell carcinoma, low-grade mucoepidermoid carcinoma, and adenoid cystic carcinoma.


BENIGN TUMORS

Figure 25

Pleomorphic Adenoma (Benign Mixed Tumor) Clinical features The pleomorphic adenoma or benign mixed tumor is the most common salivary neoplasm and accounts for over half of the tumors in the parotid and submandibular glands. The name ‘mixed tumor’ comes from the morphologic complexity and differentiation of tumor cells which vary between tumors and within the same tumor. While high in variability of cell type, the cells are rarely ‘pleomorphic’. While most common in the parotid gland, pleomorphic adenomas may occur in any major gland or in the minor salivary glands. Figure 25 shows a pleomorphic adenoma of the parotid gland with elevation of the ear lobe. Onset is commonly between the 4th and 6th decades, but they may occur in young adults and children. There is a slight female predilection. Facial nerve involvement demonstrated by facial nerve paralysis is rare. The tumor presents as a slow-growing, painless, firm and non-tender mass that is mobile in early stages. The tumor may have intermittent growth periods. As size increases, the tumor becomes more irregular and nodular upon palpation. The overlying skin seldom ulcerates. Local discomfort is noted with an increase in size. The intraoral site of preference is the hard palate (Figure 26) and sometimes the lip.

Pleomorphic adenoma of the parotid gland showing elevation of the ear lobe. Courtesy: Dr Ajit Auluck

Figure 26

Diagnostic imaging Sialography demonstrates displacement of the ducts around the benign tumor which itself is well delineated with definitive margins (ball-in-hand appearance). CT shows a similar picture, with a higher degree of attenuation within the tumor mass that demonstrates homogeneous density. A lobulated appearance is also not unusual. The margins may appear vague if there is associated inflammation or hemorrhage. Differentiation from a malignant lesion becomes difficult. Occasionally, the mass appears with lower attenuation similar to a cyst. A mixed appearance is also noted if cystic change or necrosis exists. Bleeding within the tumor mass can result in the presence of increased attenuation foci within the gland. Dystrophic calcifications are not uncommon. Figure 27A, B demonstrates the radiographic features of a persistent pleomorphic adenoma on contrast CT. Figure 28 demonstrates an axial plain CT scan of a pleomorphic adenoma of the parotid gland. Figure 29 shows a parotid gland pleomorphic adenoma via an axial CT scan heterogeneously enhancing post contrast. MRI, on the other hand, can clearly demonstrate the benign nature of the lesion with distinct margins. Most often, the apparent lobulation noted in CT is not noted, with the mass appearing solitary. The mass presents with a low T1 weighted and high T2 weighted intensity consistent with

Pleomorphic adenoma. Large dome-shaped firm sessile swelling of the hard palate. The lesion had eroded palatal shelf bone and was fairly destructive. The patient reports that the lesion had been present more than 2 years. Courtesy: Dr Indraneel Bhattacharyya

the nature of its contents and constitution. Bleeding foci appear with higher signal intensity on both types of images. Necrosis, on the other hand, appears with low T1 signal intensity and high T2 intensity. Larger lesions can be inhomogeneous. A low intensity capsule can be seen on T2 weighted studies and on fat-suppressed, contrast enhanced T1 weighted images. This feature may not be seen with recurrences as the capsule may have been penetrated at the time of previous surgical intervention. Presence of calcific foci is difficult to appreciate. The tumor exhibits moderate

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Figure 27 A

B

Persistent but stable, known pleomorphic adenoma in the left prestyloid parapharyngeal space. Courtesy: Dr Madhu Nair

Figure 28

Axial plain CT scan of pleomorphic adenoma of parotid gland. Courtesy: Dr Ajit Auluck and Dr Chandrakant Shetty

solid contrast enhancement. Recurrent pleomorphic adenomas may be multifocal, along with malignant tumors such as the acinic cell carcinoma and oncocytoma. Referral to a radiologist plays an essential role in diagnosis and localization of salivary gland tumors in the major glands. Ultrasonography results in generation of hypoechoic areas within a well-defined homogeneous mass. Detection of deep lobe tumors is difficult using ultrasonography. 292

Figure 29

Axial CT scan showing heterogeneously enhancing post-contrast pleomorphic adenoma of parotid gland. Courtesy: Dr Ajit Auluck and Dr Chandrakant Shetty

Histopathologic features The pleomorphic adenoma is usually a well-circumscribed, encapsulated tumor, composed of a mix of glandular epithelium and myoepithelial cells within a hyalinized, eosinophilic, mesenchymal stroma. The epithelium may form ducts, cystic structures, and islands or sheets of cells. Myoepithelial cells often comprise a large percentage of the


Figure 30

‘carcinoma ex pleomorphic adenoma’. Malignancy will be further discussed in the section on malignant salivary gland tumors. Monomorphic adenoma

Pleomorphic adenoma, histopathologic microscopic image of pleomorphic adenoma stained with hematoxylin and eosin (magnification 20⫻). Proliferation of islands, strands and duct-like formations of myoepithelial cells in a cartilaginous and fibrous connective tissue stroma. Courtesy: Dr Indraneel Bhattacharyya

tumor cells with variable morphology. Some demonstrate eccentric nuclei and eosinophilic hyalinized cytoplasm resembling plasma cells, called ‘plasmacytoid’ myoepithelial cells. Areas may include chondroid material and even osteoid adjacent to ductal epithelium and myoepithelial cells (Figure 30). Tumor cells may be found in the connective tissue capsule from incomplete capsule development, capsular penetration, pseudopodia, and satellite nodules. Treatment and prognosis The accepted treatment for pleomorphic adenomas is surgical excision. For tumors occurring in the superficial lobe of the parotid gland, excision of the tumor and superficial parotidectomy with conservation of the facial nerve is recommended. For deep lesions, parotidectomy is usually necessary. Submandibular gland tumors are treated by total removal of the gland with the tumor. Tumors of the hard palate are generally excised, with incision down to the periosteum. The tumor and overlying mucosa are removed and submitted for histopathological examination. In very rare situations, the pleomorphic adenoma can be intraosseous, arising from ectopic salivary tissue. Clinically and radiographically, these may resemble lesions of odontogenic origin, such as a lateral periodontal cyst. With complete removal of the tumor, prognosis is excellent. Recurrence is generally associated with incomplete removal and seeding of the primary tumor. Benign pleomorphic adenomas may become malignant. This transformation may take place in long-standing untreated tumors or in recurrent ones. In addition, the malignant component may be present at the initial excision. These rare malignant lesions are termed

The term ‘monomorphic adenoma’ was originally used to distinguish the pleomorphic adenoma from a group of benign salivary gland tumors composed of more uniform cells or a single cell type. Currently, the term is used in more than one classification scheme with differing interpretations and significance. Basal cell adenomas and canalicular cell adenomas have been termed monomorphic adenomas due to their uniform histopathology. Due to confusion in nomenclature, the term monomorphic adenoma should be replaced with the specific name of the adenoma being discussed. The following sections will describe these specific types.

Canalicular Adenoma Clinical features The canalicular adenoma is an uncommon tumor that occurs almost exclusively in the minor salivary glands and has a marked predilection for the upper lip. The buccal mucosa is the second most common location. The tumor appears in older adults and demonstrates a female predilection. The clinical presentation is a slowly growing painless mass that ranges from several millimeters to 2 cm. It may be firm or fluctuant to palpation. The overlying mucosa may be bluish or normal in color. It may be multifocal and have multiple nodules in the upper lip or buccal mucosa. Histopathology The tumor is named so for its histologic pattern which consists of uniform columnar or cuboidal cells forming canallike ductal structures. The cells may appear in a double row and enclose cystic spaces of varying size. The spaces are filled with an eosinophilic coagulum, and the supporting stroma is loose and fibrillar with fine vascularity. Large cystic spaces may be created and the epithelium may demonstrate papillary projections into the lumina. Treatment and prognosis Treatment consists of surgical excision and the outcome is very good. Recurrence is rare.

Basal Cell Adenoma Clinical features The basal cell adenoma was first reported as a distinct lesion by Kleinsasser and Klein in 1967. The basal cell 293


adenoma is an uncommon, benign salivary tumor which primarily occurs in the parotid gland. The glands of upper lip and buccal mucosa are the second most common site. It usually appears as a firm and mobile slow-growing mass. The tumor may present at any age, but is most common in older adult females. It presents as a slowly growing freely movable mass, with a clinical appearance similar to a pleomorphic adenoma and other parotid neoplasms. A special subtype, the membranous basal cell adenoma often appears with coexisting dermal cylindromas of the scalp, often occurring in combination with skin appendage tumors. Multiple bilateral tumors may develop within the parotids. Diagnostic imaging Basal cell adenomas of the parotid gland often present as small well-marginated tumors and appear as masses with central large cysts or solid masses with microcytes on CT and MRI scans. On 2-phase helical CT scans, the enhancement patterns and imaging architecture of basal cell adenomas are related to the histologic subtype of the tumor. On the 2-phase CT scan, the histologically solid-looking tumors show marked contrast enhancement on the early phase and subsequent decrease in attenuation on the delayed phase. Lee et al described that tumors with large cystic areas showed gradual and additional enhancement on the delayed phase and were classified as tubular or trabecular subtype on histopathologic evaluation. Histopathology The tumor is encapsulated, and it is named so because of basaloid appearance of the tumor cells. The basaloid hyperchromatic peripheral cells show a palisaded arrangement, similar microscopically to a basal cell carcinoma. The central cells have paler staining nuclei. Cells may also be in ribbons or cords. The trabecular subtype demonstrates narrow cord-like epithelial strands, and the tubular subtype is characterized by the formation of small round, duct-like structures. The membranous basal cell adenoma is characterized by palisading of peripheral cells and an excessive hyaline basal membrane. Multiple large lobular islands of tumor give the appearance of a jigsaw puzzle. The islands are surrounded by a thick layer of hyaline material, similar to the microscopic appearance of the dermal cylindroma. Treatment and prognosis Treatment consists of surgical removal and recurrence is rare, with one exception. Likely owing to its multifocal nature, the membranous subtype has a higher recurrence rate than other subtypes. Malignant basal cell adenomas (basal cell adenocarcinoma) may arise de novo or from malignant change of pre-existing basal cell adenomas. These have a good prognosis. 294

Papillary Cystadenoma Lymphomatosum (Warthin’s Tumor) Clinical features Warthin’s tumor is a benign neoplasm that occurs almost exclusively in the parotid gland. It represents the second most common benign parotid tumor. The pathogenesis is unclear. The traditional theory suggests that they arise from heterotopic salivary gland tissue in parotid lymph node. Aguirre et al suggested that they develop from a proliferation of salivary gland ductal epithelium that is associated with secondary formation of lymphoid tissue. The lesion is a slow-growing, painless nodular mass of the parotid and may be firm or doughy upon palpation. While uncommon, they have been reported in the submandibular and minor salivary glands by Fantasia and Miller. The onset is generally in the 6th to 7th decade of life, with males being slightly more commonly affected than females. Kotwall reported that smokers have eight times higher risk of developing a Warthin’s tumor than non-smokers. Klussmann and workers, in a large series of 185 patients with Warthin’s tumor reported that 89% of the subjects were smokers and 66% were heavy smokers. Bilateral Warthin’s tumor was seen in 17% of these patients. Diagnostic imaging CT will reveal a well-delineated, homogeneous, noncalcifying mass with a well-defined wall. Cystic appearance is quite common as are multiple lesions. Figure 31A, B demonstrates the cystic appearance of the lesion on contrast CT. The intrinsic mass demonstrates no evidence of perineural spread. MRI demonstrates a homogeneous or inhomogeneous appearance depending on the size of the tumor and presence of cystic changes. If solid, the lesions appear with low intensity on T1 weighted images and high intensity on T2 weighted images. Radionuclide imaging studies using technetium pertechnetate studies show accumulation of the tracer within the tumor, and is considered diagnostic. Positron emission tomography (PET) also indicates increased uptake of tracer. The differential diagnosis of Warthin’s tumor on MRI includes other benign cystic lesions. However, Warthin’s tumor exhibits nodularity of the cyst wall, whereas other benign cystic lesions tend to have smooth walls. Conversely, cystic and necrotic malignant tumors tend to be ill-defined. Warthin’s tumors fail to enhance, whereas pleomorphic adenomas undergo solid contrast enhancement. Histopathology Histologically, the papillary cystadenoma lymphomatosum is composed of a mixture of ductal epithelium and a lymphoid stroma. The epithelium is usually a double row of oncocytes with surrounding cystic spaces. The lining


Figure 31 A

B

Warthin’s tumor as noted on a contrast CT study reveals a multiseptated predominantly cystic mass within the tail of the parotid gland on the right side. It is intrinsic to the gland and well below the main trunk of the facial nerve and its major branches. Courtesy: Dr Madhu Nair

forms papillary projections into cystic spaces. The epithelium is supported by a lymphoid stroma which may demonstrate germinal centers. Treatment and prognosis The preferred treatment for Warthin’s tumor is surgical removal. Malignant Warthin’s tumors, carcinoma ex papillary cystadenoma lymphomatosum, have been reported, but are extremely rare.

Oncocytoma (Oxyphilic Adenoma) Clinical features The oncocytoma is a rare salivary gland tumor which usually occurs in the parotid gland (84%), but has been reported in the submandibular gland and minor salivary glands. Clinically, it cannot be distinguished from other benign salivary gland tumors. The name ‘oncocytoma’ is from the resemblance of the tumor cells to normal oncocytes, which are found in salivary glands, respiratory tract, breast, thyroid, pancreas, parathyroid, pituitary, liver and stomach. The oncocytoma occurs in elderly persons and is somewhat more common in women than in men. The tumor usually measures from 3 to 5 cm in diameter and appears as a discrete encapsulated mass. It is usually asymptomatic. Histopathology Histologically, the oncocytoma is a tumor of ductal cells that are enriched with mitochondria, giving the cell a swollen eosinophilic appearance.

Treatment and prognosis The treatment of choice is surgical excision. It does not have a high recurrence rate. Malignant transformation is uncommon.

MALIGNANT TUMORS Adenocarcinomas of salivary gland origin are quite varied in their histologic features and clinical behavior. These are diagnosed based on their microscopic features. The parotid is the most common site, followed by minor salivary glands. In the parotid, the lesions are usually firm to palpation and may produce damage to the facial nerve. The presence of enlarged lymph nodes raises the suspicion of malignancy, but also occurs in inflammatory conditions. The presence of nodal metastasis is a poor prognostic indicator. Intraorally, minor salivary glands of the hard palate are the most common location for adenocarcinomas followed by buccal mucosa, lips and base of tongue.

Mucoepidermoid Carcinoma Clinical features Mucoepidermoid carcinoma is one of the most common malignant salivary gland tumors. It was first described by in 1945 by Stewart, Foote and Becker. It occurs in individuals from the second to the seventh decade. While it is rarely seen in the first decade of life, it is the most common malignant salivary gland tumor in children. Some 295


tumors have been associated with a previous history of radiation therapy to the head and neck region. There are three grades: low, medium and high. Low-grade tumors have a limited potential to metastasize to regional lymph nodes. High-grade tumors tend to be solid rather than cystic and behave aggressively like a squamous cell carcinoma. Mucoepidermoid carcinoma most commonly presents in the parotid gland where it may initially appear as a painless swelling. Intraorally, tumors are found in the palate (Figure 32), buccal mucosa, retromolar area, and base of tongue. These may present as slowly enlarging, painless masses. The low-grade lesions contain cysts which may be filled with mucoid material. These intraoral lesions may resemble a mucocele, especially when located in the retromolar area. More high-grade tumors grow rapidly and produce pain early in the process. Facial nerve paralysis is a common feature in high-grade tumors. As these tumors tend to infiltrate surrounding tissue, they may metastasize to regional lymph nodes.

Figure 32

Mucoepidermoid carcinoma in the hard palate. Well circumscribed raised lesion of 4 months duration on the hard palate with large central umbilicated ulceration with rolled borders. Courtesy: Dr Indraneel Bhattacharyya

Histopathology Mucoepidermoid carcinoma is composed of cells from stratified squamous lines, mucous cell lines, and a third celltype, the intermediate cell. The mucous cells have abundant foamy cytoplasm that stains positively with mucicarmine stain. The epidermoid cells frequently demonstrate features of squamous epithelium, intercellular bridges, but rarely show keratinization. The intermediate cell is basaloid in appearance and may be the origin of the other mucous and epidermoid cells. A lymphocytic infiltrate is commonly seen. Low-grade tumors show all cell types. Prominent cyst formation, a high proportion of mucous cells, and minimal atypia are characteristic features. High-grade tumors consist of solid islands of squamous and intermediate cells, which can show pleomorphism and mitotic activity. Few mucus producing cells are present, which allow the lesion to be confused with a squamous cell carcinoma. The intermediate-grade tumor shows features that rank in between the low- and high-grade tumors (Figure 33). Treatment Treatment may vary according to the tumor location, grade, and staging. Surgical removal of the lobe or gland may be adequate. High-grade or large tumors merit wider resection, similar to that employed for squamous cell carcinoma. For patients with evidence of metastatic disease or large highgrade tumors, radical neck dissection may be indicated. Postoperative radiation therapy may be employed as well. Prognosis Patients with low-grade tumors and complete excision have a good prognosis. Patients with high-grade tumors have a poorer prognosis. In a large series reported by Goode et al, most patients (75%) were tumor free after the 296

initial treatment. Twenty-one patients (9%) had local recurrence only, 12 (5%) demonstrated metastasis and survived, and (11%) died of their disease. Clinical features associated with metastasis or deaths were more advanced age, tumor size, and preoperative symptoms. In a recent series of mucoepidermoid carcinomas of the minor salivary glands as reported by Triantafillidou et al, immunohistochemical assay of Ki-67 antigen expression correlated with tumor grade. Prognosis in this series of 15 tumors was a function of the histological grade, adequacy of excision and clinical staging.

Intraosseous Mucoepidermoid Carcinoma Clinical features Intraosseous mucoepidermoid carcinoma most frequently appears in the posterior jaws, mandible more frequently than the maxilla. It has been reported in all ages, from 1 to 85 years. Most cases occur in the 4th and 5th decades. Diagnosis The radiographic picture of central mucoepidermoid carcinoma may resemble an ameloblastoma or odontogenic cyst. Based on radiographic imaging, Inagaki classified these lesions into three categories: cystic, rarefying, and infiltrative. He reported that those with the infiltrative type were histologically poorly differentiated tumors, and these patients died of their tumors. Radiographic findings correlated with histologic findings and prognosis in this limited series. Other salivary lesions that have appeared centrally in the jaws include pleomorphic adenoma, adenoid cystic carcinoma and malignant mixed tumor.


Figure 33

Acinic Cell Adenocarcinoma Clinical features Acinic cell adenocarcinoma is a malignant salivary gland tumor characterized by histologic appearance showing serous acinar differentiation. The majority of acinic cell carcinomas are found in the parotid gland, and only rarely in the intraoral minor glands. The age range is broad with a peak incidence in the third decade of life. Similar to many salivary gland tumors, it may be a slow-growing mass. In a large series as reported by Ellis and Corio, tumors were usually less than 3 cm in diameter and were slow growing. Pain was a common symptom, but not indicative of prognosis. Histopathology

Mucoepidermoid carcinoma, histopathology: Microscopic image of mucoepidermoid carcinoma stained with hematoxylin and eosin (magnification 20⫻). Large aggregates of intermediate cells interspersed with cells with clear cytoplasm and mucous cells. The cellular aggregates are arranged in clusters separated by thin fibrous connective tissue septa. The peripheral cells appear more epidermoid with reduced cytoplasm and hyperchromatic nuclei. Courtesy: Dr Indraneel Bhattacharyya

Variation in presentation on CT is noted depending on the degree of differentiation of the tumor mass. Welldifferentiated lesions have well-defined margins and may mimic a benign tumor with or without cystic changes. More aggressive types have ill-defined margins and show signs of local tissue destruction. Contrast enhanced CT shows an inhomogeneous enhancement with well-defined margins. Poorly differentiated lesions show enhancing mass with irregular margins and lymphadenopathy. MRI shows inhomogeneous low to intermediate signal intensities on T1 and T2 weighted images. Nuclear medicine studies do not reveal any tracer uptake. MRI is the recommended imaging modality as perineural spread and deeper involvement are better delineated. Perineural spread is sometimes noted along cranial nerve VII. Histopathology Most centrally occurring mucoepidermoid carcinomas show the same variability and grades as found in salivary gland tumors. Most are low-grade lesions, although high-grade lesions have been reported as well. Treatment and prognosis The treatment for intraosseous mucoepidermoid carcinoma is surgery, sometimes with adjuvant radiation therapy. Radical surgical resection provides a better long-term prognosis than conservative measures such as curettage. Metastasis has been reported in a small number of cases.

The acinic cell adenocarcinoma may be composed of cells that exhibit varying degrees of differentiation, but resemble serous acinar cells. Four growth patterns have been described: solid, papillary cystic, follicular and micro-cystic. The micro-cystic variety was most commonly seen in a large series as described by Ellis and Corio. Treatment and prognosis Treatment usually consists of parotid gland lobectomy or parotidectomy. Submandibular tumors are treated by removal of the gland. In a recent series as reported by Hoffman and coworkers, worse survival was associated with high-grade lesions, age more than or equal to 30 years and the presence of metastatic disease. Although a better outcome was not statistically demonstrated for combined therapy, surgery with irradiation is the most common management in the United States for cases with regional metastases, high-grade, and microscopic positive margins.

Malignant Mixed Tumor (Carcinoma Ex Pleomorphic Adenoma) Description and clinical features Malignant mixed tumors are the malignant counterpart to the pleomorphic adenoma, or benign mixed tumor. In many cases, there are no obvious differences in clinical presentation of benign versus malignant pleomorphic adenomas. The carcinoma ex pleomorphic adenoma is characterized by malignant transformation of the epithelial component of a previously existing benign pleomorphic adenoma. Most of these are seen within the parotid gland, followed by the submandibular gland. These also occur in the minor salivary glands and sublingual gland. This lesion affects an older age group than the benign counterpart, usually occurring around 50–70 years of age. The common clinical presentation is rapid expansion of a long-standing asymptomatic mass, new onset of pain, paresthesia, and/ or fixation to the skin. Although pain or recent rapid 297


growth is common, cases may present as a painless mass, similar to a benign lesion. The risk for malignant transformation increases with the duration of the tumor. Histopathology The histolopathologic features will vary widely. In some lesions, the benign areas will be difficult to locate due to an abundance of malignant areas. In other tumors, the bulk is benign with small areas demonstrating the malignant features. Areas of the benign pleomorphic adenoma may be present with areas of malignant changes to the epithelial component. The changes include hypercellularity, increased abnormal mitotic activity, areas of hyalinization and necrosis. The malignant component will demonstrate extracapsular invasion. Sites of poorly differentiated carcinoma may be found as well. Treatment and prognosis Carcinoma ex pleomorphic adenoma is treated by wide excision, often with local lymph node dissection, and adjuvant radiation therapy. A recent study reported by Chen and coworkers showed significant improvement in a 5-year local control from 49 to 75% through the use of postoperative radiotherapy. It was also associated with improvement in survival among patients without evidence of cervical lymph node metastasis.

Metastasizing Mixed Tumor Clinical features The metastasizing mixed tumor is also quite rare. Most patients have a history of a pleomorphic adenoma which was excised many years earlier. The majority of cases originate in the parotid gland, but the primary tumor may occur in the submandibular gland or minor glands. Metastases are most frequently in the bones, lung or regional lymph nodes. Histopathology Both lesions, the initial benign mixed tumor and the tumor at the metastatic site show histopathologic features of the benign mixed tumor. Microscopic malignant changes are not observed.

neck (43%), and lung (36%). The 5-year disease-free survival was 50%. Chemotherapy and radiotherapy were of limited value.

Adenoid Cystic Carcinoma Clinical features Adenoid cystic carcinoma is a common, well-defined malignant salivary gland tumor that may occur in any salivary gland. In one series as reported by Jones et al, nearly half of the tumors arising in the oral cavity occurred in the hard palate, and the remainder occurred in other minor glands, the submandibular and parotid glands. Adenoid cystic carcinoma occurs in the 5th, 6th and 7th decades of life; rarely before the age of 20. Most series show an equal gender distribution. In the major glands, it commonly presents as a slow-growing swelling or mass. The patient may be aware of the lesion for months or years. Pain intensity may grow as the lesion progresses. Fixation to deeper structures occurs in later stages. As with other malignant salivary gland tumors, involvement of the facial nerve is a serious finding. Adenoid cystic carcinoma of the intraoral minor glands presents as a swelling or mass, usually in the palate. Eventually, pain and ulceration develop. Jones et al described one study that reported a better survival rate if tumors were in the hard palate versus other sites in the head and neck. The specific survival rate was 40% at the age of 20 years. Adenoid cystic carcinoma may also appear in the tongue, and centrally in bone. Histopathology Several histologic types are recognized. The classic pattern, the cribriform type, is recognized by the arrangement of tumor cells in the ‘Swiss cheese’ pattern. Tumor cells have deeply basophilic nuclei with scant cytoplasm (Figure 34). Other patterns include the tubular type and solid type. In the tubular pattern, tumor cells form multiple small ducts or tubules within a hyaline stroma. The solid variant is composed of sheets of tumor cells, with cellular pleomorphism and mitotic activity, and focal necrosis. It is associated with a poorer prognosis than the cribriform type. Perineural invasion is a highly characteristic feature of adenoid cystic carcinoma, but perineural invasion is seen in other salivary malignancies, particularly the polymorphous low-grade adenocarcinoma.

Treatment and prognosis Treatment consists of surgical excision of the primary tumor and the metastatic sites. In a recent report of a review of 44 cases as reported by Nouraei, most patients had local recurrences before metastasis. The mean presentation-tometastasis latency was 16 years. Bone was the most common site for metastases (45%), followed by the head and

298

Diagnostic imaging Parotid lesions appear with well-defined margins while minor gland masses have ill-defined margins. Retrograde spread along facial or mandibular nerve is not uncommon. Contrast MRI is the optimal imaging modality to visualize such extension. Varying degrees of nerve involvement


Figure 34

Polymorphous Low-Grade Adenocarcinoma Clinical features Polymorphous low-grade adenocarcinoma (PLGA) was first described in 1983 and termed ‘lobular carcinoma’ due to its resemblance to lobular carcinoma of the breast. It is a low-grade salivary gland tumor that occurs primarily in the minor salivary glands. Common presentation is a palatal mass that may range in size from 0.4 mm to 6 cm. The average age of occurrence in a large series as reported by Castle et al was 58 years with a range from 23 to 94 years. The tumors were infiltrative and characterized by a polymorphous growth pattern. Histopathology

Adenoid cystic carcinoma, histopathology: Microscopic image of adenoid cystic carcinoma stained with hematoxylin and eosin (magnification 20⫻). Invasive islands of neoplastic epithelial cells forming duct-like structures containing a pale mucoid material imparting the classic ‘Swiss cheese’ appearance. The tumor cells are basaloid in appearance with hyperchromatic basophilic nuclei and scanty eosinophilic cytoplasm. Courtesy: Dr Indraneel Bhattacharyya

can be imaged using MRI. CT also detects some changes related to nerve involvement. Widening of the nerve canal and obliteration of fat at the cranial foramina is evident on contrast CT but early subtle changes are not discernible. Treatment and prognosis Surgical excision is the treatment of choice with radiotherapy as it metastasizes to the lymph nodes. Metastatic spread most commonly involves the lungs and bones. In addition, metastatic spread to the kidney and liver has been reported. Regardless of the treatment modality, the overall prognosis is poor.

The neoplastic cells are isomorphic with vesicular nuclei. Individual tumors may demonstrate multiple patterns, including solid, ductotubular, cribriform, trabecular, and single file growth. The histologic features may resemble adenoid cystic carcinoma. Neurotropism is frequently identified. Mitotic activity is not prominent. Treatment Wide local excision is the treatment of choice. Local recurrences may occur despite having negative margins after surgery. Local recurrence may appear 15 years after initial surgery. Regional nodal metastasis and lung metastasis have been reported by Pogodzinski et al, 20 years after the procedure. These occurrences support the need for prolonged follow-up. Recently, PLGA was reported by RuizGodoy et al in the parotid gland in a 60-year-old male. Treatment included a superficial parotidectomy and postoperative radiotherapy (46 Gy). Transformation from PLGA in the palate to a high-grade carcinoma has been reported as well. Prognosis Conservative, but complete surgical excision is the treatment of choice for these tumors, with a reported 97% survival rate. While these have a tendency to recur, the metastatic potential is low.

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SECTION

V

Cysts and Tumors of Orofacial Region

12 Cysts of Orofacial Region 13 Tumors of Orofacial Region 14 Oral Cancer

303 331 380

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CHAPTER

Cysts of Orofacial Region Ravikiran Ongole, Sunanda C, NVS Sekhar Reddy, Joanna Baptist, Thomas Zachariah

➧ Classification of Cysts of Orofacial Region ➧

Theories of Cyst Expansion

➧

Odontogenic Cysts Gingival Cyst of Infants Eruption Cyst Dentigerous Cyst

➧

➧

➧

Lateral Periodontal Cyst Botryoid Odontogenic Cyst

Pseudocysts Traumatic Bone Cyst Aneurysmal Bone Cyst Stafne’s Bone Cyst

Odontogenic Keratocyst Gingival Cysts of Adults

Inflammatory Cysts Periapical Cyst Residual Cyst Paradental Cyst Mandibular Infected Buccal Cyst

Orthokeratinized Odontogenic Cyst ➧

12

➧

Cysts of Soft Tissues of Mouth, Face and Neck Anterior Median Lingual Cyst

➧

Calcifying Epithelial Odontogenic Cyst

➧

➧

Glandular Odontogenic Cyst

➧

Thyroglossal Duct Cyst

➧

Non-odontogenic Cysts

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Lymphoepithelial Cyst

Nasopalatine Duct Cyst

➧

Cystic Hygroma

➧

Nasolabial Cyst

➧

Dermoid, Epidermoid and Teratoid Cysts

➧

Mid-palatal Raphe Cyst of Infants

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Parasitic Cysts

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Cysts of Maxillary Antrum and Salivary Glands

The word ‘cyst’ is derived from Greek word kystitis meaning bladder. Kramer (1974) defined cyst as a pathological cavity having fluid, semifluid or gaseous contents and which is not created by the accumulation of pus. It is frequently, but not always, lined by the epithelium. Cysts may arise due to trauma, inflammation and degeneration or retention. They are called true cysts if lined by epithelium and, pseudocysts (false) if not lined by epithelium. During the initial stages, when the cysts are small they are usually asymptomatic. Secondary infection may result in the formation of abscess, cellulitis, osteomyelitis and subsequent sinus formation. As the cyst enlarges it may cause

Nasopharyngeal Cyst

Cysticercosis Hydatid Cyst Trichinosis

displacement of roots of teeth, resorption of roots, paresthesia, expansion of the cortical plates and eventually result in pathologic fracture of the jaw.

CLASSIFICATION OF CYSTS OF OROFACIAL REGION 1. 2. 3.

True cysts of the oral cavity (odontogenic and nonodontogenic) Pseudocysts of the oral cavity Cysts of the associated structures of the orofacial region.

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Section V – Cysts and Tumors of Orofacial Region

True Cysts of Oral Cavity (Lined by Epithelium)

Figure 1

❍

Developmental cysts – Odontogenic cysts – Gingival cyst of infants – Eruption cyst – Dentigerous cyst – Odontogenic keratocyst* – Orthokeratinized odontogenic cyst – Gingival cyst of adults – Lateral periodontal cyst and botryoid odontogenic cyst – Calcifying odontogenic cyst – Glandular odontogenic cyst ❍ Non-odontogenic cysts – Nasopalatine duct cyst – Nasolabial cyst – Mid-palatal raphe cyst of infants ❍ Inflammatory cysts – Radicular cyst – Residual cyst – Paradental cyst – Buccal bifurcation cyst

Pseudocysts of Oral Cavity (Not Lined by Epithelium) ❍ ❍ ❍

Aneurysmal bone cyst Stafne’s bone cyst Traumatic bone cyst

Cysts of Associated Structures of Orofacial Region ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍

Cysts of the salivary glands Cyst associated with the maxillary antrum Anterior median lingual cyst Nasopharyngeal cyst Thyroglossal duct cyst Branchial cleft cyst Cystic hygroma Parasitic cysts

*Odontogenic keratocyst (OKC) has been redesignated as keratocystic odontogenic tumor by the World Health Organization (WHO). OKC should not be included in the classification of cysts anymore.

THEORIES OF CYST EXPANSION Malcolm Harris (1975) summarized various theories that explain cyst expansion. Mural growth theory, hydrostatic enlargement, and role of bone resorbing factors are the theories that have been proposed by various authors to explain enlargement of cysts. 304

Enlargement of the cyst at the peripheries due to active division of the cells of the epithelium lining the cyst

Mural Growth Theory The mural growth theory is explained by two propositions. 1. Peripheral cell division: It is proposed that the cyst enlarges at the peripheries because of active division of the cells of the epithelium lining the cyst (Figure 1). It is believed that the division of these cells is a response to any irritating stimulus. The theory further suggests that once the stimulus is withdrawn the cyst regresses in size. This theory has not found many supporters as cyst regression will result in irregular inner surface of the cyst as the bone surrounding the cyst offers resistance. One should remember that the contents of the cyst will support the cystic lining and it can cause rapid resorption of surrounding bone to accommodate the enlarging cyst. 2. Accumulation of cellular contents: This theory was proposed by Kramer (1974) to explain the enlargement of OKCs. He proposed that as mural squames are shed off the lining epithelium they accumulate, thereby increasing the cyst volume. The sites of expansion and growth are represented by finger-like projections which are zones of active cell division or proliferation (Figure 2). It is also believed that these finger-like extensions are formed because keratocysts have very poor bone resorbing properties. Hence, they proliferate along the cancellous bone which is less dense than the cortical bone. This explains the fact why keratocysts very rarely cause expansion or resorption of the cortical plates. Kubota et al (2000) studied the role of interleukin-1 alpha (IL-␣) and matrix metalloproteinase-9 (MMP-9) in the expansion of odontogenic cysts. They found that an active form of MMP-9 was present in OKC fluids more frequently than dentigerous cyst and radicular cyst fluids. However, proMMP-9 was present in all cyst fluids.

Chapter 12 – Cysts of Orofacial Region

Figure 2

enters and accumulates within the cyst thereby aiding its enlargement.

Role of Bone Resorbing Factors Harris et al (1973) proposed that cyst tissue (capsule) contains a combination of prostaglandins E2 and E3, which are considered very potent bone resorbing factors. It is believed that the leukocytic and bone resorbing factors aid in bone resorption. It is believed that the keratocyst secretes comparatively lesser amount of bone resorbing factors per unit surface area compared to other cysts (periodontal cyst, radicular cyst). This explains the burrowing nature or intramedullary growth of the keratocyst.

ODONTOGENIC CYSTS Finger-like projections which are zones of active cell division or proliferation

Kubota et al (2002) in their study showed that interleukin (IL)-1␣ stimulates enzymatic degradation of the extracellular matrices of the bone around the cysts. This induces expansion of OKC. Oka et al (2005) studied the effects of positive intracystic fluid pressure in OKCs. They proposed that the positive intracystic pressure may play a crucial role in OKC growth via stimulating the expression of IL-1 in epithelial cells.

Hydrostatic Enlargement of Cysts It has been proposed that accumulation of fluids within the cystic cavity will cause expansion of the cyst wall. The fluid accumulation can occur from secretion by the goblet cells that line the follicular cysts or by transudation or exudation from capsular capillaries in periodontal cysts as proposed by Main (1970) and hemorrhage in follicular and periodontal cysts as proposed by Harris and Pannell (1973). James (1926) and Tratman (1939) proposed the osmotic theory or dialysis to explain hydrostatic enlargement of cysts. The cyst wall and the capillaries in the cystic capsule are made up of high molecular weight proteins like fibrin and ␣2-globulins which aid in increasing the permeability of the capsular capillaries and the cyst walls. It was found that the mean osmolality of cystic fluid is 10 milliosmoles higher than that of serum. This gradient helps in the accumulation of all the shed degenerated cells from the lining of the cyst. As the cyst has inadequate lymphatic drainage, the fluid from the capsular capillaries

The odontogenic cysts are derived from epithelium associated with the development of dental apparatus. It is estimated that odontogenic cysts make up approximately 90% of the jaw cysts. These cysts are generally lined by stratified squamous epithelium. However, some developmental or fissural cysts in the maxilla will have respiratory epithelium as the lining.

Gingival Cyst of Infants Gingival cyst of infants or newborns is an odontogenic cyst which is developmental in nature. Like the name suggests these cysts are seen in infants. These cysts are seldom seen after 3 months of age. They arise from the epithelial remnants of dental lamina called cell rests of Serres. Clinically, the cyst is seen on the crest of the maxillary and mandibular dental ridges and appears creamish white. These cysts are usually minute in size and rarely exceed 3 mm in diameter and commonly occur on the maxillary alveolar ridge. Histopathological evaluation reveals a keratin filled cyst lined by parakeratinized epithelium. Gingival cysts in infants need no treatment as they tend to undergo involution and disappear. Most cysts tend to rupture spontaneously.

Eruption Cyst The eruption cyst is a type of soft tissue cyst associated with erupting teeth. It surrounds the crown of a tooth that has already erupted through bone but impeded by the overlying soft tissue. Kuczek et al (2003) reported a case where a boy developed an eruption cyst who was administered cyclosporin A (potent immunomodulatory agent) subsequent to a cardiac transplantation. Cyclosporin A was replaced with tacrolimus and there was no new cyst formation. 305


The authors proposed that the formation of an eruption cyst may be an adverse effect of cyclosporin A in children with erupting teeth.

Figure 3

Clinical features Eruption cysts are usually seen in childhood. These cysts are commonly seen in the age groups of 5 and 9 years. However, Woldenberg (2004) published a case report of an eruption cyst in the maxilla of a 40-year-old female. Studies by Anderson (1990), Woldenberg (2004) and Aguiló (1998) show that these cysts are more prevalent in the maxillary arch. In a study of 24 cases of eruption cysts by Bodner et al (2004), it was found that eruption cysts were associated with natal teeth in two cases, with primary teeth in 10 cases and with permanent teeth in 12 cases. It was seen that males more commonly presented with eruption cysts than females (2:1). The primary mandibular central incisors and the permanent first molars were the most common site involved. Though most of the eruption cysts are reported as solitary entities, literature review reveals report of a patient presenting with multiple eruption cysts. Ramón Boj and García-Godoy (2000) described a case of a 15-month-old child who had six eruption cysts simultaneously. On clinical examination, the cyst is visible as a soft fluctuant mass on the alveolar ridges and may vary in size from about 1 to 1.5 cm in diameter. It may have the same coloration of healthy oral mucosa or appear bluish or bluish black. Eruption cyst histologically mimics dentigerous cyst.

Orthopantomograph (OPG) showing dentigerous cyst (multilocular) associated with impacted right lower third molar and a supernumerary tooth displaced superiorly approximating the sigmoid notch. Courtesy: Dr NVS Sekhar Reddy

Figure 4

Management Usually the cysts open up spontaneously. In some children the overlying soft tissue can be incised to facilitate the tooth to erupt. Literature reveals that marsupialization is sufficient to manage eruption cysts.

Dentigerous Cyst (Follicular Cyst) It is an odontogenic cyst formed by the accumulation of fluid between reduced enamel epithelium and enamel surface. It surrounds the crown of an impacted tooth and is attached to its neck. The crown of the involved tooth projects into the cyst lumen. It is estimated that 10% of impacted teeth are associated with dentigerous cysts. Dentigerous cysts may also be seen associated with supernumerary teeth and odontomas.

Orthopantomograph (OPG) showing dentigerous cyst (unilocular) associated with the right upper third molar. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

relatively more predisposed. It grows aggressively and produces facial asymmetry, bony expansion, displacement and resorption of teeth. Entire ramus might be hollowed if associated with mandibular third molar (Figure 6A, B). In case of maxillary canine, anterior maxilla is expanded. There will be no pain unless secondarily infected. On aspiration, yellow-colored fluid is obtained.

Clinical features It occurs frequently in association with impacted mandibular (Figure 3), maxillary third molars (Figure 4), and maxillary canines (Figure 5). Dentigerous cyst is commonly seen in the 2nd and 3rd decades of life. Males are 306

Radiographic features Radiographically, dentigerous cysts exhibit three different presentations, namely, the central, lateral and circumferential types. In central variety, the cyst symmetrically envelops


Figure 5

Figure 6 A

Orthopantomograph (OPG) showing a dentigerous cyst associated with the right upper canine. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

B

crown. The cyst occurs on lateral aspect of the crown in lateral variety and envelops crown entirely in circumferential variety (Figure 7). Dentigerous cyst may appear as welldefined unilocular or multilocular radiolucency (Figure 8A, B). Occasionally these cysts may cause displacement and resorption of the adjacent teeth (Figure 9). Large cysts often cause expansion of the cortical plates. Histologic features It has no characteristic microscopic features. It has cyst lining and connective tissue wall. The connective tissue wall consists of very loose fibrous connective tissue and sparse collagenized myxomatous tissues. It has presence of odontogenic epithelium (Figure 10). The inflammation leads to presence of Rushton bodies of hematogeneous origin in the lining epithelium. Cholesterol clefts might be present. Potential complications The odontogenic cyst has following complications: the development of mural ameloblastoma (Figure 11), squamous cell carcinoma and mucoepidermoid carcinoma. Syndrome association Multiple cysts can be formed in association with Gorlin– Goltz syndrome, cleidocranial dysplasia and Maroteaux– Lamy syndrome.

3D-reconstructed images showing hollowing of the mandible on the right side associated with the dentigerous cyst. Courtesy: Dr NVS Sekhar Reddy

ODONTOGENIC KERATOCYST Odontogenic keratocyst (OKC) was first described by Philipsen in 1956. WHO has recently designated OKC as keratocystic odontogenic tumor (KCOT) and is defined as ‘a benign uni- or multicystic, intraosseous tumor of odontogenic origin, with a characteristic lining of parakeratinized stratified squamous epithelium and potential for aggressive, infiltrative behavior’. Keratocystic odontogenic tumor is described in Chapter 13 on Tumors of Orofacial Region.

Management Surgical removal of cyst and tooth is recommended (Figure 12). Marsupialization is done in case of very large cysts. The cyst recurs if incompletely removed.

Orthokeratinized Odontogenic Cyst Philipsen in 1956, in his study of jaw cysts, described a distinct form of OKC which showed an orthokeratinized 307


pattern. Wright et al (1981) reported 60 cases of orthokeratinized odontogenic cyst (OOC) and compared with OKC and found that the OOC appears to be a distinct clinicopathologic entity. It was suggested that this cyst be called OKC, orthokeratinized variant. Iamaroon et al (2004) compared the proliferation index of the epithelial cells between OKC, OOC, dentigerous cyst and ameloblastoma. He concluded that OKC should be considered a benign tumor rather than simply an odontogenic cyst and OOC as a non-aggressive cystic lesion.

Clinical features Orthokeratinized odontogenic cyst usually presents as a solitary cyst in the posterior part of the mandible. It is usually seen in males commonly in the 2nd to 5th decade of life. In comparison to OKC it is less aggressive and has a very low recurrence rate (2.2%). Literature review reveals that almost two-thirds of the cases of OOC appear like dentigerous cyst on clinical and radiographic examination. Histopathologic features Orthokeratinized odontogenic cyst has a thin epithelial lining with a luminal surface of orthokeratin. The basal cell layer contains flattened squamous or cuboidal cells and a well-developed granular cell layer (Figure 13).

Figure 7 A

B


Central

Lateral

C

Orthokeratinized odontogenic cyst presents either as a welldefined unilocular or multilocular radiolucency. Radiographically, OOC may resemble a dentigerous cyst when it is unilocular and resembles ameloblastoma when it is multilocular. Occasionally, it may cause cortical plate expansion and thinning of the lower border of the mandible. Roots of teeth may be displaced (Figure 14). However, resorption of roots is seldom seen. The cyst should be surgically excised (Figure 15).

GINGIVAL CYSTS OF ADULTS Circumferential

Schematic diagrams showing various types of dentigerous cysts

Gingival cysts of adults are rare odontogenic cysts of developmental origin. The epithelial lining of these cysts

Figure 8 A

B

CT images showing unilocular dentigerous cyst

308


Figure 9

Orthopantomograph (OPG) showing a dentigerous cyst associated with the impacted left lower third molar causing root resorption of the adjacent second molar. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 10

Figure 11

2–3 layered epithelium Connective tissue capsule Cystic lumen

Photomicrograph of dentigerous cyst. Courtesy: Department of Oral Pathology, MCODS, Mangalore

are thin non-keratinized and are thought to arise from the rests of dental lamina. Some authors suggest that these cysts arise from the traumatic implantation of surface epithelium. Schroeder (1976), in a book titled Scientific Foundations of Dentistry suggested that the gingival cyst arises from the junction epithelium which is a derivative of the reduced enamel epithelium. These occur as swellings on the facial aspect of the attached or interdental gingiva, most commonly between 5th and 6th decade of life and usually do not exceed 1 cm in size. The common sites of involvement are the mandibular canine and premolar region. Occasionally, these may be seen in the lateral incisor, canine, premolar regions of the

Orthopantomograph (OPG) showing multilocular radiolucency associated with the impacted mandibular third molar. The radiograph showing displacement of the third molar and the lesion extends to involve the entire ramus and apices of the second molar. The lesion was histopathologically diagnosed as mural ameloblastoma. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

maxilla. The swelling is soft and fluctuant with a smooth surface and usually have the same coloration as that of the gingiva. Some authors have reported bluish and red color swellings. The teeth in relation to these cysts are vital. Radiographic findings The cyst reveals no radiographic findings. However, in large cysts superficial erosion of bone represented by a faint shadow of radiolucency may be appreciated. 309


Figure 14

Figure 12

Surgical specimen of dentigerous cyst. Courtesy: Dr NVS Sekhar Reddy

Figure 13

Photomicrograph of orthokeratinized odontogenic cyst. Courtesy: Department of Oral pathology, MCODS, Mangalore

Hegde (2004) reported a rare finding (supposedly the first case in literature) calcifications within cystic lumen of the gingival cyst. Histologic findings Histologically, these cysts have a variety of presentations. The epithelium generally has three forms of presentation: (i) extremely thin epithelium, (ii) thicker stratified squamous epithelium and (iii) localized epithelial thickenings

310

Orthopantomograph (OPG) showing a multilocular radiolucency in relation to the lower premolars, first and second molars causing displacement of the second molar in orthokeratinized odontogenic cyst. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 15

Gross specimen of orthokeratinized odontogenic cyst showing keratin. Courtesy: Department of Oral Pathology, MCODS, Mangalore

or plaque formation (similar to those evident in lateral periodontal cyst). The thinner form of epithelium mimics the reduced enamel epithelium. It is generally composed of one to three layers of flat or cuboidal cells. The thicker variety may not show any rete pegs. The nuclei are pyknotic and show perinuclear cytoplasmic vacuolation. The localized thickening of epithelium or plaque may occasionally project into the cystic cavity. The cells in the localized thickenings have a whorled morphology. Rarely, these cells are swollen and clear and are referred to as water-clear cells.


Management

Management

The cyst is removed surgically. Recurrences have not been reported.

Lateral periodontal cysts can be effectively managed with enucleation. A sound tooth can be retained. Recurrences though uncommon, have been reported in literature.

Lateral Periodontal Cyst

Botryoid Odontogenic Cyst

Lateral periodontal cyst is a non-keratinized developmental cyst occurring in the alveolar bone along the lateral aspect of a vital tooth. It is a relatively uncommon cyst that is slow growing, non-expansile developmental odontogenic cyst derived from one or more rests of dental lamina, containing an embryonic lining of 1–3 squamous/cuboidal cell thickness and distinctive focal thickenings (plaques). These appear to have no gender predilection. According to Altini and Shear (1992), lateral periodontal cysts represent about 0.8% of all central cysts (intraosseous) of maxillary bones. These cysts are usually seen in adults between the 2nd and 8th decade of life. These are usually seen by chance in routine radiographs. These are intraosseous forming beside vital tooth. These might even form near the crest of ridge. These cause no symptoms unless they erode through the bone to extend into the gingiva. Some patients may present with a swelling on the buccal aspect of the gingiva. The most common site of involvement is the mandibular premolar area followed by the anterior part of the maxilla. Many authors suggest the fact that the lateral periodontal cyst is more or less a histopathological diagnosis rather than a clinico-radiographic diagnosis.

Botryoid odontogenic cyst (BOC) is considered as a variant of the lateral periodontal cyst. Weathers and Waldron in 1973 first used this term to describe a multilocular cystic lesion of the jaw that on gross morphology resembled a bunch of grapes. The exact nature of this cyst is still not understood. Some authors consider the BOC as a multilocular variant of lateral periodontal cyst. Others consider BOC and lateral periodontal cyst as two distinct unrelated entities. They consider BOC as a multicystic odontogenic lesion with the histologic characteristics of lateral periodontal cysts. Unlike the lateral periodontal cyst that usually has a unilocular appearance, the botryoid odontogenic cyst is typically polycystic (multilocular), but occasional unilocular cases have been reported. However, histopathologically the BOC resembles lateral periodontal cyst. Another striking difference between BOC and lateral periodontal cyst is its rate of recurrence. It is estimated that the recurrence rate of BOC is between 15 and 33%, which is much higher than lateral periodontal cyst. High et al (1996) proposed the term ‘polymorphic odontogenic cyst’. This term included GOC, mucoepidermoid intraosseous carcinoma and botryoid odontogenic cyst. Greer Jr and Johnson (1998) studied the clinicopathologic features of 10 botryoid odontogenic cysts. In their study the radiographic size of the cysts varied between 5 and 45 mm radiographically. It is believed that the size and multilocular pattern could be the main factors responsible to the high recurrence rates of botryoid odontogenic cyst. The high recurrence rates warrant the need for a more aggressive treatment. Some authors suggest the systematic use of Carnoy solution along with enucleation and curettage.

Histologic features The cyst is lined by a thin non-proliferating cuboidal to stratified squamous non-keratinizing epithelium, ranging from 1 to 5 cell layers, and thus resembling the reduced enamel epithelium. The cyst wall and the lining usually show no signs of inflammation. The lateral periodontal cyst presents two important histologic features, namely, the presence of epithelial thickenings or ‘plaques’ and the presence of glycogenrich clear cells either in ‘plaques’ or in the superficial layers of the lining epithelium. Radiographic findings The cyst may appear as a round, oval or teardrop-like wellcircumscribed interradicular radiolucent area, usually with a sclerotic margin, lying usually between the apex and the cervical margin of the teeth. Resorption of adjacent teeth though uncommon, has been reported. Occasionally, loss of lamina dura and widening of the periodontal ligament space may be present.

CALCIFYING EPITHELIAL ODONTOGENIC CYST (Gorlin Cyst) It was thoroughly described by Gorlin and coworkers in 1962 and in 1963. Gold introduced the terms ‘keratinizing’ and ‘calcifying odontogenic cyst’. It reportedly accounts for about 2% of all odontogenic pathologies affecting the maxilla and mandible. It may be found along with other odontogenic tumors. However, in 24% of the cases it is associated with odontomas.

311


The calcifying odontogenic cyst can either occur as an intraosseous (central) or extraosseous (peripheral) lesion. The peripheral form is very rare. The incisor and canine regions are the most common sites of involvement. The maxilla is more commonly affected. It can occur at any age. However, most cases are seen in the 2nd decade of life.

Figure 16

Types In 1981, Praetorius and coworkers attempted to classify calcifying odontogenic cyst by categorizing it into two entities: cyst and neoplasm. Cystic entity It was classified as: ❍

Type 1: A simple monocystic type of typical Gorlin’s cyst, with or without dentinoid calcified tissue. ❍ Type 2: Monocystic odontoma creative type, with all the characteristics of the previous type, except that the hard tissue was complex or compound odontoma, and a presence of ameloblastic fibroma tissue in the cystic wall extending into the surrounding tissue. ❍ Type 3: Monocystic ameloblastomatous proliferating type which was marked by ameloblastomatous proliferation both in the walls and in the lumen, and hard dental tissue which consisted of dentinoid formation in connection with islets of epithelia in the connective wall.

Intraoral photograph showing swelling in relation to the attached gingiva of the right maxillary incisor and canine region. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 17

Neoplastic entity It was described as an odontogenic tumor with ghost cells. The epithelial elements consist of numerous ameloblastomatous proliferations of tissue in the connective tissue of the stroma. Varying amounts of ghost cells are present within the epithelial islets. The hard tissue is composed of different amounts of dentinoid in direct contact with the epithelium. Clinical features It produces slow growing painless non-tender swelling of jaws (Figures 16 and 17). It occurs more in 2nd decade of life. It is commonly seen in the anterior part of the jaws. In the maxilla, the canine region is the most commonly affected site. In the mandible, the cyst is rarely found posterior to the first molar. Occasionally the cyst may be seen crossing the midline. On aspiration, it yields viscous granular yellow fluid. According to Wood et al, 68% of cases occur in mandibular molar area. At least 52% cases are associated with unerupted tooth, occasionally associated with pain. Radiographic features The radiographic features are quite variable. The central lesion may be radiolucent with a variable margin that is 312

Intraoral photograph showing expansion of the labial and palatal cortical plates in the right maxillary incisor–canine region. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

smooth and well-defined or, irregular and poorly defined. It might contain small foci of calcified material. It is usually present as a unilocular radiolucency. However, in about 5–13% of the cases, it may present as multilocular radiolucency. Intraosseous lesions may produce expansion of the lingual cortical plate. Resorption of the roots of adjacent teeth is frequently seen (Figure 18).


Figure 18

Maxillary occlusal radiograph showing a well-defined unilocular radiolucency in the incisor–canine region containing radiopaque foci of calcification. Resorption of the apex of the right central incisor can be appreciated. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Differential diagnosis Calcifying odontogenic tumor and ameloblastoma. Management and prognosis The management of calcifying odontogenic cyst is primarily by enucleation and curettage (Figure 19). Some authors describe the possibility of malignant transformation. Only eight cases till date have shown recurrences.

GLANDULAR ODONTOGENIC CYST It is also called sialo-odontogenic cyst, mucoepidermoid odontogenic cyst or polymorphous odontogenic cyst. Padayechee and Van Wyk were the first to describe a unique cyst of the jaws in 1987 which did not fit into the standard classification of odontogenic cysts and tumors. Due to its unique histopathologic features, they suggested the term sialo-odontogenic cyst to denote a possible origin or association with salivary gland tissue. Gardner et al (1988) reported the first series of these cysts and used the name glandular odontogenic cyst (GOC), stating that the presence of mucous cells in the cyst lining did not imply an origin from salivary glands. WHO recognized the name of this pathological entity as GOC in 1992. It was classified as a developmental

Figure 19

Excised gross specimen of calcified odontogenic cyst (COC) showing the cyst and the calcified mass. Courtesy: Department of Oral Pathology, MCODS, Mangalore

odontogenic cyst, although controversy still exists regarding its origin and the terminology. Current literature review reveals the mention of only 23 cases of GOC. These appear to be odontogenic in origin and present as a well-defined radiolucent swelling of the jaws with a tendency to recur following conservative treatment. These occur over a wide age range with no gender, race or ethnic predilection. The cyst is possibly derived from rests of dental lamina and comprises both secretory elements and stratified squamous epithelium. Clinical and radiographic features Glandular odontogenic cyst is commonly seen in the anterior mandible. Occasionally maxillary involvement has been reported. The usual complaints are swelling, pain or discomfort in the involved area (Figure 20). It is usually seen as a slow-growing swelling. Pain is very unusual but has been reported. Reports in literature mention the occurrence of GOC in a wide age range (14–80 years), however it is relatively common in the 4th and 6th decades of life. Radiographically it may be a unilocular or multilocular well-circumscribed radiolucency usually displacing the roots of teeth (Figures 21 and 22). Histopathologic features The histopathologic features of this cyst have been described as a combination of findings from a botryoid odontogenic cyst and a mucoepidermoid carcinoma, often causing a diagnostic dilemma for pathologists. 313


Figure 20

❍ ❍

Little inflammation Occasional findings of hyperchromatic basal cells within the cyst lining.

Management and prognosis Glandular odontogenic cysts can be treated conservatively by enucleation and curettage. It is believed that almost 55% of the cases show recurrence. The recurrence rate is high because the thin cyst wall, tendency of epithelium to separate from connective tissue or growth through cancellous spaces of bone and presence of microcysts makes complete removal of the cyst nearly impossible. Thus, some authors suggest a local block excision. However, it is wise to follow up the patient for several years to assess any form of recurrence. Intraoral photograph showing minimal obliteration of the labial vestibule in relation to the maxillary anterior teeth. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 21

NON-ODONTOGENIC CYSTS Non-odontogenic cysts including developmental cysts account for about 6% of cysts in the orofacial region.

Nasopalatine Duct Cyst The nasopalatine duct cyst or incisive canal cyst was first described by Meyer in 1914. Nasopalatine duct cyst is the most common among the non-odontogenic cysts. It is estimated that the cyst occurs in about 1% the population. The etiopathogenesis of the cyst is still unclear. However, it is thought that the cyst arises from a cystic degeneration of the embryologic remnants of nasopalatine duct. Some authors believe that trauma, bacterial infection of the nasopalatine duct or mucous retention possibly predisposes to the formation of the cyst. Clinical features

Maxillary occlusal radiograph showing well-defined unilocular radiolucency extending from the mesial aspect of the maxillary right side lateral incisor to the mesial aspect of the left side lateral incisor, causing displacement of teeth. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Gardner proposed the diagnostic criteria for GOC which included the presence of: ❍

A cystic cavity lined by epithelium of varying thickness with a flat interface between the epithelium and underlying connective tissue ❍ Variable numbers of mucous cells in the epithelium ❍ Eosinophilic cuboidal cells in the superficial layer ❍ Localized plaque-like thickening of the epithelium 314

Nasopalatine duct cyst is seen to affect individuals between the 4th and 6th decades of life. The cyst is seen in the midline of the anterior maxilla approximating the incisive foramen. It is seen slightly more frequently in men than in women (3:1). The cysts often present as asymptomatic swelling of the palate but can present with painful swelling or discharge (mucoid or purulent in nature). The maxillary central incisors may occasionally be displaced. The associated teeth are vital. A clear or straw-colored fluid is obtained on aspiration. Histologic features The nasopalatine duct cyst may be lined by various types of epithelium such as stratified squamous epithelium, pseudostratified columnar epithelium or cuboidal epithelium. Abrams (1963), Gnanasekhar (1995) and Swanson (1991)


Figure 22

Orthopantomograph (OPG) showing well-defined unilocular radiolucency extending from the mesial aspect of the maxillary right side lateral incisor to the mesial aspect of the left side lateral incisor. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

reported that about 9.8% of the nasopalatine duct cysts are lined by respiratory epithelium. Radiographic features Radiographically, nasopalatine duct cyst is apparent as a well-defined round, oval or inverted pear-shaped radiolucency. Occasionally, the nasal spine is superimposed over the radiolucency imparting it a heart shape. It is located in the midline in the anterior maxilla. The cyst is typically located in the interradicular region, apical to the maxillary central incisor teeth. The cyst is well corticated, unless infected. Adjacent teeth are usually displaced. However, the roots are rarely resorbed. Large cysts can cause expansion of the palatal cortical plate and occasionally cause destruction of the floor of the maxillary antrum. Radiographically, when the diameter of the incisive canal exceeds 6 mm, a nasopalatine cyst should be considered. On MRI, the cyst is identified as a high-intensity, well-marginated lesion, indicating the presence of proteinaceous material. Management The cyst can be successfully managed with enucleation. It has low recurrence rates.

NASOLABIAL CYST Nasolabial cyst is classified as developmental, non-odontogenic soft tissue cyst. It occurs in the nasolabial region. It is estimated that the nasolabial cyst accounts for only 0.7% of the cysts of the jaws. The nasolabial cyst is also

known by other names such as Klestadt’s cyst, nasoalveolar cyst, nasal vestibule cyst, nasal wing cyst and mucoid cyst of the nose. Though the exact etiology for the cyst formation is unknown, Bruggeman (1920) suggested that the cyst possibly originates from the remnant of embryonic nasolacrimal duct. Clinical features Nasolabial cyst is usually seen in the 4th and 5th decade of life. It is reportedly seen 3–4 times more commonly in women. Clinically patients present with a soft tissue swelling that may cause obliteration of the nasolabial fold, and elevate the ala of the nose. Intraorally, a swelling is seen in the labial vestibule. However, about 11% of the cases present with bilateral involvement. A nasolabial cyst is usually not painful, unless it is secondarily infected. The cyst is fluctuant on palpation. The cyst may rupture spontaneously or drain orally, nasally or sometimes drains extraorally through a fistula. Occasionally, the swelling may encroach upon the lateral wall of the nasal vestibule causing nasal obstruction. Large infected cysts can cause referral of pain to the maxillary anterior teeth. Radiographic findings Although nasolabial is a soft tissue cyst, it can occasionally cause erosion of the underlying maxillary bone which may be appreciated on radiographs. Intraoral periapical radiographs and maxillary occlusal radiographs are generally sufficient to evaluate the extent of the cyst. Localization technique may help in excluding cysts of odontogenic origin. Alternatively, the content of the cyst may be aspirated and a radiopaque contrast agent can be injected into the cyst followed by a posteroanterior projection or 315


occlusal radiograph. Posteroanterior view will reveal a spherical or kidney-shaped (bean-shaped) cyst. The cyst may cause depression of the underlying labial surface of the maxillary bone (secondary to pressure). The cyst may also cause distortion of the curve of the ‘bracket-shaped’ line produced by the inferior margin of the anterior bony aperture of the nose. Literature review reveals rare cases of root resorption. Histologic features Almost all cysts are lined with pseudostratified columnar epithelium. Sixty percent of the specimens show the presence of goblet cells. Management Nasolabial cysts have been managed with injection of sclerotic substances, marsupialization and surgical removal. However, surgical excision is the treatment of choice. Occasionally, perforation of the nasal mucosa is seen owing to the close relation of the cyst to the nasal floor. Large defects have to be sutured.

MID-PALATAL RAPHE CYST OF INFANTS It is also known as median palatine, median alveolar and median mandibular cysts. The terms ‘median palatine’, ‘median alveolar’ and ‘median mandibular cysts’ are no more used in literature. It is believed that the median alveolar and median palatine cysts are the anterior and posterior extensions of the wellknown incisive canal cyst. The use of the term ‘median mandibular cyst’ is controversial as most cases in literature that describe this cyst are associated with non-vital mandibular anterior teeth (mimicking radicular cysts) or on histopathological examination resemble keratocysts. Two theories have been proposed to explain the origin of the palatal cysts of the newborn: entrapment of the epithelium along the mid-palatine raphe during fusion of the palatal shelves in embryonic life or from remnants of the epithelium derived from the development of palatal minor salivary glands. The mid-palatal raphe cyst is a developmental cyst of non-odontogenic origin. These cysts are usually present along the mid-palatal raphe at the junction of the hard and soft palate. Usually four to five cysts are seen together. They measure between 2 and 4 mm in diameter. Bohn’s nodules and Epstein pearls are common cysts that occur in an infant’s palate. Bohn’s nodules are smooth surfaced cysts that are found at the junction of the hard and soft palate, and occasionally scattered all over the palate. These nodules are usually 1–3 mm in size, and filled with keratin. Bohn’s nodules are named after the German pediatrician Heinrich Bohn (1832–1888). These are thought 316

to be derived from palatal salivary gland structures and generally regress within the first 3–4 months of life. Epstein pearls are cystic keratin-filled nodules found along the mid-palatine raphe and are thought to be derived from entrapped epithelial remnants along the line of fusion. Epstein pearls are named after Alois Epstein (1849–1918), a Czech pediatrician. Histologic features The cyst is lined by parakeratinized stratified squamous epithelium. Occasionally epithelial lined clefts are seen between the cyst and the surface epithelium of the oral mucosa. The basal cells are flat. The cystic lumen contains concentric layers of keratin. Management Mid-palatal raphe cysts disappear within the first few months of life. Studies by Moreillon and Schroeder (1982) showed that with time the cystic epithelium differentiated, fused with the oral epithelium and their contents were discharged.

CYSTS OF MAXILLARY ANTRUM AND SALIVARY GLANDS The cysts associated with the maxillary sinus are either extrinsic or intrinsic in origin. These can be classified as: 1. 2.

Extrinsic cysts Intrinsic cysts a. Mucous retention cyst b. Serous cysts c. The mucocele.

Extrinsic Cysts The extrinsic variety develops in structure adjacent to sinus and as they expand they may encroach upon the sinus air space. Extrinsic cyst may be odontogenic in origin or infrequently non-odontogenic.

Intrinsic Cysts This cyst is referred to in literature by a plethora of names like mucosal cyst, mucosal antral cyst, mucous cyst, mucous retention cyst secreting or secretory cyst, mucocele serous cyst, non-secreting or secretory cyst, mesothelial cyst, lymphangiectatic cyst, interstitial cyst, pseudocyst and false cyst. Concurrent concept permits the usage of term ‘mucosal cyst’. There are three types of mucosal cysts: a. b. c.

The mucous (secreting or retention cyst) The serous (non-secreting cyst) The mucocele.


The mucocele frequently causes the expansion of the bony antral wall whereas mucous and serous do not. If the ostium is not occluded by intra-antral or intra-mucosal inflammation, polyps or bony tumors, it provides an avenue or release for expanding cystic pressure. Release occurs either by rupture of the cyst resulting from abrupt pressure changes accompanying sneezing or blowing of the nose or by the cyst herniating though the ostium into the nasal cavity, where it is subsequently ruptured. If the ostium is blocked, cystic pressure progressively increases and erodes the antral wall. The cysts associated with such pressure atrophy are referred to as ‘mucocele’, an expanding destructive cyst.

Benign Mucosal Cysts The intrinsic benign (non-destructive) cysts are most common in maxillary sinus and are assumed to be two pathogenically different varieties: 1. 2.

A mucous or secretory retention cysts Serous, non-secreting cysts.

Mucous Retention Cysts The mucous retention cysts result from the obstruction of some ducts of the seromucinous glands in the lamina propria of the sinus lining. The obstruction is secondary to local inflammation that may be either infectious or allergic in origin. The occluded glands continue to secrete, causing their dilatation and resulting in accumulation of a mucoid material forming cyst. The cyst is lined with either normal sinus (respiratory) epithelium or a flattened cuboidal or squamous epithelium as a result of metaplasia induced by intracyst pressure. The liquid that collects inside the cyst lumen may be sampled by intranasal needling as a diagnostic aid. It is thick, tenacious, white translucent and sterile.

Serous Non-secretory Cysts The serous cysts probably arise as a result of cystic degeneration within an inflamed, thickened sinus lining or in large mucosal polyp. As the defect in the lamina propria of the affected mucosa becomes distended with edema fluid, they coalesce and form a cystic space that crowds and packs the surrounding connective tissue fibers forming the cyst wall. This sequence of events produces the development of a distinct epithelial lining, a fact surrounded by histological examination of these cysts. The fluid within the cyst is believed to be a transudate from the adjacent osmotic pressure of the cyst fluid. It is similar in composition to plasma. The cause of cyst is uncertain. It seems that inflammation accompanying sinusitis or reported allergy or a tooth extraction plays a role.

Figure 23

CT axial section showing a large mucosal cyst in the right maxillary sinus

Clinical and radiographic features The occurrence rate of this cyst is 1.47–13% of general population. This cyst is found in all age groups; about 11% of the cysts are diagnosed in children. Males are twice more affected compared to females. Symptoms accompanying this cyst are general fatigue, dizziness, pain exacerbated by jarring, a sense of fullness or numbness in the ipsilateral cheek, toothache, frontal headache, nasal obstruction and occasional copious post-nasal discharge (when the cyst ruptures), optic neuritis, serous otitis media and some arthritis, specially in the knee. Radiographically both varieties of cyst may be recognized as a single curved, homogeneous, highly radiopaque area (normal anatomic structures can usually be observed through the cyst) that is spherical, ovoid or dome shaped (Figure 23). Their outlines are usually smooth, uniform and well-defined by radiolucent air space of the sinus. The cyst can develop any where in the cavity. The base of the lesion may be broad or narrow. The mucous cysts usually have a broad base while serous cysts are more pedunculated. The lesions are usually single but multiple cysts and bilateral involvement of the sinuses have been reported. The size of the mucosal cyst varies from a few millimeters to more than 1,000 mm. The mucous cysts are usually small in size and hidden in intrasinus fluid (pus) and not recognized until it drains. The condition of lining of the other part of the sinus also helps to distinguish mucous variety which is associated with thickened mucosa in majority of the cases. The serous cysts when involved, lining appears normal. The broad based mucous cyst will not change in position while the serous cyst shows slight changes in contour in a radiograph when the position of patient is altered in second projection. Transillumination does not usually provide diagnostically useful information when compared to a radiograph. 317


It will help in distinguishing between the mucous and serous cysts by demonstrating different translucency. The mucous cyst shows decreased translucency compared to serous because the serous cyst has a high concentration of doubly refractory cholesterol crystals. When aspirated, serous type will show a clear, amber fluid with high concentration of cholesterol crystals. In contrast, the mucous cysts will show thick, whitish, opalescent mucous. Investigations Periodic radiographic studies show benign mucosal cysts remain stationary in size, completely disappear, decrease or increase in size over an interval of a month. However, majority of cysts regress spontaneously. Surgical exploration and direct examination of the cyst that have herniated into the mouth through the oro-antral fistula shows a round, distended, translucent mass with a light bluish or yellowish color. The walls are thin and rupture readily, yielding a watery fluid or a thicker sticky mucoid fluid. Microscopic studies show that the vast majority of those are non-secretory variety and that glandular elements are not associated with these cysts. There are false cysts whose lumina are not lined with epithelium but with the connective tissue. The outer surface of the cysts is lined with respiratory epithelium which shows areas of metaplasia. The lumina of these serous cysts are filled with amber fluid in which there are few inflammatory cells and suspended cholesterol crystals. This layer of submucosa is sometimes edematous and contains varying number of round cells. Its luminal lining is composed of columnar epithelium with some mucous glands. As a result of pressure, the lining epithelium may undergo metaplasia and appear as flat cuboidal epithelium. Differential diagnosis Benign mucosal cysts of the sinus must be differentiated from other soft tissue lesions of the sinus such as polyps, hyperplasia of dental infection, extrinsic cyst, sinusitis and malignant soft tissue tumors. This presents the primary concern since the character of opacities produced by the tumor fluid or thickened mucosa is not anyway different. A large cyst may fill sinus causing complete opacification and obscure cystic characteristic feature. Other lesions like intrasinus fluid, calcified entities such as condensing osteitis, root tip and other foreign bodies, antroliths and odontomas generally have characteristic outline and much denser images when compared to mucosal antral cyst, which presents as a homogeneous, only slightly radiopaque appearance. Antral polyps are much less common than benign mucosal cyst of the antrum. Antral polyps will not occur on the floor or inferolateral aspect of the sinus and are also associated with thickened mucosa in contrast to normal appearing lining mucosa. Bone displacement, destruction 318

and bony sclerosis will be associated in antral polyps and not in antral cysts. Cysts are solitary, polyps are frequently multiple. Hyperplasia as a result of chronic dental infection is frequently seen in a radiograph of the antral floor, adjacent to teeth with pulpoperiapical problems or advanced periodontal diseases. Both the lesions may show similar convex, homogeneous, faintly opaque shadows. The differentiating feature of hyperplasia of dental infection is the presence of a chronically infected tooth. Usually, dental infection is not seen in association with benign mucosal cyst or if present, is not considered as an etiological factor.

Extrinsic Cysts Cysts like radicular, dentigerous, primodial and other odontogenic cysts may encroach on the sinus, but rather easily be identified by their characteristic location in the jaws or their relationship to a tooth. Extrinsic cysts will retain a thin curved radiopaque rim of bone which separates the cyst from the antral shadow. Cysts associated with the salivary glands are described in Chapter 11 on Diseases of Salivary Glands.

INFLAMMATORY CYSTS Periapical Cyst (Radicular Cyst, Root End Cyst, Apical Periodontal Cyst) Periapical cyst is the most common inflammatory odontogenic cyst. It is associated with non-vital teeth. The tooth might be deeply carious, traumatized or improperly restored. Etiopathogenesis Bacteria invade the tooth followed by the death and degradation of pulp. The first line of defense in the periapical area to seal the apex is the proliferation of epithelial rests of Malassez in the periodontal ligament. They proliferate to form a granulation tissue called periapical granuloma. This consists of highly vascular tissue with immunocompetent cells like lymphocytes, macrophages, plasma cells. As the time elapses, the central area is deprived of nourishment. The cells undergo liquefaction necrosis surrounded by epithelium to form a cyst. Clinical features More often (60%) these occur in the maxillary anterior region. These might cause painless bony expansion of either buccal or palatal cortical plate (Figure 24). The cortex might be intact where it is hard or fluctuant. When perforated, the bone thins out and exhibits crepitus. However, occasionally the patient may complain of pain


Figure 24

Figure 25

Straw-colored aspirant from a periapical cyst. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 26

Intraoral photograph showing a discolored right maxillary central incisor and palatal swelling suggestive of a periapical cyst. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

when the cyst is secondarily infected. Sometimes, a cyst may be seen at the opening of lateral accessory root canals of a tooth, this may be referred to as ‘lateral radicular cyst’. In deciduous teeth Periapical cysts are rarely seen in deciduous dentition. It is estimated that only 0.5–3.3% of the radicular cysts occur in deciduous dentition. Most of the cysts are seen in relation to the mandibular molars and generally discovered incidentally on radiographs. It has been seen that cysts in primary teeth are characteristically present in the interradicular region and not near the apex of the teeth. Many authors believe that this is due to the short and resorbed roots as well as the presence of multiple accessory canals in primary teeth. Hence, the term ‘periradicular cyst’ is more appropriate. Expansion of the mandibular buccal cortical plate and displacement of the underlying permanent tooth buds are usually seen associated with periradicular cysts. On aspiration, the contents of the cyst may vary from brown (breakdown products of blood) to straw color (presence of cholesterol crystals) depending on the content of the cyst (Figure 25). Radiographic features It appears as well-defined periapical radiolucency associated with apex of affected tooth. A diagnosis of periapical cyst is considered when the cyst measures at least 1.5 cm or more in diameter. The lesion is continuous with the lamina dura of the tooth. The lesion will have sclerotic border

Maxillary occlusal radiograph showing a well-defined radiolucency extending from the periapex of the maxillary right lateral incisor. The cyst is bound by a well-defined sclerotic border. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

(Figure 26). In cysts that are secondarily infected and those rapidly expanding the sclerotic border may be indistinct. The radiolucency may sometimes appear hazy due to pus accumulation. Few cysts might expand into the sinus and elevate the floor. Root resorption is rarely seen. Histopathology Most of the radicular cysts are lined by stratified squamous epithelium (Figure 27). In instances where the periapical cysts are in proximity to the maxillary sinus, the cyst may exhibit pseudostratified ciliated columnar epithelium. Rarely the periapical cysts are lined with ortho or parakeratinized epithelium. It is estimated that 10% of the cases reveal the presence of Rushton’s hyaline bodies. These are generally found in epithelial linings and rarely found in the fibrous capsule. These are hairpin shaped, arch shaped or linear eosinophilic structures that are amorphous and brittle. Presence 319


Figure 27

Figure 28

Orthopantomograph (OPG) showing residual cyst in the edentulous site. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Photomicrograph of radicular cyst showing stratified squamous epithelium with arcading pattern, cystic lumen and connective tissue capsule. Courtesy: Department of Oral Pathology, MCODS, Mangalore

of cholesterol clefts is another important feature of radicular cysts. The fibrous capsule of the cyst is made up of dense bundles of collagen fibers. Usually chronic inflammatory cells are seen in the connective tissue approximating the epithelium. Simon (1980) described the presence of an epithelium lined cavity that may open to the root canal in small periapical lesions. Simon termed this ‘bay cyst’. Subsequently Nair et al (1990) studied 256 periapical lesions. Their inference was that 61% of the identified cysts fulfilled the criteria of true periapical cysts and the rest were apical inflammatory lesions that contained a sac-like, epitheliumlined cavity, continuous with the root canal. This epithelium formed an attachment that seemed to seal off the infected root canal and its apical pouch from the periapical region. It was suggested to term this a ‘periapical pocket cyst’ rather than a ‘bay cyst’.

It is estimated that 10% of the cysts of odontogenic origin are residual cysts. Residual cysts are cysts that are left behind following partial enucleation of a radicular cyst or a retained radicular cyst after the tooth has been extracted. Many authors believe that a residual cyst may also develop from partial removal of a dentigerous cyst. It may also form from a periapical granuloma after removal or exfoliation of tooth. Subsequent cystic degeneration may take place in the granuloma. Clinical features Residual cysts are mostly detected incidentally on radiographs. The cyst is evident in edentulous site (Figures 28 and 29). The patient may give a history of extraction of the tooth because the tooth was grossly carious or fractured to involve the pulp. It is almost always asymptomatic. Amber-colored aspirant is expressed on aspirating residual cysts. Management


Residual cysts are surgically removed. However, large residual cysts may be marsupialized.

The lesions that might resemble cyst radiographically are periapical granuloma, periapical scar and surgical defect.

Paradental Cyst

Management and prognosis Root canal treatment or extraction of tooth along with the removal of the cyst. Depending upon the size and involvement of other tissues, marsupialization or enucleation are done. Recurrence unlikely if removed completely. Literature review reveals descriptions of squamous cell carcinoma originating from the epithelial lining of radicular and residual cysts. 320

Residual Cyst

Craig is credited for describing the paradental cyst in 1976. The term ‘paradental cyst’ is reserved for those cysts that are located in relation to the distal aspects of the roots of partially erupted third molars. Most patients have an associated chronic pericoronitis. Craig believed that the reduced enamel epithelium provided the cells of origin of the paradental cyst. However, other authors also believe that the paradental cyst may originate from the cell rests of Malassez.


Figure 29

Clinical features It is commonly seen in young children in the 6–11 year age group. The cyst causes a buccal tilting of the crown of the involved tooth. The associated tooth is vital. On clinical examination, deep periodontal pockets may be evident on the buccal aspect of the tooth. Occasionally, pain or swelling may be present. Radiographic features Periapical radiographs, occlusal radiograph and orthopantomograph may be required to evaluate the presence of buccal bifurcation cyst. Radiographically, the lamina dura and the periodontal ligament space are unaffected. The cystic radiolucency is always located on the buccal aspect of the molar, which can be best appreciated on occlusal radiograph. Occasionally, subperiosteal new bone may be laid down, which may appear laminated.

Orthopantomograph (OPG) showing residual cyst in the edentulous site. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Management The cyst can be managed by curettage and extraction of the tooth. Some authors recommend enucleation.

PSEUDOCYSTS Clinical features Paradental cysts are mostly seen involving the mandibular third molars. However, maxillary third molar involvement has also been reported in literature. Most of the cysts cover the bifurcation of the roots and are usually attached to the buccal root surface. Teeth are vital. Both sexes may be affected. However, males are more commonly affected. These cysts are commonly seen in the 2nd and 3rd decades of life. Radiographically, a well-defined radiolucency is seen in relation to the distal aspect of a partially erupted third molar. Generally the distal part of the radiolucency is separate and distinct from the distal follicular space of the third molar. The width of the periodontal ligament space is unaffected. Histological features resemble that of radicular cyst. The paradental cyst is managed effectively by surgical enucleation. The partially erupted third molar can be removed.

Mandibular Infected Buccal Cyst (Mandibular Buccal Bifurcation Cyst) The first description of the mandibular infected buccal cyst was given by Stoneman and Worth in 1983. The buccal bifurcation cyst is an uncommon lesion associated with the permanent mandibular first or second molar in children. Usually, it is identified just prior to eruption.

It is also known as traumatic bone cyst, aneurysmal bone cyst, Stafne’s bone cyst.

Traumatic Bone Cyst The term ‘traumatic bone cyst (TBC)’ was used by Lucas in 1929. Though the term is popularly and widely used, literature review reveals that other terms such as solitary bone cyst, hemorrhagic bone cyst, simple bone cyst and unicameral bone cyst are used. The pathogenesis of the TBC is still not well understood. However, trauma is the most frequently discussed etiologic factor in the formation of a TBC. According to Pommer, trauma leads to intraosseous hematoma formation. The blood clot liquefies, unlike the normal healing process, and adjacent bone is destroyed by enzymatic activity. Blum and Thoma suggested that a previous traumatic episode to the jaws contributed to the development of TBCs. Thoma proposed that trauma initiates a subperiosteal hematoma which causes a compromised blood supply to the area, thereby leading to osteoclastic bone resorption. However, even this theory is debatable as it is estimated that almost 50% of the patients do not give history of trauma. And even if there is a history of trauma it does not coincide with the time of the development of the cyst. Another explanation against trauma as the etiological agent is that, trauma usually occurs on the anterior part of the mandible, whereas the cyst occurs more frequently in the body of the mandible. 321


Clinical features The cyst is usually seen in the 2nd decade of life. It is slightly more common in males. The cyst is generally asymptomatic and hence incidentally discovered on routine radiographic examination. Approximately 10–30% of the patients complain of pain. Traumatic bone cysts frequently affect the mandibular body (canine to molar region), followed by the mandibular symphysis and rarely the maxillary anterior region. The ramus and condylar regions are hardly involved. Other features that may be noticed are tooth sensitivity, paresthesia and delayed eruption of permanent teeth. Aspiration may occasionally yield a straw-colored fluid or bright blood. Radiographic features Most TBCs are found incidentally on routine radiographic investigations. Radiographically, it is seen as a well-defined radiolucent area with or without a sclerotic border. The radiolucent area is commonly seen in the body of the mandible and the symphyseal region and the anterior region of the maxilla. The radiolucent areas can occur unilaterally, bilaterally or in multiple sites. The cyst may extend interdentally, between the roots of teeth giving rise to a scalloped margin. Extensive lesions may cause expansion (usually buccal cortical plate is expanded) and erosion of the cortical plates resulting in pathological fracture. Occasionally the mandibular canal can be displaced. Histopathologic features The tissue specimen for histopathological examination can be taken during the surgical curettage. However the amount of tissue obtained is generally insufficient for histopathological analysis. Epithelial lining is typically absent. Other findings include presence of fibrous connective tissue and normal bone. The lesion may exhibit areas of vascularity, fibrin and erythrocytes. Giant cells may be occasionally seen adjacent to the bone surface. Management Literature review reveals that some cases of TBC undergo spontaneous resolution. However, the most preferred and widely recommended treatment modality is surgical exploration followed by meticulous curettage of the bony walls. It is believed that curettage and surgical exploration will induce bleeding. This induced bleeding will form a clot which will ultimately be replaced by healthy bone. Recurrences are rare after surgical treatment.

Radiographically, it is characterized by ballooned out expansion of the periosteum which is usually outlined by a wafer thin subperiosteum. This is, in turn, bounded by an area of disintegrated cortex. Clinical features Aneurysmal bone cyst is commonly seen in the 2nd decade of life. It is rarely seen after the 3rd decade of life. It is believed that females are more commonly affected than males. Literature review reveals that the mandible is more commonly affected than the maxilla. The molar regions of the maxilla and mandible are the most common sites of involvement. Extensive lesions in the mandible may involve the angle and ascending ramus of the mandible. Rare sites of involvement such as the coronoid process of the mandible, floor of the orbit and the zygomatic arch have been reported in literature. Clinically the swelling is firm on palpation. Aneurysmal bone cysts tend to enlarge rapidly and cause thinning and perforation of the overlying cortical plate. Some patients complain of pain. Large lesions can cause displacement of teeth and a progressive malocclusion. Associated teeth are vital. Occasionally, patients may complain of difficulty in mouth opening when the cyst involves the capsule of the temporomandibular joint. Differential diagnosis Aneurysmal bone cyst may mimic other lesions such as ameloblastoma, giant cell tumor, hyperparathyroidism, myxoma, TBC and OKC. However, on aspiration, blood may be expressed from a vascular lesion or aneurysmal bone cyst. Clinically aneurysmal bone cyst may be differentiated from a vascular lesion based on the absence of bruits or thrill and lack of pulse pressure. Radiographic features Radiographically, aneurysmal bone cyst resembles other cystic lesions of the jaw. It may appear as a well-defined unilocular radiolucent lesion or sometimes exhibit internal septa within the radiolucent lesion giving rise to a multilocular appearance (honeycomb pattern). Dabska and Buraczewski (1969) and Wilner (1982) described four stages in the radiographic appearance of aneurysmal bone cysts: 1. 2.

Aneurysmal Bone Cyst Jaffe and Lichtenstein in 1942, discovered a distinct clinicopathological entity and termed it aneurysmal bone cyst. 322

3.

Initial lytic phase: a well-defined area of bone resorption with no distinctive features is observed Phase of active development: there is the typical subperiosteal, ‘blow-out’ expansile appearance Stabilization phase: there is a distinct peripheral bony shell with internal septa and trabeculations, resulting in the so-called ‘soap bubble’ appearance


4.

Healing phase: Progressive ossification of the cyst resulting in a dense bony mass of irregular structure.

Figure 30

CT scan may reveal fluid-fluid levels within the radiolucent lesion. Fluid-fluid levels are produced due to layering of solid blood components within the cyst. Management Malghem et al (1989) reported three cases of spontaneous healing of aneurysmal bone cysts in about 7–9 months duration. Aneurysmal bone cysts can be managed by surgical curettage or by excision. Some authors have reportedly used calcitonin injections with unpredictable results. Szendröi et al (1992) recommended direct injection of calcitonin into the cyst as a useful non-invasive method for the management of hypovascular aneurysmal bone cysts. Adamsbaum et al (2003) studied the affect of Ethibloc (Ethnor Laboratories) injection, which is an alcoholic solution of zein (a vegetable protein dissolved in alcohol). It is a fibrogenic and thrombogenic agent, on 17 patients in the age group of 2–18 years. After 5 years of follow-up, 14 out of 17 patients demonstrated complete healing manifested by increased cortical and septal thickening. Inflammatory reaction following the injection such as pain and fever is seen. They concluded that the percutaneous direct Ethibloc injection is a safe, efficient and noninvasive treatment for aneurysmal bone cyst. Other modalities of treatment include introduction of demineralized bone and autogenous bone marrow that promotes self-healing of a primary aneurysmal bone cyst. It is estimated that 10–44% of the cases exhibit recurrence. Recurrences have been reported due to difficult access and incomplete removal of the cyst. It is advisable to review the patients on a regular basis to evaluate for recurrence.

Stafne’s Bone Cyst Stafne’s bone cyst is also known as static bone cyst or defect of mandible, lingual mandibular bone cavity and latent bone cyst. Stafne in 1942 recognized this entity. It is the developmental inclusion of submandibular glandular tissue within or, more commonly, adjacent to the lingual surface of the body of the mandible or indentation on the mandible (Figure 30). Name of the cyst is derived from its radiographic appearance. It is a congenital defect. Radiographic appearance It appears as an ovoid radiolucency located between the inferior canal and the inferior border of the mandible in the region of 2nd or 3rd molars. It is differentiated from

Photograph of the mandible showing the lingual defect which forms the site for lodgement of the submandibular salivary gland. Courtesy: Dr Ravikiran Ongole

TBC by location which lies superior to inferior alveolar canal. Its anterior variant is found between incisors and premolars. Rarely, complication in the form of development of neoplasm like mucoepidermoid carcinoma from salivary gland has been reported rarely.

CYSTS OF SOFT TISSUES OF MOUTH, FACE AND NECK Anterior Median Lingual Cyst Fink in 1963 described a patient with cystic swelling present in the anterior two-thirds of the tongue on the dorsal surface. He termed this as a retention cyst of the tongue or glossocele. Some authors use the term ‘intralingual cyst’ originating from the foregut synonymously with anterior median lingual cyst. Large cysts can interfere with feeding and swallowing. Occasionally the cysts can impede closure of the mouth. Histologically these cysts may be lined by parakeratinized stratified squamous epithelium. The cystic capsule may exhibit chronic inflammatory cells. The cysts can be surgically excised. However, recurrences have been reported.

NASOPHARYNGEAL CYSTS Nasopharyngeal cysts are rare entities which may either be congenital or acquired in nature. Most of the cysts are asymptomatic. However, larger cysts can cause nasal 323


obstruction, closed posterior rhinolalia (nasal quality of voice) and conductive hearing loss. Piero Nicolai et al (1989) modified the classification of nasopharyngeal cysts originally proposed by Singh and Pahor (1977). Classification 1.

2.

Midline cysts a. Congenital cysts i. Cysts of bursa pharyngea embryonalis ii. Cysts of Rathke’s pouch b. Acquired cysts i. Retention cysts of the median recess ii. Retention cysts of seromucinous glands Lateral cysts a. Congenital cysts i. Branchiogenic cysts b. Acquired cysts i. Retention cysts of seromucinous glands

Lateral Cysts These are usually branchiogenic in origin. The base of the cyst is located between the posterior pillar and pharyngeal opening of the Eustachian tube. These cysts have more fluid content and lesser cellular debris compared to the midline cysts. Unlike the midline cysts, the germinal centers are rarely present in the lateral cysts. The inner lining of the cyst is made up of cylindrical and ciliated epithelium. Clinically these soft mucosal masses can be identified by posterior rhinoscopy or by using a nasal fiberscope. Choanal polyp, sphenoid sinus mucocele and juvenile angiofibroma can mimic nasopharyngeal cysts.

Clinical features

Radiographic investigations

Midline cysts are usually seen in the 4th decade of life, whereas lateral cysts are usually seen in the 6th decade of life. Men are more commonly affected than women (3:1).

Radiographs frequently reveal a soft tissue mass with sharply defined margins high on the posterior pharyngeal wall. These cysts lack bony involvement. CT scan (axial and coronal sections) with contrast agent helps in assessing the nature of the mass, spatial relationship with adjacent structures and bone involvement. MRI shows a characteristic high signal intensity on T2-weighted and intermediate to high signal intensity on T1-weighted images. The variation in signal intensity on T1-weighted images may be related to differences in protein content or hemorrhage in the cyst.

Midline Cysts In the midline cysts, the retention variety is more common than the congenital cysts. It is believed that the retention cysts occur due to the fusion of the median recess of the pharyngeal tonsil. Hemorrhagic contents along with shed epithelial debris may be evident in the cyst. The cyst wall may show lymphoid follicles with pronounced germinal centers. The inner epithelial lining is composed of cylindrical ciliated cells. It is believed that the presence of inflammatory stimulus may produce squamous metaplasia. The congenital midline cysts may originate from the pharyngeal bursa (Tornwaldt’s bursa) or from Rathke’s pouch. The clinical and histological features of the cysts originating from the pharyngeal bursa are similar to those of the retention cysts. However, to differentiate these cysts a simple thumb rule can used—cysts deep to the pharyngobasilar fascia arise from pharyngeal bursa whereas cysts originating superficial to the pharyngobasilar fascia are more likely to be retention cysts. The pharyngeal bursa is a tubuliform invagination lying at the junction of the nasopharyngeal vault with posterior pharyngeal wall and extending between the heads of the longissimus muscles of the head just above the uppermost fibers of the superior constrictor muscle of the pharynx. It is estimated that the pharyngeal bursa persists in about 3% of the normal adults. 324

These cysts rarely originate from Rathke’s pouch. These cysts exhibit a median base which is attached to the nasopharyngeal vault. Histological picture of these cysts are very classical. These cysts are lined by stratified squamous epithelium that is related to the ectodermal origin of Rathke’s pouch.

Management Temporary relief of symptoms can be achieved by aspiration of the cystic contents or injection of sclerosing agents into the cystic lumen such as ethanolamine oleate solution. Surgical excision of the cyst is the treatment of choice.

THYROGLOSSAL DUCT CYSTS The thyroglossal duct cysts are said to arise from the remnants of the thyroglossal duct that failed to regress. These cysts can be present anywhere along the course (from the base of the tongue to suprasternal region) of the remnant of the thyroglossal duct. Cysts located near the foramen caecum are lined by stratified squamous epithelium, whereas cysts located near the thyroid gland are lined by cells similar to thyroidal acinar epithelium. It has been reported that almost half of the thyroglossal duct cysts contain normal thyroid tissue in their walls.


Clinical features Thyroglossal cysts are usually seen in the midline. However, it is estimated that about 38% of the cysts are seen slightly off the midline (located adjacent to the outer surface of the thyroid cartilage, deep to the strap muscles). Almost all cysts are present in the vicinity of the hyoid bone. Based on the anatomic location the thyroglossal cysts can be categorized as suprahyoid, at the level of hyoid and infrahyoid. About 20–25% are suprahyoid, 15–50% occurring at the level of the hyoid bone, where they may be anterior or posterior to the hyoid bone, and 25–65% occurring in the infrahyoid part of the neck. The differential diagnosis of thyroglossal duct cysts includes dermoid cyst, branchial cleft cyst, lymphadenopathy, and a cystic nodule arising from the thyroid gland. Ultrasonographic features The cyst typically appears anechoic, well-circumscribed with increased through-transmission. However, the cyst may also present as homogeneous or heterogeneous complex hypoechoic lesion. Some cysts may present as truly anechoic, some as predominantly anechoic but containing internal debris and some have a complex heterogeneous echo pattern, and few others have a uniformly homogeneous pseudosolid appearance. The coarse echo pattern is due to the proteinaceous content of the cyst secreted by the cyst lining. Occasionally, such a uniform echogenic appearance may lead to a false assumption of a solid lesion. However, when gentle but uniform pressure is applied over the cyst with the transducer, the contents tend to shift which is suggestive of a cystic lesion. It is estimated that about 45% of the cysts have thick walls due to inflammation and cellular debris. Management Sistrunk procedure involving resection of the cyst and tract, and excision of the middle third of the hyoid bone is the standard procedure employed in the management of the thyroglossal duct cyst. However, incomplete resection will cause recurrence. However, when a malignancy is evident, a near total or total thyroidectomy along with the Sistrunk procedure is recommended. The adjoining lymph nodes need to be evaluated because of the likelihood of a intrathyroidal foci of cancer.

LYMPHOEPITHELIAL CYSTS (Branchial Cleft Cysts) The word ‘branchial’ is derived from the Greek word bragchia, meaning gills. The term ‘branchial cyst’ was first used by Ascherson in 1832. He believed that these cysts arose from impaired obliteration of branchial clefts or pouches.

Howie and Proops (1982) defined branchial cysts (or lymphoepithelial cysts) as ‘lesions found behind the angle of the mandible in the anterior triangle of the neck at the junction of the upper third and lower two-thirds of the sternocleidomastoid muscle. The cysts have a lining of stratified squamous epithelium resting on a complete or incomplete band of lymphoid tissue with part of the cyst wall resembling a lymph node’. Golledge and Ellis (1994) defined these cysts according to two parameters: position and histology. With regard to position, the lesion must lie outside the midline of the neck or within any position in the lateral aspect of the neck. With regard to histology, the cyst lining is squamous or columnar and is surrounded by lymphoid tissue. Pathophysiology Literature review reveals many theories to explain the origin of these cysts such as branchial remnants, cervical sinus remnants, thymopharyngeal duct remnants and squamous epithelium inclusions in a cervical lymph node. However, most authors agree that these cysts are congenital branchial remnants. These branchial remnants may clinically present as a cyst, sinus or fistula. If a portion of a cleft or pouch fails to involute completely, the entrapped remnant will form an epithelial lined cyst called a branchial cyst. Clinical features It is estimated that almost 17% of the cervical masses in pediatric population are branchial cysts. They are typically present as a mass at the anterior border of the sternocleidomastoid muscle, at the junction of its upper and middle third. In more general terms, the cyst can occur at any level from the hyoid bone to suprasternal notch. It is seen to affect males and females equally. However some authors report that the branchial cyst is slightly more common in males. The branchial cleft cyst is an asymptomatic slowgrowing, fluctuant mass that is usually seen in the 2nd and 3rd decades of life. It is seen in close approximation to the external ear, angle of the mandible and upper lateral aspect of the neck. These cysts generally occur unilaterally. However, in approximately 2% of the patients the cyst may occur bilaterally (bilateral presentation may indicate a familial tendency). Large branchial cysts can cause difficulty in swallowing, speech and breathing. Infected cysts can turn into abscesses and form sinuses that open into the skin or pharynx. Diagnosis The diagnosis of branchial cleft cyst is made by a thorough history, clinical signs, fine needle aspiration, ultrasonography and CT. 325


Straw-colored fluid is aspirated from the cyst. Microscopically the aspirant may contain cholesterol crystals, squamous cells, lymphocytes and polymorphonuclear cells. Ultrasonographic imaging will show a circumscribed mass of homogeneous low echogenicity. CT is a useful tool to assess the topographical plane of the cyst and its proximity to the surrounding vital structures. Differential diagnosis Lipoma, cystic hygroma, thyroglossal duct cysts, lipomas, lymphomas, and dermoid cysts should be considered in the differential diagnosis of branchial cleft cysts. Management Infected cyst should be managed with appropriate antibiotics. Surgical excision of the cyst is the treatment of choice.

CYSTIC HYGROMA Cystic hygroma is a developmental entity characterized by progressive dilatation of the lymphatic vessels. It was first described by Wernher in 1843. It is estimated that 75% of the cystic hygromas affects the head and neck region. Cystic lymphangioma or macrocystic lymphatic malformation, first described by Redenbacker (1828), is a term used as a synonym for cystic hygroma. It is believed that sequestered lymphatic rests that retain their embryonic growth potential penetrate adjacent structures or dissect along fascial planes and eventually become canalized. These spaces retain their secretions and develop cystic components because of the lack of a venous outflow tract. Clinical features Approximately 60% of the cystic hygromas are present at birth. By the age of 2 years 90% are apparent. The posterior triangle of the left side of the neck is most frequently affected site. On clinical examination, these are large, soft to doughy in consistency, painless swellings that can be compressed. The skin overlying the swelling can occasionally show a bluish coloration. Transillumination is positive in cystic hygromas. Staging of cystic hygroma de Serres et al (1995) proposed a staging system based on the anatomical location: 1. 2. 3.

326

Stage I: Unilateral infrahyoid Stage II: Unilateral suprahyoid Stage III: Unilateral and both infrahyoid and suprahyoid

4. 5.

Stage IV: Bilateral suprahyoid Stage V: Bilateral infrahyoid and suprahyoid.

Rarely secondary infection or internal bleeding can result in a sudden increase in the size of the lesion. Extremely large sized cystic hygromas can impinge on the airway. Cystic hygromas are relatively more frequently seen in Turner syndrome, Down syndrome, Noonan syndrome and Klinefelter syndrome. Differential diagnosis Branchial cleft cyst, thyroglossal duct cyst and branchial cleft cyst can be considered in the differential diagnosis of cystic hygroma. Radiographic features Ultrasonography, MRI and CT can be used to image cystic hygroma. CT and MRI demonstrate ring-like margin enhancement with sharp demarcation of cystic areas. The cystic areas tend to appear circumscribed and discrete. MRI may show hyperintense areas on T2-weighted images and hypointense areas in T1-weighted images. Histologic features Most of the cystic hygromas exhibit a multicystic appearance. It is estimated that only 10% have a unilocular morphology. The lesion may vary in size from a few millimeters to several centimeters. The lumen contains cystic fluid which may appear clear or straw colored. The eosinophilic cystic fluid contains high levels of protein. Cystic hygromas are made up of large irregular sinuses with a single layer of flattened epithelial lining and fibrous adventitial coats. Management Asymptomatic cases of cystic hygroma are best left untreated with regular follow-up to evaluate for infection or secondary pressure effects on surrounding structures. Symptomatic cases can be managed with intralesional injections of sclerosing agents (OK-432 [an inactive strain of group A Streptococcus pyogenes], bleomycin, pure ethanol, and doxycycline) and surgical resection of the lesion. It is believed that the inactive bacteria used as a sclerosing agent incites an inflammatory response leading to fibrosis of the cystic hygroma. Though many authors strictly oppose aspiration of lymphatic formations as it may lead to infection and hemorrhage, Burezq et al (2006) in their article discussing their 30 years experience in managing cystic hygromas report interesting results obtained with serial aspirations. In their 5-year follow-up of 14 patients who were subjected to aspiration, no failures were reported. It is estimated that 15% of the cases show recurrence if incompletely surgically excised.


DERMOID, EPIDERMOID AND TERATOID CYSTS Dermoid Cysts Dermoid cysts may be located anywhere on the body surface, however these are characteristically located in the region of fusion of embryonic processes. It is estimated that dermoid and epidermoid cysts of the oral cavity account for about 0.01% of all oral cysts. Literature review reveals that these cysts account for about 1.6 to 6% of all cysts affecting the head and neck region. Dermoid cysts are categorized by a cystic cavity lined by epithelium which contains all skin appendages like the hair follicles, sebaceous glands and sweat glands. Subtypes of dermoid cysts Epidermoid cysts The epidermoid cyst cavity is lined by epithelium which is devoid of any skin appendages. Teratoid cysts These cysts are lined by an epithelium which contains skin appendages as well as certain components of the mesoderm such as muscle and bone. These cysts may contain respiratory, gastrointestinal, and connective tissues. Etiology The exact etiology of dermoid cysts is still unknown. It is believed that when epithelial tissue is traumatically implanted in utero or when a piece of epidermis is traumatically implanted in the lines of fusion of embryonic elements, the epithelium undergoes sequestration. Clinical features Dermoid cysts can occur anywhere in the body. However, these are commonly seen at the sites of fusion of embryonic elements. These are commonly seen on the hands and feet. Intraorally, midline of the floor of the mouth (sublingual dermoid cysts) is most commonly involved. However, other rare sites of involvement are the tongue, lips, uvula and buccal mucosa. Ultrasonographic picture Ultrasonography produces an echogenic picture in dermoid and epidermoid cysts due to the presence of cellular material, cholesterol crystals, and keratin within the cyst.

basal cell carcinoma arising from the wall of an epidermoid cyst, Ikeda et al described a case where basal cell carcinoma originated from an epidermoid cyst and Lopez-Rios et al reported a case of squamous cell carcinoma arising in the wall of an epidermoid cyst.

PARASITIC CYSTS Though parasitic cysts in the head and neck region are rare, the common cysts that may be seen are cysticercosis, hydatid cysts and trichinosis.

Cysticercosis Human cysticercosis is a parasitic infection caused by Taenia solium. Other forms of Taenia include saginata and Asian Taenia. It is believed that the Asian Taenia is an intermediate form between solium and saginata as it is morphologically similar to T. saginata and uses pigs as the intermediate host like T. solium. Ingestion of fecally contaminated food, water, fruit or vegetables containing the ova of T. solium causes human cysticercosis. Human cysticercosis is endemic in various parts of the world including Mexico, Africa, South-East Asia, Eastern Europe, Central and South America and India. Poorly cooked meat (pork) is ingested by humans who are the only definitive hosts. The undercooked meat includes eggs or proglottids of the pork tapeworm. In the stomach the larval form (Cysticercus cellulose) is released following digestion of the outer protective layer of the proglottids. These cysticerci are then disseminated by the arterial blood to various tissues, preferentially to the CNS (60%), eye (70%) and skeletal muscle (5%). Clinical features Clinically the condition may range from an asymptomatic nodule to life-threatening symptoms. Individuals may complain of nausea, vomiting and severe epigastric pain. CNS involvement may cause irritability, convulsions and loss of consciousness. On clinical examination, calcified nodules may be palpated anywhere in the body. In the head and neck region the common sites for presence of calcified cysticerci include muscles of mastication, muscles of facial expression and cervical muscles. Some of these calcified masses may be as large as 10 mm.

Management Epidermoid, dermoid and teratoid cysts are best managed by surgical excision. There is no definitive evidence for malignant transformation of epidermoid or dermoid cysts. However, individual case reports of such malignant changes have been reported in literature. Dini et al reported of

Diagnosis The diagnosis of cysticercosis should be done following thorough evaluation of the patient’s lifestyle, personal hygiene history and nature of food consumption along with the characteristic neurological and gastrointestinal 327


symptoms, presence of palpable firm calcified masses in the soft tissues and specific laboratory and radiographic imaging modalities. Serological tests such as enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunoelectrotransfer blot have the highest sensitivity and specificity in detecting isolated muscular cysticercosis. Plain radiography, CT, MRI and ultrasonography can be used. Radiographs show well-defined, homogeneously radiopaque elongated or ovoid mass which may mimic sialolith. However cysticercosis presents as multiple calcifications.

Diagnosis

Individuals should be educated to avoid the use of poorly cooked pork. Fruits and vegetables (especially coriander used for garnishing and raw leafy vegetables used in salads) should be thoroughly washed before consumption. Hands should be thoroughly washed prior to handling food substances. No treatment may be required once the larvae are no more viable and have formed calcifications. Occasionally, based on the location of these calcifications some patients may present with seizures, cerebral edema and vasculitis. In such patients, anticonvulsants and corticosteroids should be administered. Viable larvae can be effectively managed with antiparasitic drugs such as praziquantel and albendazole.

Imaging modalities like ultrasonography, CT and MRI help in diagnosing these cysts. These imaging modalities help in assessing the dimension of the cyst and its relationship to surrounding vital structures. In their study of hydatid cysts, Zeyrek et al (2008) and Köktürk et al (1999) reiterated the fact that the ‘air bubble sign’ in CT image was pathognomonic for perforated pulmonary hydatid cyst. Apart from imaging modalities, serological tests such as hydatid immunoelectrophoresis, ELISA, latex agglutination and indirect hemagglutination (IHA) test can be employed. Casoni intradermal test is also less frequently used. In this test Casoni antigen (sterile hydatid fluid) is injected intracutaneously. The presence of immediate or delayed wheal-and-flare reaction is read as a positive result. However, as the test has low sensitivity and the potential for a severe local allergic reaction, it is not routinely used.

Hydatid Cyst


Hydatid disease is caused by tapeworm (Echinococcus) infestation. Three species of Echinococcus are of relevance to medicine; the most common Echinococcus granulosus (causes cystic echinococcosis), Echinococcus multilocularis (causes alveolar echinococcosis) and the rarest Echinococcus vogeli (causes). Hydatid disease is endemic to the cattle and sheep rearing regions of the world such as the Middle East, India, Africa, South America, New Zealand, Australia, Turkey and southern Europe. Exposure to food and water contaminated by the feces of an infected definitive host or poor hygiene in areas of infestation can lead to echinococcosis.

Plain radiographs of the involved site may be taken. However, the findings may not be diagnostic and occasionally no findings are seen. Radiographically, well-defined radiolucency surrounded by a slender rim of radiopacity (calcification) may be evident. Ultrasound may show the presence of daughter cysts and hydatid sand (the scoleces, daughter cysts and calcareous corpuscles of Echinococcus tapeworms in the fluid within a primary hydatid cyst). CT and MRI can assess the extent and location of the cyst. Saint Martin and Chiesa (1984) described the presence of ‘falling snowflakes’, an ultrasound sign, as characteristic of hydatid sand. Khanna et al (2007) reported the presence of the ‘water lily sign’ in the contrast-enhanced computed tomography (CECT) of the chest of a patient. They suggest that the water lily sign (presence of a thin walled cystic cavity containing a freely floating endocyst) is pathognomonic for Echinococcus.

Management

Clinical features Hydatid disease primarily affects the liver (55–70%) and the lung (18–35%). However, the less common sites that are affected are the brain (common in children), heart, kidney, ureter, spleen, uterus, pancreas, diaphragm and muscles. Emamy and Asadian (1976), Saxena et al (1983) and Bickers (1970) reported cases of hydatid cyst affecting the parotid gland. The hydatid cyst grows slowly. It is usually diagnosed in the 3rd and 4th decades of life. Symptoms usually 328

manifest gradually unless they cause pressure effects in the brain and eyes. The cysts grow slowly, and a cyst is rarely diagnosed during childhood or adolescence unless the brain or the eyes are involved. Relatively large cysts (more than 5 cm in diameter) tend to produce pressure effects on the adjoining structures. Abdominal tenderness, tender hepatomegaly, fever and chills are common symptoms seen in hydatid disease.

Management and prognosis Hydatid cysts are best managed surgically. However, the use of albendazole (1 month prior to surgery) and 2 weeks of praziquantel (2 weeks prior to surgery) will sterilize the


Figure 31

Hydatid cysts. Courtesy: Dr S Suguna Hemachander, Mamata Medical College, Khammam, Andhra Pradesh

cyst, decrease the chance of anaphylaxis, decrease the tension in the cyst wall (thus reducing the risk of spillage during surgery) and decreases the rate of recurrence. During the surgery 0.5% of silver nitrate or hypertonic saline solution can be injected into the cystic lumen which helps in killing the daughter cysts (Figure 31) which will reduce the opportunity for spread following spillage of the cystic contents.

Trichinosis Trichinosis is caused by the ingestion of undercooked meat containing larvae of the nematode Trichinella spiralis. These larvae enter the lymphatics and blood circulatory system and migrate to well-vascularized striated skeletal muscle. The parasite has a predilection for the most metabolically active muscle groups such as the tongue, diaphragm, masseter, intercostal and pectoral muscles. The average incubation period is between 1 and 30 days. The larvae are estimated to have a 5–10 year life span. Clinical features The disease generally affects adults with no sex predilection. The disease process progresses through various phases such as intestinal phase, parenteral phase and convalescent phase. The intestinal phase of the disease presents with diarrhea, anorexia, weakness and abdominal cramps. Some individuals may present with macular rashes. High degree fever (104⬚F) is another characteristic feature. The intestinal phase lasts for about 1 week. In the parenteral phase the larvae migrate from the intestine into the circulation. This process may continue for many weeks to a few months. Patients may complain of severe myalgia. At this stage, skeletal muscles, CNS, cardiac and respiratory system are involved.

Generally, many months after the initial intestinal phase, encystment and repair takes place. This phase of repair is termed convalescent phase. Patients are usually cachexic and extremely dehydrated in this phase. Miloro and Kinney (1994) reported trichinosis affecting the lateral pterygoid muscle that led to degenerative changes in the TMJ following meniscectomies. Lopez-Lozano et al (1988) reported bilateral facial paralysis secondary to trichinosis. Bruce (1975) and Cheung (1997) reported oral squamous cell carcinoma associated with trichinosis. It is proposed that trichinosis may act as a co-carcinogen along with other chemical carcinogens. Diagnosis The diagnosis of trichinosis involves blood picture, polymerase chain reaction (PCR), imaging techniques and muscle biopsy. Eosinophilia and leukocytosis may be seen in 60% of the patients. The erythrocyte sedimentation rate is elevated. ELISA is 100% sensitive on 50th day of infection. PCR can be used for parasite isolation. CT and MRI with contrast can be used to assess involvement of the CNS. The typical finding is 3–8 mm ring-like lesions. However, muscle biopsy is still the gold standard for diagnosing this condition. Approximately 1 g of muscle tissue is obtained from the deltoid region for histopathological studies. Management and prognosis Untreated patients may die of pneumonia, encephalitis, or cardiac failure in about 4–8 weeks. Antipyretics and analgesics along with albendazole (400 mg/kg 3 times a day for 14 days) or thiabendazole (25 mg/kg twice a day for 5–7 days) will prevent systemic dissemination. Treatment of cysts of the jaws

The surgical treatment of cystic lesions of the jaws were essentially established by Partsch of Germany. The treatment of benign cysts of the jaws is surgical, and there are two main operative procedures: 1. 2.

Marsupialization of the cyst cavity Enucleation of the cyst, followed by: a. Primary closure of the wound, or b. Packing of the cystic cavity until healing by secondary intention has occurred.

Marsupialization of the cyst cavity (Partsch I procedure) It consists of removing the overlying cyst epithelium and bone, thus essentially deroofing the cyst thereby providing a wide communication between the cyst cavity and the 329


oral cavity. The result is a merging of the epithelium of the cyst with that of the oral mucosa. Modifications of marsupialization ❍

A modification of marsupialization is antrocystectomy, which is undertaken for large cysts encroaching upon the maxillary antrum. A wide opening is made between the cyst cavity and the maxillary sinus. After healing, the cyst epithelium merges with the antral epithelium just as it does with the oral epithelium in marsupialization. ❍ Waldron’s technique is a two-staged technique that combines the two standard procedures of marsupialization

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initially, followed by enucleation at a later date when the cystic cavity has shrunk adequately. Enucleation with primary closure (Partsch II procedure) In 1910, Partsch advocated the enucleation of a cyst capsule followed by primary closure, and hence it is known as the Partsch II procedure. In this method, the cyst capsule is completely detached from the bone and shelled out. The cyst cavity is then totally free of epithelium. This surgical procedure leaves the opening to the cyst covered by a mucoperiosteal flap and the space filled with blood clot which eventually organizes to form normal bone.

CHAPTER

Tumors of Orofacial Region Srikant N, Nandita Shenoy, Ravikiran Ongole, Mala Kamboj

➧ Benign Odontogenic Tumors

➧

Traumatic Neuroma Rhabdomyoma Leiomyoma Hemangiomas and Vascular Malformations Hemangioma Vascular Malformations Capillary Malformations Arteriovenous Malformations Lymphatic Malformations Fibroma Giant Cell Fibroma Fibromatoses Myofibroblastoma

Ameloblastoma Squamous Odontogenic Tumor Clear-Cell Odontogenic Tumor Calcifying Epithelial Odontogenic Tumor Adenomatoid Odontogenic Tumor Keratocystic Odontogenic Tumor Odontome Ameloblastic Fibroma, Ameloblastic Fibrodentinoma, and Ameloblastic Fibro-odontoma Benign Cementoblastoma Odontogenic Myxomas Odontogenic Fibroma Desmoplastic Fibroma

➧

Malignant Odontogenic Tumors

Benign Non-odontogenic Tumors

➧

Odontogenic Carcinomas

Squamous Papilloma Verruca Vulgaris (Oral Warts) Verrucous Hyperplasia Condyloma Acuminatum Focal Epithelial Hyperplasia/Heck’s Disease Keratoacanthoma/Self-healing Carcinoma Oral Melanoacanthoma Acquired Melanocytic Nevus Ossifying Fibroma Juvenile Ossifying Fibroma Peripheral Ossifying Fibroma Osteoma Chondroma Benign Chondroblastoma (Codman’s Tumor) Benign Osteoblastoma Giant Cell Granuloma Peripheral Giant Cell Granuloma Pyogenic Granuloma Fibrous Hyperplasia: Denture-related Congenital Epulis of Newborn Lipoma Neurogenic Tumors Schwannoma (Neurilemmoma) Neurofibroma

13

Malignant Ameloblastoma (Metastasizing) Ameloblastic Carcinoma Primary Intraosseous Squamous Cell Carcinoma Solid PIOC Clear Cell Odontogenic Carcinoma Malignant Epithelial Odontogenic Ghost Cell Tumor ➧

Odontogenic Sarcomas Ameloblastic Fibrosarcoma Odontogenic Carcinosarcoma

➧

Epithelial Malignant Tumors Epidermoid Carcinoma Verrucous Carcinoma Basal Cell Carcinoma Malignant Melanoma

➧

Connective Tissue Malignant Tumors Fibrous Tissue Origin Fibrosarcoma Malignant Fibrous Histiocytoma Synovial Sarcoma Cartilage Tissue Origin Chondrosarcoma

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Adipose Tissue Origin Liposarcoma Bone Tissue Origin Osteosarcoma Ewing’s Sarcoma Vascular Origin Kaposi’s Sarcoma Angiosarcoma

ODONTOGENIC TUMORS Odontogenic tumors are lesions of great interest and importance to oral physicians, pathologists and maxillofacial surgeons alike, who for several decades have studied and catalogued these lesions and developed modalities for adequate treatment. It is estimated that approximately 9% of tumors in the oral cavity are odontogenic in nature, out of which 94.8% are benign and 5.2% are malignant, 58.5% of benign odontogenic tumors are ameloblastoma. The age predilection for benign odontogenic tumors is around 28 years and for the malignant odontogenic tumors is more than 40 years. Most of the tumors have mandibular predilection with the ratio of 3.2:1, with the maximum in case of ameloblastoma showing a rate of 12.8:1. There are different ways of defining the content of the term ‘tumor’ in its broadest sense and not restricted to lesions that are definitively neoplastic. Benign tumor is defined as a growth made up of normal cells that have no signs of cancer. These tumors have some characteristic properties such as new uncoordinated growth that spreads by direct extension unlimited growth potential, do not metastasize, are encapsulated and resemble tissue of origin histologically.

BENIGN ODONTOGENIC TUMORS These are defined as lesions derived from epithelial or mesenchymal elements or both that are part of tooth forming apparatus. These comprise a group of lesions which have in common the fact that they arise from the odontogenic tissue. These develop from the epithelial part of the tooth germ, the ectomesenchymal part, or from both. Their behavior varies from frankly neoplastic, including metastatic potential, to non-neoplastic hamartomatous. The pathogenesis of these tumors are not clear but can be attributed to the following etiologies. 332

Muscle Origin Leiomyosarcoma Rhabdomyosarcoma Nerve Origin Neurofibrosarcoma ➧

Lymphoid Origin and Hematological Malignancies

Theories of Tumor Development These tumors have been postulated to arise from enamel organ, remnants, epithelium of odontogenic cysts and oral mucosal buddings. Etiology Various etiological and predisposing factors have been propounded for the development of tumors such as infection, irritation, trauma, dietary deficiency, viruses, hormonal changes and genetic factors. Classification With the first edition of the WHO classification on tumors, about 30 years ago, the terminology and the diagnostic framework became available, and this modern and logically constructed classification greatly intensified research into the subject, and markedly stimulated the urge to publish new findings. In 2000, the International Agency for Research on Cancer (IARC) in Lyon, France started a new book series, WHO Classification of Tumors. The new WHO Blue Books encompass both histopathological and genetic criteria for tumor classification (Table 1). Clinically it also can be classified based on site, age and gender predilection as given in Tables 2–4. The common clinical features of benign tumors include: slow growing and well-circumscribed swelling, bony expansion, displacement and abnormal mobility of teeth and absence of lymphadenopathy. Diagnosis of benign tumors ❍

Complete history: Pain, loose teeth, occlusion, swellings, dysesthesia, delayed tooth eruption ❍ Thorough physical examination: Inspection, palpation, percussion, auscultation ❍ Plain radiographs: Panaromic radiographs and dental radiographs at contrasting angles ❍ Advanced imaging: CT for larger, aggressive lesions

Chapter 13 – Tumors of Orofacial Region

Table 1

Classification of odontogenic tumors

1. Tumors of odontogenic epithelium without odontogenic ectomesenchyme a. Ameloblastoma b. Calcifying epithelial odontogenic tumor c. Squamous odontogenic tumor d. Clear cell odontogenic tumor 2. Tumors of odontogenic epithelium with odontogenic ectomesenchyme with or without dental hard tissue formation a. Ameloblastic fibroma b. Ameloblastic fibro-odontoma c. Ameloblastic fibro-dentinoma d. Odontoameloblastoma e. Adenomatoid odontogenic tumor f. Complex and compound odontoma 3. Tumors of odontogenic ectomesenchyme with or without included odontogenic epithelium a. Odontogenic fibroma b. Odontogenic myxoma c. Benign cementoblastoma 4. Advanced imaging CT for larger, aggressive lesions, ultrasonography for vascular lesions 5. Obtain tissue for histopathological evaluation a. Fine-needle aspiration—to rule out vascular lesions and inflammatory conditions b. Excisional biopsy—small tumors and unilocular tumors c. Incisional biopsy—larger lesions prior to definitive therapy

❍

Obtain tissue – Fine-needle aspiration—rule out vascular lesions, inflammatory conditions – Excisional biopsy—smaller cysts, unilocular tumors – Incisional biopsy—larger lesions prior to definitive therapy.

Ameloblastoma Churchill in 1934, defined ameloblastoma as unicentric, non-functional, intermittent growing anatomically benign but clinically persistent. These are benign, locally aggressive polymorphic neoplasms that consist of proliferating odontogenic epithelium. Classification Leon Barnes has classified ameloblastoma into four types on the basis of behavioral pattern, anatomical location, radiographic appearances and histologic features as follows: 1. 2. 3. 4.

Unicystic Multicystic Desmoplastic Peripheral.

Table 2

Tumors based on the age of predilection

0–25 years

More than 40 years

Adenomatoid odontogenic tumor Ameloblastic fibroma Ameloblastic fibro-odontoma Odontoma Peripheral ossifying fibroma Benign cementoblastoma Ameloblastic odontoma

Calcifying epithelial odontogenic tumor Ameloblastoma Squamous odontogenic tumor Odontogenic myxoma Calcifying odontogenic fibroma

Table 3

Tumors based on the gender of predilection

Male

Female

Ameloblastoma Ameloblastic fibroma Ameloblastic fibro-odontoma Ameloblastic odontoma Calcifying epithelial odontogenic tumor Odontoma Benign cementoblastoma

Adenomatoid odontogenic tumor Squamous odontogenic tumor Odontogenic myxoma Calcifying odontogenic fibroma

Table 4

Tumors based on the site of predilection

Maxilla

Mandible

Adenomatoid odontogenic tumor Calcifying epithelial odontogenic tumor Ameloblastic fibro-odontoma Squamous odontogenic tumor

Ameloblastoma Ameloblastic odontoma Odontoma Benign cementoblastoma Odontogenic myxoma Calcifying odontogenic fibroma

Clinical features Ameloblastomas may be present over a wide age range but are usually diagnosed in the 4th and 5th decades of life, although they can occur in children or the elderly. About 80% of tumors occur in the mandible, of which some 70% arise in the molar region and ascending ramus, 20% in the premolar region, and 10% in the incisor region. In the maxilla, most of these also occur in the molar region but about 15% involves the antrum. The tumor is slow growing and in the early stages may be asymptomatic and discovered as an incidental finding. As the tumor enlarges the patient may become aware of a gradually increasing facial deformity and expansion of the jaw bone (Figure 1A, B). The enlargement is usually bony hard, non-tender, and ovoid or fusiform in outline but in advanced cases, egg-shell crackling may be elicited due to thinning of the overlying bone. However, perforation of 333


bone and extension of the tumor into soft tissues are late features. In the maxilla, even large tumors may produce little expansion as the lesion can extend into the sinus and beyond. Teeth in the area of the tumor may become loosened, but pain is seldom a feature. Radiographically, the ameloblastoma appears most commonly as a multiloculated radiolucency (Figure 2A, B). Roots of teeth involved by the tumor show varying degrees of resorption. As the tumor enlarges it may become associated with an unerupted tooth, particularly an impacted third molar, and the appearances may mimic those of a dentigerous cyst. Less frequently, ameloblastomas present as a single unilocular radiolucency indistinguishable from an odontogenic cyst.

MRI findings Characteristic findings are: multilocularity, mixed solid and cystic components, irregularly thickened walls, papillary projections, and marked enhancement of the walls and septa. Histopathology There are six histologic subtypes: follicular, plexiform, acanthomatous, granular cells, basal cell and desmoplastic. These can be found combined or isolated and not related to prognosis of the tumor. The two main patterns are anastomosing epithelial strands and fields or discrete epithelial islands. The former pattern is called the plexiform (Figure 3) type, the others the follicular (Figure 4A).

Figure 1 A

B

(A) Ameloblastoma involving mandible. (B) Intraoral view of ameloblastoma involving mandible. Courtesy: Dr Foluso Owotade

Figure 2 A

B

(A) Radiographic features of ameloblastoma (honeycomb appearance). (B) Ameloblastoma (soap bubble appearance). Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

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Both may occur within the same lesion. The follicles consist of a central mass of loosely connected, angular cells resembling the stellate reticulum of the normal enamel organ, surrounded by a layer of cuboidal or columnar cells resembling ameloblasts. The nuclei of the latter are situated away from the basal ends of the cells, and this is described as reversed polarity. The follicles are separated by varying amounts of fibrous connective tissue stroma. A variety of changes can occur within the stellate area of the follicles and these include cystic breakdown, squamous metaplasia, and granular cell change. The tumor epithelium in the plexiform type is arranged as a tangled network of anastomosing strands and irregular masses, each of which shows the same cell layers as for the follicular pattern. Thus, each strand or mass is bounded by columnar or cuboidal cells resembling ameloblasts, while the Figure 3

Ameloblast-like columnar cells Stellate reticulum-like cells Interconnecting strands

central area is occupied by stellate reticulum-like cells. Microcyst formation is commonly seen. When extensive squamous metaplasia, often associated with keratin formation, occurs in the central portion of a follicular ameloblastoma, the term ‘acanthomaotus ameloblastoma’ is used (Figure 4B). Differential diagnosis Differential diagnosis of ameloblastoma are given in Box 1. Treatment The therapeutic approach to the ameloblastoma is still a controversy. There are problems to determine incidence, management or recurrence rate. Not every ameloblastoma has the same destructive potential or recurrence tendency. For unilocular cystic lesions in young patients, curettage or enucleation is effective treatment. Solid lesions show high recurrence rates (50–90%) necessitating tumor excision or partial resection of the jaw bone. There seems to be more consensus in the management of ameloblastomas in children, due to the psychological impact of an aggressive resection, and its relationship with growth and function. Key points on ameloblastoma are given in Box 2.

Box 1

Differential diagnosis of ameloblastoma

Dentigerous cyst

Histopathological picture showing plexiform ameloblastoma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

Keratocystic odontogenic tumor Odontogenic myxoma Lateral periodontal cyst

Figure 4 A

B Ameloblastic follicles Cystic degeneration Stellate reticulumlike cells Ameloblastlike cells showing palisading

Ameloblastic follicles Squamous metaplasia

Stellate reticulumlike cells

(A) Histopathological picture showing follicular ameloblastoma. (B) Acanthomatous ameloblastoma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

335


Box 2

Key points related to ameloblastoma

1. A benign but locally invasive neoplasm 2. Molar region/ascending ramus of the mandible is the most common site 3. Typically multilocular soap bubble/honeycomb appearance on radiograph but may be unilocular 4. Follicular and plexiform types are the two main histological patterns

Literature review Ameloblastoma is a tumor with a complex biological character and presents a high recurrence rate even in patients treated with radical therapy. It has been reported that the aggressiveness of ameloblastoma may be related to the histological subtype, in fact. Reichart et al in a review of the literature, found recurrence rates for plexiform, follicular, acanthomatous and unicystic ameloblastoma respectively of 16.7%, 29.5%, 4.5% and 13.7%. Proliferating cell nuclear antigen (PCNA) is a cell cycle related antigen and has been used for the evaluation of the proliferation ability of this tumor. Determinants of biological behavior Location Seventy-five percent in the mandible, but worse prognosis in the maxilla due to spongier bone that facilitates dissemination of the tumor. There is an absence of the ‘contention effect’ that provides the mandibular cortical bone. Arquitectonic pattern This pattern of the lesion does have a prognostic validity. Unicystic has a better prognosis than multicystic or solid.

Unicystic Ameloblastoma Unicystic ameloblastoma, a variant of ameloblastoma first described by Robinson and Martinez in 1977, refers to those cystic lesions that show clinical and radiologic characteristics of an odontogenic cyst but on histologic examination show a typical ameloblastomatous epithelium lining part of the cyst cavity, with or without luminal and/or mural tumor proliferation. This type of ameloblastoma typically presents in a younger age group than other variants of ameloblastoma (2nd to 3rd decade) and occurs predominantly in the mandibular third molar region. Radiographically, it appears as a well-defined unilocular radiolucency, usually associated with an unerupted tooth, and is indistinguishable from a dentigerous cyst. The pathogenesis of the lesion is unknown. Although it may represent ameloblastomatous change in a dentigerous or other type of odontogenic cyst, the possibility that it was a grossly cystic ameloblastoma from the outset cannot be excluded.

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Histopathology Based on the character and extent of tumor cell proliferation within the cyst wall, several histologic subtypes of unicystic ameloblastoma are recognized, which include those of simple cystic nature, intraluminal proliferative nodules and infiltrative tumor islands in the cyst walls. The lesion presents as a cyst lined by ameloblastomatous epithelium comprising a basal layer of columnar cells with polarization of their nuclei away from the basal lamina, covered by a loose, vacuolated layer of stellate epithelial cells. The diagnosis is made based on histopathologic examination. Treatment This variant is believed to be less aggressive, tends to affect patients at a younger age and its response to enucleation or curettage is more favorable than the classic solid or multicystic ameloblastomas.

Peripheral (Extraosseous) Ameloblastoma Ameloblastomas occasionally present in the gingival or alveolar soft tissues without involving bone. Such lesions may arise from the basal cell layer of the oral epithelium or from extraosseous rests of the dental lamina. These are much less invasive than intraosseous tumors and less drastic surgery is required for their treatment. Histologically, these may resemble intraosseous types or consist mainly of basaloid cells.

Odontoameloblastoma (OA) This is an extremely rare mixed odontogenic tumor appearing within the maxillary bone, with both epithelial and mesenchymal components. It is also known as ameloblastic odontoma, although the term ‘odontoameloblastoma’ (OA) was included in the 1971 WHO classification and seems to be more appropriate due to the behavior of the tumor like an ameloblastoma rather than as an odontoma. Thoma et al described in 1944 the first case, ‘it is an ameloblastoma in which focal differentiation into an odontoma appears to have taken place’. Histopathology The marked histological polymorphism of odontogenic tumors make the final diagnosis difficult and in some cases it must be made based on clinical, radiologic and histopathologic features. Moreover, Wachter et al could not histologically differentiate between OA and ameloblastic fibro-odontoma, and therefore suggest that they are the same entity.


Treatment


Commonly, its clinical presentation mimics an odontoma, and therefore the definite diagnosis is based on the histologic analysis following a simple extirpation and curettage.

These tumors show an irregular radiolucent area which may or may not be clearly demarcated from the surrounding normal bone. The radiolucency contains varying amounts of radiopaque bodies due to calcification within the tumor. Radiographic features which have been considered characteristic of CEOT, coronal clustering and ‘driven snow’ patterns, are seen in only a small percentage of cases.

Squamous Odontogenic Tumor The squamous odontogenic tumor is rare. Radiographically, it usually presents as a well-circumscribed radiolucency with a sclerotic border associated with the roots of teeth. Histologically, the tumor consists of irregularly shaped islands of well-differentiated squamous epithelium in a stroma of mature fibrous tissue. It is thought to be derived from the rests of Malassez.

Clear-Cell Odontogenic Tumor (Carcinoma) This is a rare jaw tumor that some consider as a carcinoma because of reported metastases. The histogenesis is unknown, although it is believed to be derived from odontogenic epithelium because of its primary occurrence in the jaws. Clear-cell odontogenic tumor (carcinoma) has been described mostly in women above the age of 60 years. It may cause some pain. Radiographically, the lesion is lucent and either unilocular or multilocular. This rare lesion has an aggressive biologic behavior. Metastases to lung and regional lymph nodes have been reported. Microscopically, nests and cords of clear cells are seen. Some peripheral palisading may be present. Differential diagnosis would include clear-cell variant of calcifying epithelial odontogenic tumor, central mucoepidermoid carcinoma, metastatic renal cell carcinoma, and poorly fixed ameloblastoma.

Histopathology The calcifying epithelial odontogenic tumor consists of sheets of polygonal cells with ample eosinophilic cytoplasm, distinct cell borders, and very conspicuous intercellular bridges. Nuclei are pleomorphic with prominent nucleoli; cells with giant nuclei and multiple nuclei are also present. The epithelial tumor islands as well as the surrounding stroma frequently contain concentrically lamellated calcifications. Stromal deposits of bone and cementum may occur (Figure 5). Treatment The treatment for CEOT has ranged from simple enucleation or curettage to radical and extensive resection such as hemimandibulectomy or hemimaxillectomy. The choice should be individualized for each lesion because the radiological and histological features may differ from one lesion to another. Prognosis The prognosis of the CEOT is good with infrequent recurrence. Malignant behavior is extremely rare. Although it has

Figure 5

Calcifying Epithelial Odontogenic Tumor The calcifying epithelial odontogenic tumor (CEOT) is a rare, benign epithelial neoplasm, also called ‘Pindborg tumor’. It is an aggressive tumor of epithelial derivation usually associated with an impacted tooth in the mandible body/ramus.

Polyherdal epithelial cells

Calcifications

Clinical features It occurs over a wide age range and is about twice as common in the mandible as in the maxilla. The chief sign is cortical expansion and pain is not normally a complaint. Most of the tumors arise in the molar or premolar area and about half are associated with the crown of an unerupted tooth. Although most tumors arise within bone, extraosseous lesions have been reported.

Histopathological picture showing calcifying epithelial odontogenic tumor. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

337


not been established in the literature, 5 years should be the absolute minimum follow-up necessary to assess the healing for this type of odontogenic tumor.

Figure 6 A

Adenomatoid Odontogenic Tumor History Adenomatoid odontogenic tumor (AOT) is a relatively uncommon distinct odontogenic neoplasm that was first described by Steensland in 1905. However, a variety of terms have been used to describe this tumor. Unal et al produced a list containing all nomenclatures for AOT reported in the literatures. Various names like adenoameloblastoma, ameloblastic adenomatoid tumor, adamantinoma, epithelioma adamantinum or teratomatous odontoma have been used before to define the lesion currently called AOT.

B

Definition Philipsen and Birn (1971), defined it as an odontogenic epithelial tumor with an inductive effect on the odontogenic mesenchyme. The nature of the lesion is uncertain and it may be hamartomatous rather than truly neoplastic. Classification Based on the location it can be classified as: ❍ ❍ ❍

Follicular Extra follicular Peripheral.

(A) Intraoral photograph showing obliteration of the labial vestibule and the expansion of the labial and palatal cortical palate on the left side of the anterior maxilla. (B) Case of adenomatoid odontogenic tumor (AOT). Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Clinical features The adenomatoid odontogenic tumor usually presents during the 2nd and 3rd decades of life. The majority of tumors arise in the anterior part of the maxilla (Figure 6A), especially in the canine areas, and there are usually few symptoms apart from a slowly enlarging swelling. Clinical features generally focus on complaints regarding a missing tooth. The lesion usually presents as asymptomatic swelling which is slowly growing and often associated with an unerupted tooth. However, the rare peripheral variant occurs primarily in the gingival tissue of tooth-bearing areas. Unerupted permanent canines are the teeth most often involved in AOT.

Histopathology Lesion is well encapsulated and may be solid or partly cystic; in some cases the tumor is almost entirely cystic. It consists of sheets, strands, and whorled masses of epithelium which in places differentiate into columnar, ameloblast-like cells. The columnar cells form duct or tubule-like structures (hence adenomatoid) with the central spaces containing homogeneous eosinophilic material. These are thought to represent abortive attempts at enamel organ formation. There is very little supporting stroma. Small foci of calcification are scattered throughout the tumor and occasionally tubular dentin and enamel matrix may be seen (Figure 7).

Radiographic features On radiographs it usually appears as a well-defined radiolucency but in some cases calcification within the tumor may produce faint radiopacities (Figure 6B). The lesion is often associated with an unerupted tooth and may simulate a dentigerous cyst (simulating a ‘target’ like appearance). 338

Differential diagnosis Radiologically, it should be differentiated from dentigerous cyst, which most frequently occurs as a pericoronal radiolucency in the jaws. Dentigerous cyst encloses only the coronal portion of the impacted tooth, whereas AOT


Figure 7

Figure 8

Duct-like space Calcifications Epithelial cells (polyherdal to spindle-shaped) Dentinoid Connective tissue

Histopathological picture of adenomatoid odontogenic tumor. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

shows radiolucency usually surrounding both the coronal and radicular aspects of the involved tooth. Common neoplastic causes, such as ameloblastoma, CEOT, ameloblastic fibroma and ameloblastic fibro-odontoma are easily differentiated on histology. Treatment All variants of AOT are well-encapsulated and show an identical benign behavior. Conservative surgical enucleation or curettage is the treatment of choice with only rare recurrence. Literature review The histogenesis of AOT is still uncertain, although recent findings strongly indicate that AOT is derived from a complex system of dental laminae or its remnants. It is often considered as a hamartomatous lesion rather than a true neoplasm.

Calcifying Odontogenic Cyst The calcifying odontogenic cyst (COC) was first described as a distinct entity by Gorlin et al in 1962. This lesion is uncommon and represents about 0.03% of the biopsy lesions and less than 2% of all odontogenic cysts and tumors. Clinical features The calcifying cystic odontogenic tumor occurs over a wide age range but is usually seen below 40 years of age. About 75% are intraosseous and either jaw may be involved. The majority, including those located in the gingival or alveolar soft tissues, arise anteriorly to the first

Radiograph of calcifying odontogenic cyst in the anterior maxilla. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

permanent molar tooth. The lesion usually presents as a slowly enlarging but otherwise symptomless swelling. The COC normally appears as a painless, slow-growing tumor, affecting equally the maxilla and mandible, with predilection to the anterior segment (incisor–canine area). It generally affects young adults in the 3rd to 4th decade, without gender predilection. Radiographically, the lesion appears as a well-defined unilocular or multilocular radiolucent area containing varying amounts of radiopaque, calcified material. It may be associated with the crown of an unerupted tooth (Figure 8). Histologically, the cyst is lined by epithelium which shows a well-defined basal layer of columnar, ameloblast-like cells and overlying layers of more loosely arranged cells that may resemble stellate reticulum. A characteristic feature is the presence within the lining of masses of swollen and keratinized epithelial cells which are usually referred to as ‘ghost’ cells since the original cell outlines can still be discerned. The ‘ghost’ epithelial cells may calcify. Breakdown of the epithelium may release keratinous debris into the supporting connective tissue resulting in a prominent foreign body, giant cell reaction.

Keratocystic Odontogenic Tumor Keratocystic odontogenic tumor is more universally known as odontogenic keratocyst, but has been renamed as there is sufficient evidence that this lesion actually represents a cystic neoplasm. First described by Philipsen in 1956, the odontogenic keratocyst (OKC) was later designated by the WHO as a keratocystic odontogenic tumor (KCOT) and is defined as ‘a benign uni- or multicystic, intraosseous 339


tumor of odontogenic origin, with a characteristic lining of parakeratinized stratified squamous epithelium and potential for aggressive, infiltrative behavior’. WHO recommends the term ‘keratocystic odontogenic tumor’ as it better reflects its neoplastic nature. Clinical features KCOTs comprise approximately 11% of all cysts of the jaws. These occur most commonly in the mandible, especially in the posterior body and ramus regions (Figure 8). They almost always occur within bone, although a small number of cases of peripheral KCOT have been reported. Patients may present with swelling, pain and discharge or may be asymptomatic. Distinctive clinical features include a potential for local destruction and a tendency for multiplicity, especially when the lesion is associated with nevoid basal cell carcinoma syndrome (NBCCS) or Gorlin–Goltz syndrome. In the recent years, published reports have influenced WHO to reclassify the lesion as a tumor. Several factors form the basis of this decision. ❍

Behavior: As described earlier, the KCOT is locally destructive and highly recurrent.

❍

Histopathology: Studies showed the basal layer of the KCOT budding into connective tissue.

Histopathology Histologically, these cysts are formed with a stratified squamous epithelium that produces orthokeratin (10%), parakeratin (83%), or both types of keratin (7%). The epithelial lining appears corrugated when viewed under a microscope. A well-polarized hyperchromatic basal layer is observed, and the cells remain basaloid almost to the surface. No rete ridges are present; therefore, the epithelium often sloughs from the connective tissue. The epithelium is thin, and mitotic activity is frequent; therefore, OKCs grow in a neoplastic fashion and not in response to internal pressure. The lumen frequently is filled with a foul-smelling cheese-like material that is not pus but rather collected degenerating keratin (Figure 9A–C). Radiographic features Radiographically, KCOT presents predominantly as a unilocular radiolucency with well-developed sclerotic borders. These may also present as a multilocular radiolucency or

Figure 9 A

Cystic space Stratified squamous parakeratinized epithelium Palisaded basal cells

B

Corrugated parakeratin layer Connective tissue

C

D

(A) Histopathological features of keratocystic odontogenic tumor. (B) and (C) Gross specimens of the resected tumor, showing removal of the cystic lining and the resultant hollowing in the bone. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore. (D) Orthopantomograph showing well-defined scalloped radiolucent area extending across the midline. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

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unilocular radiolucency at varying ratio. The multilocular appearance can be more of a unilocular with scalloped borders lacking true compartment formation. Odontogenic keratocysts of the maxilla are smaller in size compared to the mandible. When they are large, they tend to expand bone. No difference in site distribution is seen between unilocular and multilocular cysts. These lesions can also present as a small and oval radiolucency between teeth simulating a lateral periodontal cyst. They can also appear as a radiolucency simulating a residual apical periodontal cyst (Figure 9D). ❍ ❍

On CT: Increased attenuation areas in cystic cavity. On MRI: Heterogeneous intermediate signal on T1 and high signal on T2 weighted images.

Treatment A review of the literature suggests that recurrence rate is relatively low with aggressive treatment, whereas more conservative methods tend to result in more recurrences. Recurrence KCOTs have a high recurrence rate, reportedly between 25% and 60% and when associated with NBCCS, the recurrence rate is about 82%.

incisors and canines, followed by the antero- and posteroinferior regions. Complex odontomas are more often found in the area of the second and third lower molars. An increased prevalence of these tumors is observed in children and adolescents, with few differences in relation to patient sex. These lesions are normally diagnosed by routine radiological studies in the 2nd and 3rd decades of life. As regards their pathogenesis, odontomas have been associated with antecedents of trauma during primary dentition, as well as with inflammatory and infectious processes, hereditary anomalies (Gardner’s syndrome, Hermann’s syndrome), odontoblastic hyperactivity, or alterations of the genetic components responsible for controlling dental development. Radiographic features Odontomas manifest as a dense radiopaque lesion surrounded by a thin radiotransparent halo. Three developmental stages can be identified, based on the radiological features and degree of calcification of the lesion at the time of diagnosis: 1. 2. 3.

Odontome History Paul Broca (1867), defined it as a tumor formed by the overgrowth of transitory/complex dental tissues. 1946 WHO classification 1. Germinated composite odontome 2. Compound composite odontome 3. Complex composite odontome 4. Dilated odontome 5. Cystic odontome In 1950 Gorlin eliminated the term ‘composite odontome’. Recent WHO classification 1. Complex odontome: Malformation in which all the dental tissues are represented, individual tissues being mainly well formed but occurring in a more or less disorderly pattern. 2. Compound odontome: Malformation in which all the dental tissues are represented, in a more orderly pattern; consists of tooth-like structures called the tooth-lets.

First stage is characterized by radiotransparency due to the absence of dental tissue calcification. Second or intermediate stage presents partial calcification. Third or classically radiopaque stage exhibits predominant tissue calcification with a surrounding radiotransparent halo.

Compound odontomas show an irregular radiopaque image with variations in contour and size, composed of multiple radiopacities corresponding to the so-called denticles. In the complex type of lesion radiopacity is not specific; rather, a disorganized, irregular single or multiple mass is identified (Figure 10). Histology Complex odontomas consist of a usually well-delineated mass of dental hard tissues in a haphazard arrangement. The bulk of the lesion consists of dentin recognizable by the presence of tubuli. Enamel plays a minor role, usually confined to small rims in cavities in the dentin mass. The stroma consists of mature fibrous connective tissue. Sometimes, odontomas may contain areas identical to the calcifying odontogenic cyst, including ghost cells consisting of tiny teeth that may vary in number from only a few to numerous. These teeth do not resemble normal teeth, but are usually cone shaped.

Clinical features Odontomas are the most common maxillary tumors, and according to different sources in the literature account for 22–67% of all odontogenic maxillary neoplasms. As to their locations, most are found in the areas of the upper

Prognosis Odontomas are benign tumors that sometimes produce no symptoms and constitute casual findings of routine radiological studies. However, they usually tend to cause 341


Figure 10

Orthopantomograph showing odontoma. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

signs and/or symptoms such as delayed eruption. If no signs or symptoms appear then the lesions go undetected. A very infrequent situation in relation to odontomas can be in the form of eruption.

Basal Cell Nevus Syndrome or Gorlin–Goltz Syndrome Basal cell nevus syndrome (BCNS) was first described by Gorlin and Goltz in 1960, is an inherited disorder, with a high penetration and variable phenotype expression. It has a low incidence, around 1 in 56,000 persons. Its etiology is unknown, although the latest genetic studies relate this syndrome to a disturbance at gene level of chromosome 9 (9q22.3–q31), which is passed from one generation to the next, although there are only sporadic cases due to spontaneous mutation. Clinical features It is characterized by a series of associated manifestations, the most common being maxillary keratocysts and cutaneous basal cell carcinomas, and other less frequent ones which can be present, such as cardiac disturbances such as persistent ductus arteriosus, characteristic facies in the form of mandibular prognathia, frontal and parietal prominence, marked superciliary arches, wide bridged nose and hypertelorism, skeletal (brachymetacarpalism of the fourth and fifth fingers, vertebrae problems, costal synostosis or bifid ribs), skin (dermoid cysts, lipomas), neurological (congenital hydrocephalus, calcification of the cerebral falx, learning difficulties), sight such as blindness, congenital cataracts, strabismus), hormonal (hypogonadism) or associated with other malignant neoplasias. The appearance of pitted depressions, due to the lack of corneous 342

strata in the palms of the hands and soles of the feet, is the only pathognomonic data which has been described in the literature regarding this condition.

Ameloblastic Fibroma, Ameloblastic Fibrodentinoma and Ameloblastic Fibro-odontoma The ameloblastic fibroma is a rare benign tumor in which both the epithelial and mesenchymal elements are neoplastic. In ameloblastomas only the epithelium is neoplastic. It is important to differentiate the lesion from ameloblastoma since, unlike the latter, it does not exhibit a locally invasive growth pattern. Clinical features The ameloblastic fibroma usually occurs in a younger age group than ameloblastoma and is uncommon in above 21 years of age. It presents as a slowly enlarging painless swelling and arises most frequently in the premolar or molar region of the mandible. Radiographic features It is a well-circumscribed lesion and does not require the radical excision that may be necessary to affect cure with the ameloblastoma. Radiographically, the tumor appears as a well-defined, usually unilocular, radiolucency. It may be associated with an unerupted tooth and mimic a dentigerous cyst. Histopathology The tumor consists of proliferating strands and clumps of odontogenic epithelium lying in highly cellular fibroblastic


Box 4

Figure 11

Differential diagnosis of ameloblastic fibroma

❍ CEOT Highly cellular mesenchymal stroma

Proliferating odontogenic epithelium

Histopathological slide of ameloblastic fibroma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

Box 3

Key points on ameloblastic fibroma and related lesions

1. Ameloblastic fibroma and fibro-odontoma are benign neoplasms 2. Ameloblastic fibro-odontoma is probably a hamartoma 3. Well-circumscribed and occur mainly in 1st and 2nd decades 4. Comprises odontogenic epithelium and richly cellular mesenchyme 5. Fibrodentinoma contains dentin 6. Fibro-odontoma enamel and dentin

tissue resembling the dental papilla of the developing tooth. The epithelial component shows a peripheral layer of cuboidal or columnar cells which encloses a few stellate reticulum-like cells (Figure 11). The appearances are similar to ameloblastoma but the stellate cells are much less abundant and cyst formation is unusual. In some lesions dentin may be present and such tumors may be designated ameloblastic fibrodentinoma. The dentin is usually poorly formed and includes entrapped cells. Tubular dentin is rare. Literature review Tumors previously classified as dentinomas are now thought to be examples of the ameloblastic fibrodentinoma. The ameloblastic fibro-odontoma is a tumor which shows further inductive changes leading to the formation of enamel. Although the ameloblastic fibroma and fibrodentinoma are benign neoplasms, it is probable that the ameloblastic fibro-odontoma is a hamartoma. Histologically, it is difficult to distinguish from a developing complex odontome, to which it is probably closely related. Key points on ameloblastic fibroma are given in Box 3. Differential diagnosis is given in Box 4.

❍ Odontoma ❍ COC ❍ AFO

Benign Cementoblastoma Cementum is a modified form of bone and, with the exception of the cementoblastoma, disorders of the jaws containing cementum-like tissue are now classified as lesions of bone. The cementoblastoma is still classified as an odontogenic tumor because of its unique association with the root of a tooth. Cementoblastoma is classified as an odontogenic tumor because of its unique association with the root of a tooth. This is one characteristic feature that differentiates it from osteoblastoma of bone. Clinical features The cementoblastoma is a rare benign neoplasm most frequently seen in patients below 25 years of age. It usually arises in the molar or premolar area of the mandible and is attached to the root of a tooth. Most cases involve the mandibular first permanent molar. It presents as a slowly enlarging swelling which sometimes gives rise to pain, but the involved tooth is vital. Pain is main symptom, pain is severe and not relieved by NSAIDs. Radiographic features Radiographic features show a well-demarcated, mottled, or dense radiopaque mass with a radiolucent margin attached to the root of a tooth which usually shows resorption. Histologic features Tumor consists of a mass of calcified cementum-like tissue containing scattered cells lying in lacunae. Around the periphery and in other actively growing parts of the lesion, extensive sheets of uncalcified matrix formed by plump, deeply staining cementoblasts may be seen. Prognosis Lesions which are incompletely removed may recur.

Odontogenic Myxoma These are uncommon, benign neoplasms arising from mesenchymal odontogenic tissue which are locally invasive neoplasm consisting of rounded, angular cells lying in abundant myxoid stroma. 343


Clinical features

Desmoplastic Fibroma

Commonly seen in the 3rd decade of life with higher prevalence among women, and occurs mainly in the mandibular molar area. Presents as painless swelling or incidental finding.

This is a rare fibrous lesion of the jaws. It is benign, but aggressive, exhibiting a biologic behavior similar to fibromatosis of soft tissue or low-grade fibrosarcoma. It is seen in young adults, especially in the mandible. Radiographically, desmoplastic fibroma is lucent, with margins that may be distinct or poorly defined. Histologically, these lesions exhibit an interlacing or fascicular growth pattern of benign fibroblasts and collagen. They neither contain epithelial rests nor make bone. Multinucleated giant cells are rarely present. Desmoplastic fibroma should not be confused with central low-grade osteosarcoma which is more cellular and has cytologic atypia.

Radiographic features Often multilocular with internal osseous trabeculae arranged in ‘tennis racket’ pattern. MRI: Prolongation of T1 and T2, reflecting rich myxoid stroma. Gradual contrast enhancement is typically seen on contrast-enhanced images. Histopathology Odontogenic myxomas consist of rather monotonous cells with multipolar or bipolar slender cytoplasmic extensions that lie in a myxoid stroma. Nuclei vary from round to fusiform in appearance. Binucleated cells and mitotic figures are present, but scarce. Occasionally, the lesion contains odontogenic epithelial rests. The lesion spreads into the jaw bone without any encapsulation, thereby engulfing neighboring cancellous bone. Treatment Excision or partial resection of the jaw bone with high rate of local recurrence due to infiltrative growth pattern enhancement is typically seen on contrast-enhanced images.

Odontogenic Fibroma This jaw tumor is considered a neoplasm that is derived from periodontal ligament or pulp-related fibroblasts. It is a tumor of adults and appears as a well-defined radiolucency in either jaw. It is not, however, particularly aggressive, and it infrequently recurs after simple curettage. Histopathology These lesions are more collagenous than myxomas but may range from myxofibrous to densely fibrous. Characteristically seen in odontogenic fibromas are few to many islands and strands of bland odontogenic epithelium. Calcific deposits may also be found. A variant (granular cell odontogenic fibroma), in which granular cells are seen in the connective tissue, has been described. The behavior of this tumor does not appear to be different from odontogenic fibroma. Abundant rest proliferation in follicular sacs can occasionally simulate the appearance of odontogenic fibroma or ameloblastic fibroma. Clinicopathological correlation is important for the diagnosis of these lesions. 344

Treatment Ennucleation/excision or partial resection of the jaw bone.

BENIGN NON-ODONTOGENIC TUMORS ❍ ❍ ❍ ❍

Squamous Papilloma Verruca vulgaris Verrucous hyperplasia Condyloma accuminata.

The primary disease processes that give rise to swellings and tumors of the oral cavity include cysts, mucous extravasations and retention in the minor salivary glands, foci of granulation tissue and inflammation, abscesses and connective-tissue proliferations that are well-defined or encapsulated, as well as infiltrative sarcomas. Both epithelial and connective-tissue disease processes can present as tumors. From a clinical perspective the three most important defining characteristics of any soft tissue swelling are location, coloration, and palpable nature. Location Certain diseases tend to occur in specific sites to the exclusion of others, as given in Table 5. Coloration It is dependent upon the tissues present in the mass and the depth of the lesion. In general, yellowappearing lesions are comprised of lymphoid tissue or adipose tissue, red swellings are vascular, blue swellings are mucinous or venous, and brown swellings contain melanin or blood pigments. Lesions with normal mucosal pink coloration are generally composed of fibrous tissues or some other tissues lying deeper in the connective tissues (Table 6). Palpable nature Based on the consistency they can be grouped as shown in Table 7. Human papillomavirus (HPV) and oral lesions given in Box 5.


Table 5 Soft tissue swellings according to site

Table 7

Site

Type of lesion

Palpation characteristic

Swelling

Lips and buccal mucosa

Fibroma, mucocele, mesenchymal tumor, salivary tumor

Soft, fluctuant

Gingiva

Parulis, pyogenic granuloma, peripheral fibroma, peripheral giant cell granuloma, peripheral ossifying fibroma, gingival cyst, peripheral odontogenic tumors

Mucocele, ranula Developmental cysts Sialocysts Gingival cysts Parulis Abscess

Soft non-fluctuant

Lipoma Fibroma Organized mucocele

Firm fixed

Mesenchymal tumors Granulomas Salivary adenomas Adnexal skin tumors

Firm movable

Granular cell tumor Seborrheic keratosis Keratoacanthoma Fibromatosis

Palate

Abscess, torus, salivary gland tumor

Dorsum of the tongue

Fibroma, granular cell tumor, pyogenic granuloma

Ventral aspect of the tongue

Mucocele, ranula, lymphoid aggregates, lymphoepithelial cyst, osteocartilaginous choristoma

Table 6

Soft tissue swellings according to their color

Soft tissue swellings according to their consistency

Color

Soft tissue mass

Blue-purple

Hemangioma, varix, hematoma, peripheral giant cell granuloma, mucocele, Kaposi sarcoma

Red

Hemangioma, pyogenic granuloma, Kaposi sarcoma

Brown

Nevus, hematoma, seborrheic keratosis, Kaposi sarcoma, melanoma

Box 5

Black

Melanoma

Verruca vulgaris 2, 4

Yellow-orange

Lymphoid aggregates, lymphoepithelial cyst, lipoma, granular cell tumor

Squamous papilloma 6, 11

Human papillomavirus and oral papillary lesions

Condyloma acuminatum 6, 11 Focal epithelial hyperplasia 13, 32 Squamous cell carcinoma 16, 18, 31, 33, 35

Classification based on the tissue of origin is given in Table 8. Papillary lesions of oral cavity Papillary lesions are those that are tumefactive with a cauliflower surface. Some are pedunculated, others are sessile. Some are single, others are multiple or diffusely involve broad areas of the oral mucosa. The vast majority of papillomas are associated with or indeed caused by members of the HPV family, yet there are a few papillary growths that have not been associated with HPV. One lesion in particular, molluscum contagiosum, is caused by a member of the poxvirus group.

Squamous Papilloma A benign epithelial proliferation induced by HPV in most cases; several subtypes have been identified, especially HPV-6 and 11.

Proliferative verrucous leukoplakia 6, 11, 16

In the form of white lesion, usually solitary; may be multiple. Squamous papilloma affects the buccal mucosa, soft palate, uvula, tongue and gingiva. Histopathology Epithelial hyperplasia with fibrovascular cores may be seen. The papillary projections may be sharp to blunt (Figure 12). Epithelium may be dysplastic in some lesions from HIV-positive patients. Diagnosis Lesions of the condyloma acuminatum, verruca vulgaris, focal epithelial hyperplasia and verrucous carcinoma may mimic lesions of squamous papilloma.

Clinical features Exophytic, papillary mass, measuring less than 1 cm, usually pedunculated and soft in texture.

Treatment Surgical excision is the preferred modality of management. 345


Table 8

Classification based on the tissue of origin

Epithelial

Papilloma Keratoacanthoma Nevus

Connective tissue

Fibroma Giant cell fibroma Peripheral ossifying fibroma Lipoma

Vascular tissue

Hemangioma AV fistula Carotid body tumor

Lymphatic origin

Lymphangioma

Neural tissue

Neurilemmoma Neuroma Neurofibroma Neurofibromatosis

Muscular origin

Leiomyoma Rhabdomyoma

Bone origin

Osteoblastoma Osteoid osteoma Benign osteoblastoma Desmoplastic fibroma of bone

Cartilaginous

Chondroblastoma

Histopathology Histological changes can be in the form of surface hyperkeratosis, granulosis and koilocytosis. AIDS-associated oral warts may appear dysplastic microscopically. Differential diagnosis

AV: Arteriovenous.

❍ ❍ ❍ ❍ ❍

Focal epithelial hyperplasia Keratoacanthoma Papillary squamous carcinoma Squamous papilloma Condyloma acuminatum.

Treatment

Hyperplastic epithelium

Treatment may involve surgery, laser surgery, or cryotherapy. It should be noted that HPV survives in aerosol. Topical 5-fluorouracil treatment has been used on external lesions, but should be avoided in fair individuals as it can cause hyperpigmentation. It should be noted, however, that this is a specialized treatment and should only be used by those experienced with the use of this topical medication. Lesions tend to recur after treatment.

Connective tissue core

Verrucous Hyperplasia

Figure 12

Blood vessels

Histopathological slide of papilloma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

Verruca Vulgaris (Oral Warts) Infection of mucosal epithelium by members of the human papillomavirus group—usually HPV-2, 4, 6, or 11. Clinical features Papular to nodular and exophytic appearance. The warts may be cauliflower-like, spiked, or raised with a flat surface, 346

perioral skin lesions may be brownish. The oral mucosal lesions are usually white to pink. It can be pedunculated or broad based. Sites of predilection include the lips, palate, and attached gingiva. The incidence of oral warts due to HPV has dramatically increased in the potent antiretroviral therapy era. Diagnosis can be based on the clinical, microscopic and immunohistochemical demonstration of HPV common antigen.

Lesion with an unknown etiology, even though tobacco (smokeless) association has been reported, the role of HPV is unclear and is even hypothesized to be a possible precursor to verrucous carcinoma. Clinical features Presents clinically as exophytic, papillary, keratotic fronds of epithelium or can be a part of the proliferative verrucous leukoplakia spectrum. Histopathology Histologic features are in the form of papillary to verruciform surface projections in which keratin varies in thickness. They can be broad, bosselated epithelial ridges with well-differentiated cellular features and can even mimic an early verrucous carcinoma.


Differential diagnosis Verrucous carcinoma, papillary squamous cell carcinoma and proliferative verrucous leukoplakia can be considered in the differential diagnosis. Treatment Excision or ablation (e.g. laser, electrocautery) has been used successfully in the management of verrucous hyperplasia.

Condyloma Acuminatum Described in Chapter 22 on Sexually Transmitted Diseases on page 630.

below the epithelium; marked pseudoepitheliomatous hyperplasia. Diagnosis Clinical appearance can be confusing, the symmetrical nature, oval or round configuration, and keratotic core are indicative of KA. Differential diagnosis ❍ ❍ ❍

Squamous cell carcinoma Molluscum contagiosum Verruca vulgaris.

Treatment

Focal Epithelial Hyperplasia/Heck’s Disease Described in Chapter 6 on Red and White Lesions on page 165.

Keratoacanthoma/Self-healing Carcinoma Keratoacanthoma (KA) is usually encountered on the facial skin and lips yet can also arise, albeit rarely, in the mouth.

Observation and careful follow-up local excision, cryotherapy and intralesional chemotherapy have also been tried. Wong et al in their study reported oral isotretinoin to be an effective treatment of multiple as well as solitary keratoacanthomas. Canas et al reported that successful treatment was achieved with administration of oral isotretinoin. Spieth et al reported that intralesional methotrexate shows to be an effective, easy and inexpensive alternative.

Etiology Unknown, may be related to several factors, as follows:

Oral Melanoacanthoma (Melanoacanthosis)

❍ ❍

Oral melanoacanthoma is a benign acquired pigmentation of the oral mucosa characterized by dendritic melanocytes dispersed throughout the epithelium. The lesion appears to be a reactive process.

❍ ❍ ❍ ❍

Viral—HPV subtypes 11, 13, 24, 33, 57 Altered expression of cell cycle proteins including cyclin E, p53, PCNA Keratinocyte dedifferentiation reflected in deficient desmoglein production Immunosuppression Sun damage May represent a highly differentiated form of squamous cell carcinoma.

Clinical features Clinically these are characterized by a tumefaction with round, mounded borders that surround a central core of hard keratinized material that may appear pale yellow or brown. The brown appearance is caused by extrinsic pigments that become incorporated with the excessive keratin. Intraoral KAs are generally non-pigmented. They can be solitary on sun-exposed areas, including lip. They initially present as erythematous papule with rapid growth over 4–8 weeks; extremely rare intraorally.

Clinical features Oral melanoacanthoma is seen in blacks, shows a female predilection, and occurs in the 3rd and 4th decades of life. The buccal mucosa is the most common site of occurrence. The lesion is smooth, flat or slightly raised, and dark-brown to black in color. Histopathologic features Numerous benign dendritic melanocyte cells that are normally confined to the basal cell layer scattered throughout the lesional epithelium. Basal layer melanocytes are also present in increased numbers. Treatment and prognosis

Histopathology Histopathology shows keratin plus normal, peripheral epidermis and mature, premature keratinization; no invasion

Because of the alarming growth rate of oral melanoacanthoma, incisional biopsy is usually indicated to rule out the possibility of melanoma. 347


Acquired Melanocytic Nevus (Nevocellular Nevus, Mole) Nevus refers to congenital/developmental malformations. Acquired melanocytic nevus represents localized proliferation of cells from the neural crest, called ‘nevus cells’. They are called as ‘first cousins’ of melanocytes and represent the most common human ‘tumors with white adults reported to have an average to 40 cutaneous nevi per person but intraoral lesions are rare.

348

Treatment No active intervention is required, unless in case of clinical suspicion and cosmetic concern.

Ossifying Fibroma Described in Chapter 19 on Bone Diseases and Fibroosseous Lesions on page 571.

Clinical features

Juvenile Ossifying Fibroma

Acquired melanocytic nevi begin to develop during childhood and most cutaneous lesions present before 35 years of age with no sex predilection even though racial differences are seen. Head and neck region is a common site of involvement. Junctional nevus is a sharply demarcated, brown or black macule less than 6 mm in diameter. When nevus cells proliferate become slightly elevated soft papule it is called as compound nevus. The degree of pigmentation becomes less; most lesions appear brown or tan. Nevus gradually loses its pigmentation, the surface may become somewhat papillomatous, and hairs may be seen growing from the center intradermal nevus remains less than 6 mm in diameter. Ulceration is not a feature unless placed at a region of recurrent trauma. Intraoral melanocytic nevi are distinctly uncommon, they may arise on the palate or gingiva, although any oral mucosal site may be affected. More than one in five intraoral nevi lack clinical pigmentation and females are more affected; the average age at diagnosis is 35 years.

Described in Chapter 19 on Bone Diseases and Fibroosseous Lesions on page 572.

Histopathologic features

Pathogenesis

The acquired melanocytic nevus is characterized by a benign proliferation of small, ovoid nevus cells, produce melanin. Nevus cells typically lack the dendritic processes like melanocytes tend to be organized into small, round aggregates (thèques). When lesional cells are found at the junction between the epithelium and the connective tissue, this stage is known as a junctional nevus. When the groups of cells begin to drop off into the underlying dermis or lamina propria. Within the underlying connective tissue, the lesion then is called a compound nevus. When found only within the underlying connective tissue this stage is called an intradermal nevus, the intraoral counterpart is called an intramucosal nevus. The superficial cells typically appear larger and epithelioid, with abundant cytoplasm and the middle portion of the lesion have less cytoplasm, are seldom pigmented, and appear much like lymphocytes. Deeper nevus cells appear elongated and spindle-shaped, much like Schwann cells or fibroblasts.

Chronic irritation causes an abundance of fibrous connective tissue containing immature bone. Often patients traumatize the area again, and this promotes a cycle of more exuberant tissue formation and varying surface ulceration. There is a close resemblance to the pyogenic granuloma. The lighter surface color is due to hyperkeratosis produced through trauma.

Peripheral Ossifying Fibroma Peripheral ossifying fibromas (POF) are reactionary lesions thought to originate from submucosal connective tissue and the periodontal ligament. The lesions are often confused with either the more vascular (red to pink) pyogenic granuloma, or the fibroma that demonstrates more tissue colored lesions. Peripheral odontogenic ossifying fibromas are classified most often in literature as reactionary lesions rather than a benign tumor. Etiology It is thought that an exuberance of tissue is caused by an initiating factor such as calculus, or a food particle that becomes lodged in the sulcus, creating an initial irritation.

Clinical features Peripheral odontogenic ossifying fibromas occur more often in females and can be anywhere from 1 to 2 cm in size. They occur most often in young adults, originate from the periodontal ligament, and occur exclusively on the gingiva as a sessile or pedunculated mass. The lesions are normally found on the attached gingiva. The abundance of tissue is usually the same color as the surrounding tissue, with a smooth surface. Sometimes the surface may be more textured, depending upon the existing oral forces


Treatment and prognosis

Figure 13

The treatment of choice is excision of the lesion with the periodontal ligament, and no recurrence is expected in most instances. Complete removal is indicated since peripheral odontogenic ossifying fibromas can reoccur when they are not adequately removed. It is advised that the lesion be removed down to the periosteum and that the adjacent teeth be scaled to remove any remaining irritants. This will assist in lowering the rate of recurrence.

Osteoma Benign, slowly growing lesion composed of well-differentiated mature bone with a predominant lamellar structure. It is usually an incidental finding or painless hard swelling. Peripheral ossifying fibroma in the interdental regions of the upper lateral and canine. Courtesy: Department of Oral Medicine, KLE Institute of Dental Sciences, Bangalore

Etiology Sporadic form is idiopathic or may be a component of Gardner’s syndrome. Clinical features

Figure 14 Stratified squamous epithelium

Sporadic form with frontal and sphenoid sites predisposed or may be multiple. Solitary lesions are rare in jaws. Radiographic findings Well-circumscribed, dense, sclerotic. May be subperiosteal or medullary (Figure 15).

Connective tissue

Histopathology

Area of ossification

Histology reveals dense areas of normal cortical and trabeculae (Figure 16). Diagnosis

Histopathological slide of peripheral ossifying fibroma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

❍ ❍

Radiographic features Microscopic features: Normal cortical and trabecular bone.


and location in the patient’s mouth. Additionally, the surface epithelium may be more of a dark color depending upon the amount of trauma and inflammation that is produced with the lesion (Figure 13). Histopathologic features Microscopically, the tissue is composed primarily of cellular fibroblasts with various types of calcification including bone, cementum and dystrophic calcification. The surface epithelium may exhibit varying degrees of ulceration (Figure 14).

❍ ❍ ❍ ❍

Tori, exostoses Ossifying fibroma Osteoblastoma Focal sclerosing osteitis.

Treatment Local resection, if compromising. Prognosis Little recurrence potential when associated with Gardner’s syndrome, malignant conversion of intestinal polyps is assured.

349


Clinical features

Figure 15

Chondromas may be seen at any age and has no gender preference. It is seen as a slowly growing, non-painful swelling. The anterior maxilla, which is the site where vestigial cartilage rests are found, is the most commonly affected site. The posterior regions of the mandible (usually beyond the cuspids), condyle, coronoid process and the body of the mandible are the most commonly affected sites. The soft tissue chondromas are usually seen affecting the soft palate, tongue and buccal mucosa. Syndrome association

Lower occlusal view showing osteoma. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 16

Compact bone

Haversian system

Histopathological picture of osteoma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

Chondroma Chondromas are benign tumors of mesenchymal origin composed of multiple nodules of mature hyaline cartilage. It is estimated that chondromas represent approximately 2.38% of osteocartilaginous tumors. Chondromas are well-recognized tumors in the bony skeleton. However, these are relatively rare in the jaw bones. Based on the location chondromas are classified as enchondromas (account for 80% of these tumors, located in the medullary cavity of the long bones, diaphysis), juxta articular chondromas (related to extraskeletal cartilage), extraskeletal chondroma or soft tissue chondroma (rare cartilaginous tumor, involving hands, feet, tongue and buccal mucosa). 350

Enchondromas are associated with Maffucci’s syndrome and Ollier’s disease. Enchondromatosis or Ollier disease (WHO terminology) is defined by the presence of multiple enchondromas and characterized by an asymmetric distribution of cartilage lesions that can be extremely variable (in terms of size, number, location, evolution of enchondromas, age of onset and of diagnosis, requirement for surgery). The condition in which multiple enchondromatosis is associated with soft tissue hemangiomas is known as Maffucci’s syndrome. Maffucci’s syndrome is a rare non-hereditary mesodermal dysplasia characterized by the presence of multiple hemangiomas of the soft tissue and multiple enchondromas (usually of the phalanges and long bones). The syndrome can be associated with benign or malignant tumors (parathyroid adenoma, pituitary adenoma, hemangioendothelioma, adrenal tumor, ovarian tumor, chondrosarcoma and breast cancer). Radiographic features Radiographically, chondromas exhibit ill-defined to occasional well-defined radiolucent areas. Some lesions may show the presence of radiopaque foci interspersed within the radiolucent zones. Extensive lesions may cause destruction of the cortical plates. Root resorption may be seen. Histopathologic features Histologically chondromas are characterized by the presence of lobulated masses partially subdivided in nodules of hyaline cartilage immersed in a fibrous stoma. Frequently there are calcified foci and even ossification. The eosinophilic cytoplasm may exhibit vacuoles (Figure 17). Management Long-standing chondromas can undergo a sarcomatous change. Surgical resection is the treatment of choice. However, recurrences have been reported.



Figure 17

Connective tissue capsule

Chondrocytes in lacunae Hyaline cartilage

Histopathological feature of chondroma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

Benign Chondroblastoma (Codman’s Tumor) Ernest Amory Codman, in 1931 first described this tumor as a variant of the giant cell tumors. However, in the 1940s Jaffe and Lichtenstein renamed the Codman’s tumor as benign chondroblastoma in accordance to its chondroblastic origin. Chondroblastoma is a rare tumor of bones accounting for about 1% of all bone tumors. It is rarely seen in the maxillofacial region. In the long bones, chondroblastoma is believed to arise from the cartilage of the growth plates, and in the temporomandibular region, possibly from the cartilage of the condylar process.

Polygonal chondroblasts are the main proliferating cells. These have long or oval-shaped nuclei and a prominent cytoplasmic membrane with cytoplasmic granules consisting of hemosiderin pigment. Occasionally, multinucleated cells can be found. Chondroid matrix can be found outside the cytomembrane where small calcifications may occur. The most important feature is the linear deposition of calcification surrounding individual chondroblasts, giving rise to a chicken-wire pattern (Figure 17). Immunostaining occasionally can be helpful in confirming the diagnosis of chondroblastoma. S-100 protein is strongly positive. Chondroblastomas are also positive for vimentin. Reticulin stain reveals a honeycomb pattern. Management and prognosis Chondroblastoma generally exhibits local aggressive behavior with infiltration and invasion to the soft and hard tissues around. Surgical resection is the main treatment modality. It is estimated that, when located in the long bones, the curettage of this tumor has a success rate of 90%. When located in the temporomandibular region, the resection can be difficult because of the complex anatomical structure, which results in a higher recurrence rate. It is estimated that the recurrence rate is about 55%. Radiation should be avoided because of the risk of developing a chondrosarcoma.

Benign Osteoblastoma Benign osteoblastoma is an osteoid and bone forming benign tumor of bone. It is an uncommon lesion that accounts for 1% of all bone tumors and about 3% of all benign bone tumors.

Clinical features Chondroblastomas are usually seen in the 3rd decade of life. Males are slightly more commonly affected than females (1.86:1). In the maxillofacial and the temporal region, mandible, maxilla and the TMJ have been reported to be affected. Patients may complain of a local mass, auditory dysesthesia, and limitation of mouth opening. Radiographic features On radiographs, chondroblastoma affecting the extremities appears as round to ovoid radiolucencies which are well-defined, expansile in nature and usually exhibit a sclerotic margin. Chondroblastomas affecting the condyle have been reported to have caused resorptive defects and occasionally enlargement of the condyle.

Clinical features Benign osteoblastoma occurs in the 2nd and 3rd decades of life, but the age range is 5–78 years. As to sex incidence, there is male predominance 2–3:1. Benign osteoblastoma can arise in any bone, but there is a predilection for the vertebra, long bones, skull and small bones of the hand and feet. Clinically, osteoblastoma is a well-circumscribed, solitary lesion, which measures 2 cm or more and may be as large as 12 cm. Usually, the lesion is not painful, or if pain is present, it is not very responsive to salicylates. Radiographic features Radiographically, the picture may vary in accordance with the size of the tumor and with the extent to which the tissue is calcified. Osteoblastomas are well-circumscribed, expansive lesions with central radiopaque areas suggesting new 351


bone formation, but it is less likely to provoke an outstanding bony sclerosis typical of osteoid osteoma. Histopathologic features Histologically, benign osteoblastoma consists of a highly vascularized, fibrocellular stroma in which there are abundant newly formed trabeculae of immature bone and osteoid. Proliferating osteoblasts are found lining the trabeculae of immature bone and osteoid. The major problem for pathologists is the correct differentiation between benign osteoblastoma and a number of lesions that may have similar characteristics. Benign osteoblastoma and osteoid osteoma have almost identical histologic features. Based on this histologic similarity, Dahlin and Jonson in 1954 suggested a name ‘giant osteoid osteoma’ for the lesion that is denoted as the benign osteoblastoma in the present. Diagnosis The diagnostic evaluation is based on the histologic features and the clinical behavior of the lesion. Differential diagnosis Osteoid osteoma, ossifying fibroma, condensing osteitis, Paget’s disease, fibrous dysplasia, chondroblastoma, cementoblasoma, aneurysmal bone cyst and giant cell granuloma. Treatment and prognosis Surgical excision, malignant transformation (osteosarcoma) within a benign osteoblastoma is very rare.

Giant Cell Granuloma The term ‘giant cell granuloma (GCG)’ has also been introduced to account for the lack of pre-existing trauma or reparative tissue in some of these lesions. Central giant cell granuloma (CGCG) is described as a benign lesion affecting the mandible and maxilla that consists of a massive fibrohistiocytic proliferation with numerous heavily hemosidrinladen multinucleated giant cells. In 1953, Jaffe first described giant cell reparative granuloma (GCRG) as a benign lesion affecting the mandible and maxilla. Etiology Probably reactive or responsive in nature. Speculation suggests it may represent a developmental anomaly.

predominates 3:1 over that in maxilla and anterior to molar teeth with tendency for bony expansion. Most cases are non-aggressive, slow growing, and asymptomatic, with no cortical breakthrough or root end resorption. Some cases are recurrent and exhibit aggressive behavior with pain, perforation, and rapid enlargement. Radiographic findings Usually multilocular, occasionally unilocular, radiolucency with well-defined margins but borders may be scalloped. It can displace teeth; less commonly it resorbs tooth roots; they may even expand bone. MRI: Heterogeneous intermediate signal on T1 and T2 weighted image with contrast enhancement. Differential diagnosis ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍

Odontogenic lesions Ameloblastoma Odontogenic myxoma Odontogenic keratocyst Non-odontogenic lesions Hemangioma Aneurysmal bone cyst Traumatic bone cyst.

Peripheral Giant Cell Granuloma Peripheral giant cell granuloma (PGCG) is, for all practical purposes, a site-specific variant of pyogenic granuloma embedded with osteoclast-like multinucleated giant cells and arising exclusively from the periodontal ligament enclosing the root of a tooth. This unique origin, of course, means that such a lesion can only be found within or upon the gingiva or alveolar ridge, no other site is acceptable. It is also called variously giant cell reparative granuloma, osteoclastoma, giant cell epulis, and myeloid epulis, this lesion was first reported as fungus flesh in 1848. Clinical features The usual age for diagnosis is 4th to 6th decade, but there is no marked age predilection. More than 60% of cases occur in females and this predilection is more pronounced in the older age groups. Individual lesions are nodular and pedunculated, frequently with an ulcerated surface with a red, brown or bluish hue. Generally larger than pyogenic granuloma, the lesion may exceed 4 cm in size, but most lesions remain less than 2 cm in diameter.

Clinical features Most cases arise in those less than 30 years of age with female predominance. It occurs exclusivity in mandible or maxilla; rarely in facial bones. Occurrence in mandible 352

Radiographic features Any alveolar region may be affected and radiographs may show either a saucerization of underlying bone, periodontitis


Inflammatory cells

Poncet and Dor in 1897 first described pyogenic granuloma as granuloma pyogenicum. Over the years various authors have suggested other names such as granuloma gravidarum, pregnancy tumor, Crocker and Hartzell’s disease, vascular epulis, benign vascular tumor, hemangiomatosis granuloma, epulis telangiectaticum granulomatosa, and lobular capillary hemangioma.

Connective tissue stroma

Etiology

Figure 18

Epithelium

Blood vessels Giant cells

Histopathological picture of peripheral giant cell granuloma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

The etiology of the lesion is unknown, though it was originally believed to be a botryomycotic infection. It is theorized that pyogenic granuloma possibly originates as a response of tissues to minor trauma and/or chronic irritation, thus opening a pathway for invasion of non-specific microorganisms, although these microorganisms are seldom demonstrated within the lesion. Clinical features

of underlying tissues, or an isthmus of soft tissue connecting to an intraosseous central giant cell granuloma. Histopathology The peripheral giant cell granuloma is comprised of an unencapsulated aggregation of rather primitive but uniform mesenchymal cells with oval, pale nuclei and with a moderate amount of eosinophilic cytoplasm. Mitotic activity is not unusual in the lesion and may even be pronounced in lesions developing in children and adolescents. Stromal cells may be spindled with a background of collagenic fibers, or may be rounded with a less fibrotic background. A thin band of routine fibrovascular tissue separates the lesion from the overlying epithelium, often with dilated veins and capillaries. When surface ulceration is present, the ulcer bed consists of routine fibrinoid necrotic debris over granulation tissue (Figure 18). Treatment Peripheral giant cell granuloma is treated by conservative surgical excision followed by curettage of any underlying bony defect and careful scaling and root planing of associated teeth. A recurrence rate of 10% or more has been reported, hence, re-excision may be necessary.

Pyogenic Granuloma Pyogenic granuloma or granuloma pyogenicum is a wellknown oral lesion. It is a localized granulation tissue overgrowth in reaction to mild irritation. The name ‘pyogenic granuloma’ is a misnomer since the condition is not associated with pus and does not represent a granuloma histologically.

Pyogenic granuloma of the oral cavity occurs at any age and in all populations with no racial predilection. Lawoyin et al (1997) reviewed 38 cases from Ibadan, Nigeria and reported an average range of 5–75 years with the mean age of 33 years. Most studies demonstrate a definite female predilection with a female to male ratio of 2:1. This is attributed to the vascular effect of female hormones that occur in women during puberty, pregnancy, and menopause (Figure 18). The lesions tend to occur more often during the second and third trimester of pregnancy and such lesions are referred to as ‘pregnancy tumors’. Daley et al (1991) in their study indicated that the clinical diagnosis of ‘pregnancy tumor’ can be given when describing a pyogenic granuloma occurring in pregnancy, because it describes a distinct lesion not on the basis of histologic features but on etiology, biologic behavior, and treatment protocol. Marks et al reported that pyogenic granulomas may occur anywhere in the body surface and except the oral cavity, these are common around the fingers and toes. In the oral cavity, pyogenic granulomas show a striking predilection for the gingiva, with interdental papillae being the most common site in 70% of the cases. These are more common in the maxillary anterior area than any other area in the mouth. Gingival irritation and inflammation that result from poor oral hygiene, dental plaque, and calculus or overhanging restorations may be precipitating factors in many cases (Figure 19). The typical clinical presentation of pyogenic granuloma is a small, deep red to reddish-purple lesion occurring on the gingiva, which is either sessile or pedunculated. The surface may be smooth, lobulated or occasionally warty, which is commonly ulcerated and shows a tendency for hemorrhage either spontaneously or upon slight trauma. 353


Figure 19

Figure 20 Stratified squamous epithelium

Vascular spaces Inflammatory cells Connective tissue

Clinical photograph of pyogenic granuloma. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Histopathological picture of pyogenic granuloma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

Diagnosis Although pyogenic granuloma can be diagnosed clinically with considerable accuracy, radiographic, and histopathological investigations aid in confirming the diagnosis and planning the treatment. Marx et al (2003) reported that radiographs are advised to rule out bony destruction suggestive of malignancy or to identify a foreign body or sharp restorative margin that would need to be removed with the lesion. Long-standing pyogenic granulomas, like other irritation hyperplasias can show dystrophic calcifications. The radiographic appearance of such calcifications varies from barely perceptible, fine grains of radiopacities to larger, irregular radiopaque particles that rarely exceed 0.5 cm in diameter. Histopathologic features All clinically suspected pyogenic granulomas must be biopsied to rule out more serious conditions as mentioned previously. The pathology is distinct consisting of a matrix of edematous connective tissue in which numerous thin walled vascular channels can be seen. These vessels sometimes are organized in lobular aggregates, and some pathologists require this lobular arrangement for the diagnosis (lobular capillary hemangioma). There is also moderately dense mixed cellular infiltrate. The overlying stratified squamous epithelium may be atrophic or hyperplastic, and is usually degenerated or ulcerated in large areas; and the ulcer edge may have a primitive dysplastic appearance (Figure 20). Treatment Treatment of pyogenic granulomas consists of conservative surgical excision, which is usually curative. Although these are reactive hyperplasias, they have a relatively high rate of recurrence after simple excision, especially in pregnant patients. Pierson and Pierson reported a recurrence rate of 354

15% has been noted. After surgical excision of gingival lesions, curettage of underlying tissue is recommended.

Fibrous Hyperplasia: Denture-related (Epulis Fissurata) It is more of a reactive lesion rather than a neoplasm. Etiology Trauma resulting from an ill-fitting denture. Exuberant fibrous tissue repair secondary to repeated inflammation and trauma. Clinical features It is found on vestibular mucosa, usually at facial aspect of denture flange. Clinically appears as rounded folds of broadly based fibrous tissue surrounding the overextended denture flange. Ulceration often noted at depth of tissue folds and is more common in anterior segment of the jaws. It may occur on hard palate as a polypoid or leaf-like mass (Figure 21). Diagnosis Location and presence of a chronically ill-fitting denture. Treatment Excision of all tissue and relining or reconstruction of new dentures after excision. Prognosis No recurrence anticipated with properly fitting denture.


Figure 21

Differential diagnoses Differential diagnoses include hemangioma, fibroma, granuloma, embryonal rhabdomyosarcoma, malignant granular cell myoblastoma, alveolar rabdomyosarcoma, chondrogenic and osteogenic sarcoma and schwannoma. Treatment Surgery is the only possible treatment of these tumors. Surgery should not be radical; it minimizes the danger of damaging underlying alveolar bone and developing tooth buds. Delay in operation may cause airway obstruction and feeding difficulty. The tumor should be removed during the immediate postnatal period.

Epulis fissurata of the lower ridge. Courtesy: Department of Oral Medicine, Manipal College of Dental Sciences, Mangalore

Lipoma A lipoma is a benign neoplasm composed of fat cells, oral and oropharyngeal lipomas are rather rare. Etiology

Congenital Epulis of Newborn The Greek word epulis means ‘on the gum’ or ‘gum boil’ and has unfortunately been used for a variety of benign tumors and tumor-like conditions having dissimilar structures and histogenesis. Congenital epulis is a rare benign soft tissue tumor that was also named ‘gingival granular cell tumor of the newborn’ by Eppley. Since its first description by Neumann in 1871, more than 170 cases have been reported. Clinical features It occurs in females eight times more frequently than in males and affects the maxilla three times more frequently than the mandible. In 10% of cases, it may have multiple locations. The size of this nodular or lobular tumor may vary from a few millimeters to 90 mm of diameter. It has a firm consistency, is covered by a smooth erythematous mucosa and is attached by a stalk to the incisor, or sometimes, canine regions. This tumor is smooth-surfaced, pedunculated, sometimes lobulated and arises from the alveolar crest. Its size varies from a few millimeters to 9 cm. It is almost always located on the gingiva and is found predominantly on the maxilla. More frequent in females.

Its cause is unknown. Trauma and metaplasia of perivascular connective tissue have been suggested as playing a role. Clinical features Asymptomatic, slow-growing; usually circumscribed, sessile, or pedunculated. Usually soft and compressive with doughy consistency. When it is located superficially, a yellowish texture can be seen. In rare instances bilateral or multiple occurrence has been reported (Pisanty, 1976). The most common sites include buccal mucosa, tongue, floor of mouth; it can be deep seated with no color alteration but surface of larger lesions often is covered with telangiectatic vessels. Histologic examination Histologic examination of a lipoma shows a well-delineated mass of lobules of fat cells with fibrous septa interspersed between them (Figure 22). In rare instances one encounters a benign ‘infiltrative’ lipoma, which should not be confused with a liposarcoma (Bennhoff and Wood, 1978). The distinction between a benign lipoma and a low-grade liposarcoma may indeed be difficult in some cases. When fibrous tissue is a substantial part of a lipoma, the term ‘fibrolipoma’ is applied. When vascularity is a prominent feature, the term ‘angiolipoma’ is used.

Histopathology These tumors have large cells with an eosinophilic granular cytoplasm, but the congenital epulis is covered with a normal gingival epithelium. The congenital epulis is more vascularized.

Differential diagnosis ❍ ❍ ❍

Soft tissue tumor Minor salivary gland neoplasm Metastatic disease. 355


Figure 22

Figure 23

Epithelium

Antoni A tissue

Connective tissue capsule

Verocay bodies

Adipocytes

Histopathological picture of lipoma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

Treatment Surgical removal is the treatment of choice. Recurrences have not been reported with the exception of infiltrating and intramuscular lesions.

Neurogenic Tumors

material between them, the so-called Verocay bodies (Figure 23). Treatment Management consists of conservative surgical removal. Recurrence is rare.

Although the distinction between a schwannoma (neurilemmoma) and a neurofibroma may be debatable, most authors adhere to the concept that there are indeed two separate entities.

Neurofibroma

Schwannoma (Neurilemmoma)

Clinical features

A schwannoma is a benign neurogenic neoplasm composed of Schwann’s cells. In a review from the literature 152 cases of oral schwannomas were collected (Gallo et al, 1977).

A neurofibroma is asymptomatic and rarely occurs as a single lesion. Most often neurofibromas are part of von Recklinghausen’s disease. Quite often the tongue is involved; in some cases resulting in unilateral macroglossia. Moreover, the possibility of hereditary neuropolyendocrine syndrome— consisting of mucosal neuromas, pheochromocytoma of the adrenal glands, and medullary thyroid carcinoma— should be taken into account. In general, the mucosal neuromas in that syndrome are already present at childhood, being the first manifestation of the syndrome (Casino et al, 1981), Skin lesions with syndromic forms—café-au-lait macules (characteristically six or more), uniform pigmentation with smooth contoured borders are seen.

Clinical features The tumor may occur at all ages and does not show a preference for men or women. A schwannoma is a slowly growing, rather circumscribed, submucosally located tumor that may be painful. No characteristic clinical features appear. It may occur at any site in the oral cavity and rarely involves the oropharynx. Histopathologic features Histologically, one sees an encapsulated tumor composed of two cell types—the so-called Antoni type A and Antoni type B cells. The A cells have elongated nuclei and are often arranged in a palisade pattern, including hyalinized 356

Histopathological picture of neurilemmoma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

A neurofibroma is, like a schwannoma, derived from sheath cells. It actually may represent in many instances a hamartoma or a reactive process rather than a neoplasm.

Radiographic findings (when intrabony lesions are present) ‘Blunderbuss’ expansion of the inferior alveolar foramen with uniformly expanded alveolar canal in the body of the mandible.




In contrast to the schwannoma, a neurofibroma is not encapsulated. Proliferating Schwann cells are haphazardly arranged, not showing the palisade arrangement of schwannomas.

A rhabdomyoma is a well-circumscribed tumor. Based on histopathologic characteristics and gross morphology, two types are recognized: fetal and adult. The adult type is composed of large, round or polygonal cells with a slight granular cytoplasm. The cytoplasm may contain lipoid material. Cross-striations may be found in just a few cells. The fetal type almost exclusively occurs in the first few years of life. Histologically, this type is characterized by immature skeletal muscle in varying stages of developmental and undifferentiated mesenchymal cells. Differentiating a rhabdomyoma from a rhabdomyosarcoma may be difficult.

Treatment With a single neurofibroma, management consists of surgical removal. With multiple or massive involvement, surgical removal may be impossible to carry out and is indicated only when malignant changes are suspected. With von Recklinghausen’s disease, there is a 5–15% risk of malignant degeneration. This seems especially true for deeply located lesions (Maceri and Saxon, 1984).

Traumatic Neuroma A traumatic neuroma is a reactive hyperplasia caused by injury of a nerve. Clinical features Traumatic neuromas may occur anywhere in the oral cavity. Occurrence in the oropharynx is exceptional. The lesion usually manifests itself as a small submucosal nodule that may be painful at palpation. No characteristic clinical features appear.

Treatment Management of a rhabdomyoma consists of surgical removal.

Leiomyoma A leiomyoma is a benign neoplasm composed of smooth muscle cells. The source of a smooth muscle tumor in the oral cavity is believed to be the walls of blood vessels or undifferentiated mesenchymal cells. Occurrence of a leiomyoma in the oral cavity is rare. In two reviews of the literature (Natiella et al, 1982; Praal et al, 1982) approximately 80 oral leiomyomas were collected.

Histopathology Histologically, masses of irregularly arranged nerve fibers and Schwann cells are seen to spread diffusely throughout the tissue, mimicking to some extent the picture of a neurofibroma. Treatment Management consists of conservative surgical removal, if possible, followed by coagulation of the adherent nerve. Recurrence is rare.

Rhabdomyoma A rhabdomyoma is a benign neoplasm of striated muscle. It is an exceedingly uncommon tumor. Clinical features The male-to-female ratio is more than 2:1. The mean age of patients with a rhabdomyoma is about 40 years. Although extracardiac rhabdomyomas show a preference for the head and neck, occurrence in the oral cavity and oropharynx is rare. The floor of the mouth is the most common site. Multifocal appearance is exceptional (Schlosnagle et al, 1983). The clinical presentation is a submucosal swelling without any specific signs or symptoms.

Clinical features The majority of reported leiomyomas of the oral cavity and oropharynx were small, circumscribed, and asymptomatic swellings, covered with an apparently intact mucosa. They were either single or multiple. Histopathologic features A leiomyoma is composed of whorls of smooth muscle cells. The diagnosis of leiomyoma can be difficult to make just from light microscopic examination. The tumor should be differentiated from fibromatosis and schwannoma on the one hand and leiomyosarcoma on the other hand. Management Management consists of surgical removal with rare recurrence.

Hemangiomas and Vascular Malformations Congenital vascular anomalies have been and remain poorly understood. Since 1982, hemangiomas and vascular malformations have been recognized as distinct entities that exhibit unique characteristics and demand appropriately 357


tailored treatment plans. However, ‘hemangioma’ still continues to be used as a clinical and pathological description of different types of vascular anomalies. History Before the 1980s, the terminology that was used to describe vascular anomalies was confusing and ambiguous. The descriptive terminology used in the past (port-wine stain, strawberry hemangioma, salmon patch) conjure up visual approximation to the lesions but have no correlation with the biological behavior or natural history of these lesions. Mulliken and Glowacki introduced a simple classification in 1982 that was based on the clinical, histochemical, and cellular criteria to distinguish between the various vascular anomalies.

Hemangioma

Treatment The natural history of hemangiomas should influence the timing and type of intervention. Benign neglect is often advocated. A useful approach to the management of hemangiomas can be based on the following: ❍ ❍ ❍

Stage of the lesion Type of lesion Management of residual deformity.

In general, life-threatening and sight-threatening hemangiomas should be dealt with, regardless of the stage of the lesion. Active intervention should be considered in all disfiguring hemangiomas, but each case should be managed on its merits after careful discussion and counseling, to prevent potential psychosocial trauma and cosmetic deformity. Ethunandan and Mellor stated that prednisolone is the first-line drug of choice for the treatment of life- or sightthreatening hemangiomas.

Clinical features This is the most common ‘tumor’ in white infants, and the head and neck region is the most commonly involved site (60%). Most lesions are solitary (80%) and girls are more affected than boys (3:1). Multiple cutaneous lesions (three or more) are often associated with visceral involvement. Facial hemangiomas have a predilection for segmental distribution and for regions of embryological fusion (Figure 24A–C). Hemangiomas usually appear soon after birth, typically proliferate during the 1st year of life and then involute during the childhood years (up to 12 years). Classification Superficial hemangiomas originate from the papillary dermis and present as bright red macular or papular masses. Deep hemangiomas originate from the reticular dermis or subcutaneous tissues and appear as bluish or relatively colorless masses. Compound hemangiomas have superficial and deep components and were previously called capillary cavernous hemangiomas. The current classification of hemangiomas and vascular malformations is summarized in Table 9. Histopathology The histological features are dependent on the stage of the lesion. Proliferative phase: The lesion is highly cellular and contains plump proliferating endothelial cells and pericytes, with a high mitotic activity and numerous mast cells. Vascular channels are not prominent (Figure 24D). Involutive phase: The endothelial cells are flattened, the cell turnover is normal and there are few mast cells. 358

Vascular Malformations These are errors of morphogenesis that are populated by stable mature vascular endothelium. Clinical features Both sexes are equally affected. Vascular malformations are always present at birth (though some may not be apparent until a later stage) and in contrast to hemangiomas, these never proliferate or involute. Instead, these expand slowly and relentlessly throughout life, in pace with the growth of the patient. Trauma, puberty, and pregnancy can cause accelerated growth. Unlike hemangiomas, vascular malformations are associated with skeletal abnormalities in up to 35% of cases. Capillary malformations may be associated with Sturge–Weber and Klippel– Trenaunay syndromes. Classification These lesions are subclassified according to the predominant type of vessel and characteristics of flow (Box 2). Waner et al graded these lesions according to the degree of ectasia of the vessels into grades I–IV which correlate well with the clinical features and outcome of treatment. The degree of ectasia increases with age and the clinical features depend on the depth and size of the lesion. The lesions are usually soft, compressible, and enlarge in size when venous pressure is increased. Histopathology Venous malformations are characterized by an abnormal collection of veins, which do not have any demonstrable mitotic activity in endothelial or pericyte cells. Capillary


Figure 24 A

C

B

D

Proliferating capillaries Epithelium Extravasated red blood cells

(A, B, C) Clinical photograph of hemangioma. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore (D) Histopathological section of hemangioma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

malformation with cobblestone appearance in an adult lack a uniform smooth muscle layer.

Capillary Malformations Capillary malformations never regress spontaneously. They often darken and thicken with age and the rate of progression is probably related to the degree of absence of the autonomic nerves in addition to other factors such as hormonal influences and trauma. Troilius and Wrangsjo in their recent study have emphasized the psychological aspects of the birthmark and have suggested earlier intervention to counteract the undesirable psychosocial effects.

Arteriovenous Malformations These lesions show slow but relentless growth which is the norm and high-grade lesions present earlier in life and expand more rapidly, whereas low-grade lesions present

later and are more likely to expand slowly. In general, intervention should be planned as soon as the diagnosis is made and timely intervention will not only prevent complications, but also allow the extent of resection to be considerably reduced. The decision to intervene should be based on the age, location, flow characteristics, morbidity of the treatment, and the risks of an untreated lesion.

Lymphatic Malformations These lesions are the most difficult to eradicate. Microcystic lesions in particular are diffuse, do not respect tissues planes, and it is difficult to distinguish involved tissue from normal tissue. Macrocystic lesions, on the other hand, are more localized and respect tissue planes and are more easily excised. Hancock advocated these options for treatment which included laser ablation, excision, and sclerotherapy. Carbon dioxide laser should be reserved for superficial mucosal lesions. Because fluid-filled vesicles are almost always 359


Current classification of hemangioma and vascular malformations 1. Hemangiomas a. Superficial (capillary hemangioma) b. Deep (cavernous hemangioma) c. Compound (capillary cavernous hemangioma) 2. Vascular malformations a. Simple lesions (low-flow lesions) i. Capillary malformation (capillary hemangioma, port-wine stain) ii. Venous malformation (cavernous hemangioma) iii. Lymphatic malformation (lymphangioma, cystic hygroma) b. High-flow lesions i. Arterial malformation c. Combined lesions i. Arteriovenous malformations ii. Lymphovenous malformations iii. Other combinations

connected to deeper cisterns, ablation should be continued to a suitable depth to ensure destruction of most or all of these cisterns. Recurrences are not uncommon and can be treated in a similar manner. Sclerotherapy is a promising, but as yet not fully evaluated option. It can be used either as definitive treatment or for palliation when the morbidity of operation outweighs the benefits. Ogita and Tsuto tried OK-432 (lyophilized Streptococcus pyogenes treated with benzyl penicillin) and has been found to be successful in treating macrocystic lesions, with the advantage of avoiding a scar.

Fibroma The fibroma, also referred to as irritation fibroma, is by far the most common of the oral fibrous tumor-like growths. While the terminology implies a benign neoplasm, most if not all fibromas represent reactive focal fibrous hyperplasia due to trauma or local irritation. Although the term ‘focal fibrous hyperplasia’ more accurately describes the clinical appearance and pathogenesis of this entity, it is not commonly used. Clinical features A fibroma may occur at any oral site, but it is seen most often on the buccal mucosa along the plane of occlusion of the maxillary and mandibular teeth. It is a round-to-ovoid, asymptomatic, smooth-surfaced, and firm sessile or pedunculated mass (Figure 25A, B). The diameter may vary from 1 mm to 2 cm. The surface may be hyperkeratotic or ulcerated due to repeated trauma. Fibromas are most often observed in adults, but they may occur in individuals of any age and either sex. 360

Histopathology Histologically, a fibroma is an unencapsulated, solid, nodular mass of dense and sometimes hyalinized fibrous connective tissue that is often arranged in haphazard fascicles. A mild chronic inflammatory infiltrate may be present. The surface epithelium may be hyperkeratotic, either hyperplastic or atrophic, and it may be ulcerated (Figure 25C). Differential diagnosis The clinical differential diagnosis of a fibroma includes giant cell fibroma, neurofibroma, peripheral giant cell granuloma, mucocele, and benign and malignant salivary gland tumors. Treatment Conservative excisional biopsy is curative, and its findings are diagnostic. Recurrence is possible however, if the offending irritant persists.

Giant Cell Fibroma A giant cell fibroma has a distinctive histologic appearance that sets it apart from a conventional fibroma. Clinical features It appears as an asymptomatic sessile or pedunculated nodule that is smaller than 1 cm in diameter. Often, it has a bosselated or somewhat papillary surface. Most cases are diagnosed in persons aged 10–30 years. No sex predilection has been reported. The most common sites are the mandibular gingiva, followed by the maxillary gingiva, the tongue, and the palate. Histopathology Microscopically, a giant cell fibroma is an unencapsulated mass of fibrous connective tissue that contains numerous characteristic large, plump, spindle-shaped and stellate fibroblasts, some of which are multinucleated. These cells are easily observed in the peripheral areas of the lesion, while the more central areas contain typical fusiform fibroblasts. The surface epithelium is often corrugated and atrophic. Differential diagnosis The clinical differential diagnosis includes squamous papilloma, irritation fibroma, pyogenic granuloma, and peripheral giant cell granuloma. Treatment Conservative excisional biopsy is curative, and its findings are diagnostic. Recurrence is rare.


Figure 25 A

B

C

D Epithelium (stretched)

Bundles of collagen fibers

(A, B) Irritational fibroma on the buccal mucosa. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore. (C) Histopathological picture of fibroma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

Fibromatoses

Histopathology

The fibromatoses represent a group of infiltrating fibrous proliferations with a biologic behavior and microscopic appearance intermediate between those of benign fibrous lesions and fibrosarcomas. In the head and neck region, these are sometimes referred to as juvenile or aggressive juvenile fibromatoses.

Microscopically, fibromatosis is characterized by a poorly delineated, infiltrating cellular proliferation of mature spindle cells arranged in streaming and interlacing fascicles. Collagen production is usually prominent. Infiltration of the adjacent structures is common at the periphery, but cellular atypia is not present.

Clinical features


Patients of any age may be affected, but three-quarters of all cases are diagnosed when the patient is younger than 10 years. No significant sex predilection is apparent. The most frequent site of occurrence is the soft tissues adjacent to the mandible. Intraoral presentations are rare, but they most often involve the tongue or buccal mucosa. Lesions appear as firm, painless, poorly demarcated masses with a variable growth rate. They are locally aggressive and often cause resorption of the underlying bone when present.

The differential diagnosis of a soft tissue fibromatosis is myofibroma and rhabdomyosarcoma. Treatment Treatment consists of wide excision. The reported recurrence rate of 24% for oral fibromatosis is considerably lower than the 50–70% rate reported for fibromatoses of the entire head and neck region. 361


Table 9

Typical radiographic features

Typical radiographic feature

Condition

Tennis racket appearance

Odontogenic myxoma

Soap bubble appearance

Ameloblastoma, aneurysmal bone cyst, central hemangioma

Honeycomb appearance

CEOC, Od. myxoma, CGCG, central hemangioma

Driven snow appearance

CEOC

Sunburst appearance

Osteoblastoma, osteosarcoma

Sunray appearance

Osteosarcoma, central hemangioma, osteoblastoma

Ground glass appearance

FD, Paget’s, hyperparathyroidism, ossifying fibroma

Pepper pot appearance

Hyperparathyroidism

Eggshell appearance

Ameloblastoma

Onion peel appearance

Garre’s osteomyelitis

CEOC: Calcifying epithelial odontogenic cyst; CGCG: Central giant cell granuloma; FD: Fibrous dysplasia.

Myofibroblastoma Myofibroblasts are spindle-shaped cells with features of both fibroblasts and smooth muscle cells. Myofibroblasts have been identified in lesions other than myofibromas, but when they are the predominant cell type in a tumor, the terms myofibroma (if solitary) or myofibromatosis (if multicentric) are applied. Clinical features Tumors of myofibroblasts may occur in either sex and in patients of all ages, with a mean age of 26.6 years. Solitary myofibromas have a head and neck predilection, with the mandible being the most common site of occurrence. The most common oral soft tissue sites are the tongue, lips, and buccal mucosa. Radiographic features Intraosseous jaw lesions most often manifest as well-defined unilocular or multilocular radiolucencies. Differential diagnosis The clinical differential diagnosis for oral myofibroma includes irritation fibroma, fibromatosis, peripheral giant cell fibroma, neurofibroma, leiomyoma, and benign and malignant neoplasms of the minor salivary glands. Treatment Treatment for oral myofibromas is conservative excision. The recurrence rate is low, and spontaneous regression has been reported. 362

Table 10

Malignant odontogenic tumors: WHO classification (1992)

Odontogenic carcinomas

Odontogenic sarcomas

Malignant ameloblastoma

Ameloblastic fibrosarcoma (ameloblastic sarcoma)

Primary intraosseous carcinoma

Ameloblastic fibro-dentinosarcoma Ameloblastic fibro-odontosarcoma

Malignant variants of other odontogenic epithelial tumors

Odontogenic carcinosarcoma

Malignant changes in odontogenic cysts

MALIGNANT ODONTOGENIC TUMORS Odontogenesis or tooth formation depends on the various epithelial mesenchymal interactions. Thus, both epithelial and mesenchymal tissues may form neoplastic lesions, either purely epithelial or mesenchymal or showing a mixture of both. To be regarded as ‘odontogenic’, the tumor must arise in the gingiva or jaws. With their neoplastic potential, apart from forming benign odontogenic tumors, they can also form malignant odontogenic tumors. Malignant odontogenic tumors are very rare jaw entities comprising only about 4% of all odontogenic tumors. Gradual accumulation of single cases can only provide some information about their histomorphology, clinical appearances and behavior. If they arise from epithelium they are odontogenic carcinomas and if from mesenchyme they are odontogenic sarcomas or they can be of mixed type. Classification Till date, there is no well-accepted classification of these tumors most of which are pathologic curiosities. Nonetheless their importance to the unfortunate individuals so afflicted is not to be underestimated. In the recent years several classifications have been suggested by several authors. The most widely used being the WHO classification of 1992 given by Pindborg (Table 10). The classification has evolved with time as new articles have been published over the years. The latest is the WHO classification of 2004 given by Reichert and Philipsen (Table 11). Etiopathogenesis The etiopathogenesis for odontogenic carcinomas is unknown; studies to find out more are difficult because of the rarity of these groups of lesions. Generally, these tumors arise de novo within the jaw bones, from epithelium contained within cyst linings, or from malignant transformation


Table 11 Malignant odontogenic tumors: WHO classification

ODONTOGENIC CARCINOMAS

(2004) Odontogenic carcinomas

Odontogenic sarcomas

1. Metastasizing malignant ameloblastoma

1. Ameloblastic fibrosarcoma (ameloblastic sarcoma)

2. Ameloblastic carcinoma a. Primary intraosseous carcinoma b. Secondary (dedifferentiated) intraosseous c. Secondary (dedifferentiated) extraosseous

2. Ameloblastic fibrodentinosarcoma a. Ameloblastic fibroodontosarcoma

3. Primary intraosseous squamous cell carcinoma (PIOSCC) a. PIOSCC solid type b. PIOSCC derived from odontogenic cysts c. PIOSCC derived from keratinizing cystic odontogenic tumors 4. Clear-cell odontogenic carcinoma 5. Ghost cell odontogenic carcinoma

of benign odontogenic tumors. Odontogenic carcinomas arise from the epithelial components of the tooth germ. In adults, the epithelial remnants of odontogenesis consist of the reduced enamel epithelium that surrounds the crowns of impacted teeth for as long as they remain trapped and unerupted within the jaws, the rests of Malassez which are located throughout the periodontal ligament and within edentulous areas of the alveolar bone subsequent to tooth loss and remnants of the dental lamina located in the gingiva. Odontogenic cysts of various types may also serve as a tissue site for malignant transformation. Diagnosis Diagnosis of these lesions may be complicated for two main reasons: first, due to their low frequency, which causes the information about their clinical and histopathological features be scant, and secondly due to the similar histopathological pictures with benign odontogenic tumors. The diagnosis is based upon the unique histopathological features of odontogenic carcinomas. In general, all tumors classified as odontogenic carcinomas exhibit typical microscopic features of malignancy with the exception of the malignant (metastasizing) ameloblastoma and the clear cell odontogenic carcinoma. Behaviorally, all the entities in this group have the potential for either nodal or distant metastases. Odontogenic sarcomas are thought to arise from the ectomesenchymal tissue. They either arise de novo or from pre-existing ameloblastic fibroma. Odontogenic carcinomas are much more frequent than odontogenic sarcomas. A rare lesion having a mixed picture is termed as odontogenic carcinosarcoma.

Terminology used to describe diverse odontogenic carcinomas is varied and confusing. We will discuss the important lesions.

Malignant Ameloblastoma (Metastasizing) It is defined as an ameloblastoma that metastasizes in spite of an innocuous histologic appearance. This implies that the primary tumor shows no feature different from the tumors that do not metastasize. Thus, this can only be a retrospective diagnosis, after the occurrence of metastatic deposits. Therefore, it is the clinical behavior and not the histology of the lesion that justifies the diagnosis of a malignant ameloblastoma. WHO defines this as a neoplasm in which the pattern of an ameloblastoma is combined with cytological features of malignancy, a definition not based on behavior but histology. Both the primary and metastatic foci are characterized histologically by same benign tumor islands, which lack any feature of malignancy. The metastatic foci show typical ameloblastic differentiation of the peripheral ameloblasts with palisading and reverse polarization of nuclei. The outer palisaded stratum of ameloblasts surrounds a zone of stellate reticulum which may show foci of squamous metaplasia. No pleomorphism or mitotic figures are seen. The average time from initial treatment of the primary tumor to the appearance of metastasis is 9 years. These metastases generally only arises after many surgical attempts at treatment of the original lesion and are often isolated pulmonary metastases that can sometimes be treated surgically. Some also believe that metastases may be caused by aspiration or implantation at the time of surgery. Metastatic deposits of this lesion are mostly seen in lungs, lymph nodes, brain, viscera, skin and bone. The treatment of choice of the primary tumor and recurrences is excision. Radiotherapy too has been tried but its value is questionable. Overall, very few cases have been reported for a definitive treatment protocol to be evolved. Behaviorally, malignant ameloblastoma may progress to death.

Ameloblastic Carcinoma It is a malignant epithelial proliferation that is associated with an ameloblastoma (carcinoma ex ameloblastoma) or histologically it resembles an ameloblastoma (de novo ameloblastic carcinoma). It is an aggressive neoplasm that is locally invasive (extending out of bone to involve the infratemporal fossa, parapharyngeal space, the masticator space, or cervical soft tissue) and can spread to regional lymph nodes or distant sites, such as lungs and bones and myocardium. 363


The term was first used by Shafer in 1974 to denote ameloblastoma in which there had been histological transformation. Corio used the term for ameloblastoma that shows cytological features of malignancy but is otherwise recognizable as an ameloblastoma and may later metastasize. Ameloblastic carcinoma may arise de novo or from a pre-existent benign odontogenic lesion such as an ameloblastoma or an odontogenic cyst. Carcinoma ex ameloblastoma A carcinoma directly contiguous with an ameloblastoma is appropriately termed as a ‘carcinoma arising from an ameloblastoma’ (carcinoma ex ameloblastoma, carcinoma in ameloblastoma). The carcinoma arises when an ameloblastoma undergoes ‘dedifferentiation’ (i.e. when a less-differentiated proliferative clone arises from an ameloblastoma). This aggressive clone overgrows the ameloblastoma and becomes the dominant component. De novo ameloblastic carcinoma If a carcinoma lacks a component of conventional ameloblastoma, its unequivocal categorization as an ameloblastic carcinoma is considerably less secure. Its diagnosis is based on subjective interpretation. Histologically, ameloblastic carcinoma is characterized by epithelial nests and strands similar to the plexiform or follicular patterns. The cells exhibit cytological atypia and mitotic activity. Furthermore, areas of squamous cell carcinoma may be seen. If the lesions are entirely composed of this component and lack resemblance to ameloblastoma, they should be diagnosed as primary intraosseous squamous cell carcinoma. Clinical features It occurs equally in both the sexes. It causes jaw swelling, frequently causing pain and rapid growth. Mandible is more frequently involved. Radiographically, an ill-defined area of radiolucency is seen; sometimes showing the presence of focal radiopacities. Root resorption, perforated buccal and lingual cortical plates of jaw and extension into the soft tissues illustrate the destructive potential. Treatment could be aggressive surgery, but this may be followed by recurrences and extensive local spread. Radiotherapy has not shown effective results, but chemotherapy with paclitaxel and carboplatin and oral cyclophosphamide has some effect. Death has been reported because of extensive local recurrence involving base of the skull and cranial cavity. Prognosis is poor if the tumor has already metastasized. Biomarker studies for proliferation and malignant genotype (aneuploidy) have shown that ameloblastic carcinomas have a higher proliferating cell nuclear antigen (PCNA) index and a greater degree of aneuploidy than histologically benign ameloblastoma. A rare variant is that which arises from gingival or alveolar mucosa epithelium termed as peripheral ameloblastic 364

carcinoma. These arise de novo or as dedifferentiated carcinomas from a pre-existing benign peripheral ameloblastoma.

Primary Intraosseous Squamous Cell Carcinoma Primary intraosseous squamous cell carcinoma (PIOC) is a squamous cell carcinoma that occurs within the jaw bone. It is called ‘primary’ because it is not a secondary deposit. Metastasis from a distant primary to the jaw must be excluded. The WHO defines primary intraosseous carcinoma as a squamous cell carcinoma arising within the jaw, having no initial connection with the oral mucosa, and presumably developing from residues of the odontogenic epithelium. These are typical invasive squamous cell carcinomas and range from well to poorly differentiated varieties. The WHO extends the definition of PIOC to include those lesions having a distinctively odontogenic pattern with basal-type cells forming alveoli or arranged in a plexiform pattern with palisading of the peripheral cells.

Solid PIOC These occur mainly in the posterior mandible, are more often seen in males, may metastasize to regional lymph nodes, and have a poor prognosis. It occurs commonly in elderly patients (mean age 50 years). These tend to occur in the mandibular body where they may compress the inferior alveolar nerve causing pain and/or paresthesia. Loosening of teeth and mandibular expansions are signs. Radiographically, these may be well-circumscribed as well as more diffuse with irregular moth-eaten borders. The tumors metastasize regionally and distantly and show a 30–40% 5-year survival. Cystic PIOC (PIOC arising in an odontogenic cyst, PIOC ex odontogenic cyst) Cystic PIOC is a squamous cell carcinoma that demonstrates a cystic component with a lumen that contains fluid or keratin and a lining of stratified squamous epithelium that exhibits cytological atypia. Primary intraosseous carcinomas may develop from a still recognizable precursor lesion such as the epithelial lining of an odontogenic cyst. The linings of residual apical periodontal cyst, OKC and dentigerous cyst have shown malignant transformation. Moreover, reduced enamel epithelium has been documented as tissue of origin in cases in which an impacted tooth was presented within the tumor. Co-occurrence of squamous odontogenic tumor and ameloblastomas has been reported. Most carcinomas arising from the cyst linings are well or moderately differentiated. Carcinoma ex dentigerous cyst The most common odontogenic cyst to show carcinomatous changes is the dentigerous cyst. Few cases that lacked rigorous evidence of dentigerous cyst formation, but showed thickening of pericoronal soft tissue that was associated with an impacted tooth, were reported as carcinoma ex dentigerous cyst.


Intraepithelial neoplasia that involves gingival crevicular epithelium can mimic carcinoma ex dentigerous cyst histologically. Most carcinomas arising in dentigerous cysts occur in the mandibular molar area; however, they occasionally are associated with impacted canine teeth. Usually, the carcinoma is treated by surgical resection. Histologically, the lesion demonstrates membranous connective tissue that is lined by stratified squamous epithelium that exhibits evidence of intraepithelial neoplasia that is associated with an invasive well-differentiated or moderately differentiated squamous cell carcinoma. Carcinoma ex OKC Cases have been reported to arise from cyst lining of OKC. In most, the radiographic findings are those of a benign OKC and the unexpected carcinoma is recognized following incisional biopsy or enucleation. They have been usually treated by resection and postoperative radiation therapy. Intraosseous mucoepidermoid carcinoma (central mucoepidermoid carcinoma, PIOC with mucous cells) It arises from odontogenic epithelium or an odontogenic cyst. It represents a cystic primary intraosseous carcinoma that shows squamous differentiation and mucous cells; lesional cells focally exhibit cytoplasmic mucicarmine positively.

Clear Cell Odontogenic Carcinoma It is also known as clear cell ameloblastic carcinoma, clear cell ameloblastoma, clear cell odontogenic tumor. It is a low-grade carcinoma that is composed of cells that show uniform nuclei and clear cytoplasm. It was initially designated as clear cell odontogenic tumor, but this lesion behaves aggressively and metastasizes too, so it is better termed as clear cell odontogenic carcinoma (CCOC). The anterior mandible is the site of predilection but other jaw areas may be involved also. About 70% of females are affected with an age range of 17–89 years. The tumor has a varied radiographic appearance. Often, it presents as a unilocular expansile radiolucent lesion with an indistinct periphery; however, some cases are multiloculated and well-circumscribed. Confinement of the lesion to the jaws, presence of columnar cells resembling ameloblasts, and the occasional presence of dentinoid structures prove it to be odontogenic in nature. Three histopathologic patterns have emerged. The more common pattern is a biphasic tumor characterized by oval and linear nests of clear cells intermixed with smaller islands of polygonal cells with eosinophilic cytoplasm. Occasionally, these two cell types coexist in a tumor nest yielding a ‘glomeruloid appearance’. The nuclei are oval and monomorphic. If pleomorphism or hyperchromatism occur, it is generally within the nuclei of the polygonal cells. The stroma of CCOC is distinctive. Fibroblastic cellularity is high and the collagen is mature, wrapping tightly

around the tumor cells. Squamous differentiation has also been reported. Metastases are found in lymph nodes and lungs. Metastatic disease may occur more than 5 years after initial diagnosis. Differential diagnoses include metastatic renal cell carcinoma, ameloblastoma with clear cells, clear cell variant of CEOT and the clear cell variant of mucoepidermoid carcinoma.

Malignant Epithelial Odontogenic Ghost Cell Tumor It is also called odontogenic ghost cell carcinoma (OGCC), ghost cell odontogenic carcinoma, aggressive epithelial odontogenic ghost cell tumor, dentinogenic ghost cell tumor. It is an ameloblastic carcinoma that shows evidence of ghost cell keratinization. It is a tumor that combines the elements of a benign calcifying odontogenic cyst (COC) with a malignant epithelial component. The biological behavior of the tumor is unpredictable, characterized by indolent growth and others by local aggressive growth, and distant metastasis. The tumor apparently arises most often from malignant transformation of a pre-existing benign COC. OGCC has to show both the features of a COC-ameloblastoma-like tissue together with ghost cell keratinization as well as solid epithelial areas showing cytonuclear atypia. Both components may be distinct from each other or admixed. Three distinct origins are thought: occurring de novo with benign COC and a malignant epithelial component histologically present in the same lesion, occurring after the recurrence of a benign COC, or arising from odontogenic tumor. The biologic behavior of a lesion cannot be predicted from the presence of ghost cells. The tissue that surrounds the ghost cells gives the prognosis. Ghost cells are immunoreactive for amelogenin, a protein that is unique to the enamel matrix. It is seen more in males in an age range between 13 and 72 years. About 66% of the cases occur in maxilla. It is more in Asians. Radiographically, it presents as an expansile multiloculated to poorly delineated radiolucent lesion. Lesional tissue subjectively reveals features that warrant a malignant interpretation, including cytologic atypia, increased mitotic activity, an infiltrative growth pattern (perineural or intravascular invasion) and necrosis.

ODONTOGENIC SARCOMAS These tumors may arise de novo or from a pre-existent ameloblastic fibroma or ameloblastic fibro-odontoma. Whether an odontogenic sarcoma displays deposition of hard dental tissues has not shown any prognostic significance. Odontogenic sarcomas arising from pre-existing ameloblastic 365


fibroma occurs at a higher mean age (33 years) those that develop de novo (22.9 years). The main clinical problem of odontogenic sarcoma is relentless local growth.

pertaining to molecular events in the carcinogenesis of odontogenic epithelium and mesenchyme, thereby shedding more light on the origin, pathogenesis, biologic behavior, treatment and prognosis of malignant odontogenic tumors.

Ameloblastic Fibrosarcoma It is also known as odontogenic sarcoma, ameloblastic sarcoma. It is a malignant proliferation of connective tissue cells that contains benign odontogenic epithelium that is similar to ameloblastic fibroma. Typically, it presents in the mandible with an age range from 8 to 83 years. In the mandible, posterior region is affected more. It demonstrates an expansile radiolucency with indistinct margins, evidence of extraosseous soft tissue extension, and sometimes, an associated impacted molar. Other radiographic appearances include destructive/permeative, unilocular or multilocular. Typically, the patients do not develop metastases; they form the group of a locally aggressive neoplasm. The sarcoma is most often treated by a wide surgical excision and postoperative radiation therapy without elective neck dissection. Ameloblastic fibrosarcoma has the histologic architecture similar to an ameloblastic fibroma. Slender budding and branching epithelial cords of bland cuboidal to columnar cells with uniform nuclei or epithelial islands that are indistinguishable from those are seen in follicular ameloblastomas are separate widely by hypercellular connective tissue that exhibits plump polygonal to fusiform stromal cells that show mild to moderate cytologic atypia and numerous mitotic figures in a pale hypocollagenous myxoid extracellular matrix. Ameloblastic fibrosarcoma can show focal evidence of dentin formation or dentin and enamel formation, resulting in the terms ameloblastic dentinosarcoma and ameloblastic odontosacrcoma, respectively. The histologic differential diagnosis includes low grade spindled ameloblastic carcinoma that demonstrates plump fibroblastic cells that are associated with ameloblastomatous islands and sheets. The distinction between the two is made by cytokeratin which is found to be reactive by fibroblastic cells of spindled ameloblastic carcinoma.

Odontogenic Carcinosarcoma It is a tumor architecturally resembling an ameloblastic fibroma in which both the epithelial and the connective tissue components show cytologic evidence of malignancy. For these extremely rare lesions that combine carcinomatous and sarcomatous elements and recognizable as odontogenic if the epithelial component resembles that of an ameloblastoma, the designations malignant ameloblastoma and fibrosarcoma or odontogenic carcinoma with sarcomatous proliferations have been used. The increase in the number of reported malignant odontogenic tumors will help in the future to attempt studies 366

EPITHELIAL MALIGNANT TUMORS Epidermoid Carcinoma Epidermoid carcinoma or squamous cell carcinoma is described in detail in Chapter 14 on Oral Cancer.

Verrucous Carcinoma Verrucous carcinoma has also been referred to as snuff dipper’s cancer and Ackerman’s tumor. Rock and Fisher in 1960 coined the term ‘oral florid papillomatosis’. Lauren Ackerman in 1947 first described this less severe variant of squamous cell carcinoma associated with spittobacco chewing habit. He suggested that verrucous carcinoma needs to be considered as a distinct entity as it exhibits a characteristic morphologic appearance and specific clinical behavior. He noted that even extension lesions had excellent prognosis with proper treatment. This lesion has a predilection for mucous membranes of the head and neck and is most commonly found in the oral cavity followed by the larynx. Since its earlier description, verrucous carcinoma has been also reported to occur in the esophagus, paranasal sinuses, nasal fossae, genital and anal mucosa, soles of feet, breast and axilla. Enriquez et al (1980), Pomatto et al (2001) and Nooshin Mohtasham et al (2008) reported verrucous carcinoma arising from an odontogenic cyst. Predisposing and etiological factors The exact etiology is still not understood. Chewing tobacco is the primary etiologic factor for these tumors. Most of these tumors originate from the site of the placement of tobacco. It has been suggested that opportunistic viruses such as HPV-6 and 16, act in tandem with frank carcinogenesis to promote development of verrucous carcinomas. Few other authors suggest that the lesions develop at sites of chronic irritation and inflammation. Clinical features Verrucous carcinoma is usually seen between the 5th and 7th decade of life and commonly in white men. It is estimated that these tumors account for about 1–10% of all oral squamous cell carcinomas. In the initial stages, verrucous carcinoma appears as white, translucent patches on an erythematous base. As they mature they begin to take on a cauliflower-like papillomatous growth with a superficial pebbly surface (Figure 26).


Figure 26

Figure 27

Parakeratin plug Cleft lined by parakeratin Epithelium with broad pushing borders Subepithelial band of chronic inflammatory cell infiltrate

Histopathological picture of verrucous carcinoma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

Clinical photograph of verrucous carcinoma. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

The common intraoral sites that are affected are the buccal mucosa, alveolar ridge, gingiva, floor of mouth, tongue, tonsillar regions and the vermillion border of the lip. Occasionally, local invasion into underlying soft tissues and bone may be seen. The surface of the lesion may show ulceration. Rarely distant metastasis is seen. However, regional involvement of the lymph nodes may be observed. Nodes may be enlarged and tender. The other forms of verrucous carcinoma are the Buschke– Lowenstein tumor (anourologic type) and the epithelioma cuniculatum (palmoplantar type). Buschke–Lowenstein tumor occurs as a large cauliflowerlike tumor mass that is usually restricted to the glans penis, vagina, cervix and the perianal region; whereas epithelioma cuniculatum is seen as ulcerated large exophytic masses associated with sinus openings especially on the skin overlying the first metatarsal head. These tumors can also occur on the toes and heel. Occasionally, these tumors may bleed or produce foul smelling discharge. Patients may complain of difficulty in walking. Histologic features Histologically, verrucous carcinoma shows hyperkeratosis, parakeratosis and acanthosis in the superficial portions. The surface is papillary with a thick parakeratinized covering that extends into deep cleft-like interpapillary spaces. The rete ridges are broad and bulbous, that tend to ‘push’ into the underlying connective tissue (Figure 27).

Management and prognosis Most of the patients suffering from verrucous carcinoma have a good prognosis. The mainstay of treatment for verrucous carcinoma is surgical excision. However, when the tumor is not accessible for surgery, radiotherapy may be used. Radiation therapy is planned for a 6-week period. About 400–800 cGy is administered in fractions, 6–12 times. However, some authors report anaplastic transformation (almost 30%) following radiotherapy.

Basal Cell Carcinoma Basal cell carcinoma is also referred to as ‘rodent ulcer’. It is the most common cutaneous malignancy, which typically affects the sun-exposed surfaces of the skin. It is a slow growing tumor. However, long-standing tumors can cause local destruction of tissues and metastasis is seldom encountered. It is estimated that less than 0.1% tumors metastasize. The most common sites of metastasis are the lymph nodes, bones and lungs. It arises from the basal cells of the surface epidermis or external root sheath of the hair follicle. Clinical features Basal cell carcinoma is usually seen in individuals over the 4th decade of life. Men are believed to be affected twice as commonly as women as they are more frequently exposed to sun. However, this may not be true all the time. It has been noticed that fair complexioned individuals are relatively more prone to develop basal cell carcinoma compared to dark complexioned individuals. Basal cell carcinoma can have various clinical appearances. Some of the relatively common varieties are noduloulcerative type (most common variety), superficial spreading type, pigmented, morphea-form (sclerosing) and the cystic type. 367


The ulceronodular type of basal cell carcinoma, in the initial stages, appears as a large non-tender papule which slowly enlarges and exhibits a central depression. Over a period of time the central depressed area reveals ulceration associated with some bleeding and crusting. The pathognomonic feature of basal cell carcinoma is a waxy, translucent, or pearly appearing ulcer with a raised pale border. Telangiectasias are common. The pigmented form resembles melanomas. They appear as bluish-black or brown colored macules. However, unlike melanocytic nevus these lesions are not necessarily uniformly pigmented. The cystic variety of basal cell carcinoma is rare. This form of basal cell carcinoma appears as a bluish to gray colored, mucin-filled cyst-like lesions. The sclerosing type of basal cell carcinoma is uncommon. The typical lesion mimics a scar. It appears as a white or yellow waxy sclerotic plaque. It is believed that the tumor cells initiate the proliferation of fibroblasts within the dermis and an increased collagen deposition (sclerosis). The superficial type is seen as an erythematous, wellcircumscribed patch or plaque. The lesion may be associated with the formation of a white colored scale. These lesions may mimic lesions of psoriasis. Neville et al described the presence of a fine elevated ‘thread-like’ border at the margins of the lesions. It is estimated that the risk of developing a squamous cell carcinoma is increased slightly after a basal cell carcinoma, with a 6% risk at 3 years. Patients are at increased risk of developing malignant melanomas. Syndromic association Barcelos et al (2008) described Bazex–Dupré–Christol syndrome, which is a rare genodermatosis that is characterized by follicular atrophoderma, multiple milia, congenital hypotrichosis, hypohidrosis and basal cell malformations that include nevoid basal cell carcinomas. The other commonly associated syndrome is Gorlin–Goltz syndrome, which is characterized by basal cell epithelioma, jaw cyst and bifid ribs. Histopathologic features The basaloid appearance of the epithelial islands is the most striking histopathological features of basal cell carcinoma. The cells exhibit increased nuclear cytoplasmic ratio. Cells show peripheral palisading (they are arranged perpendicular to the basement membrane). The tumor has a characteristic invasive pattern with the formation of large islands. The cells within the core of the epithelial islands have non-discrete cytoplasmic borders and mimic syncytium. They do not have prominent nucleoli and lack intercellular bridges. The stroma shows varying amounts of collagen deposition with abundant mucin.

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Management Neville et al (2007) studied the efficacy of 5% imiquimod (commercially available in India as Imiquad 5% cream. Imiquimod is a keratolytic) in the treatment of nodular basal cell carcinoma after initial treatment with curettage. In their study, 5% imiquimod was applied locally once a day, 5 times per week for 6 weeks, following curettage. They concluded that imiquimod cream was an effective treatment modality. Gross et al (2007) studied the potential of 5% 5-fluorouracil cream for the treatment of small superficial basal cell carcinoma. They used 5% 5-fluorouracil cream twice daily for up to 12 weeks. The results showed that the histologic cure rate was 90% and the mean time to clinical cure was 10.5 weeks. Healsmith et al (1991) used intralesional interferon alpha-2b (IF-2b) for the treatment of basal cell carcinoma. The injected nine intralesional injections of IF-2b (1.5 million units dissolved in 0.2–0.5 ml water), 3 times per week for 3 weeks. At a 3-month follow-up, out of the 11 tumors they treated, six tumors had resolved both clinically and histologically, three tumors had reduced in size and one tumor grew larger. Surgical excision for basal cell carcinoma is still the most popular modality of treatment. It is recommended that an excision margin of 4 mm around the tumor be maintained. Mohs micrographic surgery offers high cure rates for basal cell carcinoma (5-year cure rate of 99% for primary tumors and up to 95% for recurrent basal cell carcinoma). During this surgical technique, serial frozen sections are examined histologically until all margins are clear.

Malignant Melanoma (Melanocarcinoma) Malignant melanoma is a malignant neoplasm, with its origin in the neural crest cells. It was first described by Weber in 1859. Lucke in 1869, recognized it as a distinct clinical entity and named it as ‘melanotic sarcoma’. It is estimated that oral melanomas represent about 1–2% of all oral malignancies. It accounts for about 3–5% of all malignancies affecting the skin. Apart from the oral mucosal involvement, melanomas can be seen affecting the nasal, vulval and anorectal mucosa. It is believed that tobacco smoke may play a role in the development of melanoma in the palate. Other possible risk factors include fair complexion, light hair, excessive exposure to sunlight, exposure to formaldehyde, family history of malignant melanoma and the history of dysplastic nevi. Clinical features Melanoma is usually seen in the 4th to 7th decades of life. It is seldom seen in individuals below 20 years of age.


Figure 28

❍

Color variation: Pigmentation is not uniform and may display shades of tan, brown or black. White, reddish or blue discoloration is of particular concern. ❍ Diameter: A diameter more than 6 mm is characteristic of melanoma, although some may have smaller diameters. Any growth in a nevus warrants an evaluation. ❍ Evolving: Changes in the lesion over time are characteristic. This factor is critical for nodular or amelanotic (non-pigmented) melanoma, which may not exhibit the classic criteria listed above. Types of melanoma Based on the clinical and pathological features, melanomas are broadly categorized into four types:

Clinical photograph of malignant melanoma. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

❍ ❍ ❍ ❍

Superficial spreading Nodular Lentigo maligna Acral lentiginous.

Table 12 summarizes the important features of these types of melanomas. Self-assessment tool for diagnosis of melanoma

Males are usually more commonly affected than females (approximately 3:1.8). It has also been seen that melanomas are almost 5 times more common in whites than the negroes. Melanomas are more common among Africans, Japanese and Hispanics. The common primary sites of involvement are the hard palate and maxillary gingiva. Other less commonly affected sites are the buccal mucosa, lips, tongue, floor of the mouth and the mandible (Figure 28). Clinically the lesion has varied presentations, ranging from a dark blue-black to brown and to an amelanotic variety that may appear pink. Some authors believe that there is a deficiency of tyrosine and an enzyme required for melanin production. Others believe that this enzyme system is intact and can produce melanin but the quantity is insufficient to be seen with histologic methods. The latter explanation seems convincing because electron microscopy does reveal the presence of melanosomes in all amelanotic melanomas reported till date. Amelanotic variants have a worse prognosis because of delayed recognition and subsequent treatment. Melanomas may also be seen as a nodule which may exhibit ulceration. The indicative clinical signs for malignant melanoma are referred to as the ABCDE warning signs.

Many authors believe that the ‘ugly duckling’ sign can be used as an effective self-examination tool. Individuals are asked to compare the gross appearance of moles on their body. Usually all the moles will have similar topographical appearance except for the ‘ugly ducking’ or the malignant melanoma, which will appear different from other moles. Scope et al (2008) assessed the effectiveness of the ugly duckling sign as a potential screening tool for malignant melanoma. They found that all the melanomas were generally apparent as ugly ducklings. Differential diagnosis of melanoma includes oral melanotic macule, smoker’s melanosis, amalgam tattoo, melanoplakia, Addison’s disease and Peutz–Jeghers syndrome.

❍

1.

Asymmetry: The shape of the lesion is not the same on both sides. ❍ Border irregularity: The edges are ragged, notched or blurred.

Histologic features Histologically a high concentration of melanocytes may be seen in the biopsy specimen. These atypical melanocytes are larger, exhibit nuclear pleomorphism and hyperchromatism in the epithelial and connective tissue junction (Figure 29). Based on the extent of penetration through the dermis to the subcutaneous fat, Clark suggested five levels of microstaging:

2.

Level I: Melanoma lies in the epidermis above an intact basal lamina. Level II: Melanoma cells that have compromised the basal lamina, infiltrating the papillary dermis.

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Table 12

Melanoma: characteristic features

Type of melanoma

Characteristic features

Superficial spreading

Most common type (comprises 70% of skin lesions) Usually arises from a pigmented dysplastic nevus Ulceration or varied colorations (blue, black, gray, pink) are seen Common on the head, neck, and trunk of males and the lower extremities of females

Nodular melanomas

Represent approximately 10–15% of cutaneous melanomas (almost 30% of these occur in the head and neck region) Common on the trunk of males Usually symmetrical and uniform Dark brown or black in color The radial growth phase may not be evident (due to its high risk) Amelanotic melanomas represent approximately 5% of all nodular melanomas

Lentigo maligna melanoma

Almost 10% of the cutaneous melanomas are lentigo maligna melanoma It originates from a melanoma in situ called lentigo maligna or Hutchinson’s freckle The Hutchinson’s freckle is generally in a radial growth phase for almost 12–15 years. At this time, the lesion appears as a relatively flat brown, black and occasionally grayish-white macule However, over a period of time this radial phase of growth turns into a phase of vertical growth indicating an invasion into deeper planes of tissue. During this phase the flat macule exhibits nodular changes At this stage the lesion is termed lentigo maligna melanoma

Acral lentiginous melanoma

It is the most commonly occurring oral melanoma In the initial stages it may appear as a macule, which slowly shows nodular appearance It commonly affects the oral mucous membranes, palms and soles

5. Figure 29

Level V: Melanoma extending into the subcutaneous fat.

Management and prognosis Melanoma is best managed with surgical excision of the lesion with wide margins of at least 2.5 cm. However, widespread disseminated metastatic diseases can be managed with chemotherapy and radiotherapy. Some authors have reported good results with interferon. It is believed that the prognosis of oral melanomas are poorer than skin lesions. The prognosis of the condition depends on the extent of invasion. When the invasion limited to the epidermis, the condition is almost 100% curable. However, when the lesions are less than 1 mm in thickness, the 5-year survival rate is about 95%, but when the lesions are more than 4 mm in thickness, the 5-year survival rate falls to 45%. The 5-year survival rate for oral melanomas is about 10%.

Histopathological picture of melanoma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

CONNECTIVE TISSUE MALIGNANT TUMORS Fibrous Tissue Origin Fibrosarcoma

3. 4.

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Level III: Melanoma involving the papillary dermis, extending to the papillary-reticular dermis interface. Level IV: Melanoma extending into the reticular dermis.

Fibrosarcoma is a malignant neoplasm of the fibroblastic origin. Fibrosarcoma may occur anywhere in the body. Extremities are the most commonly affected. However, only about 10% involve the head and neck region.


They can present as a soft tissue mass or as a primary (central and peripheral) or secondary bone tumor. The primary fibrosarcoma produces variable amounts of collagen. The secondary fibrosarcoma of bone arises from a pre-existing lesion or as a complication of radiotherapy involving bone or soft tissue. It is believed that the secondary fibrosarcoma is very aggressive. Patients may complain of bone pain and swelling when the tumor involves the bone. Larger tumors may lead to destruction of the bone architecture and pathological fracture. Fibrosarcomas involving the soft tissues are seldom painful. They are usually seen deep to the muscular fascia. They affect males and females equally and commonly seen in the 2nd to 4th decades of life. However, reports of fibrosarcoma involving the tongue, gingiva and jaw bones have been reported in young children. The common sites that are involved include the paranasal sinuses, lip, palate and the periosteum of the maxilla or mandible. The mandibular premolar and molar region is the most common site. Soft tissue involvement may produce a locally invasive swelling that may show secondary changes such as hemorrhage and ulceration. Occasionally, patients may report of altered sensation if the tumor involves peripheral nerves. Radiographic features Fibrosarcomas are evident as a solitary radiolucency with ragged or ill-defined borders. Peripheral lesions may show saucerization of the surface underlying bone. In many individuals the normal bone surrounding the tumor may show sclerosis. The cortices show thinning or destruction in extensive cases. The tumor can cause destruction of the sinus, nasal fossa or the mandibular canal based on its location. Displacement of teeth and alveolar bone with tooth floating in space appearance are common. Widening of the periodontal ligament space is seen. However, root resorption is seldom evident. Some authors have reported the presence of sunray appearance or Codman’s triangle appearance when associated with disruption of the periosteum.

Figure 30

Long fascicle Short fascicle

Interlacing fascicles

Histopathological picture of fibrosarcoma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

muscular immunomarkers help to differentiate fibrosarcoma from other tumors. Management Radical surgical removal of the tumor is the treatment of choice. Inaccessible tumors can be palliated with chemotherapy and radiotherapy. It is estimated that the 5-year survival rate is approximately 30%.

Malignant Fibrous Histiocytoma Malignant fibrous histiocytoma (MFH) is a sarcoma with both fibroblastic and histiocytic features. MFH typically arises in the soft tissues of the extremities and retroperitoneum, the head and neck region is rarely involved. These tumors account for about 10–20% of all sarcomas. In the present times, it is considered as one of the most common soft tissue sarcomas of adult life. These tumors typically arise in the muscles and deep fascia. However, tumors involving bone have also been reported. They can be either benign or malignant.


Clinical features

In low-grade malignancy, spindle cells are seen arranged in fascicles with low to moderate cellularity in a ‘herringbone’ pattern. Mild degree of nuclear pleomorphism is seen. However, high-grade malignant lesion shows extensive nuclear pleomorphism and increased cellularity. Atypical mitosis is present (Figure 30). Histologically, fibrosarcoma mimics malignant fibrous histiocytoma, liposarcoma or synovial sarcoma. However, positive immunostaining for vimentin and negativity for

It is commonly seen in adult males. Superficially located tumors are generally smaller in size compared to deep seated tumors. The tumors can affect any part of the body. The common sites of involvement include the extremities, nose, paranasal sinuses, orbit, larynx, meninges, lungs, vagina, ovary and submandibular glands. The intraoral sites commonly affected are the buccal mucosa, vestibule, lips and tongue. The jaws bones also 371


have reportedly been involved. The painless nodular mass may vary in size from a few millimeters to few centimeters in size. Fibrosarcoma can be considered in the differential diagnosis. Other conditions that can be included in the differential diagnosis are leiomyosarcoma, angiosarcoma and neurofibrosarcoma. Histopathologic features The tumor is characterized by a heterogeneous population of pleomorphic spindle cells arranged in a typical storiform or ‘starry-night’ pattern interspersed among zones of anaplastic giant cells. Based on the histopathological differences, malignant fibrous histiocytomas have been classified as myxoid (good prognosis), inflammatory (aggressive in nature), pleomorphic and angiomatoid (very rare) varieties. The myxoid variety has a better prognosis whereas inflammatory type is more aggressive in its course. Management Surgical management is the treatment of choice. Radiation therapy could be used as an adjunct to surgery. It is estimated that the 5-survival rate is about 65%.

Radiographic features In the head and neck region, CT image may reveal a multilocular tumor with smooth, well-defined margins and heterogeneous enhancement after injection of contrast medium. Occasionally, internal calcification may be evident. Histopathologic features Histopathologically synovial sarcoma is divided into biphasic, monophasic (fibrous and epithelial) and poorly differentiated (round cell) subtypes. A myxoid variant has also recently been described. The biphasic subtype is composed of spindle and epithelial cell elements. The monophasic type is composed primarily of spindle cells and rarely epithelial cells. The poorly differentiated subtype shares features of both the mono-and biphasic types along with poorly differentiated areas characterized by high cellularity, pleomorphism, numerous mitoses and round cell morphology. In some patients, necrosis may be evident. Immunohistochemically, the epithelial-like cells are positive for cytokeratins and epithelial membrane antigen, and the spindle cells are positive for vimentin and fibronectin. All the subtypes are characterized by a specific t(x;18) (p11.2;q11.2) chromosomal translocation.

Synovial Sarcoma Knox in 1936 proposed the term ‘synovial sarcoma’ as the earliest of the cases reported, showed some histological resemblance to synovial tissue. However, in the present times it is widely accepted that the tumor does not arise from the synovium. Synovial sarcoma arises from the pluripotent mesenchymal cells of the para-articular surfaces. It commonly affects the extremities. It is estimated that about 10% of all soft tissue sarcomas are synovial sarcomas and around 3–10% occur in the head and neck region. Clinical features Synovial sarcomas usually affect men in the 2nd to 4th decade of life. The common sites of involvement in the head and neck are the hypopharyngeal and retropharyngeal regions. Involvements of the parotid gland, tongue, buccal mucosa, soft palate, floor of mouth, mandible and TMJ have also been reported. Many of the patients may complain of a steadily growing painful mass over a period of many months. Some individuals may complain of difficulty in swallowing, dyspnea and hoarseness of voice. Almost 50% of the synovial sarcomas may metastasize to the lung. Other sites for metastases include the lymph nodes and bone marrow. 372

Management and prognosis Radical surgical excision with negative margins is the treatment of choice. Regional lymph nodes may have to be removed if clinical lymphadenopathy is evident. Occasionally an adjunctive radiotherapy (65 Gy) is used. Chemotherapy has been tried to prevent distant metastasis. Almost 60–90% of the patients may exhibit recurrence. The prognosis of the sarcoma varies on the size of the tumor and characteristics of the tumor. It is believed that primary tumors larger than 4 cm in diameter have a poorer prognosis. Calcifying-type synovial sarcoma has been reported to have a relatively better prognosis. The 5-year survival rate ranges from 36 to 76%.

Cartilage Tissue Origin Chondrosarcoma Chondrosarcomas are malignant tumors of the bone with cartilaginous differentiation. The tumor cells characteristically form cartilage. They constitute about 25% of all primary bone tumors. Phemister in 1930, reported sarcomas of bone that contained abundant cartilage as chondrosarcomas. Lichtenstein and Jaffe defined chondrosarcomas as arising from full-fledged cartilage and never containing osteoid or bone stroma.


Chondrosarcomas can have varied behavioral patterns, from slowly growing tumor to a highly aggressive and metastazing lesion. They may either occur as central or peripheral tumors. Clinical features Only 5–10% of chondrosarcomas occur in the head and neck region. The larynx and the nasal cavity are the most commonly affected. The less common sites being the maxilla (anterior maxilla) and mandible (symphyseal region). The tumor commonly affects males in the 3rd decade of life. The tumor presents as a painless mass or swelling associated with loosening of the associated teeth mimicking periodontal disease. Histopathologic features Tumors are further categorized by grade. Grade 1 represents the least aggressive in terms of histologic features, and grade 3 represents the most aggressive. Most chondrosarcomas are pathologically classified as conventional, but other subgroups are clear cell, myxoid, mesenchymal, and dedifferentiated. Evans and coworkers proposed a histological grading system for chondrosarcoma. ❍

Grade I lesions: These resemble benign cartilage, having a relatively uniform, lobular histologic appearance and no metastasis. ❍ Grade II lesions: Higher recurrence rate than Grade I lesions. These exhibit occasional mitotic figures. The rate of metastasis is approximately 10%. ❍ Grade III lesions: These are more cellular and pleomorphic in appearance, with a marked increase in the number of mitotic figures. The rate of metastasis in grade III lesions is more than 70%.

Adipose Tissue Origin Liposarcoma Liposarcoma is the malignancy arising from of the adipose tissue. Virchow was the first to describe liposarcoma. After malignant fibrous histiocytoma, it is the second common soft tissue sarcoma in adults. Clinical features Liposarcoma is commonly seen in males in the 4th to 6th decades of life and seldom seen in children. It usually affects the retroperitoneum, inguinal region and lower extremities. It is very rarely seen in the head and neck region (about 5–9% of cases). The oral cavity, larynx, hypopharynx, scalp, orbit and soft tissues of the neck are the common sites that are affected in the head and neck region. The intraoral sites include the buccal mucosa, tongue, gingiva and floor of mouth. In the early stages, liposarcoma presents as an asymptomatic slow-growing swelling. However, over a period of time, as the tumor enlarges, it may become symptomatic when it impinges on the adjacent vital structures. Histopathologic features Liposarcoma can easily be misdiagnosed clinically. On gross appearance, the tumor is well-encapsulated and circumscribed. The WHO distinguishes the four variants proposed by Enzinger and Weiss based on developmental stage of the lipoblasts and overall degree of cellularity and pleomorphism. These four entities are: well-differentiated (subtypes— lipoma-like, inflammatory, and sclerosing types), myxoid, round-cell and pleomorphic. The dedifferentiated type is the newer 5th type. Treatment and prognosis

Radiographic features Radiographically, chondrosarcomas can present as ill-defined radiolucencies with few radiopaque foci (calcification/ ossification of cartilaginous matrix). Occasionally, these may present as areas of dense radiopacification with illdefined margins. Involvement of the cortices can result in a sunburst pattern. Symmetric widening of periodontal ligament space and resorption of the roots of teeth may be evident.

Wide surgical excision is the treatment of choice for liposarcoma. Lymph node dissection is not indicated unless metastasis is strongly suspected. Some authors feel that radiation therapy along with surgical excision may improve the condition of the patient. The 5-year survival rate is approximately 60–70%.

Bone Tissue Origin Osteosarcoma (Osteogenic Sarcoma)

Management The treatment of choice is radical surgical excision with negative margins. Distant metastasis is rare. However, distant metastasis to the sternum, vertebrae and lungs has been reported.

Osteosarcomas are primary malignant bone tumors in which mesenchymal cells produce osteoid. Osteosarcomas of the jaws represent less than 10% of all bone tumors and less than 1% of all malignant tumors of the head and neck. 373


Figure 31

Clinical photograph of paraosteal osteosarcoma. Courtesy: Editor, JCDA. Illustration from non-squamous cell malignant tumors of the oral cavity: an overview. Tom Daley and Mark Darling. J Can Dent Assoc 2003;69(9):577–82

mandible are the common sites affected. In the maxilla the alveolar ridge, antrum and the palate are frequently affected. The infraorbital rim and the zygoma have also been reportedly affected (Figure 31). The main symptoms of this lesion in jaw are swelling and pain, paresthesia/anesthesia (of the lower lip and chin following involvement of the inferior alveolar nerve), loose teeth and trismus. When the tumor extends to involve the nasal cavity, maxillary sinus and orbit, clinical signs and symptoms such as epistaxis, nasal obstruction, hemorrhage, exophthalmos and blindness may be apparent. The average time between presenting of symptoms and diagnosis range from 3 to 5 months. Amaral et al (2008) suggest that the differential diagnosis for osteosarcomas of the jaw should include chondrosarcoma, Ewing’s sarcoma, bone metastasis, fibrous dysplasia, osteomyelitis and even lesions that do not usually affect the jaw bones as fibrosarcoma, leiomyosarcoma or rhabdomyosarcoma. Radiographic features

It occurs most often in the long bones, with predilection for the distal femoral metaphysis, proximal tibia, and humeral metaphysis. Most of the osteosarcomas originate intramedullary (classic or conventional osteosarcoma). However, the other relatively rare types of osteosarcomas are the juxtacortical (periosteal and parosteal [Figure 31]) and extraskeletal. Many authors have described osteosarcoma of the jaws as a specific entity, with a clinical behavior different from osteosarcoma of other skeletal bones. Predisposing factors The exact pathogenesis for the tumor is still unknown. However, various predisposing factors have been proposed such as trauma, virus, genetic mutations, pre-existing bone cyst, Paget’s disease, osteogenesis imperfecta, osteochondroma fibrous dysplasia and previous history of radiation (radiation-induced sarcomas). It is suggested that the average latent period between radiation treatment and development of sarcoma is 12.5 years, following radiation dose of 45 Gy. It is believed that individuals who harbor the mutation in tumor suppressor genes like p53 and retinoblastoma gene are more prone to develop osteosarcomas. Clinical features Osteosarcomas affecting the jaw bones are usually seen in the 3rd and 4th decades of life. However, children have also been affected. Males are slightly more commonly affected. The mandible and maxilla are equally affected. The symphysis, ramus and posterior parts of the body of the 374

The radiographic features of osteosarcoma of the jaws may vary from ill-defined radiolucent areas to mixed radiopaqueradiolucent lesions and dense sclerosis/radiopacification (Figure 32A–C). The earliest radiographic change consists of a symmetric widening of the periodontal ligament space around a tooth or several teeth as a result of tumor infiltration along the ligament space. This radiographic feature is referred to as Garrington’s sign. Occasionally, lamina dura may be lost. The other early radiographic feature was proposed by Yagan et al (1985). They suggested that the irregular widening of the mandibular canal, with areas of narrowing and loss of fine parallel cortical margins of the walls of the canal was an early sign of osteogenic sarcoma of the mandible. In some individuals, spiking resorption of the roots of teeth are seen. Other radiographic findings include ill-defined ‘motheaten’ destruction of bone (extensive sarcomas may cause pathological fracture), honeycomb-like appearance, granular appearance, sunray appearance, Codman’s triangle and onion peel appearance. Bianchi and Boccardi (1999) described three specific CT appearances of osteosarcomas: 1. 2. 3.

Radiolucent with absence of bone formation within the tumor Mottled with small areas of amorphous ossification ‘Lamellar’ ossification with bony plates radiating from a focus-like a sunburst.

Ng et al (2001) in a pioneering study described the ultrasound features of osteosarcoma of the mandible. In the mandible they recommend that the most accessible surface is the buccal cortex. Features such as bone thinning,


Figure 32 A

B

C

(A–C) 3D-reconstructed images showing changes seen in osteosarcoma. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

erosion, expansion, and the sunray appearance of the buccal cortex were all detected by ultrasound imaging.

Figure 33

Histopathologic features Histologically, osteosarcomas are categorized as osteoblastic, chondroblastic, fibroblastic and telangiectatic. The characteristic features of osteosarcoma are the presence of atypical osteoblasts. The osteoblasts are arranged in a disorderly fashion (Figure 33). Irregular sheets of osteoid may be seen. The telangiectatic type exhibits extensive blood-filled spaces. However, this type is generally seen in young adults. Management The choice of treatment for osteosarcoma is radical surgery along with adjuvant chemotherapy. As most of the

Osteoid Trabeculae of bone Chondroid tissue Pleomorphic, hyperchromatic osteoblasts

Histopathological picture of osteosarcoma. Courtesy: Department of Oral Pathology and Microbiology, MCODS, Mangalore

375


osteosarcoma metastasizes by hematogeneous route, there is a rationale for addition of adjuvant chemotherapy. Literature reveals that the 8-year metastasis-free survival rate is 60–70%. The factors associated with poor prognosis include neural sensory alteration as a presenting symptom, increasing age of patients and surgical margins less than 5 mm.

Ewing’s Sarcoma (Round Cell Sarcoma) Ewing’s sarcoma is uncommon, aggressive bone malignancy occurring in childhood. It accounts for about 4–7% of all primary bone malignancies. James Ewing (1921) was the first to describe Ewing’s sarcoma. It is believed to originate from the immature reticulum cells or primitive mesenchymal cells of the bone marrow. Although Ewing’s sarcoma commonly affects bone, it may also arise from soft tissues. Ewing sarcomas arising from soft tissues are referred to as extraskeletal Ewing’s sarcoma. Tefft et al (1969) first described this variant. The extraskeletal variety has been reported to arise in various locations such as small intestine, vagina, kidney, skin, larynx, esophagus, paravertebral region, or epidural space. Clinical features Ewing’s sarcoma is usually seen in the first 2 decades of life and affects males twice as commonly as females. It typically affects the pelvic girdle and the long bones of the lower extremities. Studies have shown that whites are predominantly affected. Only 2–7% of the tumors affect the maxillofacial region. The mandibular ramus region is relatively more commonly affected than the maxilla. About 90% of the mandibular lesions are primary tumors and about 10% are metastatic. Swelling, pain, paresthesia, and loose teeth are frequent symptoms. Occasionally, low-grade fever may be apparent. In the initial stages of the tumor, expansion of the cortical plates may be appreciable. However, as the tumor enlarges and perforates through bone, as soft, tender mass may be evident.

Histopathologic and laboratory studies Histopathologically, Ewing’s sarcoma mimics eosinophilic granuloma, malignant lymphoma and metastatic neuroblastoma. Microscopically, tightly packed round cells, compartmentalized by fibrous bands with minimal stroma are seen. Individual cells have round to oval nuclei 10–15 m in diameter with a distinct nuclear membrane. Mitotic figures are commonly seen. The cytoplasm is ill defined, scanty, and pale staining. The cytoplasm stains characteristically with periodic acid-Schiff (PAS), indicating the presence of glycogen. Immunostaining for CD99 (Mic-2) is highly sensitive for Ewing’s sarcoma. Immunostaining also shows abundant vimentin intermediate filaments. It is related to primitive neuroectodermal tumor sharing a common karyotypic translocation t(11;12)(11;22)(q24;q12). Leukocytosis and elevated ESR may be evident. Management and prognosis Ewing’s sarcoma is best treated with a combination of surgery, chemotherapy and radiotherapy. Surgery and radiation is used for local management. Systemic micrometastasis is managed with chemotherapy. It is estimated that the 5-year survival rate is about 60%. The prognosis of Ewing’s sarcoma may be poor when the tumor metastasizes to other bones, lung, lymph node and liver.

Vascular Origin Kaposi’s Sarcoma Kaposi’s sarcoma is a vascular tumor that was first described by Moritz Kaposi, a Hungarian dermatologist in 1872. He described a distinct variety of skin tumors in five male patients in their 6th and 7th decades of life. He termed these tumors as ‘idiopathic multiple pigmented sarcoma of the skin’. There is a strong evidence to show that Kaposi’s sarcoma is caused by human herpes virus 8 (HHV-8). Kaposi’s sarcoma has four distinct variants: classic or Mediterranean, endemic or African, epidemic or AIDS associated, post-transplant or iatrogenic immunosuppression associated Kaposi’s sarcoma. The histopathological and immunohistochemical features of all forms of Kaposi’s sarcoma are similar. Clinical features

Radiographic features Extensive ill-defined destruction of the bone may be the only finding in jaw lesions. A laminated periosteal reaction (onion skin/peel appearance) or sunray appearance is usually a feature of long bones. Occasionally, widening of the periodontal ligament space, loss of lamina dura, root resorption and/or displacement and destruction of unerupted tooth follicles are seen. 376

Classic Kaposi’s sarcoma usually occurs in adult males. The classic form commonly occurs in Jewish and Italian populations. Almost all individuals suffering from the classic form will tend to have an associated malignant lymphoma. Intraoral findings are extremely rare. The palate may be involved. Though the classic variety may affect any part of the body, lower extremities are commonly affected than the trunk, arms and hands. The skin of the extremities may


Figure 34

❍

Stage IV (disseminated visceral Kaposi’s sarcoma) has widespread Kaposi’s sarcoma, usually progressing from Stage II or Stage III, with involvement of multiple visceral organs.

The following modifications have also been proposed: ❍ ❍ ❍

Associated opportunistic infection(s) is evident. Patient is HIV-I seropositive. Cutaneous anergy or other evidence of severe immunodeficiency is present.

Management

Clinical photograph of Kaposi’s sarcoma in a 28-year-old HIV-positive man who presented with multifocal flat to nodular purple lesions of the facial skin and oral mucous membranes. Facial (black arrow), palatal and tongue (white arrow) lesions are illustrated. Courtesy: Editor, JCDA. Illustration from non-squamous cell malignant tumors of the oral cavity: an overview. Tom Daley and Mark Darling. J Can Dent Assoc 2003;69(9):577–82

reveal blue to purple macules which turn into painless nodules over a period of time (Figure 34). Endemic Kaposi’s sarcoma is also referred to as African Kaposi’s sarcoma. The African variety can present as benign nodular (similar to classic, occurs in young adults), infiltrative (locally invades adjacent soft tissues and bone), florid (widely disseminated with visceral involvement) and lymphadenopathic type (rapidly growing tumors of lymph nodes, seen in young children). This association of AIDS with Kaposi’s sarcoma was first described in the early 1980s. It is considered to be the most common form. It is estimated to appear in up to 40% of AIDS patients and may account for up to 90% of all cancers found in the AIDS population. The iatrogenically induced variety is seen a few months and years following organ transplants in post-transplant patients. This form of the disease results from the effects of the immunosuppressive drugs. Cessation of the therapy can result in regression of the tumor. Schwartz and coworkers in 1984, proposed the following classification system for Kaposi’s sarcoma: ❍

Stage I represents localized nodular Kaposi’s sarcoma, with more than 15 cutaneous lesions or involvement restricted to one bilateral anatomic site, and few, if any, gut nodules. ❍ Stage II includes both exophytic destructive lesions and locally infiltrative cutaneous lesions as locally aggressive Kaposi’s sarcoma. ❍ Stage III (generalized lymphadenopathic Kaposi’s sarcoma) has widespread lymph node involvement, with or without skin lesions, but with no visceral involvement.

Individual solitary lesions are surgically excised. Electron beam radiotherapy can be used effectively. Occasionally, intralesional or systemic chemotherapeutic agents are used. Vinblastine is the most commonly used antineoplastic agent.

Angiosarcoma Angiosarcoma is an uncommon malignancy originating from the vascular endothelium of either the blood vessels or lymphatic channels. It generally occurs in the skin and subcutaneous or skeletal muscle and has been reported to occur in the spleen, bone, liver, and breast. Angiosarcomas are usually seen in the 5th decade of life. However, individuals in the age range from 6 to 90 years have also been affected. More than half the angiosarcomas affect the head and neck region. The scalp and forehead are the most commonly affected sites. Oral and salivary gland angiosarcomas are exceedingly rare, comprising only about 2% of all angiosarcomas. Angiosarcomas may involve the lip, buccal mucosa, floor of mouth, gingiva, tongue and the mandible. The intraoral lesions may appear as simple bruise in the early stages. As the neoplasm advances, it tends to become nodular and ultimately ulcerate. The differential diagnosis for angiosarcoma includes hemangioma, pyogenic granuloma, hemangiopericytoma, Kaposi’s sarcoma and hemangioendothelioma. Histopathologically, the tumor is characterized by the presence of proliferation of endothelium-lined vascular channels forming a network of anastomosis with increased mitotic activity. Management Angiosarcomas are best treated with surgical excision and radiation therapy.

Muscle Origin Leiomyosarcoma Leiomyosarcoma is a malignant mesenchymal neoplasm exhibiting smooth muscle differentiation. It accounts for 377


about 6–7% of all soft tissue sarcomas. However, it rarely occurs in the oral soft tissues or jaw bones. It typically affects the adults and occurs in the retroperitoneal region, gastrointestinal tract and uterus, reflecting the affinity for affecting smooth muscles. These tumors generally affect individuals over the 4th and 5th decades of life.

Figure 35

Clinical features Oral leiomyosarcomas may occur at any age. About 3–10% of the leiomyosarcomas. Smooth muscle tumors in the oral cavity may originate from the arterial tunica media, the ductus lingualis, the circumvallate papillae, and pluripotential mesenchymal cells, which are rich sources of smooth muscle tissue. A leiomyosarcoma in the oral cavity may be primary or secondary (metastatic from another location). The common sites of metastatic involvement are the mandible for bony depositions and the gingivae and tongue for soft tissue deposits. It is estimated that 45% of the reported cases affecting the oral cavity occur in the jaw bones. Clinically they may appear as painless or occasionally painful well-circumscribed mass, firmly adherent to the surrounding tissues. Some of these tumors may reveal ulcerations. Histopathologic features Leiomyosarcoma is characterized by sheets of sweeping, alternating bundles and fascicles of densely packed spindle cells with abundant fibrillar eosinophilic cytoplasm and indistinct cytoplasmic borders. The nucleus is usually centrally located and blunt-ended, squared-off or cigarshaped. Occasional cells have perinuclear vacuoles. Masson’s trichrome staining and immunohistochemical evaluation for muscle antigens are helpful in differentiating leiomyosarcoma from other sarcomas. Positive reactions for desmin, vimentin, smooth-muscle actin and h-caldesmon have been demonstrated in this neoplasm. Management Radical surgical excision is the treatment of choice along with chemotherapy and radiotherapy. It is estimated that the 5-year survival rate is about 30%.

Clinical photograph of rhabdomyosarcoma. Courtesy: Dr Foluso Owotade

Types of rhabdomyosarcomas Based on their anatomical location of occurrence, these tumors are broadly categorized as orbital, parameningeal and non-orbital non-parameningeal forms. Parameningeal tumors are said to have the worst prognosis. The International Classification of Rhabdomyosarcoma in 1994, divides this tumor into four subgroups, namely, botryoid and spindle cell RMS, embryonal RMS, alveolar RMS, and undifferentiated sarcoma. Oral features These tumors are generally seen in the first decade of life. These are also occasionally seen in adolescents and young adults. Clinically a rapidly growing painless mass may be seen. Palate, tongue and alveolar ridge have been reported as the common sites affected (Figure 35). In the advanced stages of the disease, pain, paresthesia, loosening of the teeth, and trismus may be seen. Management The primary tumors are best managed with surgical resection, multidrug chemotherapy and radiation therapy. The 5-year survival rate is estimated to be about 60%.

Rhabdomyosarcoma Rhabdomyosarcoma (RMS) is considered as the most common soft tissue sarcoma affecting children. It is a malignant neoplasm of skeletal muscle origin. Weber in 1854 is credited for giving the first description of rhabdomyosarcoma. It is estimated that about 35% of RMS arises in the head and neck. 378

Nerve Tissue Origin Neurofibrosarcoma (Malignant Schwannoma, Neurogenic Sarcoma) Neurofibrosarcomas arise from the nerve sheath cells. These account for about 10% of soft tissue sarcomas. It is


estimated that almost 50% of these tumors originate from neurofibromatosis type 1. Clinical features Neurofibrosarcomas are uncommon in the head and neck region. These are common in 4th to 6th decades of life. The common sites affected are the lips, palate, gingiva, buccal mucosa and mandible. Clinically the tumors appear as rapidly growing mass of tissue occasionally associated with pain and paresthesia.

those of fibrosarcoma but which are usually more irregular, with wavy or comma-shaped nuclei. Some less cellular myxoid areas may also be seen. Positive immunostaining for S100 protein is often useful. Management


The tumor is managed with surgery and radiation therapy. The tumors have a high recurrence rate as they tend to spread along the involved nerve. It is estimated that the prognosis for patients with neurofibrosarcoma arising de novo is about 50% for 5-year survival, whereas it is 15% for neurofibrosarcoma arising in cases of neurofibromatosis.

Radiographs may exhibit an ill-defined radiolucency suggestive of destruction of the bone. Widening of the inferior alveolar canal may also be seen.

Lymphoid Origin and Hematological Malignancies

Histopathologic features The typical histopathological feature is the presence of fascicles of atypical spindle-shaped cells, which may resemble

Tumors of lymphoid origin, namely, Hodgkin’s and nonHodgkin’s lymphoma and hematological malignancies including leukemia and myeloma are described in Chapter 18 on Systemic Disorders and their Clinical Implications.

379

CHAPTER

14

Oral Cancer SV Kumaraswamy, V Jeevan Prakash, Praveen BN, Ravikiran Ongole

➧ Incidence of Cancer of Head and Neck ➧

Tumor Growth and Metastasis Molecular Abnormalities

Etiology and Risk Factors Genetic Susceptibility Immune Status Environmental Factors

➧

Clinical Signs of Cancer

➧

Clinical Examination of a Patient with Suspected Malignancy

➧

Tobacco

➧

TNM Staging

➧

Alcohol

➧

Nodal Metastasis

➧

Systemic Health

➧

Diagnosis of Oral Cancer

Ionizing Radiation Role of Viruses Role of Nutrition Oral Hygiene and Dental factors

➧

Management of Oral Cancer

➧

Surgical Treatment Radiation Therapy Chemotherapy

Molecular Basis of Cancer Cellular Kinetics

Malignant tumors are popularly referred to as ‘cancer’. However, the term ‘tumor’ is scientifically more appropriate. Tumor is defined as an autonomous new growth of tissue or an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissue and persists in the same excessive manner even after the cessation of stimuli which evoked the change. Hippocrates described various types of cancers. He referred to benign tumors as oncos (swelling in Greek) and malignant tumors as carcinos (crab or crayfish in Greek). He compared malignant tumors to a crab since the sectional morphology of the tumor along with its vascular supply mimicked the body of a crab with its claws and feet outstretched. Aulus Cornelius Celsus, a Roman encyclopedist, translated carcinos into the Latin cancer, which also means crab. Galen, the Roman physician used oncos to describe all tumors, which laid the foundation for the use of the present day term ‘oncology’. Oral malignancies may arise from the epithelium, muscle mass, odontogenic structures, specialized structures like the tongue and the eye, from the salivary glands both major and minor and also from the bone. However, it is virtually impossible to describe all the forms of cancer in this chapter. 380

As oral carcinoma is one of the most prevalent cancers and is one of the 10 major causes of death, this chapter will attempt to highlight the etiology, clinical features, diagnosis, investigations and the treatment options.

INCIDENCE OF CANCER OF HEAD AND NECK According to the World Health Report (2004), cancer accounted for 7.1 million deaths in 2003 and it is estimated that the overall number of new cases will rise by 50% in the next 20 years. Oropharyngeal cancer is more common in developing countries than developed countries. The prevalence of oral cancer is particularly high among men, the eighth most common cancer worldwide. Incidence rates for oral cancer vary in men from 1 to 10 cases per 100,000 population in many countries. In South-Central Asia, cancer of the oral cavity ranks among the three most common types of cancer. In India, the age standardized incidence rate of oral cancer is 12.6 per 100,000 population. More than 90% of all oropharyngeal cancers occur in patients over the age of 45. As with other head and neck tumors, male predominance is common, with a male to female ratio of 4:1, because of the greater use of tobacco by men.

Chapter 14 – Oral Cancer

It has been estimated that 43% of cancer deaths worldwide are due to tobacco, unhealthy diet, physical inactivity and infections. Tobacco use and excessive alcohol consumption have been estimated to account for about 90% of cancers in the oral cavity; the oral cancer risk increases when tobacco is used in combination with alcohol or areca nut. About 96% of all oral cancers are carcinomas and the remaining 4% are sarcomas. Majority of oral carcinomas are squamous cell carcinomas. It is estimated that 9 out of every 10 oral malignancies is squamous cell carcinoma. It is a disease of increasing age with 95% of the patients older than 40 years of age. In India, it is estimated that there are 2–2.5 million cancer patients at any given point of time with about 0.7 million new cases diagnosed every year and nearly half of them die every year. Two-thirds of the new cancers is diagnosed at a very advanced and incurable stage. More than 60% of these affected patients are in the age group of 35 and 65 years. Fifty percent of all male and 25% in female are tobacco related cancers.

ETIOLOGY AND RISK FACTORS FOR ORAL AND MAXILLOFACIAL CANCER The exact etiology for oral cancer is still questionable. However, it is well known that a plethora of factors predispose an individual to developing oral cancers. Historically, the widely known six “S” has been mentioned in literature, namely, smoking, spirit, sharp teeth, sunlight, syphilis, spicy food and sepsis. However, over a period of time many predisposing factors have been proposed and suggested such as genetic susceptibility, environmental factors, systemic health of an individual and abusive habits such as the consumption of tobacco and alcohol.

Genetic Susceptibility Family history of oral cancer is considered a risk factor. Head and neck cancer patients show an increased susceptibility to chromosome damage by mutagens. Some studies suggest that lip cancers have shown some amount of genetic predisposition. Mork et al (1999) reported a significantly increased odds ratio for developing head and neck squamous cell carcinoma in female patients, aged less than 45 years, who had first-degree relatives with cancer. It is suggested that familial oral cancer may be attributed to both shared environmental factors within families and a common oral cancer susceptibility gene with low penetrance.

Immune Status It has been noticed that immunosuppressed individuals tend to show an increased incidence of oral malignancies.

It is also a well-known fact that the host response diminishes with advancing age. HIV-positive immunocompromised individuals, may usually exhibit Kaposi’s sarcoma and non-Hodgkin’s lymphomas.

Environmental Factors Exposure to actinic radiation There is enough evidence in literature to show that skin and lip cancers are more frequently seen in individuals whose occupation necessitates long working hours in the sun such as fishermen and farmers. It has been reported that fair skinned individuals, people residing in high latitudes with clear atmosphere (UV light can penetrate easily) such as Finland and Sweden, residents closer to the equator (long periods of sunshine) such as Greece are more susceptible to develop lip cancers. The wavelengths of the light thought to be responsible for the actinic damage are in the range of 2,900–3,200 A. Sunscreen lotions are effective in protecting the lip from the damaging effects of UV light. Melanin pigment acts as a protective agent against actinic radiation. Atmospheric pollution Air pollution arising from industrial wastes and automobile exhausts are particularly harmful. Other sources include gases emitted from burning firewood/coal for domestic purposes. Sulfur dioxide, carbon monoxide, nitrogen gases have been implicated in causing pharyngeal, laryngeal and lower respiratory tract cancers.

TOBACCO All the forms of tobacco (smoke and the smokeless/ chewable/inhaled) such as cigarettes, pipes, cigars, beedis, paan and snuff have been implicated in the development of oral cancers. It is believed that tobacco use is responsible for 90% of the oral cancers in males.

Consumption of Tobacco in India It is estimated that 80–85% of tobacco is consumed for smoking either as beedis or cigarettes (Figure 1). Almost 13% chew tobacco in the form of paan (Figure 2, betel leaf, areca nut, tobacco, slaked lime and flavoring agents) or gutkha. Almost 15% are addicted to both habit of chewing and smoking. Only about 1–3% use tobacco in the form of snuff.

Smokeless Form of Tobacco People in the Indian subcontinent exhibit various forms of tobacco chewing habits such as khaini, mishri, zarda, gutkha (Figure 3), mawa and nass. Paan is chewed (betel quid) and the quid is usually placed in the buccal vestibule. 381


Figure 1

Figure 3

One of the popularly consumed packets of gutkha. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore A typical road-side shop selling various tobacco products ranging from cigarettes, beedis, paan to gutkha. Ironically displaying the fact that tobacco causes cancer. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Figure 4

Figure 2

Various constituents of paan. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Tobacco is also used in the form of a powder for inhalation (Figure 4, snuff). Tobacco (Figure 5) contains nicotine (nitrosamine), nitrosodiethanolamine, nitrosoproline, polonium and polycyclic aromatic hydrocarbon (tars). Areca nut (Figure 6 contains cholinergic muscarinic alkaloids such as arecholine and guavacoline) chewing is also widely practiced in India. 382

Snuff used for inhalation. One of the risk factors for causing nasopharyngeal and maxillary sinus cancers. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Smoke Form of Tobacco In India, beedi (Figure 7), cigarette and chutta smoking is commonly seen. However, other popular forms of smoking include use of pipe, cigar and hookah. It is believed that cigar and pipe smoking is more hazardous than cigarette


Figure 5

Processed tobacco leaf ready for use. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Figure 7

Beedis made of tobacco wrapped in a tendu (Diospyros melanoxylon) leaf, and secured with thread at one end. The tobacco content in beedis is approximately 10–20%. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Figure 6

Figure 8

Mature areca nut and the areca nut that is obtained after it is dehusked, processed and dried. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

smoking. Palatal cancers are more common in individuals who place the lit end of the beedis and cigarettes inside the mouth (reverse smoking). It has been proposed that smoking causes pooling of carcinogens in saliva thereby increasing the incidence of cancers of the floor of the mouth, ventral and lateral surface of tongue. It is estimated that in the combustion mainstream of one cigarette (Figure 8), there are approximately 500 mg (92%) of gaseous content (mainly oxygen, nitrogen and carbon dioxide and to a little extent carbon monoxide) and 8% of particulate matter. Aromatic hydrocarbons in the form of ‘tars’ may constitute less than 1 g to 35 mg. Nicotine content varies from 1 to 3 mg. Other constituents of tobacco smoke include carbon monoxide, hydrogen cyanide and thiocyanate. Benzopyrene is considered the most potent carcinogen. It preferentially binds to nucleoproteins. The enzyme

Cigarettes with filters. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

aryl hydrocarbon hydroxylase that is principally produced in human leukocytes, is said to increase the carcinogenic potential of benzopyrene. The carcinogenic properties of marijuana smoke are similar to those of tobacco. Marijuana may interact with mutagen sensitivity and other risk factors to increase the risk of head and neck cancer. Marijuana smoke has a four times higher tar burden and 50% higher concentrations of benzpyrene and aromatic hydrocarbons than are present in tobacco smoke. 383


ALCOHOL Alcohol consumption is the most important risk factor for development of oral cancer in non-smokers. It is also considered as the second independent major risk factor for the development of oral cancer. It is estimated that an average consumption of over 30 ml of alcohol per day increases the risk of oral cancer linearly with the quantity of alcohol consumed. Though any form of alcohol when consumed in large quantities is dangerous, it is believed that dark colored drinks are more hazardous (as they may contain higher beverage congeners such as nitrosamines, hydrocarbons and other impurities which are known carcinogens). Carcinogens present in the tar are insoluble in saliva but are highly soluble in alcohol and easily absorbed in the oropharynx. The International Agency for Research on Cancer published a monograph in 1982, which details the various methods in which alcohol predisposes to head and neck cancers. ❍

Ethyl alcohol increases the permeability of oral mucosa. It also dehydrates the mucosa. It has a solvent action on the keratinocyte membrane thereby allowing the passage of carcinogens into proliferating cells where they may exert a mutagenic action. ❍ The immediate metabolite of ethanol is acetaldehyde, which readily damages cells. It is believed that those who are rapid acetylators are at increased risk of developing cancers. ❍ Alcoholic liver disease is common in heavy drinkers and this minimizes the detoxification of carcinogens. ❍ Alcohol, owing to its high calorific value, suppresses appetite in heavy drinkers. This predisposes to nutritional deficiency which in turn is a risk factor for cancers. Compared to non-users, alcohol users are 3.6 times more likely to have oropharyngeal cancer, 5.8 times for tobacco users, and 19 times for users of both alcohol and tobacco.

SYSTEMIC HEALTH Candidiasis Autoimmune polyendocrinopathy candidiasis– ectodermal dystrophy an autosomal recessive disease associated with a limited T lymphocyte defect, presumably supports the growth of Candida albicans and predisposes to chronic mucositis and oral cancer. Diabetes In diabetic patients, alterations occur in the oxidative equilibrium of free radicals. Elevated blood glucose levels can lead to excessive formation of free radicals. Moreover, due to protein breakdown, the activity of antioxidant scavengers and enzymes is reduced. Both the increase in free radicals and oxidative stress promote carcinogenesis. It has been suggested that poor diabetic control is associated with an increased cancer risk due to enhanced 384

oxidative damage to DNA. Production of reactive oxygen species and lipid peroxidation are increased in diabetic patients, especially in those with poor diabetic control and hypertriglyceridemia. Increased oxidative damage can be due to superoxide radical generation by monocytes through nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Superoxide can undergo either enzymatic or nonenzymatic dismutation to generate hydrogen peroxide. In the presence of transition metals, such as Fe and Cu, both these substances contribute to the generation of highly reactive hydroxyl radicals causing damage to cells. Hence, patients with poorly controlled diabetes are at great risk of developing oral cancer. Syphilis In the older literature, syphilis was considered an important predisposing factor for oral leukoplakia and oral cancer. It was suggested that syphilitic infection caused endarteritis and subsequently atrophy of the overlying epithelium. This made the tongue more vulnerable to the etiological factors. In modern times, tertiary syphilis is rarely encountered in clinical practice due to effective treatment. Trieger et al (1958) reported a study that suggests an increased prevalence of syphilis (approximately up to 60%) in patient groups with squamous cell carcinoma of the tongue. It was seen that this association was stronger in males than females. Michalek et al (1994) reported a study of 16,420 people with syphilis resident in the United States that showed a significantly raised frequency of cancer of the tongue (and Kaposi’s sarcoma) in males. Dickenson et al (1995) screened 63 patients of United Kingdom suffering from squamous cell carcinoma of the tongue. Five of these patients had serological evidence of past syphilis when detected by both specific and non-specific tests.

Ionizing Radiation Exposure to large amounts of ionizing radiation such as in a nuclear mishap is a known risk for causing cancers. Radiation exposure, known to cause DNA damage, may be a potential source of field cancerization of the upper aerodigestive tract. Hashibe et al (2005) evaluated the possible risk of developing second primary cancers following radiotherapy for head and neck cancers in 30,221 oral squamous cell carcinoma patients. Patients treated with radiation only or radiation with surgery had elevated risks of developing a second primary tumor, whereas patients treated with surgery only did not appear to be at increased risk. They also suggested that the expected latent period between radiation exposure and tumor occurrence, radiation became a risk factor after 10 years of follow-up for solid cancers of the oral cavity, pharynx, esophagus, and lung, and after 1–5 years of follow-up for second primary leukemia.


Role of Viruses The role of viruses remains unclear. Varying viral genomes have been frequently found within cancer cells. Viruses have been known to modify the DNA and the chromosomal structures and induce proliferative changes in the cells they infect. Evidence of a viral carcinogenesis is perhaps strongest for infection with human papilloma viruses (HPV). D’Souza et al (2007) in a multicenter case-control study reported that infection with HPV-16 increased the risk of cancer of the oral cavity and particularly oropharynx. The role of infection with Epstein–Barr virus (EBV) and herpes simplex viruses (HSV) remains uncertain. The role of HSV, HSV-1 and HSV-2, as co-factors in association with tobacco, alcohol, or HPV-16 infection has also been proposed in causing oral cancers. Human immunodeficiency virus (HIV), due its effect on immunosurveillance, acts as a cofactor along with other viruses such as EBV and cytomegalovirus in predisposing the affected individual to oral cancer.

Role of Nutrition Various studies have shown that a diet with low vitamin A, vitamin C, vitamin E, iron, selenium, folate and other trace element content is associated with an increased risk of oral, laryngeal, lung, gastric, ovarian, breast and cervical cancers. Certain dietary deficiencies may cause epithelial atrophy which renders the epithelium vulnerable to the action of carcinogens. The relationship between sideropenic dysphagia and oral cancer is well recognized (sideropenic dysphagia may be associated with epithelial atrophy in the upper alimentary tract). Garewal (1994) summarized the findings of 54 studies that evaluated fruit and vegetable intake in the development of cancers in the upper aerodigestive tract; he found that 52 of the studies demonstrated a protective effect of the antioxidant content of fruits and vegetables. It has been shown that patients who ingest high levels of vitamin C and fiber have half the risk of developing oral cancer as those with minimal level of consumption. Block (1991) and Mirvish (1986) showed that a low intake of vitamin C is associated with an increased risk of cancers of the stomach, esophagus, oral cavity, larynx, and cervix. Gridley et al (1992) in a study involving 2,000 individuals proposed that the use of vitamin E supplements correlated with a diminished risk for oral and pharyngeal cancers.

Oral Hygiene and Dental Factors Though the exact etiological role of poor oral hygiene, faulty restorations, ill-fitting dentures, sharp teeth in causing oral cancers is not substantiated, these may be the possible contributing factors. It is believed that chronic

trauma along with other carcinogens may aid in the malignant transformation of epithelial cells. Shah (2003) suggests that the microorganisms from dental plaque, by way of chemical carcinogenesis, may produce nitrosating enzymes which are toxic. It is also believed that individuals who do not maintain good oral hygiene (inadequate brushing) may fail to dilute the carcinogens present in the oral cavity, especially derived from various tobacco-related habits.

MOLECULAR BASIS OF CANCER Though no one truly understands how these conditions either in their individual standing or in conjunction with other entities leads to cancer, the greater understanding of the importance of genetics and the role of pro-oncogenes and tumor suppressor genes has given us a more detailed insight into the evolution of a cancerous growth. Cellular and molecular basis of malignancy though needs more detailed discussion it could be best summarized under the following sections.

Cellular Kinetics Generation time is the time required for a quiescent cell to enter the cell cycle and give rise to two daughter cells. Malignant cells usually have a shorter generation time than non-malignant cells and a smaller percentage of cells in G0 (resting phase), so a larger proliferation fraction exists. Initial exponential tumor growth is followed by a plateau phase when cell death equals the rate of formation of daughter cells. Compared to large tumors, small tumors have a greater percentage of actively dividing cells and thus show greater rates of proliferation.

Tumor Growth and Metastasis As a tumor grows, nutrients are provided by direct diffusion from the circulation. Local growth is facilitated by enzymes (e.g. collagenases) and cytokines that alter or destroy adjacent tissues. As the ratio of surface area to volume becomes smaller with increased tumor growth, tumor angiogenesis factors are produced, forming the independent vascular supply required for further tumor growth. Almost from inception, a tumor may shed cells into the circulation. From animal models, it is estimated that a 1-cm tumor sheds more than 1 million cells/24 h into the venous circulation. Although most circulating tumor cells die as a result of intravascular trauma, a tiny number (much less than 1 in 1 million) adhere to the vascular endothelium and penetrate into surrounding tissues, generating independent tumors (metastases) at distant sites. Metastatic tumors grow in much the same manner as primary tumors 385


and may subsequently give rise to other metastases. Experiments suggest that metastasis is not a random event and that the primary tumor may regulate the growth of metastatic tumors, for example, removal of the primary tumor sometimes results in rapid growth of the metastases.

Molecular Abnormalities Genetic mutations are largely responsible for the generation of malignant cells. These mutations alter the quantity or function of protein products that regulate cell growth and division and DNA repair. Two major categories of mutated genes are oncogenes and tumor suppressor genes. Oncogenes are abnormal forms of normal genes (protooncogenes) that regulate cell growth. Mutation of these genes may result in direct and continuous stimulation of the molecular biologic pathways (e.g. intracellular signal transduction pathways, transcription factors, secreted growth factors) that control cellular growth and division. There are more than 100 known oncogenes that may contribute to human neoplastic transformation, for example, the ras gene encodes the Ras protein, which regulates cell division. Mutations may result in the inappropriate activation of the Ras protein, leading to uncontrolled cell growth and division. In fact, the Ras protein is abnormal in about 25% of human cancers. Other oncogenes have been implicated in specific cancers. These include various protein kinases (bladder cancer, breast cancer), bcr-abl (chronic myelocytic leukemia, B-cell acute lymphocytic leukemia), C-myc (small cell lung cancer), N-myc (small cell lung cancer, neuroblastoma), and C-erb B-2 (breast cancer). Specific oncogenes may have important implications for diagnosis, therapy, and prognosis (see individual discussions under the specific cancer type). Oncogenes typically result from acquired somatic cell mutations secondary to point mutations (e.g. from chemical carcinogens), gene amplification (e.g. an increase in the number of copies of a normal gene), or from insertion of viral genetic elements into host DNA. Occasionally, mutation of germ cell lines results in vertical transmission and a higher incidence of cancer development in an offspring. Tumor suppressor genes are inherent genes that play a role in cell division and DNA repair and are critical for detecting inappropriate growth signals in cells. If these genes, as a result of inherited or acquired mutations, become unable to function, genetic mutations in other genes can proceed unchecked, leading to neoplastic transformation. As with most genes, two alleles are present that encode for each tumor suppressor gene. A defective copy of one gene may be inherited, leaving a person with only one functional allele for the individual tumor suppressor gene. If an acquired mutation occurs in the other allele, the normal protective mechanisms of the tumor suppressor gene are lost, and dysfunction of other protein products or DNA damage may escape unregulated, leading to cancer. 386

Another mechanism that results in defective function and transcription of tumor suppressor genes is aberrant methylation of the promoter region of these genes, which inhibits gene transcription. Greater degrees of aberrant methylation and greater numbers of affected genes cause tumors to be more malignant and are associated with shortened survival in lung, bladder, and prostate cancers. In vitro alteration of the aberrant methylation has caused reversion to a non-malignant, non-proliferative phenotype, suggesting a potential therapeutic target. Another important regulatory protein, p53, prevents replication of damaged DNA in normal cells and promotes cell death (apoptosis) in cells with abnormal DNA. Inactive or altered p53 allows cells with abnormal DNA to survive and divide. Mutations are passed to daughter cells, conferring a high probability of neoplastic transformation. The p53 gene is defective in many human cancers. Gross chromosomal abnormalities can occur through deletion, translocation, or duplication. If these alterations activate or inactivate genes that result in a proliferative advantage over normal cells, then a tumor may develop. Chromosomal abnormalities occur in certain human cancers. In some congenital diseases (Bloom syndrome, Fanconi syndrome, Down’s syndrome), chromosomes break easily, putting children at high risk of developing acute leukemia and other cancers. Most cancers are likely to involve several of the mechanisms described above that lead to neoplastic conversion. As with oncogenes, mutation of tumor suppressor genes in germ cell lines may result in vertical transmission and a higher incidence of cancer in an offspring. Telomeres are nucleoprotein complexes that cap the ends of chromosomes and maintain their integrity. Telomere shortening (with aging) results in replicative senescence, increased genetic instability, and potential tumor formation. Telomerase is an enzyme that carries out telomere synthesis and maintenance, thus telomerase may potentially allow for cellular immortality. Telomerase activity may promote tumors through multiple, complex mechanisms, especially by subverting the normal DNA synthetic checkpoints.

CLINICAL SIGNS OF CANCER The hardest part of treating cancer is diagnosing it early, but it is also the most easiest part of treating cancer because if discovered early, the lesions are amenable to simple excision and patients have a good chance of a 5-year disease-free survival rate. It makes it easier to remember if the clinical signs are discussed based on the regional anatomy. The many signs and symptoms of oral cancer (Table 1) are usually divided into early and late presentations. They can be so diverse that the differential diagnosis may not lead to oral malignancy.


The clinical presentation varies in most cases and there are no two cases that are similar in presentation and treatment. However, there could be a few similarities that are peculiar to the geographic area that could be grouped together and explained as an entity, for example, carcinoma of the buccal mucosa and the gingivobuccal sulcus that are peculiar to the Indian subcontinent and have been nicknamed as ‘Indian Cancers’. Cancers of the floor of the mouth are more common in the western countries because of their habits. The following section is just a brief explanation of the various clinical signs and symptoms based on their area of presentation.

period of time. The tumor may appear as small nodules and enlarges to from a wart-like growth which ultimately ulcerates or may even begin as an ulceration that does not heal. The lesion is often not painful and is noticed by the patient only when there is a secondary infection of the ulcer. There is induration and infiltration into the deeper tissues. Extension into the muscle of mastication, buccinators, alveolar mucosa and ultimately into the bone may occur and if left unchecked which may cause perforation of the overlying skin (Figure 10). The induration of the skin is a bad clinical sign and necessitates wider excision along with the overlying skin.

Carcinoma of buccal mucosa

Figure 9

The lesions develop most frequently along or inferior to a line opposite the plane of occlusion. It usually occurs at the regions of the third molar area (Figure 9) as there is a habit of keeping the quid (tobacco) in that area for a long

Table 1

Clinical signs of oral cancer

Early signs

Late signs

• Persistent red and/or white patch • Non-healing ulcer • Progressive swelling or enlargement • Unusual surface changes • Sudden tooth mobility without apparent cause • Unusual oral bleeding or epistaxis • Prolonged hoarseness of voice

• Indurated area • Paresthesia, dysesthesia of the tongue or lips • Airway obstruction • Chronic earache (chronic serous otitis media)/otalgia • Trismus and dysphagia • Cervical lymphadenopathy • Persistent pain or referred pain • Altered vision • Epiphora

Carcinoma of the left buccal mucosa extending into the buccal vestibule. Courtesy: Dr Abhinandan

Figure 10 A

B

Carcinoma causing perforation of the cheek. Courtesy: Dr Abhinandan

387


Some cases appear to be growing outward from the surface rather than invading the tissues is called exophytic or verrucous growth. The most common site of metastasis is the submandibular lymph nodes as they are the primary echelon nodes for these regions. Carcinoma of floor of mouth It is seen more commonly in men; reasons being cited that they tend to smoke and abuse tobacco a lot more than women and the chemicals that mix with the saliva tend to pool in the floor of the mouth for a longer time. It is seen most frequently in the anterior portion of floor. The typical carcinoma of the floor of mouth is an indurated ulcer of varying size, on one side of the midline. It may take the form of wart-like growth (Figure 11), which tend to spread superficially rather than in depth. It may spread in four primary directions, i.e. extend to the other side crossing the midline, may extend upward involving the base of the tongue or may come anteriorly invading the lingual mucosa and ultimately invade the bone causing loosening of the anterior teeth (Figure 12). Loosening of teeth is seen only in advanced cases. However, patients seek an early consultation because of the restriction in the movements of the tongue often causing peculiar thickening or slurring or the speech. There may be excessive salivation. In some cases, there may be referred pain in the ears. Carcinoma of floor of mouth may invade the deeper tissues and may even extend into the submaxillary and sublingual glands. Metastasis from the floor of the mouth are found most commonly in the submandibular group of lymph nodes and also sometimes in the facial nodes, since the primary lesion frequently occurs near the midline where

a lymphatic cross-drainage exists, contralateral metastasis is often present. Carcinoma of labial mucosa It is frequently seen in people who habitually keep a mixture of tobacco and lime in the labial vestibule. The lower labial mucosa (Figure 13) is more commonly involved than the upper though the upper lip often gets involved in such cases due to inadvertent contact exposure to the carcinogens. The most common initial signs and symptoms are growth

Figure 12

Orthopantomograph (OPG) showing extensive destruction of the alveolus in the anterior portion of the mandible with teeth floating in space appearance secondary to infiltration of the carcinoma of floor of mouth to the alveolus. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Figure 11 Figure 13

Wart-like growth in the anterior portion of the floor of the mouth suggestive of carcinoma floor of mouth. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

388

Carcinoma of the lower lip showing signs of extensive induration. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore


Figure 14

Ulcero-proliferative lesion on the lower lip and labial vestibule. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Figure 16

Carcinoma affecting the right lateral margin of the tongue. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Figure 17 Figure 15

Extensive lesions affecting the lower lip, upper lip and the right commissure. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

or swelling, soreness and ulceration of the lip which does not heal (Figure 14). Advanced lesion may be ulcerativeinfiltrative type which may restrict the movement of the lower lip. Lymph node involvement may be unilateral or bilateral as they drain primarily into the submandibular nodes. Occasionally, the carcinoma may spread to the corners of the mouth and extend extraorally (Figure 15). Carcinoma of tongue The tongue is the most common intraoral site of cancer in most countries. Of all potential etiologic factors, cancer of the tongue is correlated the closest with the use of tobacco

Carcinoma affecting the ventral surface of the tongue. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

products. Squamous cell carcinoma is by far the most common malignancy of the tongue, typically having three gross morphologic growth patterns: exophytic, ulcerative, and infiltrative. The infiltrative and ulcerative types are observed most commonly on the tongue. Lateral margins (Figure 16) and ventral surface (Figure 17) of the tongue are more frequently affected. The most common finding is an indurated, ulcerated area of the tongue. The induration may extend deep into the tongue musculature and root of the tongue. Malignancies of the tongue may grow to significant size before they cause symptoms. Because of the relative laxity of the tissue planes separating the intrinsic 389


Figure 18

Carcinoma of the palate causing perforation. Courtesy: Dr Abhinandan

tongue musculature, the cancer may spread easily and become symptomatic only when its size interferes with movement. Squamous cell carcinoma of the tongue may arise in apparently normal epithelium, in areas of leukoplakia, or in an area of chronic glossitis. These lesions are usually larger than 2 cm at presentation, with the lateral border being the most common subsite of origin. At this point, the patient may develop speech and swallowing dysfunction. Pain occurs when the tumor involves the lingual nerve, and this pain may also be referred to the ear. Carcinomas of the tongue base are clinically silent until they deeply infiltrate the tongue musculature. These are usually less differentiated. Because of the difficulties with direct visualization, these may extend into the oral tongue or have clinical lymph metastases before the diagnosis is established. Carcinoma of palate It is common in areas where reverse smoking is practiced or also among people who use pipe smoke. Palatal cancer usually manifests as a poorly defined ulcerated painful lesion on one side of the midline (Figure 18). Most other lesions are exophytic and with broad base and nodular surface. It frequently crosses the midline and may extend laterally to include tonsillar pillars or even the uvula. The tumor of hard palate may invade the bone or occasionally the nasal cavity whereas infiltrating lesions of the soft palate may extend into the nasopharynx. Carcinoma of maxillary sinus It is caused by sinusitis, snuff and smoke abuse, occupational hazards like in boot factories, metal workers and 390

Figure 19

Carcinoma involving the right maxillary antrum and the alveolus. Courtesy: Dr Abhinandan

others of such type. As it is seen over periods of prolonged exposure the mean age of occurrence is 60 years. Males are commonly affected more than females in the ratio of 2:1. It is the most common primary tumor of paranasal sinuses comprising 80–90% of cancers in this site. There is facial pain, swelling, nasal obstruction and lymphadenopathy. Medial wall involvement leads to nasal obstruction, discharge, bleeding and pain. Epiphora will result if the lacrimal sac or nasolacrimal duct is obstructed. Involvement of the floor of the sinus leads to expansion of the alveolus, unexplained pain, numbness of teeth, loose teeth and swelling of the palate or alveolar ridge (Figure 19) and malfitting dentures. It may erode the floor and penetrate the oral cavity. Lateral wall involvement leads to facial and vestibular swelling, pain and hyperesthesia of maxillary teeth. Roof involvement leads to diplopia, proptosis and pain over the cheek and upper teeth. Posterior wall involvement leads to painful trismus as the pterygoids get involved, obstruction of Eustachian tube causing stuffy ear, referred pain and hyperesthesia over the distribution of second and third divisions of trigeminal nerve. It may involve the infraorbital nerve and produce paresthesia of the cheek or erode blood vessels giving rise to epistaxis. Paresthesia of mandibular nerve can also occur if the tumor invades the cranium. Primary intra-alveolar carcinoma These lesions are rarely seen and surface only when they invade the overlying mucosa either on the facial or the lingual/palatal side as an exophytic growth. Most often they present only as a non-healing socket or as loose teeth which on radiographs appears as ‘hanging teeth’ with no


bony support. There may be evidence of paresthesia as the nerve gets involved.

Table 2 Stage

CLINICAL EXAMINATION OF A PATIENT WITH SUSPECTED MALIGNANCY Since most of the lesions are innocuous, they escape early detection and present only when it is too late. Good illumination, access and aseptic techniques go a long way in aiding proper diagnosis. Patients should often be examined thoroughly for any suspicious red or white lesions that have no explainable etiology. If any etiology is found such as sharp teeth margins or ill-fitting dentures and bad restorations, they should be removed and all habits must be stopped. The lesions should be reviewed on 2-weekly intervals and must be recorded by photographic evidence. Oral therapy of antioxidants may sometimes make the lesion disappear but nevertheless the risk remains and the patient must be present for 6-month follow-up. After a proper history taking, suspicious or sinister looking lesions must be examined for: (i) extent of the lesion/ swelling; (ii) margin characteristics of the ulcerations if any; (iii) presence or absence of induration around or on the lesion; (iv) involvement of the overlying skin/mucosa (v) trismus; (vi) radiating pain to the ear; (vii) foul smell; (viii) loss of function/mobility as in the case of tongue with slurred speech and excessive salivation; (ix) paresthesia or anesthesia of the nerve in the vicinity of the lesion; (x) discharge from the nose or persistent post nasal drip; and (xi) diplopia of the eye on the affected side.

TNM STAGING The tumor-node-metastasis (TNM) staging system was first reported by Pierre Denoix in the 1940s. The International Union Against Cancer (UICC) eventually adapted the system and compiled the first edition of the TNM staging system in 1968 for 23 body sites. It is important to realize that the TNM staging system is simply an anatomic staging system that describes the anatomic extent of the primary tumor as well as the involvement of regional lymph nodes and distant metastasis. Tumor size and the extent of spread are considered to be the best indicators of the patient’s prognosis. Table 2 summarizes the most widely accepted staging protocol, the TNM classification of oral cancer. This system has three basic clinical features: 1. 2. 3.

The size (in centimeters) of the primary tumor The presence, number, size, and spread (unilateral or bilateral) to the local lymph nodes The presence or absence of distant metastasis.

TNM stage grouping T stage

N stage

M stage

Stage 0

Tis

N0

M0

Stage I

T1

N0

M0

Stage II

T2

N0

M0

Stage III

T3 T1 T3

N0 N1 N1

M0 M0 M0

Stage IV A

T4a T4a T1 T2 T3 T4a

N0 N1 N2 N2 N2 N2

M0 M0 M0 M0 M0 M0

Stage IV B

Any T T4b

N3 Any N

M0 M0

Stage IV C

Any T

Any N

M1

TNM Staging System for Oral Carcinoma Primary tumor (T) TX: Primary tumor cannot be assessed T0: No evidence of primary tumor Tis: Carcinoma in situ T1: Tumor 2 cm or less in greatest dimension T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension T3: Tumor more than 4 cm in greatest dimension T4 (oral cavity): Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or skin of face, i.e. chin or nose T4a (oral cavity): Tumor invades adjacent structures (e.g. through cortical bone, into deep [extrinsic] muscle of tongue, maxillary sinus, skin of face) T4b: Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery. Note: Superficial erosion of bone/tooth socket by gingival primary is not sufficient to classify a tumor as T4. Regional lymph nodes (N) NX: Regional lymph nodes cannot be assessed N0: No regional lymph node metastasis N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greater dimension N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; in multiple ipsilateral lymph nodes, not more than 6 cm in greatest dimension; in bilateral or contralateral lymph nodes, not more than 6 cm in greatest dimension 391


N2a: Metastasis in single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension N2b: Metastasis in multiple ipsilateral lymph nodes, not more than 6 cm in greatest dimension N2c: Metastasis in bilateral or contralateral lymph nodes, not more than 6 cm in greatest dimension N3: Metastasis in a lymph node more than 6 cm in greater dimension. Distant metastasis (M) MX: Presence of distant metastasis cannot be assessed M0: No distant metastasis M1: Distant metastasis. The individual clinical parameters in the TNM classification system are grouped to determine the appropriate disease stage; stages are ranked numerically from 0 (which has the best prognosis) to IV (the worst prognosis). In general, oral staging classifications do not use histopathologic findings except to determine the definitive diagnosis.

NODAL METASTASIS Involvement of regional lymphatic by primary squamous cell carcinomas of the upper aerodigestive tract is dependent on various factors related to the primary tumor. These include the site, size, T-stage and location of the primary tumor. In addition to this, histomorphologic features of the primary tumor also influence the risk of nodal metastases. The risk of nodal metastasis increases in relation to location of the primary tumor, as one progresses from the anterior to posterior aspect of the upper aerodigestive tract meaning: the risk of the lips oral cavity oropharynx hypopharynx. For tumors of the larynx and pharynx, the risk of nodal metastasis increases as it progresses from the center to the periphery, meaning the risk of regional lymph node metastasis from carcinoma of the true vocal cord is exceedingly small. The risk, however, increases as one progress for the vocal cords to the false vocal cords, aryepiglottic fold, pyriform sinus, and pharyngeal wall. Nearly two-thirds of patients with primary carcinomas of the hypopharynx present with clinically palpable regional lymph node metastasis. Certain primary sites have a significantly increased risk of nodal metastases compared to the other sites in the same region, for example, floor of mouth versus hard palate in the oral cavity. In general, T-stage usually reflects tumor burden or invasiveness and therefore the risk of nodal metastases increase with increasing T-stage of the primary tumor at any site. Similarly, tumor size (large versus small) increases the risk of dissemination to regional lymph nodes. Certain histomorphologic features of the primary tumor also increase the risk of nodal metastasis. Endophytic tumors 392

in that regard are more inclined to metastasize compared to exophytic tumors. It has been well documented that for tongue and floor of mouth cancers, tumor thickness is related to the risk of nodal metastases. Poorly differentiated carcinomas have a higher risk of nodal metastases compared to well-differentiated lesions. In general, if the risk of occult metastases exceeds 15–20%, then elective treatment of regional lymph nodes is recommended due to its significantly adverse impact on prognosis. Risk of nodal metastases from cutaneous malignancies is highly variable. Small size (2 cm) squamous cell carcinomas of the skin of the face and neck have a very low risk of nodal metastases. Similarly, small cancers of the sweat gland or adnexal origin also have a low risk of metastases to regional lymph nodes. Therefore, elective treatment of regional lymph nodes is generally not recommended except for patients with massive tumors. On the other hand, cutaneous melanomas have a predictably high risk of nodal metastases with increasing thickness and site of the primary tumor. Therefore, one can justify elective treatment of regional lymph nodes for thicker primary melanomas although increasing popularity of sentinel node mapping techniques negates the consideration of ‘elective lymph node dissections’. Metastatic spread from primary carcinomas of salivary origin is generally low (20%). Therefore, elective dissection of cervical lymph nodes is recommended for high stage (T3–T4) and high grade (poorly differentiated) carcinomas.

Cervical Lymph Nodes Patients who present with tumors localized at the primary site without dissemination to regional lymph nodes enjoy an excellent prognosis. On the other hand, once dissemination to regional lymph nodes takes place, the probability of 5-year survival, regardless of the treatment rendered, reduces by nearly 50% of those patients with early staged patients. Clearly, therefore, the single most important prognostic factor in the treatment of patients with squamous cell carcinoma of the head and neck is the status of cervical lymph nodes. Thus, management of cervical lymph nodes becomes a vitally important component of the overall treatment strategy for patients with cancers of the head and neck. The patients seeking surgical intervention for malignancies in the Indian scenario is only when it is in a very advanced stage, and all the levels of nodes are involved and is almost inoperable.

Anatomy of Regional Lymphatics The lymphatic drainage from the scalp and skin of the head and neck region, the mucosa of the upper craniofacial regions, salivary glands, and the thyroid gland occurs to specific regional lymph node groups. Surprisingly, tumor


dissemination via regional lymphatic to these lymph node groups occurs in a predictable and sequential fashion too. Hence, specific regional lymph node groups should be appropriately addressed in the treatment planning for any given primary site. The plans should encompass all the nodes both accessible to surgical ablation and those not accessible to surgery. The anterior half of the scalp, the skin of the forehead and the upper part of the face drain first to the preauricular, periparotid and intraparotid lymph nodes are thus the first echelon lymph nodes. The initial drainage of the posterior half of the scalp and the posterior aspect of the external ear takes place to the post-auricular and suboccipital group of lymph nodes. Cervical lymph nodes in the lateral aspect of the neck primarily drain the mucosa of the upper aerodigestive tract. These include the submental, prevascular facial, and submandibular group of lymph nodes located in the submental and submandibular triangles of the neck, deep jugular lymph nodes include the jugulo-digastric, juguloomohyoid, and supraclavicular group of lymph nodes adjacent to the internal jugular vein. Lymph nodes in the posterior triangle of the neck include the accessory nerve and the transverse cervical chain of lymph nodes in the floor of the posterior triangle of the neck. Parapharyngeal and retropharyngeal lymph nodes are at risk of metastatic dissemination from tumors of the pharynx. The central compartment of the neck includes the delphian lymph node overlying the thyroid cartilage in the midline draining the larynx and perithyroid lymph nodes adjacent to the thyroid gland. Lymph nodes in the tracheoesophageal groove provide primary drainage to the thyroid gland as well as the hypopharynx, subglottic larynx, and cervical esophagus. Lymph nodes in the anterior superior mediastinum provide drainage to the thyroid gland and the cervical esophagus, and serves as a secondary lymphatic basin for anatomic structures in the central compartment of the neck. Each anatomic subgroup of lymph nodes described above specifically serves as primary echelon lymph nodes draining a specific site in the head and neck region. Thus, location of a palpable metastatic lymph node may often indicate the potential source of a primary tumor. The Head and Neck Service at Memorial Sloan Kettering Cancer Center has described a leveling system dividing the lymph nodes in the lateral aspect of the neck into five nodal groups of levels to establish a consistent and easily reproducible, user-friendly method for description of regional cervical lymph nodes which establishes a common language between the clinician and the pathologist. The lymph nodes in the central compartment of the neck are assigned levels VI and VII. Level I Submental group: The lymph nodes between the anterior bellies of the digastric muscles and above the hyoid bone. Submandibular group: Lymph nodes in the triangular area bounded by the anterior and posterior bellies of

the digastric muscle and the inferior border of the body of the mandible. The lymph nodes adjacent to the submandibular salivary gland and along the facial artery (facial nodes) are included in this group. Level II Upper jugular group: Lymph nodes around the upper portion of the internal jugular vein and the upper part of the spinal accessory nerve, extending from the base of the skull up to the bifurcation of the carotid artery or the hyoid bone (clinical landmark). The posterior limit for this level is the posterior border of the sternocleidomastoid muscle and the anterior border is the lateral limit of the sternohyoid muscle. Level III Mid-jugular group: Lymph nodes around the middle third of the internal jugular vein from the inferior border of Level II up to the omohyoid muscle or the inferior border of cricoid cartilage (clinical landmark). The anterior and posterior borders are the same as those for Level II. Level IV Lower jugular group: Lymph nodes around the lower third of the internal jugular vein form the inferior border of Level III up to the clavicle. The anterior and posterior borders are the same as those for Levels II and III. Level V Posterior triangle group: Lymph nodes around the lower portion of the spinal accessory nerve and along the transverse cervical vessels. It is bounded by the triangle formed by the clavicle, posterior border of the sternocleidomastoid muscle, and the anterior border of the trapezius muscle. Level VI Central compartment group: Lymph nodes in the prelaryngeal, pretracheal (Delphian), paratracheal, and trachoesophageal groove. The boundaries are: hyoid bone to suprasternal notch and between the medial borders of the carotid sheaths. Level VII Superior mediastinal group: Lymph nodes in the anterior superior mediastinum and tracheoesophageal grooves, extending from the suprasternal notch to the innominate artery. Clinical features and diagnosis Lymph nodes in the head and neck region may be present for many reasons although the presence of a clinically palpable, unilateral, hard, enlarged lymph node in the adult should be considered metastatic until proven otherwise. The location of a palpable lymph node may point to the potential site of a primary tumor. The important features to note during examination of the neck for cervical lymph nodes are the location, size, consistency, and number of palpable lymph nodes as well as signs of extracapsular spread such as invasion of the overlying skin, fixation to deeper soft tissues, or paralysis of cranial nerves. Histologic diagnosis of metastatic carcinoma is usually established by a needle aspiration biopsy and cytologic 393


examination of the smears. An enlarged metastatic cervical lymph node may be the only physical finding present in some patients whose primary tumors are either microscopic or occult at the time of presentation. A systematic search for a primary tumor should be undertaken in these patients prior to embarking upon therapy for the metastatic nodes. If a thorough head and neck examination, including fiberoptic nasolaryngoscopy, fails to show a primary tumor, then the diagnosis of metastatic carcinoma to a cervical lymph node from an unknown primary (occult primary) is established.

Patterns of Neck Metastasis Dissemination of metastatic cancer to regional lymph nodes from primary sites in the upper aerodigestive tract occurs in a predictable and sequential fashion. Thus, all regional lymph node groups are usually not at risk of nodal metastases initially from any primary site, in the absence of grossly palpable metastatic lymph nodes. On the other hand, when clinically palpable lymph nodes are present at the time of initial diagnosis, comprehensive clearance of all regional lymph node groups at risk is warranted. Understanding the sequential patterns of neck metastasis therefore greatly facilitates surgical management of regional lymph nodes in the clinically negative neck where the lymph nodes are at risk of harboring micrometastasis. For primary tumors in the oral cavity the regional lymph nodes at highest risk for early dissemination by metastatic cancer are limited to Levels I, II and III. This means the regional lymph node groups are contained within the supraomohyoid triangle of the neck. The lymph node groups contained in the supraomohyoid triangle are: submental, submandibular, prevascular facial, jugulodigastric, upper deep jugular, superior spinal accessory chain of lymph nodes, and mid-jugular lymph nodes. Skip metastasis to Levels I, II, or III is exceedingly rare. Therefore, if the neck is clinically negative, Levels IV and V lymph nodes are generally not at risk of harboring micrometastasis from primary squamous carcinomas of the oral cavity. An exception to this observation is primary squamous cell carcinomas of the middle third of the lateral border of the tongue where skip metastases to Level IV have been reported. Tumors on the lateral aspect of the oropharynx, hypopharynx and larynx, the first echelon lymph nodes are the deep jugular lymph nodes at Levels II, III and IV on the ipsilateral side and they are at highest risk of harboring micrometastasis in the clinically negative neck. Primary tumors which involve both sides of the midline have a potential of microscopic dissemination of metastatic disease to jugular lymph nodes on both sides of the neck. Similarly, tumors of the medial wall of the pyriform sinus are reported to have an increased risk of contralateral neck metastases. 394

Only 20–25% of patients with carcinoma of the parotid gland develop regional lymph node metastasis. The lymph node groups at highest risk for early dissemination of metastatic cancer from primary carcinoma of the parotid gland are those in the preauricular, periparotid, and intraparotid regions as well as lymph nodes in the upper deep jugular chain and those in the upper spinal accessory chain in the posterior triangle of the neck. Initial dissemination of metastatic cancer from primary malignant tumors of the submandibular salivary gland occurs at lymph nodes in the supraomohyoid triangle. Thus, lymph nodes in the submandibular triangle and upper and mid-jugular chain of lymph nodes are at the risk of micrometastasis from malignant tumors of the submandibular salivary gland in the clinically negative neck. Cutaneous malignant tumors of the scalp, such as squamous carcinoma and melanoma, also spread to regional lymph nodes in a predictable fashion. A line joining the helix of one ear to the helix of the opposite ear in a coronal plane separates the watershed areas of the scalp. Tumors located anterior to this line metastasize to preauricular, periparotid and anterior cervical lymph nodes (Levels I– IV) and seldom metastasize to the posterior triangle of the neck. On the other hand, primary tumors of the scalp posterior to this line metastasize to the suboccipital and postauricular group of lymph nodes as well as those in the posterior triangle of the neck and the deep jugular chain (Levels II–V).

Sentinel Node Mapping The procedure of sentinel node mapping employs one or all of the following three techniques: (i) radioisotope scan imaging; (ii) injection of blue dye; and (iii) use of a handheld isotope tracer probe for localization. It has been shown that the combination of all three techniques increases the accuracy and the yield of sentinel lymph node identification. A preoperative technetium scan is obtained first. This requires injection of radioactive technetium (99mTc) labeled sulfur colloid. Generally, 0.05 mCi of the isotope is injected in four quadrants around the primary lesion and a gamma camera is used for obtaining visual images at 3 minutes, 15 minutes, and a delayed image at 1 hour. Usually, the first lymph node identified by the technetium scan is considered the sentinel lymph node. In some patients, more than one sentinel lymph node is identified. Immediately prior to the surgical procedure, isosulfan blue dye 1% (Lymphazurin®) is injected similarly in four quadrants around the primary tumor (Figure 18). No more than 0.5 ml of the dye is injected into the subdermal plane around the tumor. The operative procedure then is carried out within 30 minutes of the injection. A handheld gamma probe is used before placing the incision to localize the lymph node seen on the preoperative scan. The background activity is averaged from measurements in four quadrants


of the neck and any node that has an in vivo 10-second count more than three times that of the background is considered ‘hot’. Correlation is made with the preoperative scan and this area is marked out with a marking pen on the skin. An incision is placed directly overlying the localized sentinel lymph node and by careful alternate blunt and sharp dissection, the ‘blue node’ is localized. The handheld probe is again used to measure the count of highest radiotracer activity. If the blue node corresponds to the area of highest radiotracer activity, then the lymph node is excised and sent for pathologic analysis. The surgical area after excision of the lymph node is tested with the handheld probe to show that the radiotracer activity is now reduced to that observed in the adjacent background area, confirming that the true ‘sentinel lymph node’ has been excised and sent for pathologic analysis. If the residual radioactivity in the basin is more than 10% of the ex vivo count of the hottest node in the basin, further exploration to find more sentinel nodes is warranted. The radiotracer activity is measured with a handheld probe from the lymph node ex vivo to demonstrate that the lymph node itself has a count at least 10 times that of an adjacent non-sentinel node. This ensures that the excised lymph node is indeed a true sentinel lymph node. At present, opinions regarding the value of frozen section for a sentinel node vary. Because of the special processing required by sub-serial sectioning of the lymph node to identify occult metastasis some investigators prefer not to send the lymph node for frozen section and wait for ‘rush paraffin sections’ within 24 hours to get a more detailed analysis of the sentinel lymph node. Further surgical management of regional lymph nodes then depends on the pathologic analysis of the excised sentinel lymph node.

DIAGNOSIS OF ORAL CANCER Various diagnostic tests can be employed to detect potentially malignant and malignant lesions. In routine practice, vital staining, brush biopsy, exfoliative cytology, tissue biopsy and various imaging modalities (plain radiographs, CT, MRI, ultrasonography, etc.) can be used effectively. Newer diagnostic tools such as VELscope and ViziLite Plus, Raman spectroscopy, high performance laser spectroscopy-laser induced fluorescence (HPLC-LIF) also play a significant role in the early diagnosis of oral malignancies. The VELscope is based on the direct visualization of tissue fluorescence and the changes that occur when abnormal cells are present. The VELscope handpiece emits a safe blue light into the oral cavity, causing tissue fluorescence from the surface of the epithelium through to the basal membrane—where pre-malignant changes typically start. By utilizing special optical filters in the VELscope handpiece the clinician is able to immediately view the different fluorescence signatures in the oral tissue to help differentiate between normal and abnormal cellular activities.

ViziLite Plus is another popular screening tool for detection of oral cancers. As ViziLite Plus is passed over oral tissue that has been treated with the rinse solution, normal healthy tissue will absorb the light and appear dark, abnormal tissues will appear white. Venkatakrishna et al (2003) developed a HPLC-LIF technique to detect and record simultaneously spectra and chromatograph of physiological samples. This system enables the detection of multiple ‘markers’ in a single physiological sample in a short time. Samples of saliva and serum from normal and oral cancer subjects have been studied with the set-up. Their study showed that body fluids like saliva and serum of normal, premalignant and malignant subjects had substantially different protein profiles. They suggest that by simultaneous recording of the chromatographic peaks and corresponding fluorescence spectra, it is possible to carry out unambiguous discrimination between normal, premalignant and malignant cases even when markers are present in femto/subfemto mole quantities, which should assist in early diagnosis of neoplasia.

Imaging Modalities Plain radiographic examination may include the use of OPG, occlusal and intraoral periapical radiographs. Paranasal sinus view is useful for assessing extent of bone involvement in the maxillary sinus region. Plain radiographs Intraoral periapical radiographs are useful to assess finer details such as subtle bone invasion, bony trabecular architecture (Figure 20) and destruction of the lamina dura. Occlusal radiographs (Figure 21) may help in evaluating destruction of bone in the anterior portion of the jaws which cannot be assessed adequately in an OPG. The mandible is more commonly affected than the maxilla. The typical radiographic features of carcinoma invading bone include: ill-defined destruction (moth-eaten appearance) of bone with ragged borders (Figure 22), cortical plates may be thinned out leading to a pathological fracture (Figure 23), extensive lesions may cause destruction of floor of the nasal fossa, maxillary sinus (Figure 24), and the cortical lining of the mandibular canal. Lamina dura around teeth are lost. However, roots of teeth show no signs of resorption as seen in benign tumors. This destruction of bone around teeth gives rise to ‘floating in space’ appearance (Figure 25). CT, MRI and PET Cross-sectional imaging modalities such as CT and MRI help in assessing the size and extent of a tumor in three dimensions. MRI imaging is considered more sensitive in evaluating the possibility of intracranial invasion. On the 395


Figure 20

Intraoral periapical radiograph showing fine details of loss of normal trabecular architecture in carcinoma involving bone. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Figure 22

Orthopantomograph showing ill-defined destruction of bone with ragged borders in the anterior portion of the mandible. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Figure 23

Figure 21

Pathological fracture. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Lower occlusal radiograph showing destruction of bone in the anterior portion of the mandible. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

other hand, the extent of bony involvement by the tumor mass is best assessed with CT. Extensive metastasis (involvement of carotid artery, cranium, parapharyngeal space, etc.) may be evaluated using a CT scan with intravenous contrast or an MRI scan with gadolinium contrast. Lymph nodes which are not amenable for clinical examination (retropharyngeal and parapharyngeal nodes) or for FNAC may be assessed using CT and MRI. 396

Metastatic nodes can be differentiated from normal nodes by their size, presence of central necrosis, rim enhancement and extranodal invasion. The size criterion for nodes in the neck which are considered radiologically positive for metastasis is as follows: nodes larger than 15 mm in the longitudinal diameter in the jugulodigastric area and submandibular triangle, other nodes in the neck are considered radiologically positive if larger than 10 mm. However, when retropharygeal nodes are larger than 8 mm they are considered positive. When axial diameters are considered, 11 mm and above is regarded positive for jugulodigastric nodes and 10 mm and above for other nodes in the neck. The shape of the node can be denoted in terms of the LT ratio (longitudinal and transverse diameters). An LT


Figure 24

Ultrasound, specially using high resolution probes (7.5–15 MHz) has always been considered a powerful tool for assessment of cervical lymph nodes. Apart from locating lymph nodes, ultrasonography can evaluate their number, shape, dimensions, margins, and internal structure. Vital staining

Orthopantomograph showing destruction of the alveolus in the right molar region with involvement of the floor of the maxillary sinus. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

Figure 25

Orthopantomograph showing extensive destruction of bone in the anterior portion of the mandible extending to the molars on either side. Blue arrow indicates thinning of the lower cortical plate. White arrows show ‘teeth floating in space’. Courtesy: Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore

ratio of two nodes suggests metastasis (a rounded node is considered positive compared to a bean-shaped node). A newer imaging tool that is gaining favor among radiologists is the positron emission tomography (PET). PET is advantageous for the fact that it not only helps in localizing a lesion but even demonstrates its metabolic activity. As malignant cells are known to divide rapidly, their increased activity is easily picked up by the PET scan. Distant metastasis imaging Distant metastasis from the oropharynx can be assessed using chest radiography (traditional/CT), abdominal ultrasonography (to evaluate liver metastasis), radionuclide imaging and blood studies (tumor markers).

In 1964, Niebel and Chomet first reported the use of toluidine blue (tolonium chloride) as a vital tissue stain to aid in the early detection of oral precancerous and malignant lesions. Though it is not cancer specific, it has been reported to stain mitochondrial DNA, altered DNA in premalignant and malignant epithelial lesions and cells with relatively increased amounts of DNA. Warnakulasuriya and Johnson (1996) reported that toulindine blue-positive lesions with minimal or no identifiable dysplasia on initial biopsy were almost four times more likely to transform to carcinoma than lesions found to be toluidine blue-negative. Toluidine blue is also an useful adjunct to clinical examination and biopsy. Toluidine is a basic metachromatic dye that stains for acidic tissue components and thus binds more readily to DNA. In addition, it can help to determine the most appropriate biopsy sites and to surgically delineate margins. Meta-analysis of toluidine blue staining in oral cancer screening found that its sensitivity ranged from 93.5 to 97.8%, and specificity from 73.3 to 92.9%. TBlue630 is a patented, pharmaceutical-grade toluidine blue-based metachromatic dye. It provides the deep blue staining that allows identified lesions to be seen clearly under normal light. Exfoliative cytology It is a known fact that dysplastic and cancerous cells tend to have fewer and weaker connections to each other and to their neighboring normal cells in the surrounding tissue. Dysplastic and cancerous cells therefore, tend to ‘slough off’ or exfoliate preferentially and can easily be collected from the surface of the lesion. A sample of these cells applied to a microscope slide will often contain abnormalities if obtained from a dysplastic or cancerous lesion. Sample can be obtained using firm strokes with a tongue blade, cement spatula or a newer technique using a brush (referred to as brush biopsy). The cytology is reported as: ❍ ❍

Class I (normal)—normal cells. Class II (atypical)—indicates the presence of minor atypia but no malignant changes. ❍ Class III (indeterminate)—the cells display wider atypia that may be more suggestive of cancer, pre-cancer, or carcinoma in situ. Biopsy is recommended. ❍ Class IV (suggestive of cancer)—a few cells with malignant characteristics or many cells with borderline characteristics. Biopsy is mandatory. 397


Brush biopsy This technique was introduced in 1999 as a substitute to the conventional exfoliative cytology procedure. A commercially available kit is used (oral CDX). This biopsy method utilizes a brush to obtain a complete transepithelial biopsy specimen with cellular representation from each of the three layers of the lesion: the basal, intermediate, and superficial layers. Unlike previous cytologic instruments, which collect only exfoliated superficial cells, when used properly and rubbed against an area of suspect tissue aggressively (to the point of minor bleeding) the biopsy brush penetrates to the basement membrane, removing tissue from all three epithelial layers of the oral mucosa. The oral brush biopsy does not require topical or local anesthetic and causes minimal bleeding and pain. The brush biopsy instrument has two cutting surfaces, the flat end of the brush and the circular border of the brush. Either surface may be used to obtain the specimen. In a recent study, paired, same site samples of tongue tissue were obtained from patients, first by brush biopsy and then by surgical punch biopsy. The study demonstrated that the brush biopsy technique, unlike cytology, sampled the full thickness of oral epithelium. Results of brush cytology specimen are classified into one of the four categories: 1. 2. 3. 4.

Inadequate: incomplete trans-epithelial specimen Negative: no epithelial abnormality Atypical: abnormal epithelial changes of uncertain diagnostic significance Positive: definitive cellular evidence of epithelial dysplasia or carcinoma.

Histopathologic features All suspicious lesions should be subjected to an excisional or incisional biopsy and the specimen should be subjected to histopathological evaluation. In general, all carcinomas exhibit the following features: epithelial dysplasia, keratinization (varies with degree of differentiation), local invasion by break in the basement membrane and invasion and proliferation into the underlying connective tissue (clinically manifested as fixation and induration of the lesion), metastasis by blood or lymphatic channels histopathologically seen as invasion of tumor cells into the capillaries and lymphatic ducts permeation and perineural invasion—some of the tumor cells may have atypical invasion pattern along the nerve sheath. The histopathological features are graded into three types depending upon the degree of differentiation of the neoplastic proliferating cells. They are: 1.

398

Well-differentiated or highly differentiated squamous cell carcinoma

Figure 26 Normal epithelium

Dysplastic epithelium

Islands of tumor epithelium

Keratin pearl

Histopathological features of squamous cell carcinoma. Courtesy: Department of Oral Pathology, MCODS, Mangalore

2. 3.

Moderately differentiated squamous cell carcinoma Poorly differentiated squamous cell carcinoma.

Well-differentiated squamous cell carcinoma It consists of sheets and nest of cells with characteristic appearance of squamous origin. These cells are generally large and show distinct cell membrane. These resemble the cells of squamous epithelium, both structurally and functionally. The intercellular bridges are prominent (Figure 26). The nuclei are distinctly dark staining. Increased number of mitotic figures but relatively few when compared to moderately differentiated carcinoma. It also shows hyperchromatism prominent and multiple nucleoli and increased nucleocytoplasmic ratio. Most prominent features are the presence of individual cell keratinization and formation of numerous keratin pearls of varying size. Each keratin pearl consists of a central area of keratin surrounded by whorls of prickle cells. Pleomorphism of cells, keratinization, and keratin pearls deep to epithelial surface and loss of intercellular bridges or cohesiveness may be seen. Moderately differentiated/less well-differentiated squamous cell carcinoma The tumor cells are less differentiated and have less resemblance to squamous epithelium. The characteristic shape of an epithelial cell may not be evident. The cell to cell contacts and relation and arrangement are altered. The greater number of mitotic figures shows that the growth rate is more rapid. These may be of varied size and


shape. Keratin pearls may not be present. Numerous epithelial islands of prickle cells with peripheral basal cells may be seen. Poorly differentiated squamous cell carcinoma This is the tumor with proliferation of anaplastic cells, highly invasive with poor prognosis. The tumor cells bear little resemblance to their cells of origin and often will present diagnostic difficulties because of the primitive and uncharacteristic histologic appearance. These cells show lack of cohesiveness and are extremely vagarious. The mitotic figures are extremely high. Management There are three recognized treatment modalities for managing head and neck cancers: surgery, radiotherapy and chemotherapy. As a thumb rule, Stage I and Stage II cancers can be managed either by surgery or radiotherapy. However, Stage III and Stage IV cancers are managed using a combination of radiation therapy and surgery. Based on the nature of the tumor, the treatment modality is chosen. Factors that influence the choice of treatment include: site and location of the primary (tongue, floor of mouth/anteriorly or posteriorly), size of the tumor (based on T stage), proximity to the bone, status of nodal involvement, histological typing of the tumor (cell type and degree of differentiation), ability to achieve adequate surgical margins and preserve functions, physical and mental status of patient and history of any treatment. Surgical management Surgical treatment aims at complete removal of the primary as well as the metastatic nodes. It is never used as a palliative mode of treatment. Criteria for choosing surgical management are: tumors which are non-sensitive to radiation, tumors involving bone, recurrent tumors in sites that have been previously irradiated, to reduce bulk of tumor prior to radiation therapy (debulking), where side effects of surgery are expected to be less significant than those associated with radiation and when nodes are to be removed. Surgical management aims at clearance of both the primary lesion and the involved regional lymphatics. The extent of resection of the primary lesion depends upon the size and the adjacent structures that may have been infiltrated. Neck dissection (cervical lymphadenectomy) In this procedure, all lymph nodes are removed beginning from the lower border of the mandible superiorly to the clavicular region inferiorly, and from the trapezius muscle posteriorly to the midline anteriorly. The sternocleidomastoid muscle, omohyoid muscle, jugular vein and submandibular salivary gland are resected. Based on the clinical involvement of lymph nodes, neck dissections can be categorized as prophylactic (clinically non-palpable nodes, may or

may not be microscopically involved) and therapeutic (clinically palpable nodes and presumed to be microscopically involved). Commando surgery A combined resection wherein the primary tumor, affected lymphatics and involved adjacent structures are removed is referred to as a commando surgery. Microscopically frozen–section oriented histologic surgery (MOHS) technique In this technique, surgically resected specimens are immediately frozen and histologically analyzed to assess for clear margins. This immediate assessment will aid in removing all tumor cells. Radiation therapy Radiotherapy plays an important role in the management of head and neck cancer. The majority of new cases of invasive head and neck cancer will need radiotherapy as a primary treatment. This radiation, in effect, disrupts the electron orbital structure of tissue atoms, which subsequently damages individual cells and tissue. Normal tissue function depends primarily on cell integrity and viability, as well as on the ability of the cells to replace and maintain their structure and organization. Cells are most vulnerable to injury when they are in the process of dividing and multiplying. The ionizing radiation exerts its effect on cells by displacing the electrons from the molecules and atoms with which they collide, causing ionization and inducing a cascade of events that may alter the cells transiently or permanently. The most important target of ionizing radiation is DNA. The radiation may damage the DNA directly (Direct Target Theory), or indirectly by inducing the formation of free radicals, particularly those that form from the radiolysis of water (Indirect Target Theory). Other cell molecules that may also be directly or indirectly damaged include the lipids in cell membrane and proteins that function as critical enzymes. In addition to anti-tumor effects, ionizing irradiation causes damage in normal tissues located in the field of radiation. This becomes particularly evident in the head and neck region, a complex area composed of several dissimilar structures that respond differently to radiation: mucosal linings, skin coverings, subcutaneous connective tissue, salivary gland tissue, teeth, and bone/cartilage. Acute changes produced by radiotherapy are observed in the oral mucosa (erythema, pseudomembrane-covered ulceration), salivary glands (hyposalivation, changed salivary composition), taste buds (decreased acuity), and skin (erythema, desquamation). Radiation dose The radiation dose needed for the treatment of cancer is based on location and type of malignancy, and whether or not radiotherapy will be used solely or in combination with other modalities. Most patients with head and neck carcinomas, treated with a curative intent, receive a dose between 50 and 70 Gy. This dose is usually given over a 5- to 7-week period, once a day, 5 days a week, 399


2 Gy per fraction. The total dose for preoperative radiotherapy or radiotherapy for malignant lymphomas is usually lower. Fractionated radiation Fractionated radiation is used because there is a difference in the responses of tumor tissue and normal tissue. In general, normal tissue repairs sublethal DNA damage, especially in the low-dose range, better than tumor tissue. The sparing effect of fractionated radiation is the largest for late-responding tissues, whereas early-responding tissues respond more like tumor tissue. Next to DNA-repair advantages, fractionated irradiation allows for the re-population of tissue between fractions (especially during the weekend, when the tumor and normal tissues are not radiated), thereby reducing early effects. This, however, also applies for rapidly proliferating malignant tissue. Another advantage is that fractionated irradiation allows for re-oxygenation of radio-resistant hypoxic tumors between fractions, leading to a higher percentage of radiosensitive oxygenated cells. Ideal candidates for radiotherapy Small lesions less than 3 cm and superficial without necrotic areas can be readily managed with radiation therapy. The choice of treatment also depends on functional and cosmetic concern. If regional excision can be accomplished without much morbidity, surgery should be the treatment of choice. On the contrary, if the lesion involves large areas like tongue, floor of the mouth or buccal mucosa, and if excised it would result in morbidity, thus local irradiation would be the treatment of choice. But if the lesion is invasive involving the bone, radiation sterilization of the tumor is not possible without extensive normal tissue damage, therefore surgery or a combination of irradiation and surgery may be required. Lesions that are extremely radiosensitive such as lymphomas, radiation therapy should be the treatment of choice. If the location and clinical behavior of a lesion indicates significant lymphatic permeation, then radiotherapy alone or in combination with surgery is the treatment of choice as a wider volume. Radiation technique Radiation therapy may be administered to a localized lesion by using brachytherapy (applicators or implants) or to a region of the head and neck by using teletherapy (external beam radiation). External beam radiation therapy The source of radiation can either be low energy (orthovoltage: 50–300 kVp) or high energy (cobalt-60 or linear accelerators of 4 million electron volts). Low energy beams are used for small sized intraoral tumors, lip, and skin cancers. The high energy radiation provides variable penetration due to its ability to vary the energy of the photons. It spares bone and skin. For teletherapy, three principal field arrangements are planned: wedged-pair fields, parallel-opposed fields and three-field technique. The wedged-pair field allows a therapeutic dose to unilateral disease while sparing a high 400

dose to the opposite side. When a large tumor or midline lesion is present, a parallel-opposed field set-up or threefield set-up may be needed, which produces relatively uniform exposure for midline disease. Brachytherapy Brachytherapy involves inserting radioactive wires/seeds directly into a tumor, such as in the tongue. One of the advantages of this type of therapy is there is less radiation exposure to other parts of the body. In interstitial implant treatment, implants deliver the radiation in the immediate vicinity of the implanted isotope and also deliver it a relatively low dose rate, thus sparing the normal tissues. Interstitial sources can be placed directly or preferably, after loaded into tubes or needles. The sources most commonly used include 192Ir,137Cs,125I, and 198Au. Another variant of these radioactive implants are applicators which are radioactive substances that are impregnated into prosthesis which may be placed on the surface of the cancerous tissue. Newer modalities of radiation therapy Intensity modulated radiation therapy (IMRT) is most applicable in the treatment of head and neck cancers (especially nasopharyngeal lesions). IMRT employs a computer directed radiation source that targets the cancer more accurately than conventional radiation therapy. This is accomplished with computer algorithms to design treatment plans whose goals are to maximize dose to tumor targets while limiting dose to normal structures. Thus, the major advantage of IMRT over conventional head and neck radiation is the potential to significantly limit dose deposition to normal structures, such as the parotid glands, thereby reducing the degree of xerostomia. A potential disadvantage of IMRT is an increased volume of normal tissue exposure. This is because multiple small fields of radiation, called beamlets, rotate around the patient. Additional ability to modify dose and fields and radiation has been introduced with image-guided radiotherapy (IGRT) in which integrated CT, guides the changes in radiation throughout the course of treatment as treatment causes a change in volume of tumor during treatment. Radiation therapy combined with chemotherapy The rationale for administering drugs prior to radiation therapy is to control already disseminated tumor cells, potentiate the killing effects of ionizing radiation, be more effective against the remaining tumor growth fraction once radiation has reduced tumor bulk and elimination of subclinical metastasis. Effects of radiation therapy Following radiation therapy various mucocutaneous changes are seen in the patient. Some of these changes include: hyperpigmentation of the skin surface in the field of radiation, transient loss of hair, mucositis, loss of taste, salivary dysfunction, radiation caries, fungal infections, pain, post-radiation osteoradionecrosis, and difficulty in speech and mastication.


Mucocutaneous changes In about 2 weeks following radiation therapy the skin in the radiation field turns erythematous and may show hyperpigmentation along with mucositis. Radiation dose of about 180–220 cGy per day is sufficient to produce mucositis. It is characterized by intense erythema of the mucosa, pain and occasionally associated with sloughing. Topical anesthetics in the form of viscous xylocaine, topical analgesics (benzydamine hydrochloride) are effective in managing radiation mucositis. Loss of taste sensation When the taste buds are in the radiation field there is partial or complete loss of cells in taste buds. Patients may report of a significant change in the perception of all types of tastes. In most patients, the cells of the taste buds regenerate in 4 months duration. Patients may be advised to incorporate a change in diet to facilitate better taste perception. Zinc sulfate capsules (220 mg twice daily with food, elemental zinc 100 mg) are beneficial. Salivary function Radiation induces fatty degeneration, fibrosis, acinar atrophy and cellular necrosis within the salivary glands. Comparatively, serous acini are more radiosensitive than mucous acini. Patients present with reduced amount of salivation and the saliva is typically thick and ropy. Radiation-induced xerostomia may occasionally reverse in about 12 months. However, irreversible changes are seen at a total dose of 6,000 cGy for 5 weeks. Patients are advised to frequently sip water and chew on sugarless gum to stimulate salivation. If the xerostomia is very severe, salivary substitutes such as carboxymethylcellulose can be prescribed. Salivary stimulants such as pilocarpine hydrochloride (5 mg 4 times a day) and bethanechol (25–200 mg/day) have also proven to be beneficial. Radiation caries Radiation caries occurs secondary to the alteration in the chemical composition of saliva or reduction in salivation following radiotherapy and not due to the direct action of radiation on the tooth. The most common sites of involvement are the cervical areas followed by cuspal/incisal tips of teeth. Three distinct types are seen: dark pigmentation of crown, circumferential caries/amputation caries (generally involves cervical third) and widespread superficial caries especially involving the smooth surfaces of the crown. Patients should be encouraged to maintain good oral hygiene. Three percent hydrogen peroxide rinses and topical fluoride application will help in preventing further damage to the tooth structure. Effects on developing teeth Tooth eruption may be delayed. The teeth may be malformed with stunted roots. Occasionally, the tooth may not be formed. Candidiasis Owing to the poor oral hygiene and nutritional status, patients may present with pseudomembranous or

erythematous candidiasis. In such patients, topical application of anticandidal agents may not be effective as the salivation is compromised. Osteoradionecrosis Radiation therapy causes endarteritis obliterans, which in turn results in hypovascularity, hypocellularity and finally hypoxic tissue. Owing to its inherent poor vascularity, the mandible is more commonly affected than the maxilla. Trauma (external, iatrogenic), periodontal diseases, illfitting dentures, peridontally weak or pulpally affected teeth in the line of radiation are predisposing factors for osteoradionecrosis. Patients complain of pain, foul taste, paresthesia/ anesthesia and intraoral or extraoral discharging sinuses. Lymphadenopathy may be seen. As the condition worsens, pathological fracture occurs. Radiographically, it is difficult to differentiate between the ill-defined patchy destruction of bone that is seen in cancer of the bone, osteoradionecrosis and suppurative osteomyelitis. As a preventive measure, if extractions are planned, it is desirable to allow as much healing time as possible. Seven to 14 days and up to 21 days have been suggested as healing times prior to radiotherapy. Patients should be instructed to avoid mucosal irritants, discontinue the use of dental appliances if they contact the area of the lesion, maintain nutritional status, stop smoking and alcohol consumption. Osteoradionecrosis is best managed with topical antibiotic (tetracycline) or antiseptic (chlorhexidine) rinses. Hyperbaric oxygen (HBO) therapy increases the oxygenation of tissue, increases angiogenesis, and promotes osteoblast and fibroblast function. HBO therapy (Figure 27A, B) is usually carried out for a period of 20–30 dives at 100% oxygen and 2–2.5 atmospheres of pressure. Sequestrated bone may be managed with limited resection or may require mandibulectomy. If surgery is required, postsurgical HBO therapy of 10 dives is recommended. Chemotherapy It is provided as an induction therapy before local therapies. It is also an adjunctive modality for other cancers. The objective of induction chemotherapy is to promote initial tumor reduction and to provide early treatment of micrometastases. The goal of chemotherapy is to eradicate the rapidly growing cells of the tumor or modify their growth. Chemotherapeutic agents affect the rapidly dividing cells of the target tumor and the lining epithelium, the oral ecology and the vascular, inflammatory and healing responses of the oral cavity. These alterations may result in mucositis and ulceration of the oral mucosa. Chemotherapeutic agents also target the hemopoietic cells of the bone marrow, resulting in anemia, thrombocytopenia and leukopenia. Unfortunately, chemotherapy is often toxic to other cells that rapidly divide normally. These include bone marrow, hair, and the 401


Figure 27 A

B

(A) Patient being shifted into the HBO chamber. (B) Doctor monitoring the patient’s condition undergoing hyperbaric oxygen (HBO) therapy. Courtesy: Sechrist Industries, Inc., La Palma Ave, Anaheim, CA 928

mucosa of the entire gastrointestinal tract, including the oral cavity. The chemotherapy cycle consists of cytotoxic drug administration followed by a rest period for healthy tissue recovery prior to repeated drug administration. An important clinical implication of this format is that peripheral white blood cell counts change dramatically during the course of this cycle. Majority of the cytotoxic drugs have more profound effect on rapidly multiplying cells, because the most important target of action are the nucleic acids

402

and their precursors; rapid nucleic acid synthesis occurs during cell division. Drugs used in oral cancer chemotherapy Various drugs are seen in cancer chemotherapy of the head and neck such as cetuximab (epidermal growth factor receptor inhibitor), docetaxel, cisplatin, 5-fluorouracil, leucovorin, methotrexate, and bleomycin. We shall describe four drugs in the following text namely: methotrexate, bleomycin, cisplatin and 5-fluorouracil. Methotrexate Methotrexate is an antimetabolic and an inhibitor of folic acid metabolism. The rationales for intraarterial route are that, prolonged contact of the tumor cell population with the antimetabolite will result in sequential death of cells as the cells enter the most fragile metabolic phase of cellular division. It can be administered either intra-arterially or per orally. Systemic methotrexate is given in intermittent weekly or semiweekly IV injections of 40–60 mg/m2 of body surface area. Methotrexate is known to cause bone marrow suppression, mucositis, anorexia, nausea, emesis, renal toxicity and hepatic dysfunction. Bleomycin It is part of a group of antibiotics that was isolated in Japan from Streptomysis verticillus. Bleomycin acts by interfering with the DNA function of the cell. The ideal dose of belomycin is 0.25–0.50 unit/kg given weekly or twice weekly. However, care should be taken not to exceed a dose of 400 units and this dose can cause pulmonary toxicity and death. Some patients may complain of skin rashes and erythema. The greatest advantage with bleomycin is its lack of causing myelosuppression. Cisplatin Cisplatin is a relatively new drug which acts by altering DNA structure. It is given IV (80–120 mg/m2, IV for 3–4 weeks). Dehydrated patients may suffer from renal impairment. Hence, it is important to maintain adequate hydration before the drug is administered. 5-Fluorouracil This drug is usually administered along with cisplatin. Its acts by interfering with the cellular metabolism. The standard dosage is 1,000 mg/m2/day. Stomatitis is a common side effect. Bone marrow suppression is seen when weekly or daily bolus injections are administered.

SECTION

VI

Teeth and Periodontium

15 Dental Caries, Pulp and Periapical Lesions 16 Gingival and Periodontal Diseases 17 Regressive Alterations of Teeth

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CHAPTER

Dental Caries, Pulp and Periapical Lesions Vivekananda Pai, Ravikiran Ongole

15

➧ Definition and Etiology

➧

Radiographic Evaluation of Carious Lesions

➧

Contributory Factors in Dental Caries

➧

Fascial Space Infection

➧

Classification of Dental Caries

➧

Ludwig’s Angina

➧

Microbiology of Dental Caries

➧

Osteomyelitis

➧

Clinical Diagnostic Methods

DEFINITION AND ETIOLOGY Dental caries is a microbial disease of the calcified tissues of the teeth, characterized by demineralization of the inorganic portion and destruction of the organic substance of the tooth. The World Health Organization (WHO) defines caries as a localized post-eruptive, pathological process of external origin involving softening of the hard tooth tissue and proceeding to the formation of a cavity. Dental caries is derived from the Latin word caries which means decay or rotten. Etiology Dental caries is considered as the most prevalent disease in humans, second only to the common cold. Dental decay is complex and multifactorial. Various theories have been proposed to explain the etiology of dental caries. The acidogenic theory, proteolytic theory and proteolysischelation theory have been the most discussed.

Miller’s Chemicoparasitic Theory/Acidogenic Theory Willoughby Miller in 1882 suggested that dental decay is a chemoparasitic process. He believed that caries was caused by a variety of microorganism and the acids in the oral cavity were synthesized by the action of microorganisms. He recognized four important factors in his study of the carious process which are: role of microorganisms, role of carbohydrate substrate over the tooth surface, role of acids and the role of dental plaque.

According to Miller, the carious process occurs in two distinct steps: in the initial stages there is decalcification of enamel and destruction of dentin, and in the second stage there is dissolution of the softened residue of the enamel and dentin. The acidic attack which causes destruction and dissolution of the residue is carried by the proteolytic action of the bacteria. This two-step process is supported by the presence of carbohydrates, microorganisms and dental plaque. Role of carbohydrates According to Miller’s observations, teeth decalcify when incubated in saliva and bread/sugar mixture and show no change when incubated with fat. His simple experiment demonstrated the cariogenic effects of carbohydrates. However, the cariogenic potential of dietary carbohydrates varies on their physical form, chemical composition and frequency of intake. It is a well known fact that carbohydrates which have a slow clearance rate from the oral cavity are more cariogenic than those which have a higher clearance rate. The risk of caries incidence increases greatly if the dietary sugar is sticky in nature, and when there is increased frequency of ingestion of the sugars. Polysaccharides are less easily fermented by plaque bacteria than monosaccharides and disaccharides. Glucose, sucrose and fructose which are highly fermentable have a greater role to play in the causation of dental caries. These sugars are readily broken down by the bacteria to produce acids that in turn cause the dissolution of the hydroxyapatite crystals of the enamel and dentin. Sucrose is readily fermented by the cariogenic bacteria (mainly Streptococcus mutans) to produce acids, which can 405

Section VI – Teeth and Periodontium

demineralize the tooth. S. mutans use sucrose to synthesize an extracellular insoluble polysaccharide with the help of the enzyme ‘dextran’, which helps in adhering the plaque firmly on to the tooth surface. The pH of plaque falls to 4.5–5 in about 1–3 minutes of sugar intake. It is estimated that pH returns to neutral levels in approximately 30 minutes. The physical nature of the diet intake also has a bearing on the incidence of carious lesions. Coarse fibrous foods aid in greater clearance rate from the oral cavity thereby minimizing the carious incidence. However, sticky refined food and sweetened soft drinks predispose to debris accumulation and the increased likelihood of carious lesions. Role of microorganisms Lactobacillus acidophilus along with a combination of other bacteria such as S. mutans and Actinomyces species are closely associated with the causation of dental caries. It is believed that a few types of bacteria may be intimately involved in the initiation of the carious process whereas some may be involved in the progression of the carious process. Role of acids

Proteolysis–Chelation Theory

Miller in his observations reported that many of the microorganisms in the oral cavity were capable of producing acids and these acids were usually present in deeper carious lesions. In many of the lesions studied, lactic acid was identified in carbohydrate saliva combined mixtures. A specific microorganism, Leptothrix buccalis, was isolated from the dentinal tubules, suggesting that the microorganisms and the acids may have a synergistic action to dissolve the organic portion of the tooth.

Some of the minor flaws of the acidogenic and the proteolytic theories were addressed in the proteolysis–chelation theory. This theory was put forward by Schatz and coworkers in 1955. Chelation is a process in which there is complexing of the metal ions to form complex substance through coordinated covalent bond which results in poorly dissociated and/or weakly ionized compound. Chelation is independent of the pH of the medium. The proteolysis–chelation theory considers dental caries to be a bacterial destruction of organic components of enamel and the breakdown products of these organic components to have chelating properties and thereby dissolve the minerals in the enamel even at the neutral/alkaline pH. Mucopolysaccharides, lipids and citrates may also act as secondary chelators. Schatz and coworkers observed that there is a simultaneous microbial degradation of organic component by proteolysis and the dissolution of inorganic part by the process of chelation.

Role of dental plaque Plaque as described by GV Black is a ‘gelatinous plaque of the caries fungus in a thin, transparent film that usually escapes observation, and which is revealed only by careful search’. It generally consists of salivary components such as mucin and desquamated epithelial cells and of microorganisms. However, long-standing plaque may accumulate to a perceptible degree in 24–48 hours. It is estimated that cariogenic plaque contains 2 ⫻ 108 bacteria/mg weight. The pH of plaque also varies in caries free and individuals with high caries activity. The pH is about 7.1 in caries free individuals and approximately 5.5 in individuals with high caries activity.

Proteolytic Theory The initial work on the proteolytic theory was done by Heider and Bodecker in 1878 and Abbott in 1879. Studies showed that the organic portion of the tooth plays an important role in the development of dental caries. 406

It is believed that enamel lamellae and enamel rods which are composed of organic material form the pathways for the advancing microorganisms. It has been established that enamel contains 0.56% of organic matter of which 0.18% is keratin and 0.17% is a soluble protein. Gottlieb in 1944 suggested that the initial lesion of the carious process is due to the proteolytic enzymes attacking the lamellae, rod sheaths, tufts and walls of tubules. He believed that the yellow pigmentation that is characteristic of caries was due to pigment produced by the proteolytic organisms. He also proposed that the Staphylococcus plays a vital role in initiating proteolytic activity. Pincus in 1949 proposed that the proteolytic breakdown of the dental cuticle is the first step in the carious process. He proposed that the Nasmyth’s membrane and the enamel proteins are mucoproteins, which are acted upon by the sulfatase enzyme of the bacilli yielding sulfuric acid. The sulfuric acid thus produced combines with the calcium of the hydroxyapatite crystal and destroys the inorganic component of the enamel.

Sucrose Chelation Theory This theory proposes that if there is a very high concentration of sucrose in the mouth of a caries-active individual, there can be formation of complex substances like calcium saccharate and calcium complexing intermediaries by the action of phosphorelating enzymes. These complexes cause release of the calcium and phosphorus ions from the enamel and thereby resulting in tooth decay.

Chapter 15 – Dental Caries, Pulp and Periapical Lesions

Autoimmune Theory

Figure 1

According to this theory few odontoblasts, within the pulp of few certain teeth are damaged by the autoimmune mechanisms, leading to a compromised defense mechanism and the loss of integrity of enamel or dentin. These targeted sites are potential sites for the development of carious lesions.

Host factor

Enzymatic Theory Diet

This theory is based on the fact that plaque bacteria produces enzymes. Enzymes involved may include phosphatase (dissolves apatite), chondroitin sulfatase (dissolves dentinal chondroitin sulfate), hyaluronidase (dissolves dentinal hyaluronic acid) and proteases (dissolve dentinal collagen). All these enzymes are produced by plaque bacteria.

Dental caries

Time

Microorganisms

Acid–enzyme Theory Diagram depicting the contributing factors for dental caries

This theory is a combination of the acidogenic and the enzyme theories. It is believed that the acids produced have a major role in enamel dissolution and the enzymes probably play a greater role in dentinal dissolution.

Levine’s Ionic See-saw Theory This theory was proposed by Levine in 1977. According to this theory, there is a chemical relationship between enamel plaque and the factors which determine the movement of minerals from saliva/plaque to enamel and vice versa, which was termed as the ionic see-saw mechanism. Levine proposed that the demineralization and remineralization of enamel is a continuous process. If in a given interval of time, more ions leave the enamel than enter it, then there is a net demineralization, which heralds the beginning of the carious process. It was proved that the ions are constantly exchanged between enamel and plaque. This theory emphasizes the importance of pH of plaque, calcium and phosphate ion concentration at the interphase and fluoride ion concentration.

CONTRIBUTORY FACTORS IN DENTAL CARIES The four factors contributing to the caries process are (Figure 1): 1.

Host factor a. Tooth factor i. Morphology and position in the arch ii. Chemical nature b. Saliva i. Composition, pH and antibacterial activity ii. Quantity and viscosity of flow

2. 3. 4.

Microflora Substrate or diet (physical nature and chemical nature) Time.

Host Factor Tooth Factor Morphology and position in arch Compared to the smooth surfaces of teeth, deep pits and fissures are more prone to carious attack because of food lodgment and bacterial stagnation. Owing to their, complex occlusal morphology consisting of numerous pits and fissures, the permanent mandibular first molars followed by the maxillary first molars and mandibular and maxillary second molars are more prone to carious attack. Apart from the morphology of the tooth, the position of the tooth in the arch has a heavy bearing on the incidence of carious lesions. Irregularities in the arch form, crowding and overlapping of the teeth also favor the development of caries as these regions provide an excellent environment for plaque accumulation. Partially impacted third molars are more prone to caries and so are the buccally or lingually placed teeth. Chemical nature The chemical components of enamel such as dicalcium phosphate dihydrate and fluorapatite make the enamel resistant to carious attack to a certain extent. 407


The presence of mineral ions such as Ca, F, Zn and Fe in higher concentrations, decreases the enamel solubility. Higher the solubility of the enamel surface greater is the possibility of caries development. Hence, they can be seen in case of enamel hypoplasia. The mineral content of enamel tends to increase with advancing age. Such teeth have an increased resistance to carious attack.

Saliva Composition Hay et al (1982) and Lagerlof (1983) in their reports reiterated the fact that human salivary secretions are supersaturated on calcium and phosphate. The concentrations of inorganic calcium and phosphorus show considerable variation within resting and stimulated saliva. Caries prone individuals have low calcium and phosphorus levels. Salivary proteins such as statherin, acidic proline-rich proteins (PRPs), cystatins, and histatins help in the maintenance of the homeostasis of the supersaturated state of saliva. According to Hay and Moreno (1989), statherin is present in stimulated saliva in concentrations sufficient to inhibit the precipitation of calcium and phosphate salts. Studies by Gibbons and Hay (1988) have shown that statherin may contribute to the early colonization of the tooth surfaces by certain bacteria, such as Actinomyces viscosus. The acidic PRPs account for 25–30% of all proteins in saliva, and they have high affinity for hydroxyapatite in vitro (Hay and Moreno, 1989). The acidic PRPs bind free calcium, adsorb to hydroxyapatite surfaces, inhibit enamel crystal growth, and regulate hydroxyapatite crystal structure (Hay and Moreno, 1989). The amount and quality of acidic PRPs and agglutinins are found to be different in caries-free and caries-active individuals as shown by the studies of Rosan et al (1982) and Stenudd (1999). The role of cystatins in the caries process is still unclear. However, they may play a minor role in the regulation of calcium homeostasis in saliva. Phosphorylated and nonphosphorylated cystatins bind to hydroxyapatite. Salivary flow rate, pH and buffer capacity Saliva has the most important function of caries prevention by way of its flushing and neutralizing effects, commonly referred to as ‘salivary clearance’ or ‘oral clearance capacity’. As a thumb rule, the higher the flow rate, the faster the clearance and the higher the buffer capacity. Reduced salivary flow rate and the concomitant reduction of oral defense systems may cause severe caries and mucosal inflammation. Though, patients with impaired saliva flow rate often show high caries incidence (Papas et al, 1993; 408

Spak et al, 1994) or caries susceptibility, it is still a mystery as to how much saliva is adequate enough. The pH of saliva at which it ceases to be saturated with calcium and phosphorus is referred to as the ‘critical pH’. Normally, the critical pH is 5.5. Below this value, the inorganic content tends to demineralize. The normal pH of resting saliva is 6–7. Buffering capacity The buffer capacity of both unstimulated and stimulated saliva involves three major buffer systems: the bicarbonate (HCO–3), the phosphate, and the protein buffer systems. These systems have different pH ranges of maximal buffer capacity. The bicarbonate and phosphate systems have pH values of 6.1–6.3 and 6.8–7.0, respectively. Since most of the salivary buffering capacity operative during food intake and mastication is due to the bicarbonate system, sufficient saliva flow provides the oral cavity with the neutralizing components. The phosphate and protein buffer systems make a minor contribution to the total salivary buffer capacity, relative to the bicarbonate system. The phosphate system is, in principle, analogs to the bicarbonate system but without the important phase-buffering capacity, and it is relatively independent of the salivary secretion rate. Lagerlof and Oliveby in 1994 showed that a low flow rate combined with a low or moderate buffer effect indicated poor salivary resistance against microbial attack. It is a well-established fact that the buffer capacity of the saliva and the caries experience are inversely related. The buffer effect of saliva is influenced by the hormonal and metabolic changes, as well as by altered general health. It is generally accepted that the buffer effect is greater in men than in women (Heintze et al, 1983). In women, the buffer effect decreases gradually, independent of flow rate, toward late pregnancy and promptly recovers after delivery. Introduction of either hormone replacement therapy in menopausal women (Laine and Leimola-Virtanen, 1996) or low-dose oral contraceptives (Laine et al, 1991) can slightly increase the buffer capacity. Carbonic anhydrases (CAs) participate in the maintenance of pH homeostasis in various tissues and biological fluids of the human body by catalyzing the reversible hydration of carbon dioxide. Recent research suggests that salivary CA VI plays a role in protecting the teeth from caries (Kivela et al, 1999a, b). CA VI has been reported to bind to the enamel pellicle and retain its enzymatic activity on the tooth surface. It is also believed that the urea and saline in saliva become hydrolyzed to produce ammonia and the later can cause rise in the salivary pH. This rise in pH can counter the attacks on the tooth surface during the progression of caries. Antibacterial activity The primary oral innate defense factors are peroxidase systems, lysozyme, lactoferrin, and


histatins. In vitro studies have shown that these proteins are known to limit bacterial or fungal growth, interfere with bacterial glucose uptake or glucose metabolism and promote aggregation and, thus eliminate bacteria. Hanstrom et al (1983) and Tenovuo and Larjava (1984) reported that the salivary peroxidase and myeloperoxidase systems eliminate H2O2, which is highly toxic for mammalian cells. The immunoglobulins, IgG, IgM, IgA, and secretory IgA (sIgA), form the basis of the specific salivary defense against oral microbial flora, including Streptococcus mutans. The most abundantly available immunoglobulin in saliva is dimeric slgA, which is produced by plasma cells located in the salivary glands. Two IgA subclasses are present in saliva; IgAl forms the major component of immunoglobulins, although the relative amount of IgA2 is higher in saliva than in other secretions (Tappuni and Challacombe, 1994). In human beings, IgG, mainly of maternal origin, is the only detectable immunoglobulin in the saliva of neonates. Salivary IgA is absent at birth but is generally detectable by the age of 1 week. The IgG concentration decreases to non-detectable levels after some months but appears again after tooth eruption (Brandtzaeg, 1989). Low concentrations of IgG can be detected in stimulated parotid saliva (Brandtzaeg, 1989), but most of the IgG detected in whole saliva enters the mouth from the gingival crevicular fluid, thus originating from sera. In most children above 3 years of age, salivary IgAs against S. mutans can be detected, and their amount increases with the length of exposure (Smith and Taubman, 1992). Salivary Igs can bind to the salivary pellicle, and they are found also in dental plaque (Newman et al, 1979; Fine et al, 1984). In the oral cavity, immunoglobulins act by neutralizing various microbial virulence factors, limiting microbial adherence, and agglutinating the bacteria, as well as by preventing the penetration of foreign antigens into the mucosa. IgGs are also capable of opsonizing bacteria for phagocytes, which are reported to remain active in dental plaque and saliva (Scully, 1980; Newman, 1990). Quantity and viscosity of flow The consistency or viscosity of the saliva and the amount of saliva produced has a significant influence on the incidence of dental caries. The average person produces at least 500 ml of saliva over a period of 24 hours. The unstimulated flow rate is 0.3 ml/ min, whereas the flow rate during sleep is 0.1 ml/min and during eating or chewing, it increases to 4.0 to 5.0 ml/min. Any reduction in this quantity of saliva as seen in diseases such as Sjögren’s syndrome, diabetes, etc. predisposes to dental caries.

Increased viscosity of saliva may hinder its natural cleansing action thereby promoting the deposition of plaque on the tooth surface. Likewise when the salivary viscosity is low, the amount of minerals and bicarbonates are inadequate thereby limiting its anticaries activity.

Microflora The main etiological agent in occlusal and pit and fissure caries is the S. mutans. Deep dentinal caries is commonly associated with lactobacilli, certain gram-positive anaerobes and filaments such as Eubacterium and Actinomyces. Root caries or cemental caries is predominantly associated with Actinomyces viscosus. However other species of Actinomyces such as A. naeslundii and A. nocardia have also been isolated.

Substrate and Dietary Factors The role of diet in the causation of dental caries has been extensively studied. A variety of dietary factors have been implicated in the causation of dental caries. Physical nature of diet It is believed that coarse and fibrous food helps in cleansing the debris from the tooth surface thereby minimizing the incidence of carious lesions. However, refined and sticky starchy food aid in the formation of dental caries. Chemical nature of diet It is a well-known fact that food with high refined carbohydrate content has the greatest potential to give rise to carious lesions. The type of carbohydrate (monosaccharide, disaccharide or polysaccharide), frequency of intake and the time for which the ingested food remains stagnant in the oral cavity or on the tooth surface determine the incidence and severity of the carious lesions. Animal studies have shown that sugar in the solid and sticky form is more harmful to the tooth than the same amount of sugar in a liquid form. It is believed that vitamin B deficient individuals have lower incidence of dental caries. Vitamin B is essential for the growth of oral acidogenic flora and also serves as a component of coenzymes involved in glycolysis. Vitamin D plays an important role in the normal development of teeth. Various studies have shown that the teeth are hypoplastic and usually have higher incidence of dental caries in vitamin D deficiency. Teeth may be poorly calcified in individuals exposed to low doses of calcium during intrauterine life and infancy. 409


Such poorly calcified teeth may be susceptible to carious attack. Higher levels of selenium is known to predispose to the carious lesions affecting permanent teeth. Fluoride content in the diet has no significant role because of its metabolic unavailability. Therefore, the fluoride content in cooking salt and its effect on reducing the incidence of carious lesions is still questionable. However, fluoridated water minimizes the caries incidence. Phosphates, molybdenum and vanadium in the diet helps in minimizing the incidence of carious lesions.

CLASSIFICATION OF DENTAL CARIES 1.

2.

Dental caries based on location a. Pit and fissure caries b. Smooth surface caries c. Root surface caries Dental caries based on severity a. According to morphology of teeth b. According to severity and progress c. According to age pattern d. According to rapidity of progress.

Role of heredity Literature review reveals various studies to assess the genetic modifications in dental enamel, genetic modification of immune response, genetic regulation of salivary function and inherited alterations in sugar metabolism. Bachrach and Young (1927) compared the caries incidence of monozygotic twins with same-sex dizygotic (93 pairs) and different-sex dizygotic (78 pairs) twins. Their results showed that the monozygotic twins had a more similar caries incidence than dizygotic twins and that different-sex dizygotic twins had the greatest variance. The authors concluded that heredity plays a subsidiary part in the incidence of caries. It is believed that heredity affects the dental decay only in as much as it controls the shape of a tooth and its pits and fissures and its position in the dental arch. Senpuku et al (1998) and Acton et al (1999) have correlated specific HLA-DR types with binding S. mutans antigens and S. mutans colonization. Acton concluded that ‘genes within MHC modulate the level of oral cariogenic organisms’. Mariani et al (1994) in their study of celiac disease, enamel defects and HLA typing observed that HLA-DR3 was associated with increased enamel defects and HLA-DR5, 7 were associated with a reduced frequency of enamel defects. Studies have shown that the genes in the HLA complex are associated with altered enamel development and increased susceptibility to dental caries. Role of immunity Salivary IgA and immunoglobulins secreted in the gingival crevicular fluid such as IgG, IgM and IgA along with neutrophil leukocytes and macrophages play an important role in the prevention of dental caries. It is believed that the immune response exerted by the gingival crevicular immune system is more potent compared to the salivary immune mechanism. Salivary IgA prevents S. mutans from adhering to the tooth surface. The IgG antibodies acting as opsonins, facilitate phagocytosis and the death of S. mutans by the action of macrophages and neutrophil leukocytes. 410

According to Morphology of Teeth i.

Pit and fissure caries (also called type-1 caries): Caries occurring on anatomical pits and fissures of all the teeth. The specific areas or surfaces involved include occlusal surfaces of molars (Figure 2) and premolars, buccal and lingual surfaces of molars (Figure 3) and lingual surfaces of maxillary incisors. The lesions are smaller in the beginning but become wider as they spread toward the dentin due to orientation of enamel rods. In these places there can be entrapment of food leading to fermentation of carbohydrates with lack of neutralization of acid produced by salivary buffers which leads to destruction of enamel and dentin. The enamel bordering the pit and fissure may appear opaque and bluish-white as it becomes undermined. Clinically these lesions appear brown or black, with little softening and opaqueness of the surface. When the lesion is examined by a fine explorer tip, a ‘catch point’ is often felt, where the explorer teeth catches the area. When the lesion reaches the dentinoenamel junction (DEJ), they spread laterally to cause undermining of the enamel. ii. Smooth surface caries (also known as type-2 caries): These carious lesions occur on the smooth surfaces of the teeth (e.g. proximal surfaces or gingival areas of the buccal and lingual aspect of tooth). Proximal caries usually begins just below the contact point, and appears in the early stage as a well demarcated faint white opacity of the enamel without apparent loss of continuity of enamel. The white spot lesion becomes pigmented yellow or brown and it often extends buccally and lingually. The surrounding enamel becomes bluish white as the lesion continues to progress (Figure 4). The surface of the affected enamel becomes rough and later on, there is formation of a cavity (Figure 5). iii. Root caries: Caries occurring at the cementoenamel junction or cementum. This occurs predominantly in the older age when there is gingival recession.


Figure 2

Figure 4

Pit and fissure carious lesion on the occlusal surface of a mandibular molar. Courtesy: Department of Oral Pathology, MCODS, Mangalore

The early stages of a proximal carious lesion. The surface of the enamel reveals a bluish-black hue with no discontinuity of the enamel surface. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 3

Figure 5

A carious lesion on the buccal surface of the mandibular molar. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

iv. Linear enamel caries: Caries occurring on the labial surfaces of anterior teeth. This is also known as ‘odontoclasia’. The caries occurs at neonatal zone because of trauma at birth or metabolic disturbances.

Proximal surface carious lesion. Courtesy: KLE Society’s Institute of Dental Sciences, Bangalore

•

According to Severity and Progress i.

Incipient caries: Initial carious lesion limited to the teeth is called incipient caries and is characterized by a virtually intact surface but a porous subsurface (subsurface demineralization).

ii.

Incipient lesion can undergo remineralization thereby reversing the process. Rampant caries: This is an acute fulminating type of carious process, which is characterized by simultaneous involvement of multiple number of teeth (may be all teeth) in multiple surfaces (Figure 6A, B). 411


Figure 6 A

B

Extensive destruction of teeth in child suffering from rampant caries. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

•

Rapid coronal destruction occurs within a short span of time, causing early involvement of the pulp. • The common age of occurrence is 4–8 years for the deciduous teeth and 11–19 years for the permanent teeth. • It can even occur in persons who maintain a good level of oral hygiene regularly. • Moreover, this type of caries attacks those surfaces of teeth, which are otherwise considered immune to the disease. iii. Arrested caries • Any carious lesion usually an incipient one may become arrested, if there is a change in oral environment. Arrested caries, clinically appears as a dark brown pigmentation with smooth surface, referred to as ‘eburnation’, which is a Latin word that means arrested caries. • It can be on occlusal as well interproximal surfaces. • It can occur in both enamel and dentin. iv. Recurrent caries: It occurs at the interface of tooth and restorative material because of many factors such as defective cavity preparation, microleakage and combination of these (Figure 7). v. Radiation caries: One of the complications of radiotherapy of oral cancer lesions is xerostomia, which leads to an early development of widespread caries.

According to Age Pattern Nursing bottle caries: A type of acute carious lesion, which occurs among those children who take milk or fruit juice

412

Figure 7

Recurrent carious lesion beneath faulty restorations. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

by the nursing bottle, for a considerably longer duration of time, preferably during sleep. 1.

2.

It has been variously attributed to prolonged use of • A nursing bottle containing milk or milk formula, fruit juice or sweetened water • Breast feeding • Sugar or honey-sweetened pacifiers. Invariably there is a prolonged habitual use of one of the above after 1 year of age, usually as an aid for sleeping at night or naptime.


3.

4.

5.

Clinically presents as widespread destruction of deciduous teeth, most commonly the four maxillary incisors, followed by the first molars and then the cuspids if the habit is prolonged. The lower teeth are not usually affected as they remain under the cover of the tongue, so the absence of caries in the mandibular incisors distinguishes this disease from ordinary rampant caries. Both the nursing bottle and rampant cause early pulp involvement.

Figure 8

Because they spread at a very rapid pace and as a result, the pulp hardly gets any time to protect itself by forming secondary dentin.

According to Rapidity i.

ii.

Acute dental caries • It is a form of caries which runs a rapid clinical course and results in early pulp involvement by carious process. • It occurs most frequently in children and young adults, presumably because the dentinal tubules are large and open and show no sclerosis. • The process is usually so rapid that there is little time for the deposition of secondary dentin. Chronic dental caries • Slowly progressing in nature and tends to involve the pulp much later than the acute caries. • Most common in adults. • These caries lesions exhibit a large cavity with brownish pigmentation (Figure 8). • Pain is not a common feature of chronic caries because of the protection afforded by secondary dentin. • The slow progression of the lesion allows sufficient time for both sclerosis of the dentinal tubules and deposition of secondary dentin in response to the adverse irritation.

MICROBIOLOGY OF DENTAL CARIES The predominant group of microorganism is streptococci. Among these strains S. mutans is responsible. These are gram-positive organisms which are round or ovoid. These may appear rod shaped, non-sporulating and non-motile. These can be cultured on blood agar with formation of refractory colonies measuring 0.5–1.5 mm at 37⬚C. These are pathogenic to human beings. The three common organisms seen to be associated with secondary caries are S. mutans, lactobacilli and Actinomyces viscosus. Fontanna et al (1996) observed a definite relationship of S. mutans and secondary caries. S. mutans is also

Deep occlusal caries with brownish pigmentation. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

present in saliva and in dental plaque in individuals with rampant caries due to xerostomia as well as in children nourished with bottle milk. S. mutans and lactobacilli have been found to increase in significant numbers in the plaque as well as dentin of teeth restored with amalgams having marginal defects wider than 40 ␮m. Fitzergerald et al (1994) were of the view that in association with these three major microorganisms, others also played a role in secondary caries. They found S. mutans, S. sanguis and S. salivarius in 35%, 24% and 14% of growth positive samples respectively. Other isolates like S. gordonii, S. milleri, S. oralis and S. mitis were also recognized. Certain organisms, which occurred very frequently were Propionibacterium, Bifidobacterium, Eubacterium and Peptococcus. Actinomyces were found in 46% of the samples. A. viscosus and A. naeslundii were most prevalent followed by A. israelii and A. odontolyticus. S. mutans can adhere to the tooth surface by glucan which is produced by utilization of dietary sucrose. These organisms ferment mannitol and lactose with the production of acid. These can take up dietary sucrose and breakdown into glucose and fructose by means of the enzyme, invertase. Finally glucose and fructose is broken down to lactic acid. These have the ability to store glucose and fructose from degradation for the synthesis of acids in the absence of dietary sucrose. Clinical features of dental caries, pulp and periapical lesions are given in Table 1. Sequelae of pulpitis is depicted in Flowchart 1.

413


Table 1

Clinical features of dental caries, pulp and periapical lesions

Extent of carious lesion

Signs and symptoms

Clinical findings

Clinical diagnosis

Radiographic diagnosis

Final diagnosis

Caries involving enamel

Asymptomatic patient rarely notices blackish discoloration of the tooth

Chalky white discoloration of the tooth or blackish discoloration of the tooth usually seen in the pits and fissures and proximal aspects of teeth

Enamel caries

May not be evident on a radiograph until at least 40% demineralization occurs Ill-defined radiolucency involving the enamel cap

Enamel caries

Caries involving dentin

Sensitivity on consuming hot, cold or sweet food Sensitivity subsides on removal of stimulus Food lodgment patient may notice blackish discoloration of the tooth

Blackish discoloration of the tooth Catch experienced on using an explorer Frank cavitation

Dentinal caries or reversible pulpitis

Ill-defined radiolucency involving the dentin (Figure 9)

Dentinal caries

Caries involving pulp

Dull aching pain, which has periods of exacerbation Food lodgment

Frank cavitation involved tooth non-tender on percussion Grossly decayed tooth/root stump (Figure 10)

Chronic irreversible pulpitis

Radiolucency involving the pulp No periapical changes (Figure 11) Widening of the periodontal ligament space at the periapex (Figure 12) Discontinuity of the lamina d ura at the periapex or ill-defined periapical radiolucency (Figure 13) Well-defined radiopacity at the periapex (Figure 14)


Well-defined radiolucency measuring ⬍1.5 cm in diameter at the periapex of the tooth (Figure 15) Well-defined radiolucency measuring ⬎1.5 cm in diameter at the periapex of the tooth bounded by a sclerotic border

Chronic apical periodontitis

Chronic periapical abscess

Focal sclerosing osteomyelitis or condensing osteitis seen in young individuals with good immune response or when the virulence of the microorganisms is low Periapical granuloma (Figure 16) Periapical cyst

(Contd.)

414



Signs and symptoms

Clinical findings

Clinical diagnosis


Final diagnosis


Pain Food lodgment Patient usually avoids chewing on the affected side Patient may complain of fever and malaise

Frank cavitation Involved tooth tender on percussion Calculus build up on the occlusal surfaces of the teeth on the affected side is indicative of unilateral chewing Intraoral or extraoral swelling tender on palpation (Figure 17A, B) Vestibular tenderness and/or obliteration

Acute apical periodontitis

Radiolucency involving pulp No periapical changes

Acute apical periodontitis

Radiolucency involving pulp with widening of the periodontal ligament space at the periapex Caries involving pulp Generally no periapical changes or may be associated with widening of the periodontal ligament space at the periapex

Acute exacerbation of chronic apical periodontitis Acute periapical abscess

Dull aching pain or asymptomatic Food lodgment Deep carious lesion, grossly decayed tooth, root stump Patient may complain of halitosis, bad taste or a salty taste (usually indicative of pus discharge)

Frank cavitation Involved tooth nontender on percussion Intraoral or extraoral non-tender swelling may or may not be present (Figure 18) Sinus opening on the attached gingiva or vestibule associated with the affected tooth (Figure 19) or in close proximity (occasionally sinus openings may be seen distant from the affected site as the sinus tracts may follow the path of least resistance (through the bone) Vestibule may be obliterated When the involved tooth is tender along with the above findings


Radiolucency involving pulp with discontinuity of lamina dura at the periapex and or diffuse radiolucency at the periapex (Figure 20)


Diffuse extraoral swelling, tender, stretched and shiny overlying skin, local raise in temperature (Figure 21) Limited mouth opening (extent and clinical features of the fascial spaces are described in the section on fascial space infections) Involved tooth is carious and tender on percussion Presence of intraoral swelling and vestibular obliteration

Cellulitis


Caries with pulpal involvement

Pain Diffuse extraoral swelling (sudden onset) Fever, malaise Based on the fascial space involved, patient may complain of difficulty in eating, swallowing, limited mouth opening and occasionally difficulty in breathing

Acute periapical abscess

Acute exacerbation of a chronic periapical abscess (Phoenix abscess)

Phoenix abscess

Ill-defined radiolucency involving pulp Usually very minimal periapical changes such as widening of the periodontal space or illdefined radiolucency at the periapex may evident at acute nature of the condition is the reason for the very minimal bone changes

Cellulitis of the infraorbital, buccal, submandibular space, etc.

(Contd.)

415


Table 1

Continued


Signs and symptoms

Clinical findings

Clinical diagnosis


Final diagnosis

Caries with pulpal involvement

Patient may complain of dull aching pain or may be asymptomatic

Tooth involved shows a deep carious lesion, tender or non-tender on percussion Diffuse expansion of the cortical plates. The affected site may reveal a well-defined bony hard swelling (usually mildly tender or non-tender on palpation) (Figure 22) Occasionally ‘egg shell crackling’ of the cortical plates may be appreciated on palpation

Periapical cyst

Well-defined radiolucency measuring ⬎1.5 cm in diameter at the periapex of the tooth surrounded by a sclerotic border (Figures 23 and 24). Absence of the sclerotic border may be indicative of an infected cyst (Figure 25)

Periapical cyst

Clinical Diagnostic Methods Diagnostic methods for caries in common use include visual inspection, tactile examination with a probe, bitewing radiography, intraoral periapical radiographs and certain diagnostic aids such as fiberoptic transillumination, endoscopic techniques, light scattering, laser fluorescence, ultraviolet illumination, dye penetration, iodide penetration and electrical resistance. Early diagnosis enables small lesions to be identified so that remineralization of lesions by preventive measures can be attempted. In the clinical examination for dental caries every assessable surface of each tooth must be examined for localized changes in color, texture, and translucency. Dental caries is most prevalent in the faulty pits and fissures of the occlusal surfaces, where developmental lobes of the posterior teeth fail to coalesce, partially or completely.

Visual, Tactile Methods of Caries Detection Earlier sharp explorers were used to detect incipient fissure caries. However, in recent times it is strongly discouraged as it was found to fracture enamel and serve as a source for transferring pathogenic bacteria among various teeth. It was also noted that the use of an explorer did not increase diagnostic validity compared to visual examination. Visual examination of the tooth surface should be carried in a dry, well-illuminated field. Chalkiness or apparent softening or cavitation of the tooth structure is diagnostic of the carious process. Occasionally 416

Flowchart 1 Enamel caries

Dentinal caries or reversible pulpitis


Acute

Apical periodontitis

Periapical abscess

Cellulitis

Infected

Acute suppurative osteomyelitis Followed by chronic phase

Ludwig’s angina/fascial space infections

Cavernous sinus thrombosis

Death

Sequelae of pulpitis

Chronic

Periapical abscess

Dentoalveolar abscess

Periapical granuloma

Periapical cyst


Figure 9

Figure 10 A

B Radiograph showing proximal caries involving dentin suggestive of dentinal caries. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

a brown-gray discoloration is seen. However, one should be careful to distinguish between superficial staining and a carious lesion. Occlusal enamel can be evaluated for loss of translucency and change in color, which are characteristics of caries. Proximal surface caries is usually diagnosed radiographically. Clinically when the carious process has invaded the proximal surface enamel and dentin, a white chalky appearance or a shadow under the marginal ridge may be seen. Careful probing with an explorer on the proximal surface may detect cavitation (defined as a break in the surface contour of enamel). Proximal caries can also be detected by tooth separation or through transillumination. Brown spots on intact hard proximal surface of enamel adjacent to and usually gingival to the contact area are often seen in older patients whose caries activity is low. Such a spot is no longer carious and, in fact, are more resistant to caries as a result of fluorhydroxyapatite formation. Transillumination is accomplished by placing the mirror or light source on the lingual side of the anterior teeth and directing the light through the teeth. Use of a dental floss in the interdental regions along the proximal surfaces of teeth may also be used to detect initial proximal carious lesions. A frayed floss is usually diagnostic of proximal caries. Another form of smooth surface caries often occurs on the facial and lingual surfaces of the teeth, particularly

Grossly decayed teeth and root stumps. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

in gingival areas that are less accessible for cleaning. The earliest clinical evidence of incipient caries on these surfaces is a white spot that is visually different from the adjacent translucent enamel and will partially or totally disappear on wetting. Drying again will cause it to reappear. This disappearing and reappearing phenomenon distinguishes the smooth incipient caries form the white spots resulting from non-hereditary enamel hypocalcificaton. In patients with attachment loss, care must be taken to inspect for root surface caries. Carious lesion occurs on the cemental surfaces of the teeth. Active root caries is detected by the presence of softening and cavitation. Advanced smooth surface caries will exhibit discoloration and demineralization and will feel soft to penetration by the explorer. The discoloration may range from white to dark brown, with rapidly progressive caries usually being light in color. With slowly progressive caries in a patient with low caries activity, darkening occurs over time because of extrinsic staining and remineralization of decalcified structure occasionally may harden the lesion. Such an 417


Figure 11

Figure 13


No periapical changes

Illustration showing the radiographic features in chronic irreversible pulpitis. Coronal radiolucency involving pulp with no periapical changes

Illustration showing loss of lamina dura at the periapex and diffuse radiolucency at the periapex suggestive of chronic periapical abscess

Figure 14 Figure 12

Widening of periodontal ligament space at the periapex

Illustration showing the radiographic features of chronic apical periodontitis. Coronal radiolucency involving pulp with widening of the periodontal ligament space at the periapex

arrested lesion may at times be rough, although cleanable and a restoration is not indicated except for esthetics. The dentin in an arrested remineralized lesion is termed eburnated or sclerotic. Following a visual clinical examination the carious lesion can be scored using the International Caries Detection and Assessment System (ICDAS). 418

Radiograph depicting well-defined radiopacity at the periapex suggestive of condensing osteitis. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Scoring system for visual changes associated with carious lesions (ICDAS) Score 0: Sound tooth surface Score 1: First visual change in enamel Score 2: Distinct visual change in enamel Score 3: Microcavitation


either with white light or with filtered fluorescence excited by a blue curing light have shown an increased sensitivity to detect initial occlusal lesions in comparison to clinical visual examination.

Figure 15

Well-defined periapical radiolucency less than 1.5 cm

Illustration showing the radiographic features of periapical granuloma. Well-defined radiolucency measuring less than 1.5 cm at the periapex

Figure 16

The histopathological picture of a periapical granuloma. Courtesy: Department of Oral Pathology, MCODS, Mangalore

Score 4: Underlying dark shadow from dentin with or without cavitation Score 5: Distinct cavity with visible dentin Score 6: Extensive distinct cavity with visible dentin. Endoscopic methods Initial studies by Longbottom and Pitts (1992) on the potential benefits of endoscopic examination,

Fiberoptic transillumination Friedman and Marcus (1970) described the use of fiberoptic transillumination for the detection of approximal caries. The working principle is that the decayed tooth material scatters light more strongly, and thus has a lower index of light transmission than a sound tooth structure. Use of fiberoptic transillumination for the diagnosis of occlusal dentinal decay was studied by Verdonschot et al (1992) as part of a comparison of various systems available for the diagnosis of the dentinal decay of occlusal surfaces in vivo. They found a very low sensitivity (0.13) and a high specificity (0.99). Light-scattering In a study by Angmar-Mansson and Ten Bosch (1987) to assess the scattering of light by carious lesions, incipient caries lesions looked whiter than the surrounding sound enamel because of the strong scattering of light within the lesion. Presumably, this is primarily due to the fact that the remaining small mineral particles in the lesion are embedded in water rather than in mineral-rich sound enamel. Ogaard and Ten Bosch (1993) were of the opinion that this technique is useful only for caries lesions on smooth surfaces. Laser autofluorescence Visible light within the blue-green region has been used as the light source for the development of a sensitive method for the detection of smooth surface and fissure caries at an early stage (Bjelkhagen et al, 1982). The tooth is illuminated with a broad beam of bluegreen light of 488 nm wavelength from an argon ion laser. The fluorescence in the enamel occurring in the yellow region (about 540 nm) is observed through a yellow highpass filter (520 nm) to exclude the tooth-scattered blue laser light. Demineralized areas appear dark in this situation. Natural lesions (diameter ⬍1 mm) with a lesion depth as small as 5–10 ␮m can be detected and measured using laser autofluorescence. Ultraviolet illumination Ultraviolet (UV) light has been used to increase the optical contrast between the carious region and the surrounding sound tissue. The natural fluorescence of tooth enamel, as seen under UV illumination, is decreased in areas of less mineral content, such as in caries lesions, artificial demineralization, or developmental defects (Alfano and Yao, 1981). The caries lesion appears as a dark spot against a fluorescent background. Alfano and Yao showed that the UV illumination method was more sensitive than simple visual/ tactile methods. 419


Figure 17 A

B

(A) Intraoral photograph showing a well-defined swelling on the palatal surface of decayed maxillary molar suggestive of an acute periapical abscess. (B) Tender extraoral swelling suggestive of an acute periapical abscess. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 18

Swelling associated with maxillary molar suggestive of a periapical abscess. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Foreman (1988) stated that, in UV light, there is generally an inverse correlation between the intensity of fluorescence and the degree of mineralization in mineralized dental tissues, just as there is with the laser fluorescence method. Penetration of dyes Various dyes, fluorescent or nonfluorescent, have been used for staining the porous caries lesion to enhance the contrast between the carious region and the surrounding sound enamel. 420

Figure 19

A sinus opening in the vestibule associated with the discolored central incisor. Courtesy: Department of Oral Medicine and Radiology, KLE Society’s Institute of Dental Sciences, Bangalore

Shern and coworkers (1990) compared sodium fluorescein with potassium iodide to disclose the porosity of an artificial incipient lesion. The extent of porous (active) white spot lesions was disclosed only by fluorescein. Van de Rijke et al (1991) presented an optical quantification of approximal in vitro caries using a fluorescent dye, Fluorol.


Figure 20

Radiograph reveals diffuse periapical radiolucency associated with the mandibular molar suggestive of a periapical abscess. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 22

Extraoral photograph showing an extraoral swelling over the right side of the mandible which was bony hard on palpation. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 21 Figure 23

Well-defined periapical radiolucency more than 1.5 cm with sclerotic border

Extraoral photograph showing diffuse extraoral swelling involving the left submandibular, buccal and infraorbital fascial spaces. Courtesy: Dr Francisco Lopez Sanchez, University of Michoacan, Morelia, Mexico

O’Brien et al (1989) used a blue tracer dye to increase the color contrast in the detection of approximal incipient caries lesions by fiberoptic transillumination. Artificial incipient caries lesions were photographed by transillumination with or without the blue dye added. The color difference

Illustration showing the well-defined periapical radiolucency measuring more than 1.5 cm in diameter suggestive of a periapical cyst

was registered by a reflectance colorimeter, and a four times increase between the lesion and the surrounding sound area was shown with the dye. Iodide penetration The iodide penetration method for measuring enamel porosity of the incipient caries lesion on 421


Figure 24

Figure 25

Maxillary occlusal radiograph showing a well-defined periapical radioluceny associated with a fractured maxillary central incisor suggestive of a periapical cyst. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

smooth surfaces was developed by Brudevold and coworkers and was later improved by Zero et al. Potassium iodide was applied for a specified period of time to a well-defined area of the enamel surface, and thereafter the excess was removed. Permeability was estimated by measurement of the quantity of iodide that could be eluted from the test area. Electrical resistance The electrical resistance method is based on the assumption that electrical conductivity is a function of porosity. Enamel demineralization results in increased porosity, and saliva fills the pores and forms conductive pathways for electrical current. Thus, the greater the amount of demineralization, the higher the electrical conductivity through the affected enamel is expected to be. An instrument (Vanguard electronic caries detector) has been designed to measure the electrical conductivity of a tooth to evaluate the presence of lesions in the occlusal surface by measuring the electrical conductivity from the probe tip in the fissure through the dental pulp to a handheld earth. The electrical conductivity is expressed numerically on a scale from 0 to 9. In an in vitro study of occlusal pit-and-fissure caries in molars, Flaitz et al (1986) compared electrical conductivity data of extracted teeth with the histologically measured lesion depth. The results showed a linear relation between scale value and depth. Ultrasonic imaging Ng et al (1988) introduced ultrasonic imaging for detecting early caries in smooth surfaces. They showed that artificial enamel lesions with less than 57% of the sound enamel mineral content in the 422

Intraoral periapical radiograph showing a periapical cyst with no definitive sclerotic border suggestive of a secondary infection (infected periapical cyst). Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

body of the lesion could be differentiated acoustically from intact enamel on the basis of amplitude changes of the enamel surface echo and the amelodentinal junction echo. They also found that there was a correlation between the mineral content of the body of the lesion and the relative echo amplitude changes, which was explained by changes in specific acoustic impedance. However, the authors concluded that the method is not sensitive enough to detect changes of shallow caries lesions in vivo. Vitality tests The tooth is said to be vital when it is capable of responding to stimuli. To check the vitality there are three basic stimuli in the form of thermal, electrical or mechanical: ❍ ❍

Thermal heat/cold application Electric pulp testing: Direct electric stimulation of sensory nerves in the pulp ❍ Mechanical stimulation: Blowing air to the exposed dentin and test cavity preparation.

Thermal Test Cold test Adjacent or contralateral unaffected teeth should be tested for baseline comparisons because the duration of pain may differ among individuals.


A cotton applicator tip sprayed with a freezing agent or carbon dioxide snow, icesticks, and ethyl chloride spray applied directly to the tooth. The cold stimulus is applied immediately to the middle one-third of the facial surface of the crown of the tooth/exposed metal surface of crowns and kept in contact for 5 seconds or until a point the patient begins to feel pain.

Figure 26

Heat test The tooth in question is isolated. A 3-inch gutta percha stick is warmed over a flame until it becomes soft and just begins to glisten. The heated stick is then applied to the middle one-third of the facial surface of the crown. Normally a response is appreciated in about 2 seconds.

Use of electric pulp tester. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Interpretation of the results 1.

2. 3. 4.

No response—a non-vital pulp. However, a false negative response can be encountered when the tooth exhibits excessive calcification, immature apex, recent trauma and a premedicated patient. Momentary mild-to-moderate response—normal pulp. Exaggerate response that subsides quickly—reversible pulpitis. Painful response that lasts for several minutes after the stimulus is removed—irreversible pulpitis.

Electric Pulp Tester Evaluation of responding nerve endings can be done with an electrical pulp tester (Figure 26). A small electric current delivered to the tooth causes a tingling sensation is suggestive of vital pulp. The teeth to be tested must be isolated and dried with 2 ⫻ 2 inch gauze and the area must be kept dry with a saliva ejector. The patient must be made aware of the procedure. The electrode should be coated with a viscous conductor. The electrode should then be applied to the dry enamel of the tooth being tested on the middle one-third of the facial surface of the crown. The digital reading that indicates the current flow should always start with zero. The current flow should be increased slowly to allow the patient to respond for tingling sensation. If a positive response is not obtained the electrode should be applied to several different locations on the lingual and facial surfaces of the tooth to ensure that the negative response is not due to the result of improper electrode placement. Each tooth should be tested at least two or three times and an average result should be recorded. Enamel thickness influences the results. Thinner enamel in the anteriors yields faster response than thicker enamel of the posteriors. Electrodes should not be applied on restorations.

False positive response (when a patient reports sensation in a tooth with a necrotic pulp) can be encountered under the following conditions: ❍ ❍ ❍

Patient anxiety Saliva conducting the stimulus to the gingiva Metallic restoration conducting the stimulus to the adjacent teeth ❍ Liquefaction necrosis conducting the stimulus to the attachment apparatus.

False negative response (although the pulp is vital, patient does not indicate that any sensation is felt in the tooth) can be encountered under the following conditions: ❍ ❍ ❍ ❍ ❍ ❍

Premedication with drugs or alcohol Immature teeth Trauma Poor contact with the tooth Inadequate media Partial necrosis with vital pulp remaining in the apical portion of the tooth ❍ Individuals with atrophied pulps or with high pain thresholds. Limitations There is no reasonable assurance; however, these nerves are located in an intact pulp. Necrotic and degenerating pulp tissue often leaves an excellent electrolyte in the pulp space. This electrolyte can easily conduct the electrical current to nerves further down into the pulp space, simulating normal pulp response. This is more complicated in a multi-rooted tooth, where the status of the pulp varies in each root. Electrometric pulp tester should not be the primary instrument of choice when assessing pulpal health. A positive cold test provides a more accurate response that is easier 423


to interpret. However, neither of these tests ensures vitality of the pulp if the results are positive. The above mentioned pulp vitality assessment methods rely on stimulation of A-delta nerve fibers and give no direct indication of blood flow within the pulp. These testing methods have the potential to produce an unpleasant and occasionally painful sensation and inaccurate results (false positive or negative can be obtained in many instances). In addition, each is a subjective test that depends on the patient’s perceived response to a stimulus as well as the dentist’s interpretation of that response. Many studies have shown that blood circulation and not innervation is the most accurate determinant in assessing pulp vitality as it provides an objective differentiation between necrotic and vital pulp tissue. The newer techniques that have been tried effectively to evaluate the vitality of the pulp include pulse oximetry, dual wavelength spectrophotometry and laser Doppler flowmetry.

Pulse Oximetry The pulse oximeter is a non-invasive oxygen saturation monitoring device widely used in medical practice for recording blood oxygen saturation levels during the administration of intravenous anesthesia. The pulp oximeter is based on the modification of the principle of Beer’s law, which relates the absorption of light, by a solute to its concentration and optical properties at a given light wavelength. It also depends on the absorbance characteristics of hemoglobin in the red and infrared range. In the red region, oxyhemoglobin absorbs less light than deoxyhemoglobin and vice versa in the infrared region. The system consists of a probe containing a diode that emits light in two wavelengths: 1. 2.

Dual wavelength spectrophotometry (DWLS) is a method independent of a pulsatile circulation. The presence of arterioles rather than arteries in the pulp and its rigid encapsulation by surrounding dentin and enamel make it difficult to detect a pulse in the pulp space. This method measures oxygenation changes in the capillary bed rather than in the supply vessels and hence does not depend on a pulsatile blood flow. It detects the presence or absence of oxygenated blood at 760 and 850 nm. The blood volume or concentration channel (760 ⫹ 850 nm) is arranged to respond linearly to the increase in light absorption. The oxygenation channel (760 ⫺ 850 nm) senses the oxygenated blood because of the greater absorption at 850 nm as compared to 760 nm. In vivo and in vitro studies were conducted to differentiate between pulp chambers that were empty, filled with oxygenated blood or fixed pulp tissue. DWLS was able to differentiate with reproducible readings between a pulp chamber of a vital and non-vital tooth in vivo. In young children, in cases of avulsed and replanted teeth with open apices, the blood supply is regained within the first 20 days after replantation but nerve supply lags behind. Repeated spectrophotometric readings taken at the start of the replantation and continuing up to 40 days later revealed an increase in blood oxygenation levels indicating a healing process and that the pulp of the avulsed tooth was recovering. Hence, endodontic treatment need not be undertaken. A major advantage is that it uses visible light that is filtered and guided to the tooth by fiberoptics. Thus, unlike laser light, added eye protection is unnecessary for the patient and the operator.

Red light of approximately 660 nm Infra-red light of approximately 850 nm.

A silicon photo detector diode is placed on the opposing surfaces of the tooth, which is connected to a microprocessor. The probe is placed on the labial surface of the tooth crown and the sensor on the palatal surface. Ideal placement of the probe is in the middle third of the crown. If placed in the gingival third, disturbances from gingival circulation or any gingival trauma or bleeding will interfere with the readings. Incisally, less of pulp tissue is present for adequate detection of the pulse. A number of clinical studies have proved that the pulse oximetry is an effective and objective method of evaluating dental pulp vitality. Though the surrounding insulation of the enamel and dentin are hindrances to the detection of a pulse in the pulp, it has proved to be a successful method in 70% of the clinical trials. It is also useful in cases of impact injury where the blood supply remains intact but the nerve supply is damaged. 424

Dual Wavelength Spectrophotometry

Laser Doppler Flowmetry Laser Doppler flowmetry is a non-invasive, electro-optical technique, which allows the semi-quantitative recording of pulpal blood flow. The laser Doppler technique measures blood flow in the very small blood vessels of the microvasculature. This technique depends on the Doppler principle whereby light from a laser diode incident on the tissue is scattered by moving RBCs and as a consequence, the frequency broadened. The frequency broadened light, together with laser light scattered from static tissue is photo detected and the resulting photocurrent processed to provide a blood flow measurement. The Doppler shifted laser light, back-scattered out of the tooth is detected by a photocell on the tooth surface. The output is proportionate to the number and velocity of the blood cells.


Radiographic Evaluation of Carious Lesions It has been proved time and again over the years that more dental caries are detected by intraoral radiographs than by clinical examination alone. Radiographic detection of dental caries is based on the fundamental principle that as the caries process proceeds, the mineral content of enamel and dentin decreases with a resultant decrease in the attenuation of the X-ray beam as it passes through the teeth. This is recorded as a radiolucent image on the image receptor. Detection of the carious lesion may be influenced by a number of factors such as the extent of demineralization of the carious lesion (minimum of 40% demineralization of the tooth structure is required to be evident on a radiograph), location of the carious lesion, exposure parameters, type of image receptor, image processing, display system, viewing conditions, and ultimately, the training and experience of the human observer. Cervical burnout, abrasion, attrition, proximal wear and restorative materials that appear radiolucent may mimic dental caries. Radiographs are taken to evaluate the extent of the carious lesions and to assess periapical changes secondary to the caries attack. Intraoral periapical radiographs and bitewing radiographs are widely used for assessing carious lesions. White and McMullin (1986) concluded that both ultraspeed film and xeroradiography (XR) were somewhat preferable to Ektaspeed film. Wenzel et al (1991) compared conventional film radiographs, digitized film radiographs, and radiovisuography (RVG) for the detection of occlusal caries in non-cavitated extracted teeth. Histologic sections served as the validation criterion. The two digital methods with contrast enhancement tended to perform better than, although not significantly different from, the other three methods. The authors concluded that radiography can much improve diagnosis compared to clinical inspection. They also concluded that digital techniques, no matter which, improve the sensitivity without substantial loss of specificity. Occlusal caries Incipient carious lesions occurring on the occlusal surface of teeth usually begins in the pits and fissures. The carious lesion starts at the side of the fissure than at the base and it tends to penetrate perpendicular toward the DEJ. Radiographs can help to detect occlusal lesions only when the carious process reaches the dentin. A moderate carious lesion will generally show definitive radiographic findings such as a broad-based thin radiolucent zone in the dentin with little or no changes apparent in the enamel. As the carious process advances into a severe form, the underlying dentin is extensively involved and hence fails to support the overlying enamel structure resulting in the

breakdown of the occlusal surface. Radiographically, an extensive ill-defined radiolucent area is seen. Proximal caries The proximal carious lesion is clinically apparent as a chalky white discoloration. It is estimated that it takes about 4 years for an initial proximal carious lesion to be seen clinically. In the initial stages a discrete radiolucent ‘wedge-shaped defect’ or notch may be visible usually confined to the enamel cap. Moderate carious lesions usually involve more than the outer half of the enamel to extend into the DEJ. Radiographically, proximal caries can present either as a triangle with its broad base at the surface of the tooth or a diffuse radiolucent image or a combination of the above. In advanced lesions the carious process involved the DEJ. Radiographically, the entire thickness of enamel is involved. The carious lesion may either present as a triangular process or appear ill-defined and diffuse or may appear as a combination of the above. In a severe form of the proximal carious process, a radiolucent area involving more than half the dentin and approaching the pulp chamber is characteristic. Facial, buccal and lingual caries Smooth surface carious lesions will usually begin along the pits and fissures. Almost all carious lesions occurring on the facial and lingual surface of teeth have a very sharply defined outline. In the initial stages these lesions are round and as the carious process advances they appear as large elliptical defects. Occasionally, these carious lesions may be difficult to detect as they may be superimposed over the DEJ mimicking occlusal caries. Generally, these lesions appear as well-defined circular radiolucent areas surrounded by dense area of noncarious tooth structure. Root caries Root surface carious lesions are those that involve the cementum and dentin. These are typically seen in teeth which exhibit gingival recession or interdental bone loss. Older individuals are more likely to show the presence of root surface carious lesions. Radiographically, a saucer like or a notched radiolucency is seen at the cervical margin of the tooth that usually extends apically along the root surface. Recurrent caries Recurrent caries or secondary caries occurs adjacent to a restoration. It may result from poor marginal adaptation of a restoration, which allows marginal leakage; inadequate extension of a restoration, incomplete excavation of the primary carious lesion and fractured restoration. 425


Radiographs show radiolucent areas adjacent to a restoration. Restorative materials such as composite, silicate and acrylic can resemble recurrent caries. These radiolucent restorative materials can be differentiated from recurrent caries by their well-defined and smooth outlines (Figure 27). Rampant caries Rampant caries usually occurs in children. There will be extensive smooth surface caries involving many teeth. Radiation caries Radiation caries can be considered as a type of rampant caries seen in patients who receive radiation therapy for head and neck tumors. It occurs secondary to xerostomia. Caries begins at the cervical region and may aggressively encircle the tooth causing entire crown to be lost with only root fragments remaining in the jaws. Radiograph shows dark radiolucent shadows appearing at the cervical margins of teeth.

FASCIAL SPACE INFECTION Cellulitis or fascial space infection is characterized by a diffuse inflammation of soft tissues. Fascial space infections in the head and neck region usually occur as an extension of periapical, periodontal and pericoronal infections.

Concepts of Fascia and Fascial Spaces Fasciae are extensive, broad sheets of dense connective tissue. Fasciae envelop anatomic structures such as the muscles, glands and organs and thereby separate structures that must move over each other during movement. These fasciae also serve as pathways for the course of vascular and neural structures. Shapiro defined fascial spaces as potential spaces between layers of fascia. These spaces are normally filled with loose connective tissue and vital structures. The use of the term ‘space’ is a misnomer as tissues show no evidence of voids. The pus destroys the loose connective tissue and separates the anatomical boundaries of the compartment as it increases in volume, thus creating an abscess cavity bounded by muscles, tissues and bone. Superficial fascia It is a layer of dense connective tissue that courses deep to the subcutaneous tissue throughout the entire body. Below the mouth the muscles of facial expression lie deep to the superficial fascia, whereas in the upper face the muscles of facial expression are positioned superficial to this layer. The superficial cervical fascia is a sheet of fibrous connective tissue that encircles the head and neck and is attached to the fascia of the thorax, shoulders and axilla. It contains the platysma muscle. Deep fascia

Figure 27

Radiograph showing recurrent carious lesion below the margins of the radiopaque restorative material. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

426

The deep cervical fascia is divided into the superficial or investing layer, the middle or visceral layer and the deep or prevertebral layer. The superficial layer of the deep cervical fascia completely encircles the neck with its attachments being superiorly: the external occipital protuberance, the mastoid process and the zygoma, and anteriorly the mandible and the hyoid bone and inferiorly the scapula, the clavicle and the manubrium of the sternum. It envelops the trapezius and sternocleidomastoid muscles. The middle layer encircles the viscera of the neck including the pharynx, esophagus, larynx, trachea and thyroid gland. It also encloses the strap muscles anteriorly. The deep layer envelops the paraspinous muscles and vertebral bodies. More importantly, anterior to the vertebral bodies it divides into a prevertebral layer and a more anterior alar layer. This creates three potential spaces, namely, the prevertebral space, the danger space and the retropharyngeal space. The carotid sheath is formed from contributions of all three layers of the deep cervical fascia and runs from the base of the skull to the level of the clavicle. The deep spaces of the neck can be divided into those which involve the entire length of the neck (including the retropharyngeal space, the danger space and the prevertebral space), those that are limited to above the hyoid bone (the submaxillary, the sublingual and the parapharyngeal


spaces) and those limited to below the hyoid bone. Refer to line diagrams (Figures 28 to 32). The retropharyngeal space is the potential space that exists between the posterior aspect of the visceral layer and the alar division of the deep layer. It extends from the base of the skull to the level of the first or second thoracic vertebrae. It contains two lateral chains of lymph nodes separated by a midline raphe. The danger space lies between the alar and prevertebral layers of the deep cervical fascia. It extends from the base of the skull to the posterior mediastinum at the level of the diaphragm and is limited laterally by its fusion with the prevertebral layer and the vertebral transverse process. The prevertebral space lies between the vertebral bodies and the prevertebral layer of the deep cervical fascia. It extends from the base of the skull to the level of the coccyx. Figure 28

The parapharyngeal space can be compared to an inverted cone with its base lying superiorly at the base of the skull and its apex inferiorly at the hyoid bone. It is divided into a prestyloid and a poststyloid component. Its medial and lateral borders are, respectively, the lateral pharyngeal wall and the superficial layer of the deep cervical fascia as it overlies the mandible, the parotid gland and the internal pterygoid. The submandibular space is divided by the mylohyoid muscle into the sublingual space above and the submaxillary space below. These two spaces communicate freely around the posterior edge of the mylohyoid muscle. The entire space is bounded by the mandible anteriorly and laterally. The hyoid bone limits its inferior aspect and the intrinsic muscles of the base of tongue from its posterior border. The sublingual space contains the sublingual gland, the

Figure 30

Buccinator muscle

Temporalis muscle

Tongue

Superficial temporal space Buccal space Infratemporal space

Sublingual space

Lateral pterygoid muscle Submandibular space

Pterygomandibular space Masseteric space Medial pterygoid muscle

Illustration showing submandibular and buccal spaces Masseter muscle

Illustration showing infratemporal and superficial temporal spaces

Figure 29 Medial pterygoid muscle Parotid gland

Parotid space Masseter muscle Submasseteric space

Parapharyngeal space Superior constrictor muscle

Peritonsillar space

Figure 31 Lateral pharyngeal space Prevertebral space Retropharyngeal space Superior constrictor muscle Pterygoid muscle

Pterygomandibular space

Mandible Masseter muscle

Buccal space Buccinator muscle

Buccinator muscle Mylohyoid muscle

Illustration showing pterygomandibular and submasseteric spaces

Illustration showing retropharyngeal and lateral pharyngeal spaces

427


❍

Figure 32 Buccopharyngeal fascia Alar fascia Prevertebral fascia

Retropharyngeal space

By lymphatics to the regional lymph nodes and eventually into the blood stream ❍ By the blood stream. General factors ❍ Host’s resistance or immunocompetence of the host ❍ Virulence of microorganisms. Local factors Intact anatomical barriers: ❍ Alveolar bone ❍ Periosteum ❍ Adjacent muscles and fascia.

LUDWIG’S ANGINA Prevertebral space

Prevertebral fasciae and prevertebral space

hypoglossal nerve and Wharton’s duct. The submandibular space contains the submandibular gland. The anterior visceral space lies in the anterior aspect of the neck, is enclosed by the visceral layer and completely surrounds the trachea, esophagus and thyroid gland. It extends from the thyroid cartilage to the level of the fourth thoracic vertebrae in the superior mediastinum. Pain and swelling are commonly present and may help identify the space involved. Dysphagia is more common when the parapharyngeal and retropharyngeal spaces are involved. Trismus is seen with involvement of the submaxillary space or anterior aspect of the parapharyngeal space. Other symptoms may include respiratory distress if the abscess partially compromises the airway or dental complaints if this is the source of infection. Other findings may include oropharyngeal abnormalities such as swelling of the lateral or posterior pharyngeal walls, in parapharyngeal or retropharyngeal abscess. Nearly 40% of deep space infections are caused by mixed flora. Other changes include the emergence of gram-negative organism, primarily Klebsiella pneumoniae, as important pathogens as well as an increase in the prevalence of anaerobic infections. Notwithstanding, streptococcal species, primarily alpha Streptococcus and Staphylococcus aureus, are still the most commonly isolated organisms. Spread of orofascial infection Infections in the head and neck region usually spread by hydrostatic pressure, along the path of least resistance. Routes of spread and factors affecting spread of oral infections (Table 2) ❍ By direct continuity through tissues 428

The necrotizing fasciitis, Ludwig’s angina, was first described by German surgeon Karl Wilhelm Friedrich von Ludwig in 1836. It is a potentially life-threatening, rapidly expanding, diffuse inflammation of the submandibular and sublingual spaces that occurs most often in young adults with dental infections. Clinical features Ludwig’s angina begins as a mild infection and can rapidly progress to brawny bilateral induration of the upper neck. Anxiety, cyanosis and sitting posture are late signs of impending airway obstruction, and indicate the need for an immediate artificial airway. The most serious complication of Ludwig’s angina is asphyxia caused by expanding edema of soft tissues of the neck. The symptoms include severe neck pain and swelling, fever, malaise and dysphagia. Stridor suggests an impending airway crisis. Patient may report of severe toothache, trismus and foul breath. The mortality rate can go up to 20–50% if the infection spreads to the mediastinum, carotid sheath, skull base and meninges. Complications such as descending necrotizing mediastinitis usually occurs through the retropharyngeal space (71%) and the carotid sheath (21%). Predisposing factors These include deep dental caries, severe periodontal infection, a compromised immune system and recent trauma. Ludwig’s angina in children can occur de novo, without any apparent precipitating cause. Mode of spread Ludwig’s angina is a rapidly progressive, potentially fulminant cellulitis involving the sublingual, submental and submandibular spaces. It typically originates from an infected or recently extracted tooth, most commonly the lower second and third molars. The submandibular space is involved by penetration of the thin inner cortex of the


Table 2

Head and neck fascial spaces

Space

Boundaries

Contents

Submental space

Lateral: Lower border of mandible and anterior bellies of digastric muscles Superior: Mylohyoid muscle Inferior: Suprahyoid portion of the investing layer of deep cervical fascia

Submental lymph nodes and anterior jugular veins

Submandibular space

Anteromedially: The floor is formed by mylohyoid muscle, which is covered by loose areolar tissue and fat Posteromedially: The floor is formed by hypoglossus muscle Superolaterally: Medial surface of mandible below the mylohyoid ridge Anterosuperiorly: Anterior belly of digastric Posterosuperiorly: Posterior belly of digastric, stylohyoid and the stylopharyngeus muscles Laterally: Platysma and skin

Superficial lobe of submandibular salivary gland and submandibular lymph nodes, facial artery and vein

Sublingual space

Superiorly: Mucosa of floor of the mouth Inferiorly: Mylohyoid muscle Laterally: Medial side of the mandible, above the mylohyoid muscles Medially: Hyoglossus, genioglossus and geniohyoid muscles Posteriorly: Hyoid bone laterally and inferiorly by mylohyoid muscle and lingual side of mandible

Geniohyoid and genioglossus muscles, the hyoglossus muscle complex It also contains submandibular salivary gland, sublingual salivary gland, lingual nerve and hypoglossal nerve

Canine space

Inferiorly: Caninus muscle Anteriorly: Orbicularis oris Posteriorly: Buccinator muscle Medially: Anterolateral surface of maxilla

Buccal space

Buccal space is the potential space between buccinator and masseter muscle Anteromedially: Buccinator muscle Posteromedially: Masseter overlying the anterior border of ramus of mandible Laterally: By forward extension of deep fascia from the capsule of parotid gland and by platysma muscle Inferiorly: Limited by the attachment of the deep fascia to the mandible and by depressor anguli oris Superiorly: The zygomatic process of the maxilla and the zygomatous major and minor muscles

Buccal pad of fat, Stensen’s duct, facial artery

Infratemporal fossa space (retrozygomatic space)

Bounded laterally, by ramus of mandible, temporalis muscle and its tendon Medially: Medial pterygoid plate, lateral pterygoid muscle, medial pterygoid muscle, lower part of temporal fossa of the skull and lateral wall of pharynx Superiorly by infratemporal surface of greater wing of sphenoid and by zygomatic arch Inferiorly: Lateral pterygoid muscle, which forms the floor of the fossa, and its lower head is said to mark the border between pterygomandibular and infratemporal spaces Anteriorly: Infratemporal surface of maxilla Posteriorly: Parotid gland

Medial and lateral pterygoid muscles, maxillary artery, mandibular nerve and middle meningeal artery

Temporal space (masticatory space)

Spaces in relation to temporalis muscle: 1. Superficial temporal space—lies between temporal fascia and temporalis muscle 2. Deep temporal space—lies deep to temporalis muscle and skull Communicates with infratemporal and pterygopalatine fossa (Contd.)

429


Table 2

Continued

Space

Boundaries

Contents

Parotid space

The space is formed by splitting of the superficial layer of deep cervical fascia surrounding the parotid gland, and lies posterior to the masticator space Inferiorly: Stylomandibular ligament, which separates parotid space from the mandibular space

Parotid gland and parotid lymph nodes, facial nerve, retromandibular vein, and external carotid artery

Submasseteric space (masticatory space)

Anterior: Anterior border of masseter muscle and buccinator Posterior: Parotid gland and posterior part of masseter Inferior: Attachment of the masseter to the lower border of mandible Medial: Lateral surface of the ramus of mandible Lateral: Medial surface of the masseter muscle

Masseter, lateral and medial pterygoids, part of mandible and branches of mandibular division of trigeminal nerve

Pterygomandibular space

Lateral: Medial surface of ramus of mandible Medial: Lateral surface of medial pterygoid muscle Posterior: Parotid gland Anterior: Pterygomandibular raphe Superior: Lateral pterygoid muscle

Lingual nerve, mandibular nerve, inferior alveolar nerve or mandibular artery, mylohyoid nerve

Lateral pharyngeal space

Superiorly: Base of skull Inferiorly: Hyoid bone (submandibular gland and posterior belly of digastric) Anteriorly: Bounded by pterygomandibular raphe Laterally: Bounded by the ramus of mandible, insertion of medial pterygoid muscle and deep lobe of parotid gland Medially: Bounded by pharyngeal wall and pharyngeal constrictors Posteriorly: Bounded by styloid muscle and upper part of carotid sheath, prevertebral fascia

Anterior compartment: Lymph nodes, ascending pharyngeal, facial artery, loose areolar connective tissue Posterior compartment: Carotid sheath (internal jugular vein, internal carotid artery and vagus nerve), glossopharyngeal nerve, spinal accessory nerve, hypoglossal nerve and cervical sympathetic trunk

Retropharyngeal space

Laterally: Carotid sheath The retropharyngeal space is continuous with retroesophageal space into the posterior mediastinum to the level of the sixth thoracic vertebra There are no middle attachments in the retropharyngeal space, thereby permitting unimpeded inferior extension of inflammatory and neoplastic processes into mediastinum Spread of infection through the carotid sheath into the mediastinum is referred to as ‘spread of infection via the Lincoln’s highway’

Parapharyngeal space Lateral pharyngeal and retropharyngeal spaces These spaces form a ring around pharynx and communicate with submandibular space and retromandibular space

mandible by periapical dental abscesses. Spread to the sublingual space is around the posterior margin of mylohyoid muscle. It has, however, been reported as a result of mandibular fracture, submandibular sialadenitis, peritonsillar abscess, epiglottitis and oral malignancies. Microbiology Causative bacteria include many gram-negative and anaerobic organisms, streptococci and staphylococci. The bacterial

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isolates vary and are often mixed. Alpha-hemolytic streptococci, staphylococci and Bacteroides are commonly reported. Other anaerobes such as peptostreptococci, peptococci, Fusobacterium nucleatum, Veillonella species and spirochetes are also seen. A foul breath/odor usually indicates the presence of an anaerobe. Gram-negative organisms such as Neisseria catarrhalis, Escherichia coli, Pseudomonas aeruginosa and Hemophilus influenzae have also been reported.


Anatomical considerations The submandibular space is composed of two spaces separated anteriorly by the mylohyoid muscle: the sublingual space, which is superior, and the submaxillary space, which is inferior. The spread of infection is halted anteriorly by the mandible and inferiorly by the mylohyoid muscle. The infectious process expands superiorly and posteriorly, elevating the floor of the mouth and the tongue. The hyoid bone limits the process inferiorly, and swelling spreads to the anterior aspect of the neck, causing distortion and a ‘bull neck’ appearance. This then evolves to an infectious compartment syndrome of the submandibular and sublingual spaces. Investigations Conventional radiographs such as intraoral periapical radiographs or orthopantomograph (OPG) may help to identify the offending tooth. However, a contrastenhanced computed tomography (CECT) scan is helpful in assessing the extent of spaces involved. Treatment The treatment plan for each patient should be individualized and based on a number of factors. The stage of the disease and co-morbid conditions at the time of presentation and the resources available. Treatment includes assessment and protection of the airway, use of intravenous antibiotics, surgical evaluation and, if necessary, operative decompression. Intravenous dexamethasone and nebulized adrenaline have been used to reduce upper airway edema in such cases to defer or avoid airway instrumentation altogether. Distorted airway anatomy, tissue immobility, and limited access to the mouth make orotracheal intubations by direct laryngoscopy difficult. In advanced cases, induction of general anesthesia is dangerous because this may precipitate complete airway closure and make mask ventilation and intubation impossible. Securing of the airway in the awake state is therefore the safest option. Blind nasal intubation is to be avoided as, besides having a high failure rate, it could cause catastrophic bleeding, laryngospasm, airway edema, rupture of pus into the oral cavity and aspiration. Complete airway obstruction could be precipitated, potentially necessitating an emergency cricothyrotomy. Classically, tracheostomy was considered as the standard of care for establishment of a definitive airway. Elective awake tracheostomy has been suggested for all patients with deep neck infections to avoid the dangers of emergency tracheostomy in a severely compromised airway.

Endotracheal intubation is associated with high rate of failure with acute deterioration in respiratory status resulting in emergency ‘slash’ tracheostomy. Although distorted anatomy, edema, and secretions may contribute to difficulty with fiberoptic intubation, in skilled and experienced hands, flexible fiberoptic nasal intubation is the preferred method of airway management and has a high rate of success. Application of topical anesthesia enables the patient to tolerate the procedure with greater comfort. When fiberoptic bronchoscopy is not feasible, not available, or has failed, cricothyrotomy and tracheostomy are the options. Tracheostomy may be difficult or impossible in advanced cases of neck infection because of the position needed for the procedure and anatomical distortion of the anterior neck. The choice of airway maneuvers must be individualized, depending on the judgment and experience of the physician in charge. Recommended initial antibiotics are high-dose penicillin G, sometimes used in combination with an antistaphylococcal drug or metronidazole. In penicillin-allergic patients, clindamycin hydrochloride is a good choice. Alternative choices include cefoxitin sodium or combination drugs such as ticarcillin–clavulanate, piperacillin– tazobactam or amoxicillin–clavulanate (Augmentin). Intravenous dexamethasone sodium phosphate (Decadron), given for 48 hours, has been beneficial in reducing edema, which helps maintain airway integrity and enhances antibiotic penetration. Dexamethasone reduces edema and cellulitis, provides the initial chemical decompression protecting the airway and allows improved antibiotic penetration into the area. Surgical drainage may be indicated if no clinical improvement is seen within 24 hours.

OSTEOMYELITIS By strict definition, osteomyelitis is the inflammation of medullary portion of bone. However, clinical evidence has shown that it is seldom limited to the endosteum and it usually affects the cortical plates and the periosteum. Considering the extent of the bone involvement, osteomyelitis may best be described as an inflammatory condition of bone that usually begins as an infection of the medullary cavity which rapidly involves the haversian system and quickly extends to the periosteum of the area. Osteomyelitis can be broadly categorized as exogenous osteomyelitis (47%), osteomyelitis secondary to vascular insufficiency (34%) and hematogeneous osteomyelitis (19%). The implantation of pins, plates, screws, dental implant and artificial joint can also seed infection as a nidus for pathogens, and therefore create postoperative osteomyelitis.

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Predisposing factors Conditions affecting host resistance Systemic, metabolically compromised individuals (factors such as age of patient, malnutrition, immunosuppression and congenital or acquired pathophysiology disrupting microvascular perfusion of the calcified tissue structure and investing soft tissue envelope). Examples include diabetes, AIDS, use of steroids, agranulocytosis, leukemia, severe anemia and cancer chemotherapy. Conditions affecting jaw vascularity Conditions that affect the vascularity of the jaw bones include radiation, bone malignancy, osteoporosis, osteopetrosis, Paget’s disease of bone, fibrous dysplasia and bone necrosis (mercury, bismuth, arsenic poisoning, long-term chemotherapeutic agents like bisphosphonates).

either of the two major events: extension of a periapical abscess, periodontal abscess or post-traumatic/post-surgical complication. Naidu et al (2008) reported a case of osteomyelitis of the mandibular symphysis caused by bite of a brown recluse spider. Other predisposing conditions include bony pathologies such as Paget’s disease and osteopetrosis, compound fractures, history of local irradiation, host-debilitating conditions such as diabetes mellitus and long-term systemic steroid therapy. The mandible is more prone osteomyelitis compared to other craniofacial bones due to its morphological characteristics such as a relatively thin cortical plate and poor vascular supply to its medullary portion. The regions in the mandible that are at higher risk of perforation include the lingual aspect of molar teeth and in the labial aspect of anterior teeth (Thadepalli and Mandal, 1988).

Microbiology of osteomyelitis Microorganisms specific for different age groups (Osteomyelitis of other bones) Newborns (younger than 4 months): S. aureus, Enterobacter species, and group A and B Streptococcus species. Children (aged 4 months to 4 years): S. aureus, group A Streptococcus species, Hemophilus influenzae, and Enterobacter species. Children, adolescents (aged 4 years to adult): S. aureus (80%), group A Streptococcus species, H. influenzae, and Enterobacter species. Adult: S. aureus and occasionally Enterobacter or Streptococcus species. Osteomyelitis of jaw bones The microorganisms responsible for osteomyelitis affecting the jaw bones reflect the polymicrobial nature of odontogenic infections in general and agents associated with suppurative infection and periapical abscesses in specific. Fusobacterium nucleatum, Prevotella intermedia, Peptostreptococcus, Actinomyces and Streptococcus species (alpha hemolytic) are the predominant isolates from osteomyelitis affecting the jaws. Hosts who have serious underlying illnesses may exhibit the presence of facultative gram-negative bacilli and S. aureus. Mycobacterium tuberculosis, Treponema pallidum and Actinomyeces spp. produce specific forms of osteomyelitis. Tubercular osteomyelitis of the spine is referred to as Pott’s disease. Burkholderia cepacia complex have been implicated in vertebral osteomyelitis in intravenous drug abusers. Systemic mycotic (fungal) infections may also cause osteomyelitis. The two most common pathogens involved in such infections are Blastomyces dermatitidis and Coccidioides immitis. Osteomyelitis of jaw bones Osteomyelitis of the mandible occurs primarily from odontogenic infection caused by 432

Pathogenesis With the initiation of the infection, the intramedullary pressure increases substantially, compromising the vascularity, thus heralding the beginning of a stage of bony necrosis. The purulent material traverses networks of Haversian and perforating canals, eventually accumulating under the periosteum and lifting it from the bony cortex. As the pus accumulates, periosteal perforation can occur ultimately forming abscesses and often fistulous tracts within mucosal and cutaneous tissues. In chronic cases granulation tissue, dead bone (sequestrum) separated from surrounding healthy tissue, and eventually, a reactive sleeve of new periosteal tissue (involucrum) formation may also be seen.

Classification of Osteomyelitis Waldvogel classification system for osteomyelitis ❍ ❍

Hematogeneous osteomyelitis Osteomyelitis secondary to contiguous focus of infection – No generalized vascular disease – Generalized vascular disease ❍ Chronic osteomyelitis (necrotic bone).

Cierny–Mader staging system for osteomyelitis Anatomic type Stage 1: Medullary osteomyelitis—involved medullar bone without cortical involvement; usually hematogeneous Stage 2: Superficial osteomyelitis—less than 2 cm bony defect without cancellous bone


Stage 3: Localized osteomyelitis—less than 2 cm bony defect on radiograph, defect does not appear to involve both the cortices Stage 4: Diffuse osteomyelitis—defect more than 2 cm, pathologic fracture, infection, nonunion. Physiologic class A host: Healthy B host – Bs: Systemic compromise – Bl: Local compromise – Bls: Local and systemic compromise ❍ C host: Treatment worse than the disease. ❍ ❍

Factors affecting immune surveillance, metabolism and local vascularity are: ❍

Systemic factors (Bs): Malnutrition, renal or hepatic failure, diabetes mellitus, chronic hypoxia, immune disease, extremes of age, immunosuppression or immune deficiency. ❍ Local factors (Bl): Chronic lymphedema, venous stasis, major vessel compromise, arteritis, extensive scarring, radiation fibrosis, small-vessel disease, neuropathy, tobacco abuse. Classification based on the clinical course and radiographic features Suppurative osteomyelitis Acute suppurative osteomyelitis Chronic suppurative osteomyelitis Primary (no preceding acute phase) Secondary (follows acute phase) Infantile osteomyelitis.

❍ ❍ ❍ ❍ ❍

Non-suppurative osteomyelitis ❍ Focal sclerosing osteomyelitis (condensing osteitis) ❍ Diffuse sclerosing osteomyelitis ❍ Proliferative periostitis (periostitis ossificans) ❍ Osteoradionecrosis. Clinical features Osteomyelitis may be acute, subacute or chronic, and presents a different clinical course depending on its nature.

Acute Suppurative Osteomyelitis In maxilla, the disease usually remains fairly well localized to the area of infection. In mandible, bone involvement tends to be more diffuse and widespread. It may occur at any age. Infants affected are seriously ill and may not survive. In adults, there is severe pain and elevation of temperature with regional lymphadenopathy. The skin overlying the

affected bone is warm, erythematous and tender on palpation. Patients complain of fever, malaise and anorexia. Teeth in the area of involvement are loose and tender on percussion. Pus discharge may be present around the sulcus of the tooth (Figure 33A, B). Patients may complain of a fetid odor. Paresthesia and anesthesia of lip is seen. The WBC count is elevated. If the acute phase is not controlled within 10–14 days after onset then subacute suppurative osteomyelitis is established. Radiographic features Generally, no radiographic findings are associated with acute osteomyelitis. A minimum of 40% demineralization of bone is required to be evident. Radiographic evidence of acute osteomyelitis may be detected at least 4–14 days after onset of acute osteomyelitis. The full extent of bone dissolution may be evident 3 weeks after the initial attack. The radiographic features always lag behind the actual progress of the condition. Bony trabeculae appear indistinct and fuzzy. The initial radiolucent areas appear as ‘moth-eaten’ regions with ill-defined margins. Histopathologic features Histologic sections show medullary spaces filled with inflammatory exudate, chiefly composed of neutrophils. Other cells that are seen include lymphocytes and plasma cells. Osteoblasts bordering the bony trabeculae are generally destroyed, leading to loss of trabecular viability and slow resorption of the bone. Management High dose intravenous antibiotic therapy, identification and correction of host compromise factors is required. Careful enquiry and investigation may reveal diabetes, autoimmune disease, alcohol-starvation syndrome, intravenous drug abuse, severe anemia, HIV, steroid, chemotherapy. Factors that delay recovery should be identified and corrected. Initial management is often aided by hospitalization. Once the infection is controlled treatment is continued on an outpatient basis using home intravenous therapy with percutaneous indwelling catheter and antibiotic pumps. Specimens should be obtained for Gram staining, aerobic and anaerobic cultures and antibiotic sensitivity testing. Conventional radiographs and bone scans should be obtained to determine the extent of the disease and causative factors such as fractures and presence of sequestra. Once the acute stage has resolved with antibiotics, other procedures like sequestrectomy, debridement, direct placement of antibiotics into the wound by means of indwelling catheters or antibiotic impregnated beads, hyperbaric oxygen therapy, decortication, resection of infected bone and immediate or late bone graft reconstruction. 433


Figure 33 A

B

Intraoral sinus opening and diffusely enlarged gingiva associated with acute osteomyelitis. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Antibiotic therapy Antibiotics of value in the treatment of osteomyelitis are penicillins, extended spectrum penicillin, semisynthetic penicillins, clindamycin, cephalosporins and metronidazole. Many organisms responsible for osteomyelitis are now penicillin resistant, including prevotella, porphyromonas and fusobacterium. Therefore, a drug resistant to these organisms such as metronidazole should be added to penicillin. Some of the newer antibiotics providing effective coverage for the more refractory organisms include metronidazole, clindamycin, ticarcillin and clavulanic acid, a variety of cephalosporins, carbapenems, vancomycin in combination with other antibiotics and fluoroquinolones such as ciprofloxacin.

Penicillin V, 2 g, in combination with metronidazole, 0.5 g q8h PO, for 2–4 weeks after last sequestrum removed and patient without symptoms. Or Clindamycin, 600–900 mg q6h IV, then clindamycin, 300–400 mg q6h PO. Or Cefoxitin (mefoxin), 1 g q8h IV or 2 g q4h IM or IV, until no symptoms, then switch to cephalexin, 500 mg q6h PO, for 2–4 weeks for penicillin allergic patients clindamycin (as above) cefoxitin (as above), if allergy not of anaphylactoid type.

Antibiotic regimen for osteomyelitis of jaw Regimen 1: For hospitalized/medically compromised patient or when intravenous therapy is indicated. Aqueous penicillin, 2 million units IV q4h, in combination with metronidazole 500 mg q6h. When improved for 48–72 hours switch to penicillin V, 500 mg per oral q4h, in combination with metronidazole 500 mg PO q6h, for an additional 4–6 weeks. Or Ampicilin/sulbactam, 1.5–3 g IV q6h when improved for 48–72 hours, switch to amoxicillin/clavulanate (augmentin), 875/125 mg per oral b.i.d., for an additional 4–6 weeks. Regimen 2: For outpatient treatment.

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Chronic Suppurative Osteomyelitis This may develop after the acute phase of the disease has regressed, or sometimes can occur without a preceding acute phase. Clinical features are similar to that of the acute type, except that all signs and symptoms are milder. Pain is less severe. Temperature is mildly elevated. Teeth may tend to become loose and occasionally tender on palpation. Acute exacerbation may occur periodically. Intraoral or extraoral draining fistulas may be seen (Figure 34). The cortical plates may be expanded and in severe cases pathological fracture may be evident. The bone is thickened and assumes a ‘wooden’ character on palpation (Figure 35). Leukocytosis is slightly more than the normal.


Figure 34

Figure 35

Extraoral draining sinus in chronic suppurative osteomyelitis. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Extraoral swelling in chronic suppurative osteomyelitis. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 36 A

B

Radiographs showing ill-defined radiolucent areas with moth-eaten appearance characteristic of chronic suppurative osteomyelitis. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Histologic features The typical histological picture shows intertrabecular areas of bone filled with chronically or subacutely inflamed fibrous connective tissue. Presence of scattered sequestra and pockets of abscess are common.

extending to involve the lower border of the mandible in severe cases (Figure 36A, B). Evidence of sequestrum/ involucrum may be found. Extensive destruction of the bone may cause pathologic fracture. Management

Radiographic features Radiographs will reveal a poorly defined radiolucency (moth-eaten appearance) within the body of the mandible

After intraoral debridement, saucerization or decortication, small pediatric nasogastric feeding tubes, French catheters, or polyethylene irrigation tubes 3–4 mm in diameter and

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6–10 inches long are placed into the bone bed through separate skin incisions along the lateral bony surface through holes drilled into bone. These drains are held to the skin with sutures or tape. Alternatively, two tubes may exit from one stab incision or a single tube may be used for instillation and suction. The tubes are flushed with saline solution and the irrigation solution is introduced through one tube while the other tube is connected to low pressure suction. Various irrigating solutions can be used often containing antibiotics, wetting agents and proteolytic enzymes. Antibiotics in high concentration also may be placed in direct contact with the bone manually or with an implantable pump. Tobramycin or gentamicin is contained in acrylic resin bone cement beads. Impregnated chains of beads are useful, especially in chronically infected bone associated with fractures and in chronic sclerosing osteomyelitis refractory to systemic antibiotics. The beads and drain are left in place 10–14 days and then removed through a small incision. Hyperbaric oxygen (HBO) therapy has been used to promote healing in refractory chronic osteomyelitis. In the acute stage, surgery should be limited to removal of severely loose teeth and bone fragments and incision, drainage of fluctuant areas. Deeply located or extensive abscesses may require treatment with the patient under general anesthesia. Sequestrectomy Sequestra can be cortical, cancellous or cortical-cancellous and generally are not seen until at least 2 weeks after the onset of infection. These can persist for several months. In the chronic state, the involucrum or shell of bone produced by the periosteum may be perforated by tracts (cloacae) through which the pus escapes to epithelial surfaces. Sequestra are avascular, so are poorly penetrated by antibiotics. Once the sequestra are formed, they can be removed with a minimum of surgical trauma. Saucerization Saucerization is the unroofing of the bone to expose the medullary cavity for thorough debridement. Saucerization is useful in chronic osteomyelitis because it permits removal of formed and forming sequestra. The procedure can be done after resolution of the acute phase. This decompresses the bone to allow ready extrusion of pus, debris and avascular fragments. The patient is more comfortable. Decortication This refers to removal of chronically infected cortex of bone. Once the disease is in its subacute or chronic stage, use of decortication promotes resolution based on the premise that the affected bone is avascular and harbors microorganisms. This can be used as initial treatment of primary and secondary chronic osteomyelitis, or when initial regimens have failed. Resection and reconstruction Resection of osteomyelitic area with immediate or delayed reconstruction may be 436

necessary to resolve low-grade persistent chronic osteomyelitis. Using an extraoral approach bone is debrided until bleeding surfaces are encountered distally and proximally. Single or multiple blocks of autologous corticocancellous bone grafts are placed for immediate reconstruction.

Infantile Osteomyelitis Infantile osteomyelitis usually occurs few weeks after birth and generally involves the maxilla. This uncommon condition involves risks with ocular, intracranial spread and facial deformities. It is believed to occur by hematogeneous route or from perinatal trauma. Generalized symptoms include fever, irritability, malaise, anorexia, dehydration and even convulsions and vomiting. Facial cellulitis is seen centered about the orbit associated with inner and outer canthal swelling, palpebral edema, closure of the eye and proptosis. Purulent discharge from the nose and the medial canthus may be evident.

Chronic Focal Sclerosing Osteomyelitis (Condensing Osteomyelitis or Osteitis) Condensing osteitis is a focal sclerosing form of osteomyelitis that occurs in very mild infection (microorganisms of low virulence) or when the host immunity is at its peak. The bone reacts unusually to infection by laying down bone rather than getting destructed. In individuals with high tissue resistance, the infection acts as a stimulant thereby resulting in proliferation of the tissue. Clinical and radiographic features Condensing osteitis is generally seen in young adults. The mandibular first molars are most commonly affected. The tooth in question presents with a deep carious lesion. Patients may either present with mild pain or may occasionally be asymptomatic. Radiographic evaluation will reveal a deep carious lesion approximating pulp with a well-defined radiopacity at the periapex of one or more roots. The root outline is usually sharply defined and visible. The boundaries of the periapical radiopacity may appear well circumscribed or occasionally blend with the surrounding bone. Management As condensing osteitis is an extension of pulpal infection beyond the periapex of the tooth, endodontic treatment or extraction is the only treatment option. Eliasson et al (1984) studied the effectiveness of endodontic treatment for periapical condensing osteitis on


49 roots of 36 teeth. These patients were followed up by means of radiographs and patient files after endodontic treatment for a mean observation period of 4.3 years. Their study showed that there was total regression of periapical condensing osteitis on 36 of the 49 roots. No condensing osteitis showed progress. They concluded that there was rebuilding of bone structures to normal appearance after endodontic treatment of periapical condensing osteitis. Following extraction of the affected tooth the residual dense bone may be remodeled. However, on occasions, this residual sclerotic bone may remain unaltered for many years and referred to as a ‘bone scar’.

Chronic Diffuse Sclerosing Osteomyelitis The diffuse form of sclerosing osteomyelitis is also a proliferative response to a generalized form of mild infection. However, a distinct difference between the diffuse form and the focal form is that the former occurs due to an extension of a diffuse periodontal disease. Clinical features The diffuse sclerosing form may occur at any age. However, it is usually seen in edentulous areas of the mandible in elderly individuals. The disease progresses in an insidious manner and seldom presents clinical signs and symptoms. The chronic phase of the condition may exhibit periods of acute exacerbation that manifests as vague pain, bad taste, minimal suppuration and fistulous tracts that may open intraorally. This may occur at any age, but is most common in older persons, especially in edentulous areas. The disease is often of an insidious nature so usually presents no clinical features. In case of acute exacerbation there can be mild suppuration, many times with fistulous opening. In such cases, there can be vague pain and bad taste in the mouth. Montonen et al (2006) conducted an immunohistopathological study of diffuse sclerosing osteomyelitis in the clinically acute and subacute phases and compared it with healthy bone. They found that the receptor activator of nuclear factor kappa B ligand (RANKL) was found in the lesions of diffuse sclerosing osteomyelitis. They also observed that the periods of acute exacerbations were characterized by RANKL and induction of cathepsin K in mononuclear precursor cells, which subsequently seemed to differentiate into osteoclasts or foreign body giant cells. The proportion of bone to soft tissue increased with the duration of disease. They concluded that RANKL-driven osteoclastogenesis and acidic cysteine endoproteinase cathepsin K seemed to play important roles in diffuse sclerosing osteomyelitis as osteoclast-mediated bone resorption may represent the primary disease process later followed by new bone formation.

Radiographic features Radiographs reveal diffuse sclerotic patchy ‘cotton-wool’ appearance of bone. Extensive involvement of the mandible bilaterally and occasionally the maxilla and mandible may be affected. The borders of the patchy sclerosis are diffuse and cannot be differentiated from the surrounding normal bone (Figure 37). Management Owing to the extensive bone involvement surgical management is not indicated. In some patients the resolution of the causative periodontal disease results in improvement of this condition. However, antibiotics have been employed to combat periods of acute exacerbations.

Periostitis Ossificans (Chronic Osteomyelitis with Proliferative Periostitis) Wood et al (1988) in their two part series of articles titled ‘Periostitis ossificans versus Garrè’s osteomyelitis. Part I. What did Garrè really say?’ and ‘Periostitis ossificans versus Garrè’s osteomyelitis. Part II. Radiologic analysis of 93 cases in the jaws’, described their opinions and observations on the use of the terms Garrè’s osteomyelitis and periostitis ossificans. 1.

2.

3.

4.

The name ‘Garrè’ is correctly written as Garrè and not Garré as mentioned in many textbooks and articles in scientific literature. Garrè did not describe the typical radiologic, histologic and bacteriologic features if acute osteomyelitis since these investigative aids were not available to him (X-rays were discovered by Röntgen only 2 years after Garrè published his article in 1893. Chronic sclerosing osteomyelitis was never really outlined by Garrè. He described recalcitrant osteomyelitis, which was essentially untreatable at that time. The term Garrè’s osteomyelitis should not be used.

Gorman is given the credit for using the term periostitis ossificans in 1951 to describe a productive inflammatory condition of the mandibular periosteum. Lovemann (1941) was probably the first to recognize the condition. Tong et al (2006) reported a case of osteomyelitis with proliferative periostitis. The authors believe that the term chronic osteomyelitis with proliferative periostitis is the most accurate description of periostitis ossificans. Nortjé et al (1988) conducted a radiological analysis of 93 cases of periostitis ossificans occurring in the jaws. In their study, the age at initial consultation ranged from 2 to 69 years with a mean of 13.3 years. Males were more commonly affected than females (1.27:1). The causes for periostitis ossificans were due to periapical lesions 437


Figure 37

Orthopantomograph showing diffuse sclerosis of the mandible giving rise to cotton-wool appearance. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

secondary to dental caries, untreated fractures and primary tuberculosis of the mandible. Two patients in their study had lateral inflammatory odontogenic cysts. The mandibular left first molar was most commonly involved. The other sites involved were mandibular second molar, mandibular premolar, mandibular primary second molar, angle of the mandible, mandibular third molar and maxillary premolar. The periosteal reaction was visible at the buccal, lingual and inferior aspects of the mandibular body. The authors also reported of periosteal reaction occurring in the maxilla and sigmoid notch. In their study, the number of the periosteal laminations ranged from 1 to 12. The size of most of the sequestra ranged from 1 to 2 mm. Larger sequestra were seen in patients with infected fractures. The size of the sequestra was age dependent with smaller sequestra present in younger patients (Figure 38). In about 63% of their patients, follicles of unerupted teeth adjacent to the site of periostitis showed destruction. Other changes that were noted included supraeruption of teeth, bodily movement of unerupted tooth bud and widening of the periodontal ligament space of the teeth inciting the infection and occasionally of the adjacent vital teeth. The periosteal reaction can either occur as long, narrow periosteal reaction (common in adults) or fusiform, short and wide periosteal reaction (seen in children). When X-ray beams interact with successive layers of periosteal new bone on the buccal cortical plate, they get attenuated and the resultant image will show a patchy or granular radiopacity in the body of the mandible on lateral projections (Figure 39A, B). Periostitis occurring in the maxilla has been referred to as ‘halo-shadow’, which results from periosteal stripping and subsequent bone formation in the floor of the maxillary sinus related to a first molar tooth. 438

Figure 38

Illustration showing formation of periosteal new bone

Radiographic investigations Nortjé et al (1988) recommended the use of lateral oblique and panoramic radiographs (lateral radiographs) to demonstrate the periosteal reaction. If the periosteal reaction is not evident on lateral radiographs, occlusal radiographs have to


Figure 39

Periosteal new bone

X-rays

Patchy radiopacity

Illustration showing the appearance of granular radiopacity in the body of the mandible on lateral projections

Figure 40

been noted. Although the incidence appears to be low (0.2–1.5%) the occurrence of neoplastic disease considerably complicates the resolution of inflammatory process. There can be surgically induced discontinuity defects, necessitating jaw reconstruction. Anachorectic pulpitis Bacterial infection of an intact pulp is referred to as anachorectic pulpitis. It is suggested that the bacteria in the circulation may tend to affect inflamed pulp. The tooth in question is not necessarily carious. Focal reversible pulpitis or pulp hyperemia It is a reversible, transient pulpitis caused due to irritation of the pulpal terminal of the dentinal tubules upon application of thermal stimulus (especially cold stimulus). However, the pain subsides on removal of the irritant. Chronic hyperplastic pulpitis

Pulp polyp. Courtesy: Department of Oral Medicine and Radiology. KLE Society’s Institute of Dental Sciences, Bangalore

be employed. The authors suggest that the posteroanterior view of the mandible is occasionally the only radiograph that will adequately show the periosteal reaction. Complications of osteomyelitis With chronic osteomyelitis, neoplastic conversion of inflammatory metaplasia to squamous cell carcinoma has

It is an excessive exuberant proliferation of a longstanding inflamed dental pulp. Usually affects teeth with large carious lesions. Commonly seen in children and young adults and often associated with the primary or permanent first molars. Clinically it appears as red to pink mass of tissue protruding from the pulp into the large open cavity of the carious tooth (Figure 40). There can be progressive, diffuse sclerosis of the medullary and cortical portions of the maxillofacial skeleton, especially mandible, over time.

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CHAPTER

16

Gingival and Periodontal Diseases Praveen BN, Jeeth Rai, Francisco Lopez Sanchez

➧ Classification System in Periodontal Disease ➧

Plaque Microbiology Organisms in Various Periodontal Diseases ➧

➧

Periodontal diseases range from simple and early inflammation of marginal gingiva to advanced gingivitis and subsequently periodontitis. A good classification system is crucial in identifying and differentiating the various kinds of periodontal diseases. Periodontal disease classification is useful to help establish diagnosis, determine prognosis and facilitate treatment planning. Different classification systems of periodontal diseases have been used for years and also replaced by newer classification systems as the knowledge of understanding microbiology, etiology, pathogenesis and host response have improved vastly over the past few decades. Currently, the most accepted classification is the ‘1999 World Workshop Classification System’.

CLASSIFICATION SYSTEM IN PERIODONTAL DISEASE The classification is based on the 1999 International Workshop for Periodontal Disease.

Periodontal Diseases Local Contributing Factors Iatrogenic Factors

Host–Microbial Interaction Defense Mechanism Plaque-induced Gingivitis Non-plaque-induced Gingivitis Gingival Diseases Associated with Medications Gingival Diseases Associated with Systemic Diseases Gingival Diseases Associated with Malnutrition Gingival Diseases Associated with Heredity Gingival Diseases Associated with Ulcerative Lesions Gingival Lesions Manifested in Childhood Diseases Gingival Lesions Associated with Chicken Pox

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Gingival Lesions Associated with Mononucleosis Acute Inflammatory Gingival Enlargement Gingival Changes Associated with Tooth Eruption

Gingival Diseases

➧

Syndromes Hormonal Factors

➧

Sex Hormones

➧

Stress and Psychosomatic Factors

➧

Nutritional Factors Effects of Vitamin Deficiency

➧

Radiographic Evaluation of Periodontal Diseases

I. Gingival diseases A. Dental plaque-induced gingival diseases: These diseases may occur on a periodontium with no attachment loss or on one with attachment loss that is stable and not progressing. 1. Gingivitis associated with dental plaque only a. Without local contributing factors b. With local contributing factors 2. Gingival diseases modified by systemic factors a. Associated with endocrine system i. Puberty-associated gingivitis ii. Menstrual cycle-associated gingivitis iii. Pregnancy-associated gingivitis and pyogenic granuloma iv. Diabetes mellitus-associated gingivitis b. Associated with blood dyscrasias i. Leukemia-associated gingivitis ii. Others 3. Gingival diseases modified by medications a. Drug-influenced gingival diseases b. Drug-influenced enlargements c. Drug-influenced gingivitis

Chapter 16 – Gingival and Periodontal Diseases

B.

d. Oral contraceptive-associated gingivitis e. Others 4. Gingival diseases modified by malnutrition a. Ascorbic acid deficiency gingivitis b. Others Non-plaque-induced gingival lesions 1. Gingival diseases of specific bacterial origin a. Neisseria gonorrhoeae b. Treponema pallidum c. Streptococcal species d. Others 2. Gingival diseases of viral origin a. Herpes virus infections i. Primary herpetic gingivostomatitis ii. Recurrent oral herpes iii. Varicella zoster b. Others 3. Gingival diseases of fungal origin a. Candida species infections—generalized gingival candidiasis b. Linear gingival erythema (LGE) c. Histoplasmosis d. Others 4. Gingival lesions of genetic origin a. Hereditary gingival fibromatosis b. Others 5. Gingival manifestations of systemic conditions a. Mucocutaneous lesions i. Lichen planus • Pemphigoid • Pemphigus vulgaris • Erythema multiforme • Lupus erythematosus • Drug-induced • Others b. Allergic reactions i. Dental restorative materials • Mercury • Nickel • Acrylic • Others ii. Reactions attributed to • Toothpastes or dentifrices • Mouthrinses or mouthwashes • Chewing gum additives • Foods and additives iii. Others 6. Traumatic lesions (factitious, iatrogenic or accidental) a. Chemical injury b. Physical injury c. Thermal injury 7. Foreign body reactions 8. Not otherwise specified

II.

Chronic periodontitis A. Localized (less than 30% of sites involved) B. Generalized (more than 30% of sites involved) C. Slight (1–2 mm clinical attachment loss) D. Moderate (3–4 mm clinical attachment loss) E. Severe (more than 5 mm clinical attachment loss)

III. Aggressive periodontitis A. Localized—slight, moderate or severe B. Generalized IV. Periodontitis as a manifestation of systemic diseases A. Associated with hematological disorders 1. Acquired neutropenia 2. Leukemias 3. Others B. Associated with genetic disorders 1. Familial and cyclic neutropenia 2. Down’s syndrome 3. Leukocyte adhesion deficiency syndromes 4. Papillon–Lefevre syndrome 5. Chediak–Higashi syndrome 6. Histocytosis syndrome 7. Glycogen storage disease 8. Infantile genetic agranulocytosis 9. Cohen syndrome 10. Ehlers–Danlos syndrome (types IV and VIII) 11. Hypophosphatasia 12. Others V.

Necrotizing periodontal diseases A. Necrotizing ulcerative gingivitis (NUG) B. Necrotizing ulcerative periodontitis (NUP)

VI. Abscess of the periodontium A. Gingival abscess B. Periodontal abscess C. Pericoronal abscess VII. Periodontitis associated with endodontic lesions A. Combined periodontic–endodontic lesions VIII. Developmental or acquired deformities and conditions A. Localized tooth-related factors that modify or predispose to plaque-induced gingival diseases/ periodontitis i. Tooth anatomic factors ii. Dental restorations/appliances iii. Root fractures iv. Cervical root resorption and cemental rear B. Mucogingival deformities and conditions around teeth i. Gingival/soft tissue recession, facial or lingual surfaces, interproximal (papillary) ii. Lack of keratinized gingiva iii. Decreased vestibular depth iv. Aberrant frenum/muscle position

441


v. Gingival excess • Pseudopocket • Inconsistent gingival display • Excessive gingival display • Gingival enlargement vi. Abnormal color C. Mucogingival deformities and conditions on edentulous ridges i. Vertical and/or horizontal ridge deficiency ii. Lack of gingival/keratinized tissue iii. Gingival/soft tissue enlargement iv. Aberrant frenum/muscle position v. Decreased vestibular depth vi. Abnormal color D. Occlusal trauma i. Primary occlusal trauma. The current classification has many changes seen which is drastically different from the previous classifications. The most noticeable change is that periodontitis is now classified based on the rate of progression of the disease and not on the age of onset. Adult periodontitis–chronic periodontitis The term ‘adult periodontitis’ is discarded since this form of periodontitis is seen in wide range of ages and found both in primary and permanent dentitions. Hence, the term ‘chronic periodontitis’ was chosen because it does not reflect the age of individual rather reflects the rate of progression of periodontal disease, which is slow in nature. Early onset forms of periodontitis–aggressive periodontitis The term ‘early onset periodontitis’ has been discarded as this form of periodontitis is seen in various ages and in older individuals too. Thus, the term ‘aggressive periodontitis’ was chosen. Progressive periodontal disease can be either localized or generalized. The term ‘localized aggressive periodontitis’ replaces localized juvenile or localized early onset periodontitis. The term ‘generalized aggressive periodontitis’ replaces generalized juvenile or generalized early onset periodontitis. The term ‘pre-pubertal periodontitis’ has been discarded and is currently described as localized or generalized periodontitis or periodontitis as manifestations of systemic disease.

Necrotizing forms of periodontitis Necrotizing ulcerative gingivitis (NUG) and NUP are now collectively referred to as ‘necrotizing periodontal disease’. NUG and NUP are different stages of same infection and should not be classified as separate disease entities.

GINGIVAL DISEASES Increasing evidence indicates that gingivitis is not a single disease, but an assortment of diseases that are the end result of a variety of different processes. Inflammation of gingiva by bacteria is most common, but pathological changes in the gingiva can also result from systemic conditions (e.g. puberty), drugs (e.g. amlodipine) and neoplasms (e.g. leukemia). Hence, any disease that primarily affects gingival tissues should be primarily classified as a gingival disease. The gingival diseases associated with children, adolescents and young adults have several common characteristics. Universal features include clinical signs of inflammation, signs and symptoms that are confined to the gingiva, reversibility of the disease on removal of the etiology, and the presence of microbial plaque to initiate or exacerbate the severity of the lesion.

Plaque Microbiology Oral cavity can be regarded as a single microbial ecosystem or macroenvironment because the colonization of oral cavity starts at the time of birth. Within hours of birth the sterile oral cavity gets colonized by facultative and aerobic bacteria, which will be followed by anaerobic bacteria by 2nd day. By 2 years of age there will be around 400 different kinds of bacteria. After tooth eruption, a more complex oral flora is established. However, all these species are seen to be living in harmony with the host. But, however, there is an imbalance in this relationship between the host and microorganisms, disease prevails which is controlled by various other factors. Oral environment is dominated with saliva, which is very complex in composition. Although saliva is not a good medium for supporting the growth of bacteria, it is likely that organisms shed from intraoral reservoirs find transient residence in saliva. Oral cavity provides two types of surfaces for colonization—soft and hard tissue (teeth)—main difference being soft tissue desquamation; hence the colonies are shed frequently whereas the hard surface provides a solid medium for the bacteria to adhere and develop complex layers.

Systemic diseases and forms of periodontitis The present classification system highlights the role of certain systemic conditions like smoking and diabetes that can modify periodontitis and that certain systemic conditions that can cause destruction of periodontium such as neutropenia and leukemias. 442

Terminology Dental plaque: Dental plaque is clinically defined as a structural resilient yellow-grayish substance that adheres tenaciously to the intraoral hard surfaces, including removable and fixed restoration.


Biofilm: Biofilm is the term that describes the relatively indescribable microbial community associated with tooth surface or any other hard non-shedding material. Materia alba: Materia alba refers to soft accumulation of bacteria and tissues cells that lack the organized structure of dental plaque and is easily displaced with a water spray.

e. f. 5.

Generalized aggressive a. F. nucleatum b. Lactobacillus c. Eubacterium d. A. naeslundii e. A. actinomycetemcomitans B. forsythus P. gingivalis Campylobacter

6.

NUG/NUP a. P. intermedia b. Fusobacterium c. F. nucleatum d. P. gingivalis

7.

Periodontal abscess a. F. nucleatum b. P. micros c. P. intermedia d. P. gingivalis e. B. forsythus.

Formation of plaque It is a complex procedure initially involving the formation of pellicle (glycoprotein, phosphoproteins) around the tooth surface. Then the early bacterial colonization takes place with facultative aerobic gram-positive organisms. Some of the early colonizers are Actinomyces and Streptococcus sanguis which adhere to the pellicle through adhesins. Later plaque maturation takes place with co-aggregation of secondary colonizers including Fusobacterium nucleatum, Prevotella intermedia, Porphyromonas gingivalis, Capnocytophaga, etc. Thus in maturation of plaque there is a transition from the early aerobic gram-positive facultative species to an anaerobic gram-negative species.

Organisms in Various Periodontal Diseases 1.

Periodontal health a. Streptococcus b. Actinomyces c. Veillonella d. Fusobacterium

2.

Gingivitis a. Streptococcus b. Actinomyces c. Peptostreptococcus d. Eubacterium e. Capnocytophaga f. Fusobacterium g. Veillonella

3.

Chronic periodontitis a. Streptococcus b. Peptostreptococcus c. Eubacterium d. Actinomyces e. Lactobacillus f. P. gingivalis g. Campylobacter rectus h. F. nucleatum i. Selenomonas j. Actinobacillus actinomycetemcomitans k. Eikenella corrodens

4.

Localized aggressive a. A. actinomycetemcomitans b. Eubacterium c. A. naeslundii d. F. nucleatum

C. rectus Veillonella

HOST–MICROBIAL INTERACTION Health is not a static condition, it is a dynamic state in which the living and functioning individuals remain in balance with a constantly changing environment. These changes in environment also cause changes in tissue activity so that normal function can continue, a process known as homeostasis. If the environmental changes over-ride this homeostasis, the normal function cannot continue and this change is termed as disease.

Defense Mechanism These protect the body from attack from microorganisms and can be classified as: ❍ ❍

Non-specific mechanism Specific mechanism.

Non-specific mechanisms ❍ ❍ ❍ ❍ ❍

Bacterial balances Surface integrity Surface fluid and enzymes Inflammatory reaction Neutrophil and macrophage activity.

Specific mechanisms ❍ ❍

T-cell response (cell-mediated immune system) B-cell response (antibody-mediated immune system). 443


Plaque bacteria produce a number of factors (virulence factor), which causes disease directly, or individually by stimulating the immune and inflammatory system. It is now known that individuals prone to periodontal disease have an aberrant immune inflammatory response to plaque which is genetically determined. ❍

Direct effects of bacteria A. Evasion of host defense i. Direct damage to polymorphonuclear leukocytes (PMNs) and macrophages ii. Reduced PMN chemotaxis iii. Degradation of immunoglobulins iii. Modulation of cytokine function iv. Degradation of fibrin v. Altered lymphocyte function B. Damage to crevicular epithelium i. Production of volatile sulfur compounds C. Degradation of periodontal tissues by bacterial enzymes i. Proteolytic enzymes ii. Hydrolytic enzymes ❍ Indirect effects of bacteria i. Inflammation ii. Production of reactive oxygen species iii. Immunity iv. Production of cytokines and prostaglandins v. Production of matrix metalloproteinases (MMPs). Host modulation: Periodontal disease is multifactorial in nature as a result of interaction between plaque microorganism and host responses. Host modulation refers to the alteration/modification of host response to the microbial stimulus by the use of number of medications. The two major categories are NSAIDs and inhibition of MMPs.

Plaque-induced Gingivitis It is the inflammation of gingiva which results from the bacteria located at the gingival margin. The association of plaque with gingival inflammation made it a frequently postulated cause of gingivitis. The initial histologic changes from health to plaque-induced gingivitis may not be evident clinically (Page and Shroeder, 1976; Bimstein et al, 1985) but as gingivitis progresses, clinical signs becomes more obvious. Plaque-induced gingivitis begins at the gingival margin and can spread into the deeper gingival component. Clinical signs of gingival inflammation involve the change in color, contour, size, shape, consistency and surface texture are associated with a stable periodontium which exhibits no loss of periodontal attachment or alveolar bone. The classic clinical indicators of signs of inflammation are bleeding on probing and color change from pink/coral pink to reddish pink or erythematous gingiva. In children, gingivitis is not intense as that found in young adults with similar quantity of accumulation of dental plaque (Mattson and Goldberg, 1985). In the initial and established stages of gingivitis, dental plaque is predominantly comprised of gram-positive aerobic microorganisms including Streptococcus mitis, S. sanguis, Actinomyces viscosus, A. naeslundii and Eubacterium spp. As age advances, development and severity of gingivitis is mainly dependent on the quality of the plaque rather than the quantity and the other contributing factors like the host immune response, environmental, genetic and the behavioral factors. The common clinical signs and symptoms of gingivitis include redness, edema, bleeding on probing, tenderness and enlargement (Loe et al, 1965; Suzuki, 1988) (Figure 1). Radiographically no changes will be seen as the inflammation is confined only to the gingival sulcus. Histologic

NSAIDs Prostaglandin E2 (PGE2), a product of cyclooxygenase pathway has been shown to increase the amount of alveolar bone destruction by amplifying local inflammation. NSAIDs block COX pathway thus decreasing PGE2 synthesis. A number of NSAIDs have been used including ibuprofen, flurbiprofen, indomethacin, ketoprofen and naproxen.

Figure 1

Matrix metalloproteinases Matrix metalloproteinases are a family of proteolytic enzymes secreted by a number of cells including leukocytes, epithelial connective tissue cells whose primary function is degradation of extra-cellular matrix components. Tetracycline and other drugs of the same group show to inhibit the MMPs production from the host, primarily the neutrophil MMPs. In doing so they increase host resistance to connective tissue destruction forms of tetracycline are submicrobial dose of tetracycline/doxycycline and chemically modified tetracycline. 444

Edematous gingival margin associated with gingivitis. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore


changes include proliferation of basal junctional epithelium leading to apical and lateral cell migration, vascular dilatation and vasculitis of blood vessels adjacent to the junctional epithelium, progressive destruction of collagen fibers, cytopathologic alteration of resident fibroblasts and progressive inflammatory cell infiltrate (Page and Shroeder, 1976).

Non-plaque-induced Gingivitis Gingival diseases associated with endogenous sex steroid hormones Since the 19th century, evidence suggests that the tissues of the periodontium are modulated by androgens, estrogens and progesterone. Much of this evidence has come from observing the changes in gingival tissues during distinct endocrinologic events (puberty, menstrual cycle, pregnancy, etc.). The principal explanation for sex steroid hormoneinduced changes in the gingiva has pointed to changes of microbiota in dental plaque, immune function, vascular properties and cellular function in the gingiva. Sex steroid hormones will affect the host by influencing cellular function (in the blood vessels, the epithelium and the connective tissue) and immune function, and together with hormoneselected bacterial populations occupying the gingival sulcus, induce specific observable changes in gingival tissues (Mariotti, 1994). Puberty-associated gingivitis Puberty is not a single episode but a complex process of endocrinological events that produce changes in the physical appearance and behavior of adolescents. Average age of menarche is 12–13 years. The early onset of puberty, particularly for adolescent girls, increases the time of exposure of periodontal tissues to steroid hormones and the possibility of gingival disease. The incidence and severity of gingivitis in adolescents are influenced by a variety of factors, including plaque levels, dental caries, mouth breathing, crowding of teeth and tooth eruption (Stamm, 1986). A number of studies have demonstrated an increase in gingival inflammation in circumpubertal individuals of both sexes without a concomitant increase in plaque levels (Sutcliffe, 1972; Hefti et al, 1981). Although puberty-associated gingivitis has many of the clinical features of plaque-induced gingivitis, this disease will develop frank signs of gingival inflammation in the presence of relatively small amounts of local irritants (plaque) during the circumpubertal period.

changes in the gingiva have been observed (Muhlemann, 1948). However, the number of women who exhibit overt gingival changes fluctuating in conjunction with the menstrual cycle is small (Marriotti, 1994). The most common gingival changes involve minor signs of inflammation during ovulation. More specifically, gingival exudates have been shown to increase at least 20% during ovulation in more than three-fourths of women tested (Hugoson, 1971). Since these changes in crevicular fluid flow are not observable unless measured electronically, most young women with gingival inflammation-induced by menstrual cycle will present with a very mild form of the disease. Pregnancy-associated gingival disease Some of the most remarkable endocrine and oral alterations accompany pregnancy as a result of the rise in plasma hormone levels over several months. During human gestation, pregnancy-associated gingivitis is characterized by an increase in the prevalence and severity of gingivitis during the second and third trimesters (Loe and Silness, 1963; Hugoson, 1971). In spite of the same plaque scores, gingival inflammation is significantly higher during pregnancy than postpartum. In addition, gingival probing depths are higher and bleeding on probing or toothbrushing is increased (Miyazaki et al, 1991), and gingival crevicular fluid flow is elevated in pregnant women. Clinical features of pregnancy-associated gingivitis is similar to that of plaque-induced gingivitis, except for the propensity to develop frank signs of gingival inflammation in the presence relatively little local irritation by plaque during pregnancy. Pregnancy tumor Pregnancy-associated pyogenic granuloma or ‘pregnancy tumor’ was described over a century ago (Coles, 1874). The pregnancy-associated pyogenic granuloma ‘is not a tumor but an exaggerated inflammatory response during pregnancy to an irritation resulting in a solitary polypoid capillary hemangioma which can easily bleed on mild provocation’ (Sillis et al, 1996). These granulomas present clinically as a painless, protuberant, mushroom-like exophytic mass attached by a sessile or pedunculated base arising from the gingival margin or more commonly from an interproximal papilla. It is more common in the maxilla and may develop as early as first trimester ultimately regressing or completely disappearing following parturition (Ziskin and Nesse, 1946).

Gingival Diseases Associated with Medications Menstrual cycle-associated gingivitis Following menarche, there is a periodicity of sex steroid hormone secretion over a 25–30 days period—the menstrual cycle—during which clinically significant inflammatory

The use of chemical for the benefit of human beings has led to an astonishing array of drugs for the alleviation of human afflictions as well as the creation of new maladies that affect the gingiva. 445


Drug-induced gingival enlargement

Phenytoin

The disfiguring overgrowth of gingiva is a significant outcome principally associated with antiepileptic drugs such as phenytoin sodium, immunosuppressors such as cyclosporine and calcium channel blockers such as nifedipine, amlodipine, verapamil, diltiazem and sodium valproate (Hassel and Hefti, 1991; Seymour et al, 1996). Most common clinical features seen in drug-induced gingival enlargement are as follows:

The first reported case of phenytoin-induced gingival enlargement was reported by Kimball (1939). Phenytoin is indicated in treatment of epileptic seizures. Phenytoin induces gingival enlargements in approximately 50% of patients (Angelopoulos and Goaz, 1972) (Figure 2A, B). One prominent theory of the etiology of phenytoin-associated gingival enlargements suggests that the growth of genetically distinct populations of gingival fibroblasts results in the accumulation of connective tissues because of reduced catabolism of the collagen molecule (Hassel and Hefti, 1991).

❍

❍ ❍ ❍ ❍

❍

Individual variations in the pattern of gingival enlargement, i.e. genetic predisposition (Hassel and Hefti, 1991; Seymour et al, 1996). A tendency to occur more in the anterior gingiva. A higher prevalence rate in younger age groups. Onset within 3 months of usage of the medication, usually involves the interdental papilla. Usually manifests as bead-like enlargement of the papilla and marginal gingiva, and in severe cases gingival enlargement covers major portion of the teeth and thereby interfere in occlusion, which is a rare entity. Although the condition can be found in a periodontium with or without bone loss, there is no association with attachment loss or tooth mortality.

Furthermore, all of these drugs produce clinical lesions and histological characteristics that are indistinguishable from one another (Hassel and Hefti, 1991; Seymour et al, 1996). Finally, the influence of plaque on the induction of gingival enlargement by drugs in humans has not been fully elucidated (Hassel and Hefti, 1991); however, it does appear that severity of the lesion is affected by the oral hygiene of the patient.

Calcium channel blockers (Figure 3A, B) Calcium channel blockers are a class of drugs that exert their effects principally at voltage-gated Ca channels located in the plasma membrane, and are commonly prescribed as antihypertensive, antiarrhythmic and antianginal agents. In 1984, calcium channel blockers were first linked to gingival enlargements (Ramon et al, 1984) and the prevalence of gingival lesions associated with these drugs has been estimated to be approximately 20% (Barclay et al, 1992). The mechanism of gingival enlargement is still under investigation, but these drugs may directly influence the gingival connective tissues by stimulating an increase of gingival fibroblasts as well as an increase in the production of connective tissue matrix (Fu et al, 1998). Cyclosporine Cyclosporine is a powerful immunoregulating drug used primarily in the prevention of organ transplant rejection

Figure 2 A

B

Enlargement of the labial and palatal aspects of the gingiva in patients using phenytoin sodium. Gingival enlargement leads to the formation of pseudopockets. Courtesy: Dr Francisco, Mexico

446


Figure 3 A

B

Enlargement of the labial and palatal aspects of the gingiva in a patient on nifedipine. Courtesy: Dr Francisco, Mexico

(Seymour and Jacobs, 1992). The clinical features of cyclosporine-induced gingival enlargement were first described in 1983 (Rateitschak-Pluss et al, 1983). The drug appears to affect 25–30% of the patients taking this medication (Hassel and Hefti, 1991; Seymour et al, 1987). Hypotheses explaining why cyclosporine affects the gingiva are diverse; but a leading theory suggests that the principal metabolite of cyclosporine, hydroxycyclosporine (M-17), in conjunction with the parent compound stimulates fibroblast proliferation (Mariotti et al, 1988). The increase in cell number coupled with a reduction in the breakdown of gingival connective tissues (Hassel and Hefti, 1991) has been postulated to be the cause of excessive extracellular matrix accumulation in cyclosporine-associated gingival enlargements (Figure 4A, B). Oral contraceptive-associated gingivitis Oral contraceptive agents are one of the most widely used classes of drugs across the globe. The earlier onset of menarche, changing social mores and increased emphasis on family planning has increased the use of oral contraceptives in younger age groups. Case reports have described gingival enlargement induced by oral contraceptives in otherwise healthy women with no history of gingival overgrowth (Lynn, 1967; Kaufman, 1969; Sperber, 1969); in all cases, the increased gingival mass was reversed when oral contraceptive was discontinued or the dosage was reduced. Clinical studies have demonstrated that women using hormonal contraceptive drugs have a higher incidence of gingival inflammation than women who do not use these agents (Lindhe and Bjorn, 1967; El-Ahisry et al, 1970; Pankhurst et al, 1981) and that long-term use of oral contraceptives may affect periodontal attachment levels (Knight and Wade, 1974). All studies recording changes to gingival

tissues by oral contraceptives were completed when dosage levels were much higher than today. A recent clinical study in young women found that oral contraception had no effect on gingival tissues (Marrioti et al, 2000). It appears that current oral contraceptives are probably not as harmful to the periodontium as the early formulations.

Gingival Diseases Associated with Systemic Diseases Leukemia-associated gingivitis Leukemia is a progressive, malignant hematological disorder characterized by an abnormal proliferation and development of leukocytes and precursors of leukocytes in the blood and bone marrow. Leukemia is classified according to its duration (acute or chronic) and the type of cell involved (myeloid or lymphoid) and the number of cells in the blood (leukemic or aleukemic). There are noticeable correlations of leukemias with age. For example, acute lymphoblastic leukemia constitutes 80% of all childhood leukemias, whereas acute myelogenous leukemia usually affects the adults. Oral manifestations have primarily been described in acute leukemias; they consist of cervical adenopathy, petechiae and mucosal ulcers as well as gingival inflammation and enlargement (Lynch and Ship, 1967). Signs of inflammation in the gingiva include swollen, glazed and spongy tissues which are red to deep purple in appearance (Dreizen et al, 1984). Gingival bleeding is a common sign in patients with leukemia and is the initial oral sign or symptom in 17.7% and 4.4% of patients with acute and chronic leukemias (Lynch and Ship, 1967). Gingival enlargement has also been reported initially beginning at the interdental papilla and followed by the marginal and attached gingiva. Although local irritants 447


Figure 4 B

A

Cyclosporine-induced gingival enlargement. Courtesy: Dr Francisco, Mexico

can predispose to and exacerbate the gingival response in leukemia, they are not prerequisites for lesions to form in the oral cavity (Dreizen et al, 1984). Linear gingival erythema (LGE) Infection with the human immunodeficiency virus (HIV) produces an irreversible and progressive immunosuppression that renders the person infected susceptible to a variety of oral diseases. In humans, HIV depletes CD4 lymphocytes (T helper cells), which leads to the development of a variety of fungal, viral and bacterial oral infections (Connor and Ho, 1992). Oral manifestations of HIV infection have been used to stage HIV disease (Justice et al, 1989; Royce et al, 1991) to identify prophylactic treatment of other serious infections (Force, 1993), and to indicate disease prognosis (Dodd et al, 1991; Katz et al, 1992). In the gingiva, manifestations of HIV infection were formerly known as HIV-associated gingivitis but are now known as LGE. This condition is distinguished by a 2–3 mm marginal band of intense erythema in the free gingiva (Winkler et al, 1988), which may extend into the attached gingiva as a focal diffuse erythema and/or extend beyond the mucogingival line into the alveolar mucosa (Winkler et al, 1988). The characteristics of LGE may be localized to one or two teeth but more commonly involvement of marginal gingiva is generalized. The etiology of this gingival lesion is not well understood; however, research has begun to investigate the relationship of periodontal pathogens and the local host response in regard to how HIV infection affects the gingiva. The anaerobic microflora from the subgingival sites of HIV-infected patients with gingivitis seems to be essentially the same as in non-infected patients (Moore et al, 1993). Despite the similarities in anaerobic microflora, organisms not generally associated with gingivitis in HIV-negative patients, such as Candida species, have been identified in LGE 448

(Lamster et al, 1998). In addition, LGE lesions have been shown to have reduced proportions of T cells and macrophages and an increased number of immunoglobulin G plasma cells and polymorphonuclear leukocytes (Gomez et al, 1995). These host cell responses and unusual microbiota may be responsible for the refractory nature of this lesion to the conventional periodontal treatment of gingivitis.

Gingival Diseases Associated with Malnutrition Although some nutritional deficiencies can significantly exacerbate the response of the gingiva to plaque bacteria, the precise role of nutrition in the initiation or progression of periodontal diseases remains to be elucidated. Studies of the periodontal status of individuals in developed and developing countries have failed to show any relationship between periodontal disease and general nutrition (Russell, 1962; Waerhaug, 1967; Wertheimer et al, 1967). Severe vitamin C deficiency or scurvy was the earliest nutritional deficiency to be examined in the oral cavity (Lind, 1953). Even though scurvy is unusual in areas with an adequate food supply, certain populations on restricted diets (e.g. infants in families of low socioeconomic class) are at risk of developing this condition (Oeffinger, 1993). In scurvy the gingiva is typically red, swollen, ulcerated and susceptible to hemorrhage (Van Steenberghe, 1997). Although there is no dispute about the necessity of dietary ascorbic acid for periodontal health, in the absence of frank scurvy, the effect of declining ascorbic acid levels on the gingiva can be difficult to detect clinically (Woolfe et al, 1980) and when it is detected usually has characteristics that are similar to plaque-induced gingivitis.

Gingival Diseases Associated with Heredity Benign, non-inflammatory fibrotic enlargement of the maxillary and/or mandibular gingiva associated with a familial


aggregation has been designated by terms such as gingivostomatitis elephantiasis, familial elephantiasis, juvenile hyaline fibromatosis, idiopathic gingival fibromatosis and hereditary gingival fibromatosis. Although there were almost 100 published reports of hereditary-associated gingival overgrowths in the 20th century, information about the natural history of this rare disease is extremely limited and its etiology is unknown. Hereditary gingival fibromatosis appears to be a slowly progressive gingival enlargement which develops upon eruption of the permanent dentition. However, gingival enlargement can also occur in the primary dentition (Emerson, 1965; Jorgenson and Cocker, 1974; Lai et al, 1995; Miyake et al, 1995). The disease can be localized or generalized and may ultimately cover the occlusal surfaces of teeth. The enlarged gingiva is non-hemorrhagic and firm, but there can be an overlay of gingival inflammation which can augment the enlargement. The histologic features of hereditary gingival fibromatosis include dense fibrotic connective tissue as well as epithelial hyperplasia with elongated and increased rete pegs (Johnson et al, 1986; Clark, 1987). Hereditary gingival fibromatosis can be inherited as a simple mendelian trait, in some chromosomal disorders and as a malformation syndrome (Witkop, 1971; Jones et al, 1977; Takagi et al, 1991; Goldblatt and Singer, 1992; Hallet et al, 1995). Although the specific genes for this disease have not been identified, genetic analysis supports the presence of two different gene loci on chromosome 2p (Shashi et al, 1999). Research into the cellular responses of this disease suggests an accumulation of specific populations of gingival fibroblasts resulting in an abnormal accumulation of connective tissues (Huang et al, 1997; Tipton et al, 1997).

Gingival Diseases Associated with Ulcerative Lesions Necrotizing ulcerative gingivitis has been known for centuries by numerous names including ‘trench mouth’ and Vincent’s infection. Acute NUG is a term used to describe the clinical onset of the disease and should not be used as a diagnostic classification, since some forms of NUG may be recurrent or possibly chronic. Onset is usually sudden with intense gingival pain, which prompts the patient to seek professional care. Clinical signs include papillary necrosis, giving a ‘punched-out’ appearance of the gingival papilla and gingival bleeding that requires little or no provocation (Grupe, Johnson and Engel, 1986). Although these symptoms and signs must be present for a diagnosis of NUG, other features may occur such as fever, malaise, lymphadenopathy, metallic taste and fetor ex ore (malodor) (Schluger, 1943; Wilson, 1952; Murayama et al, 1994). Systemic reactions of acute NUG are usually more severe in children. Significant destruction of the gingival connective tissue is possible with NUG

but when attachment loss occurs this condition should be considered as an NUP. The cause of NUG may be bacterial. The four zones of the NUG lesion include the bacterial zone (the superficial area consisting of various bacteria and some spirochetes); the neutrophil rich zone (follows the bacterial zone and consists leukocytes and bacteria including spirochetes); the necrotic zone (consisting of disintegrated cells and connective tissue elements with many large and intermediate spirochetes); and the spirochetal infiltration zone (the deepest zone that is infiltrated with no other bacteria but with intermediate and large spirobacteria but with intermediate and large spirochetes) (Listgarten, 1965). The cultivable flora of NUG that predominates includes Prevotella intermedia and Fusobacterium species, while microscopically, Treponema and Selenomonas species are observed (Loesche et al, 1982; Rowland et al, 1993). Additional factors include smoking (AAP, 1996), psychological stress (Moulton et al, 1952; Cohen-Cole et al, 1983), malnutrition (Grupe and Wilder, 1956; Goldhaber and Giddon, 1964; Johnson and Engel, 1986) and immune suppression (Moulton et al, 1952; Rowland et al, 1993) can predispose and individual to NUG. Although NUG can affect any age group, it is considered to be a disease of young adults in developed countries (Melnick et al, 1988). In developing countries, NUG is a disease found in children from families with low socioeconomic status (Melnick et al, 1988). The onset of NUG in children is associated with inappropriate nutrition intake, especially low protein consumption (Sheiham, 1966; Taiwo, 1995). In addition, viral infections such as measles can induce NUG in malnourished children (Enwonwu, 1972; Osuji, 1990). Even though NUG has occurred in epidemic patterns, this disease is not considered communicable (Rosebury, 1942).

Gingival Lesions Manifested in Childhood Diseases Acute herpetic gingivostomatitis The herpes simplex virus produces some of the most common acute infections in humans. Of the two herpes simplex virus serotypes, type 1 is responsible for most oropharyngeal infections, including acute herpetic gingivostomatitis. This disease is observed in young adolescents and adults but has its highest incidence in infants and children younger than 6 years of age (Scott et al, 1941). There are no predilection for either sex with the primary infection. Following the primary infection, the virus moves through nerves to neuronal ganglia where it remains dormant until reactivated by various stimuli including trauma, exposure to sunlight or ultraviolet lamps, fever, stress, fatigue, menstruation, pregnancy, upper respiratory tract infection, allergy or gastrointestinal disturbances (Stevens, 1975; Shafer et al, 1974). 449


Although most cases of primary herpetic infection are symptomatic (Gibson et al, 1990; McDonald et al, 1994), the primary infection in some cases may manifest as acute herpetic gingivostomatitis, which is characterized by several oral and systemic manifestations. The symptomatic infection is characterized by fever, malaise, headache, irritability, dysphagia and lymphadenopathy. In the oral cavity, lesions can affect the lips, tongue and pharynx. Initially, gingival inflammation is characterized by a diffuse, erythematous, shiny appearance precedes the appearance of vesicles (White, 1998). The vesicles vary in size and are usually discrete, spherical sacs which rupture to form small, ragged and painful ulcers that are covered by a gray membrane and surrounded by an erythematous, elevated halo (White, 1998). The ulcers persist for 7–10 days and heal spontaneously, leaving no scars (White, 1998). The diagnosis for this infection is usually determined by the patient’s history and clinical signs and symptoms, and confirmed laboratory culture of the herpes simplex virus. Lesions of recurrent aphthous stomatitis have often been confused with acute herpetic gingivostomatitis, but can be distinguished clinically by the absence of diffuse erythema of gingiva, acute toxic systemic symptoms and herpes simplex virus culture.

may be expressed. The lesion is generally self-limiting, ultimately rupturing if permitted to progress. The gingival abscess should not be confused with the periodontal abscess, which affects the supporting periodontal structures.

Gingival Changes Associated with Tooth Eruption As the crown penetrates the oral mucosa, the marginal gingiva and sulcus form. During the physiologic process of eruption, the gingival margin becomes edematous and erythematous. It is not uncommon for erupting primary or permanent teeth to be associated with a form of dentigerous cyst (also called eruption cyst/eruption hematoma). The eruption cyst usually appears as a site of translucent, fluctuant, circumscribed swelling over the erupting tooth. When the cystic cavity contains blood, the swelling appears as a purple or deep blue fluctuant, circumscribed swelling termed as eruption hematoma. Primary canines and molars appear to be more frequently involved than primary incisor teeth.

PERIODONTAL DISEASES Local Contributing Factors

Gingival Lesions Associated with Chicken Pox Varicella, which primarily affects individuals below the age of 15 years (Preblud, 1986), produces the skin lesions characterized by vesicles and pustules that break and crust over. In the oral cavity, small ulcers may develop in any area of the mouth; however, lesions are found most often on the palate, gingiva and buccal mucosa (Badger, 1980). The ulcers that appear during the course of the skin rash are usually not painful.

It is well known that the primary cause of gingival inflammation and periodontal destruction is bacterial plaque. These factors that tend to accelerate the disease locally, are termed as local contributing factors in the progression of periodontal disease. The local factors are: ❍ ❍

Gingival Lesions Associated with Mononucleosis Mononucleosis is produced by the Epstein–Barr virus and is primarily a disease of children and young adults. The clinical symptoms are most prominent in young adults, and common signs and symptoms include fatigue, malaise, headache, fever, sore throat, enlarged tonsils and lymphadenopathy. Alterations in the oral cavity include gingival bleeding, petechiae of the soft palate, ulceration of the gingiva and buccal mucosa and pericoronitis.

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Acute Inflammatory Gingival Enlargement A gingival abscess is an acute, painful, rapidly expanding lesion localized to the gingiva. Most gingival abscesses are detected on the marginal gingiva or the papilla. Gingival abscesses usually arise from an insult such as trauma caused by food which forces bacteria into the tissue. Within hours, a bright red gingival swelling will convert to a lesion that is pointed and fluctuant mass from which purulent exudates 450

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Calculus Iatrogenic factors – Overhanging restoration – Margins of restoration – Contours – Restorative materials – Occlusion – Restorative procedures – Pontic – Improper removable partial dentures Malocclusion Food impaction Orthodontic therapy Anatomic contributing factors – Proximal contact relationship – Cervical enamel projections and enamel pearls – Bifurcation ridges – Developmental grooves – Root anatomy—morphology and length – Root fusion, cemental tears – Proximity to adjacent teeth Endodontic lesions Caries


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Habits – Toothbrushing trauma – Mouth breathing, tongue thrusting and other habits – Factitial injuries Smoking Trauma from occlusion Trauma – Physical – Chemical – Thermal Radiation therapy Mucogingival problems Cysts and tumors.

Figure 5

Calculus Calculus is mineralized dental plaque that forms on surface of teeth and dental prosthesis. It is one of the most important and commonly occurring local contributing factor as it is invariably covered with bacterial plaque on its surface.

Thick band of subgingival calculus firmly adherent to the cervical margin of the tooth. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Types Supragingival calculus It is white or whitish yellow in color hard with clay-like consistency and is easily detached from the tooth. It is most commonly found on lingual surface of mandibular teeth and buccal surface of maxillary teeth. Subgingival calculus It is located below the crest of marginal gingiva and appears dark brown or black in color and flint-like consistency. It is firmly attached to the tooth (Figure 5). Composition Calculus consists of organic and inorganic constituents. organic contents are mainly desquamated epithelial cells, leukocytes and microorganisms. Inorganic constituents are mainly calcium, calcium phosphates and calcium carbonates, magnesium phosphates and other metals. Significance of calculus Calculus is a local factor in periodontal disease because it always has a layer of plaque on its surface. Because calculus is firmly attached to the tooth through an organic pellicle, it resists removal through routine oral hygiene techniques. Calculus plays an important role in the progression of periodontal disease by keeping plaque in close contact with the periodontal tissues in gingiva.

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Iatrogenic Factors ❍

Overhanging restorations: These contribute to periodontal disease by acting as a local plaque retentive area causing accumulation of plaque and changing the ecology that favors the growth of microorganisms.

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Margins of restoration: A subgingival margin is associated with more plaque accumulation and more periodontal destruction than supragingival margins, margins placed at the level of gingiva. Contours: Overcontoured restorations tend to accumulate more plaque, and the natural self-cleansing mechanism fails. Open contours: These are associated with increased food impaction and papillary inflammation. Restorative materials: Silicate cements and self-curing acrylic resins accumulate more plaque. Restorative procedures: Rubber dam, clamps, matrix band wedges, gingival retraction chords are shown to cause injury to the periodontium. Pontics: When pontics are in contact with gingival tissue, they tend to accumulate more and oral hygiene techniques are more difficult. Improper removable partial denture: It causes an increase in mobility of abutment teeth and also favors accumulation of plaque leading to gingival inflammation and periodontal pocket. Malocclusion: Plaque control is more difficult in individuals with malocclusion. Malocclusion is usually associated with recession if the tooth is buccally placed and plaque control is difficult because of lack of attached gingiva. Food impaction: It is forceful wedging of food into the periodontium by occlusal forces. This harbors more microorganisms in interproximal area leading to periodontal destruction. Orthodontic therapy: Orthodontic appliances are associated with food debris and plaque accumulation and changing the ecosystem. These also cause increase in forces on the periodontium. 451


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Carious tooth: Endodontically treated tooth and root stumps act as plaque retentive areas leading to periodontal diseases. In some instances patients with pulpal/periapical diseases avoid chewing food from the affected side leading to more deposition of calculus. Anatomic contributing factors: Proximal contact relationship—open proximal contact may cause food impaction, which in turn causes periodontal disease. Cervical enamel projection and enamel pearls: Cervical enamel projections are narrow wedge-shaped extrusions of enamel extending from cementoenamel junction toward the furcation area. Enamel pearls are bead-like projections commonly found in furcation area. The clinical significance of cervical enamel projection and enamel pearls is that they act as a local plaque retentive area and also periodontal attachment does not take place in them, hence leading to periodontal diseases. Bifurcation ridges: It is a convex excrescence of cementum that runs longitudinally between the mesial and distal roots of mandibular molars. Thus, it makes removal of plaque and calculus more difficult. Palatogingival groove: It is a developmental groove that begins at the cingulum and extends apically in the anterior teeth. Most commonly it is seen in maxillary lateral incisor. These grooves act as a plaque retentive area. Cemental tears: It is a piece of detached cementum with some amount of dentin attached to the alveolar bone through periodontal ligament. This is often induced by some form of acute trauma leads to rapid bone destruction with vertical bone loss. Root fusion: Progression of periodontal disease is faster if roots are fused. Root proximity: There is a thin interseptal bone when the roots are in close proximity, which has an increased rest for periodontal destruction. Extraction of impacted third molars: This results in periodontal problems distal to second molar with pockets of recession and bone loss.

Figure 6

Cervical abrasion and localized gingival recession. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Habits ❍

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Smoking It is one of the etiological factors in ANUG. It is classified as an environmental factor with local and systemic effects. The local effects are peripheral vasoconstriction and localized ischemia. The individual harbors more pathogenic and virulent subgingival microorganisms. The systemic effects are decreased immunity with non-specific (decreased polymorphoneutrophils, chemotaxis, phagocytosis) and specific (decreased IgG, IgA). There is also activation of proinflammatory cytokines including IL-1. TNF- IL-6 all lead to periodontal diseases. Since immunity and inflammation are reduced in smokers there are lesser clinical signs of gingival inflammation with increased local deposits and periodontal destruction; it is one of the etiological factor in NUG. 452

Toothbrush trauma: This can abrade the epithelium leading to gingival recession (Figure 6). It also causes abrasion of the tooth surface. Mouth breathing, tongue thrusting and other habits: Mouth breathing causes dehydration of gingival tissue increasing their susceptibility to inflammation. Tongue thrusting causes anterior open bite and spacing between the teeth causing difficulty in maintaining good oral hygiene. Factitial injury: It is self-inflicted injury, which include picking of gingiva with finger nail; tooth picks, pins and other materials. This causes a direct damage to the periodontium. Radiation therapy: It causes soft tissue ischemia, fibrosis and osteoradionecrosis in bone. Periodontal tissue destruction is more in patients who underwent radiation therapy. Mucogingival problems: Mucogingival area is defined as a generic term used to describe the mucogingival junction and its relationship to the gingiva, alveolar mucosa, frenum, muscle attachments, vestibular fornices and the floor of the mouth. A mucogingival deformity may be defined as a significant departure from the normal shape of the gingival and alveolar mucosa.

Some of the common mucogingival problems are decrease in the width of attached gingiva, gingival recession crossing the mucogingival junction, high frenal attachments and shallow vestibule. Mucogingival problems are commonly associated with plaque accumulation, as the patient cannot perform the routine oral hygiene techniques. ❍

Traumatic injuries: These can be physical, chemical and thermal in nature and can cause injury to gingival and


supporting periodontal tissues. These directly affect the gingiva and make routine plaque control procedures difficult. ❍ Cysts and tumors: Some of the cysts and tumors because of their expansile growth cause destruction of the periodontium.

Figure 7

Systemic factors It is well known that bacterial plaque is a main etiological factor responsible for gingival inflammation and periodontal destruction. The bacterial plaque causes a marked host response that varies from one individual to other, hence susceptibility of individual to periodontitis depends on various factors, including systemic and genetic factors. Genetic factors Periodontal disease is multifactorial with plaque being major factor, but some of these factors fail to explain the variation of disease in different individuals with same amount of local factor. This is attributed to genetic susceptibility. Genetic pleomorphism in IL-1 has been shown to be associated with chronic periodontitis. Studies have shown a link between susceptibility of aggressive periodontitis and the human leukocyte antigen of chromosome 6, which is responsible for production of IgG2, which in turn is responsible for periodontal destruction. The genetic polymorphism in the genes for the Fc- receptor on the phagocytic cell is identified in localized aggressive periodontitis. Polymorphism in the gene promoter region of chromosome 6, results in increased production of TNF-, which has been shown to be associated with periodontitis.

Extensive destruction of supporting bone and missing teeth in Papillon–Lefevre syndrome. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Chediak–Higashi syndrome It is an autosomal recessive disease that affects the production of organelles in many cells including melanocytes, platelets and leukocytes. Neutrophils are characterized by abnormal giant lysosomes containing enzymes and with impaired ability to release them. It is associated with severe gingivitis, periodontal disease and loss of dentition at an early age. Lazy leukocyte syndrome It is a rare disease characterized by defect in PMN chemotaxis and an abnormal inflammatory response. Leukocyte adhesion deficiency (LAD)

SYNDROMES Down’s syndrome It is a congenital disease characterized by mental deficiency, growth retardation and severe periodontal disease. Incidence is about 1:800–1,000. Both deciduous and permanent dentitions are affected. The destruction increases with age. The rapid periodontal destruction is commonly attributed to immunologic defects.

It is a rare inherited genetic disorder resulting from inability to produce or express CD18, an integrin useful in leukocyte adhesion. Both primary and secondary dentitions are affected in LAD which presents as acute inflammation and rapid destruction of bone. Ehlers–Danlos syndrome It is an inherited condition affecting connective tissue with reduction of collagen fiber production. The oral mucosa, gingiva and periodontium are affected.

Papillon–Lefevre syndrome It is an inherited autosomal recessive disease characterized by diffuse palmoplantar hyperkeratosis, severe destruction of periodontium and calcification of dura. Incidence is 1–4:10,00,000. Deciduous teeth are usually lost by 5–6 years and permanent teeth a few years later (Figure 7). Defects in PMNs adherence and chemotaxis has been reported.

Hypophosphatasia It is an autosomal recessive condition where there is a deficiency of the enzyme alkaline phosphatase and characterized by abnormal mineralization of bone and dental tissues. There is premature exfoliation of deciduous teeth, loss of alveolar bone, absence of gingival inflammation and absence of cementum. The permanent teeth are not affected. 453


Mucopolysaccharidoses (MPS)

Figure 8

It is a group of inherited disorders characterized by disturbances in mucopolysaccharide metabolism and their increased storage in various tissues. These include Hurler’s syndrome (MPS I) and Hunter’s syndrome (MPS II). The teeth in both these conditions are small and widely spaced and exhibit delayed eruption. Gingival enlargement may be commonly seen.

Hormonal Factors Diabetes: It is a complex metabolic disorder characterized by glucose intolerance. It is associated with: ❍ ❍ ❍ ❍ ❍

Microvascular diseases (retinopathy, neuropathy and nephropathy) Macrovascular diseases (cardiovascular, cerebrovascular) Increased susceptibility to infections Delayed wound healing Periodontitis.

Extensive periodontal abscess in a diabetic patient. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 9

Oral effects Patients with diabetes have diminished salivary flow, burning mouth and candidiasis. Diabetes also has profound effect on periodontium resulting in gingivitis, gingival enlargement, periodontal abscess formation, periodontitis and loss of teeth (Figures 8 and 9). Pathogenesis ❍ ❍ ❍

Alteration of bacterial flora Altered neutrophil function Altered collagen metabolism.

SEX HORMONES The female sex hormones affect periodontal tissues. Estrogen promotes keratinization and increased mucopolysaccharide content, the gingival connective tissue. Progesterone increases the permeability and gingival blood vessels. Changes seen are: ❍

Puberty: There is an increased prevalence and severity of gingivitis. ❍ Menstrual cycle: Gingival crevicular fluid (GCF) flow increases at the time of ovulation. ❍ Pregnancy: The changes in gingiva usually starts around the 3rd month of gestation and the severity of inflammation gradually increases during pregnancy. Gingiva becomes bright red, swollen, sensitive and bleeds spontaneously. There is an increase in GCF production and tooth mobility. There is an increased level 454

Extensive destruction of interdental bone and loss of teeth in a diabetic patient. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

of Prevotella intermedia during pregnancy. In some cases a soft, pedunculated granuloma is present in the interdental papilla, which is a slow-growing lesion referred to as pregnancy tumor. ❍ Oral contraceptives: These are associated with increased GCF flow and a greater prevalence of gingival inflammation. ❍ Menopausal gingivostomatitis: In this the gingiva appears dry and shiny. It varies in color from pale to bright red and bleeds easily.


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Hyperparathyroidism: It causes a disease known as osteitis fibrosa cystica or von Recklinghausen’s bone disease.

Oral changes include increased tooth mobility. Radiographically, it shows widening of periodontal ligament space with absence of lamina dura, closely meshed trabaculae and cystic space known as Brown’s tumor.

STRESS AND PSYCHOSOMATIC FACTORS Stress and other psychosomatic factors have direct antiinflammatory and anti-immune effects or can have behaviormediated effects on the body’s defenses. Stress is also one of the etiological factor in acute NUG. Stress increases cortisol hormone which suppresses immune system by suppressing neutrophil activity and decreasing IgG and IgA production, thus allowing the periodontal pathogens to cause more destruction. Psychosomatic disorders can result in periodontal tissue destruction through development of certain habits like nail biting, using foreign objects, self-inflicted gingival injuries can be seen in patients with mental disabilities.

NUTRITIONAL FACTORS There are no nutritional factors that causes gingivitis or periodontitis, but they produce changes in the oral cavity including the gingiva and alveolar bone that can accelerate the process of gingivitis and periodontitis.

Scurvy is associated with enlarged, hemorrhagic, bluish, red gingiva. Gingivitis is not caused by vitamin C deficiency but the severity of gingivitis increases with vitamin C deficiency. Gingival healing is also impaired. Vitamin C deficiency also results in osteoporosis of alveolar bone, hemorrhage in the periodontal ligament and increased tooth mobility. Vitamin D It is necessary for the calcium–phosphorus balance. Deficiency of vitamin D causes rickets in children and osteomalacia in adults. Vitamin D deficiency in animals causes osteoporosis of alveolar bone, uncalcified osteoid, reduction in width of periodontal ligament, severe osteoclastic resorption of alveolar bone. Vitamin E There is no relationship between vitamin E deficiency and periodontal disease in humans. In animals vitamin E accelerates gingival wound healing. Protein deficiency In experimental animals the oral changes of protein deficiency include degeneration of CT of periodontium, osteoporosis, delayed wound healing and abnormal deposition of cementum. Hematological disorders Leukemia: Its characterized by diffuse replacement of bone marrow with proliferating leukemic cells, abnormal number or form of WBCs in blood and widespread metastasis. It can be lymphocyte or myelocytic, acute, subacute or chronic.

Effects of Vitamin Deficiency

Oral manifestations There is a widespread infiltrate of leukemic cells in oral cavity, particularly gingiva, which appears bluish red with enlargement and spontaneous bleeding. Oral ulceration and infections are commonly noticed in these patients; microscopically the gingiva exhibits a dense infiltrate of immature leukocytes.

Vitamin A In experimental animals, vitamin A cause hyperkeratosis and hyperplasia of gingiva with a increased rate of pocket formation. In humans studies are inconclusive.

Leukocyte disorders These are usually associated with severe periodontal destruction as PMNs are the first line of defense against periodontal pathogens.

Vitamin B complex Thiamin deficiency (beriberi) causes hypersensitivity of oral mucosa, minute vesicles and erosion of oral mucosa. Riboflavin deficiency (riboflavinosis) causes glossitis, angular cheilitis and seborrheic dermatitis. Niacin deficiency (pellagra) causes glossitis, stomatitis, black tongue and severe gingival inflammation with necrosis. Folic acid deficiency causes necrosis of gingival, periodontal ligament and alveolar bone without inflammation. Vitamin C Ascorbic acid deficiency results in scurvy, where there is defective formation of collagen fibers and impaired osteoblastic activity. There is also an increased capillary permeability, susceptibility to traumatic hemorrhages, hyperreactivity of contractile elements and sluggish blood flow.

Neutropenia It is a leukocyte disorder in which there is a low count of neutrophils in blood (1,500 cells/l). Neutropenia can be genetic, familial, idiopathic or secondary to some kind of infections. There are many kinds of neutropenias all of which affect the periodontal health. Agranulocytosis It is a leukocyte disorder in which there is a low count of circulating granulocyte in blood. Ulcerations with the absence of inflammatory reaction of the oral cavity is one of the characteristic sign of agranulocytosis. Gingival hemorrhage, necrosis and fetid odor are also present. Cyclic neutropenia It is an inherited condition where there is cyclic depression of neutrophils in peripheral blood at intervals varying from 15 to 55 days and manifested 455


with pyrexia, oral ulceration and skin infections. Oral features include oral ulcerations, severe gingivitis, periodontal destruction and alveolar bone loss. Chronic benign neutropenia of childhood There is moderate neutropenia with absolute lymphocytosis and monocytosis. Oral findings include bright red hyperplastic edematous gingiva which bleeds easily and permanent destruction with generalized bone loss. Familial neutropenia It is an inherited condition which can occur in benign and severe forms. There is moderate to severe form of neutropenia in these conditions. Oral findings are similar to that of chronic benign neutropenia of childhood. Chronic idiopathic neutropenia This occurs mainly in females with persistent neutropenia from birth. Oral findings are similar to that of chronic benign neutropenia of childhood.

Gingivitis Presence of local factors like calculus and/or at least one of the following clinical features: • Erythematous gingiva • Soft and edematous gingiva • Blunting of the interdental papilla • Loss of gingival stippling • Gingiva bleeds spontaneously on palpation or probing Periodontitis Gingivitis plus at least one of the following clinical features: • Gingival recession • Periodontal pocket • Mobility • Pathologic migration • Pus discharge from the gingival sulcus • Furcation involvement

Lazy leukocyte syndrome There is a defect in leukocytic chemotaxis and mobility associated with severe gingivitis.

RADIOGRAPHIC EVALUATION OF PERIODONTAL DISEASES

Chronic granulomatous disease It is an inherited condition characterized by inability of neutrophils to generate hydrogen peroxide due to absence of the enzyme NADPH oxidase. Oral condition includes severe and diffuse gingivitis with ulcerations.

Thumb rules

Anemia It is defined as the reduction of concentration of hemoglobin in blood below at normal level. Oral findings include recurrent aphthous ulcers with angular cheilitis, smooth and bald tongue, gingiva becomes pale in color. Fanconi’s anemia which is an inherited form of anemia is associated with early tooth loss. Acatalasia It is an inherited disease with the absence of acatase enzyme in RBCs and WBCs. Catalase is responsible for conversion of hydrogen peroxide (H2O2) to O2 and H2O; thus preventing oxidation of hemoglobin in RBCs. Thrombocytopenic purpura It is characterized by low platelet count, spontaneous bleeding into skin and mucous membrane. Oral finding includes petechia in oral cavity. Gingiva is inflamed, soft and friable. Spontaneous bleeding in commonly seen. Agammaglobulinemia It is an immune deficiency resulting from a low antibody production from B cells. It is commonly associated with severe periodontal destruction and tooth loss. Multiple myeloma It is a multifactorial neoplasm of plasma cells with infiltration into maxilla and mandible. Oral lesions include gingival ulceration with bleeding and alveolar bone destruction. 456

Summary of the clinical features of gingivitis and periodontitis

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Radiographs will not show soft tissue changes (e.g. destruction of the periodontal ligament and pocket depth). However, contrasting agents such as use of periodontal probe, gutta percha points may help delineate soft structures. Intraoral periapical (IOPA), bitewing radiographs and orthopantomograph (OPG) reveal only two-dimensional images of three-dimensional structures. Hence, bone loss in different planes may not be evident in a single radiographic projection. The disease process is always ahead of the radiographic presentation. It is estimated that for radiographic visualization a minimum of 40% demineralization is required. Intraoral periapical radiographs have the best resolution when compared to CT and OPG. Early and minimal bone changes and bone marrow morphology are hence best appreciated in an intraoral periapical radiograph. Infrabony defects are impossible to be detected on intraoral radiographs as one or both cortical plates superimpose over the defect.

Need for taking radiographs ❍

Evaluate the nature and extent of the causes for periodontal destruction (subgingival calculus, overhanging margins of proximal restorations and poorly contoured crowns). ❍ Assess the width of the periodontal ligament space. ❍ Evaluate crestal bone loss. ❍ Assessment of the pattern and extent of alveolar bone destruction (horizontal, angular, furcation involvement).


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Assessment of the anatomic morphology of the roots and the crown root length. ❍ Assessment of the location of various anatomical structures. ❍ Evaluation of periapical pathologies, endo-perio lesions, bone pathology and systemic conditions resulting in periodontal destruction.

Interpretation of radiographs ❍

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Paralleling technique to be followed wherever feasible. Use wire grids along with the film (will help in accurate assessment of bone loss). ❍ 70 kVp, 8 mA machines are most ideal. ❍ Low contrast with long gray-scale are most suited for evaluation of periodontal destruction. Lighter radiographs tend to depict the cortical margins. Choice of radiographs ❍

Orthopantomograph can be used as a scout radiograph to evaluate generalized destruction of periodontium. It can also be used for assessing cortical plate width and density for implant placement and relationship of teeth/implant to adjacent anatomical structures. ❍ Intraoral periapical radiographs can be used for assessing height and pattern of interdental bone, involvement of furcation area, widening of the periodontal ligament space, root resorption, periapical lesions and endo-perio lesions. ❍ Bitewing radiographs can be used to assess crowns and interdental regions of a few upper and lower teeth in one radiograph. These radiographs are used for assessing crestal bone loss and factors that cause periodontal destruction such as subgingival calculus deposits, illfitting crowns and poor restorative margins. ❍ Full mouth IOPA radiographs are excellent means to assess the periodontal status in a patient. The full mouth series consists of 16 IOPA radiographs (excluding four radiographs for the third molars) and four bitewings.

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Radiographs have to be always mounted and viewed using a viewer box. Wet films should not be interpreted. Compare the normal anatomical findings with those that are diseased. Normally the crestal bone is pointed in the anterior regions and flat topped in the posterior teeth and parallel to the line joining the cementoenamel junctions of adjacent teeth. The crest of the alveolar bone lies about 1.5 cm below the cementoenamel junction. Presence of a well-defined radiopaque cortical border in the alveolar crest is indicative of healthy periodontium. Widening of periodontal ligament space at the cervical portion of the tooth may indicate initial periodontitis. In healthy periodontium, the lamina dura forms a definitive, sharp angle with the alveolar crest. Interproximal crater (type of angular defect) is evident as a trough-like depression that forms in the crest of the interdental bone.

Radiographic features of periodontitis: Early to advanced stage • Localized erosion of interdental alveolar bone crest • Blunting of the alveolar crest • Loss of the sharp angle between the lamina dura and the alveolar crest • Loss of the cortical surface of the crest • Widening of the periodontal ligament space along the lateral margins of the tooth • Interdental horizontal/vertical bone loss • Vertical bone loss may appear either as an interproximal crater (seen as a trough-like depression in the interdental bone below the level of the crestal edges) or as infrabony defect (vertical radiolucency within bone extending apically along the root from the alveolar crest) • Bone surrounding the periodontal lesion may exhibit sclerosis owing to the inflammation.

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CHAPTER

17

Regressive Alterations of Teeth Ravikiran Ongole, Sumati Nagappa Baddannavar, Praveen BN

➧ Classification of Regressive Alterations

Occupations Associated with Exposure to Acidic Fumes Abfraction

Affecting Teeth ➧

Tooth Surface Loss

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Attrition

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Abrasion

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Erosion (Corrosion) Causes for Corrosion Erosion Associated with Common Food Substances Erosion Associated with Medications Erosion Related to Deleterious Habits Occupation-related Dental Erosion

Classification of Tooth Wear Classification of Severity of Tooth Wear Classification Based on Clinical Presentation

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Resorption of Teeth Regressive Alterations of Dentin Regressive Alterations of Pulp Regressive Alterations of Cementum Hypercementosis Cementicles

With increasing oral health awareness and the advances in healthcare delivery system the incidence of carious lesions and periodontal diseases have drastically reduced over the ages. As such many individuals tend to retain healthy teeth even in their old age. However, these teeth are subject to functional wear and tear in addition to the natural agerelated regressive alterations affecting the tooth and its supporting structures. Early recognition of the signs and symptoms of these regressive changes and understanding the basic pathophysiology behind such alterations will help the physician plan an effective treatment plan.

– Secondary to other pathology – Resorption of roots of deciduous teeth ❍ Changes in dentin – Secondary dentin – Reparative dentin – Dead tracts ❍ Changes in pulp – Reticular atrophy of pulp – Pulp calcifications ❍ Changes in cementum – Cementicles – Hypercementosis.

CLASSIFICATION OF REGRESSIVE ALTERATIONS AFFECTING TEETH

TOOTH SURFACE LOSS

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Tooth wear – Attrition – Abrasion – Erosion (corrosion) – Abfraction ❍ Resorption of teeth Internal – Internal inflammatory – Internal replacement External – Idiopathic 458

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Eccles in 1982 described ‘tooth surface loss’ or ‘tooth wear’ as pathological loss of tooth tissue by a disease process rather than dental caries. Tooth wear was earlier referred to as wasting diseases affecting teeth. Mair in 1992 described the term ‘non-carious cervical lesions’ or ‘cervical wear’ to refer to loss of tooth substance at the cementoenamel junction. These non-carious cervical lesions include cervical erosion, abrasion and abfraction. Clinical studies by Kitchin (1941) have shown that cervical wear lesions are often situated on the vestibular surfaces of teeth, seldom on lingual surfaces and rarely on proximal surfaces. These are also more pronounced on incisors,

Chapter 17 – Regressive Alterations of Teeth

canines, and premolars and more prevalent in the maxilla than in the mandible. The term tooth wear or tooth surface loss will include attrition apart from the cervical wear lesions.

ATTRITION Pindborg defined attrition as the loss of enamel, dentin or restoration by tooth-to-tooth contact. Tooth-to-tooth friction causes the form of wear called ‘attrition’. Two types of attrition have been described. They are physiologic and pathologic. Physiologic attrition is referred to as the gradual and regular loss of tooth structure as a result of normal mastication. However, pathologic attrition is confined to local areas or specific groups of teeth caused by abnormal friction. The physiologic causes for attrition include mastication and deglutition. Pathologic causes that cause attrition are abnormal occlusion, bruxism and habits such as tobacco and betel chewing and defective tooth structure such as in dentinogenesis imperfecta. Attrition involves occlusal/proximal surfaces of teeth. It occurs more frequently in males than in females due to greater masticatory forces. It appears as a small polished facet on cusp tips and causes flattening of incisal edges in case of anterior teeth (Figure 1). The wear will lead to exposure of the dentin causing hypersensitivity. The worn surfaces of opposing teeth occlude together very accurately.

Figure 1

Attrition of the mandibular posterior teeth in a patient with the habit of tobacco chewing. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Wear of the proximal surface causes decrease of arch length. Lambrechts et al (1989) reported that the rate of attrition is about 29 ␮m/year for molars and 15 ␮m/year for premolars. Yip et al (2004) studied the differential wear of teeth and restorative materials. They found that the lowest wear rates for restorations and the opposing dentition occur with metal alloys, machined ceramics, and microfilled and microfine hybrid resin composites. Radiographic findings Radiographically the morphology of the crowns is lost and the occlusal and incisal edges of teeth are bereft of the radiopaque enamel cap. The curved cuspal edges are reduced to single flat plane. The incisocervical length of the crown is shortened. Owing to the secondary dentin formation, the size of the pulp chambers are reduced. In severe cases, the pulp chamber and the pulp canals may be obliterated. Occasionally, hypercementosis may be seen associated with attrited teeth. Clinical significance Attrition of teeth leads to esthetic and functional disturbances. Dentinal hypersensitivity is usually the most common complaint. Severe attrition leads to pulpal exposure (Figure 2), non-vital teeth and periapical pathology. The razor sharp cuspal or incisal edges of teeth may cause traumatic ulcers.

Figure 2

Severe attrition of the mandibular incisors causing exposure of the pulp. Photograph also showing attrition of incisal edges of maxillary central incisors. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

459


It is often believed that generalized attrition will also result in a reduction in occlusal face height (vertical dimension of occlusion). However, it has been often noticed that in spite of the extensive loss of tooth surface the resting facial height appears to remain unaltered primarily because of dentoalveolar compensation. Bruxism-associated attrition may be associated with temporomandibular dysfunction.

Figure 3

Management Patients should be educated regarding the consequences of attrition. Sharp edges of teeth can be smoothened. Desensitizing toothpastes will help patients presenting with dentinal hypersensitivity. A soft bite guard will help break the habit of bruxism and prevent further loss of tooth structure. Teeth with pulpal exposure warrant endodontic treatment. Finally, crowns may be fabricated for restoring esthetics.

ABRASION Pathologic wearing away of tooth substance through some abnormal mechanical process especially in the presence of abrasive materials is known as abrasion. It usually occurs on exposed root surfaces of teeth. Different foreign bodies produce different patterns of abrasion. Most common type of abrasion is toothbrush and dentifrices (toothpaste and/or tooth powder) abrasion. Many of the residents in the villages of the Indian subcontinent use charcoal, brick and ash to cleanse teeth. These indigenous dentifrices abrade teeth further.

Cervical abrasion with respect to the upper molar along with gingival recession. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 4

Clinical features It is seen frequently on exposed root surfaces and in cervical regions of labial and buccal surfaces due to overzealous toothbrushing in horizontal manner. Maxillary teeth are involved more than mandibular teeth, and left side is affected commonly in case of right-handed persons and vice versa. It appears as a V-shaped or a wedge-shaped ditch on the root side of the cementoenamel junction in teeth with some gingival recession (Figure 3). The exposed dentin appears highly polished (Figure 4). Improper use of dental floss and tooth picks may also produce such lesions on the exposed proximal root surfaces. In habitual pipe smokers, notching of teeth can be seen that conforms to the shape of the pipe stem. It can also be seen as occupation-related oral finding in carpenters and tailors who hold objects against the teeth during work. Exposure of dentinal tubules and the consequent irritation of odontoblastic processes stimulates the formation of secondary dentin. When tooth wear is accelerated by chewing an abrasive substance between opposing teeth, the process is termed demastication and it exhibits the feature of both attrition and abrasion. 460

Highly polished surface of the cervically abraded teeth. Courtesy: Department of Oral Medicine and Radiology, KLEDC, Bangalore

Grippo et al (2004) described a term, ‘masticatory abrasion’ to refer to tooth wear on the occlusal or incisal surfaces due to friction from the food bolus. They reported that the masticatory abrasion can also occur on the facial and lingual aspects of teeth as coarse food is forced against these surfaces by the tongue, lips and cheeks during mastication. Radiographic features Radiographically, abrasive lesions caused by toothbrush are seen as half-moon shaped, well-defined radiolucent areas in the cervical regions of the teeth. These defects are usually seen involving the maxillary premolar teeth.


However, abrasive lesions caused by dental floss are usually slender half-moon-shaped radiolucent areas in the proximal regions of the neck of the teeth. Owing to the normal flossing pattern, the distal surface of teeth exhibit relatively deeper radiolucent areas compared to the mesial surfaces of teeth. Pulp chambers may be obliterated. Radiographically, these radiolucent areas mimic cervical carious lesions, root surface caries and cervical burn out.

Figure 5

Management Patients should be educated regarding the correct brushing and flossing technique. They should be advised to discontinue any deleterious habits associated with their occupations. Use of abrasive dentifrices should be strongly discouraged. Pulpal exposure is rarely a complication of cervical abrasion as the formation of secondary dentin protects the pulp from being involved. Dentinal hypersensitivity when present can be managed with the use of desensitizing toothpastes and mouthrinses.

EROSION (Corrosion) Eccles in 1982 described erosion as the loss of dental hard tissues by chemical action not involving bacteria. In simple terms, erosion is the chemical or electrochemical dissolution of teeth. Grippo et al (2004) quoting the description of erosion by The American Society for Testing and Materials Committee on Standards proposed that the term erosion should be replaced by the term corrosion. The American Society for Testing and Materials Committee on Standards defines erosion as ‘the progressive loss of a material from a solid surface due to mechanical interaction between that surface and a fluid, a multicomponent fluid, impinging solid or liquid particles’. In order to explain this in simple terms Grippo gave an example of river water flowing forcefully against the bridge supports leading to its erosion. It is a common fact that no such powerful gush of oral fluids exists in the oral cavity. Thus, the term erosion may be replaced by corrosion to describe chemical dissolution of teeth. Clinical features Erosive lesions are usually smooth surface lesions evident on the buccal and labial surface of teeth. Occasionally, proximal surfaces may be involved. Clinically, erosions appear as wide, polished and smooth areas on the enamel approximating the cervical margin of the tooth (Figure 5). The erosive areas are almost always shallow and exhibit ‘scooped-out’ architecture. The common teeth to be affected by erosion are the anterior teeth.

Erosive lesions on the buccal surface of the maxillary teeth. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Typically, when the occlusal surfaces of posterior teeth with restorations are eroded, the margins of the restorations appear higher than the level of the eroded enamel.

Causes for Corrosion (Flowchart 1) 1. Endogenous/intrinsic causes Frequent episodes of vomiting as seen in pregnancy, acid reflux or regurgitation, anorexia nervosa and bulimia cause corrosion of teeth. Bodecker (1945) showed that the gingival crevicular fluid is acidic and may cause corrosion when in contact with the cervical regions of the teeth. Typically, the enamel is translucent and thin. The common sites for erosion are the palatal surfaces of anterior teeth and occlusal surfaces of posterior teeth. Occasionally other sites that may be affected include the areas of pooling of the contents of the gastric reflux. The erosion occurs from the action of hydrochloric acid and the proteolytic enzyme pepsin that is contained in gastric juice. Erosion of the lingual or palatal surface of teeth due to regurgitation of the acidic contents of the stomach, aggravated by the circular movement of the tongue is termed perimolysis (Figure 6). Another term used with regards to regurgitation of the acidic contents is stress reflux syndrome. This syndrome typically affects young working adults. The acidic reflux usually occurs during the working hours at day. The regurgitated acidic contents are held in the mouth before being swallowed again. This syndrome produces erosion of the buccal surfaces of mandibular posterior teeth. 461


Flowchart 1 Erosion

Intrinsic causes

Frequent vomiting • Anorexia nervosa • Pregnancy • Bulimia

Reflux • Gastroesophageal reflux disease • Stress reflux syndrome

Extrinsic causes

Carbonated drinks (pH of 2–3) • Citrus food • Occupational hazards (wine tasters, workers in acidic environments)

Intrinsic and extrinsic causes for tooth erosion

Figure 6

Evans and Briggs (1994) reported a pregnant woman who had tooth surface loss on the palatal surfaces of maxillary incisors due to prolonged pregnancy-induced vomiting. 2. Exogenous/extrinsic causes Acids present in the food consumed such as fruits, carbonated soft drinks, etc. cause corrosion of teeth. Other causes for corrosion include occupations where an individual is exposed to acidic fumes, habitual sucking of lemon, tamarind, etc. Chewable forms of certain medications such as vitamin C tablets can aggravate the corrosion of teeth. pH of the erosive agent though an important factor for the erosive potential, other factors such as frequency and method of contact of the erosive agent and the proximity of toothbrushing after exposure to the erosive substance have a substantial bearing on the tooth erosion.

Erosive lesions on the palatal surface of the maxillary anterior teeth. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Pregnancy and dental erosion Laine (2002) described the effect of pregnancy on periodontal and dental health. He reported that the tooth environment is significantly altered in pregnancy. He stated that a number of salivary cariogenic microorganisms may increase in pregnancy, along with decrease in salivary pH and buffer effect. These changes in salivary composition in late pregnancy and during lactation may temporarily predispose the individual to dental caries and erosion. Rockenbach et al (2006) studied the salivary flow rate, pH, and concentrations of calcium, phosphate and sIgA in Brazilian pregnant and non-pregnant women. In their study, there was no difference in salivary flow rates and concentrations of total calcium and phosphate between pregnant and non-pregnant women. However, pregnant women had lower pH (6.7) than non-pregnant women (7.5). 462

Erosion Associated with Common Food Substances Many of the commonly used food substances have an acidic pH. Most of these commodities have a pH less than the critical pH of 5.5 that causes demineralization of teeth. It is believed that brushing teeth immediately after consuming acidic food may further weaken the tooth and make it vulnerable to erosive potential of dietary acids. Table 1 summarizes the acidic content of some commonly consumed food substances.

Erosion Associated with Medications Pierro et al (2005) evaluated the free sugar concentration and pH of pediatric medicines. The median of pH values of the syrups varied from 2.6 to 6.1. In their study, most of the pediatric syrup medicines showed high concentration of free sugars and pH below the critical value (5.5), which can increase their cariogenic and erosive potentials.


Table 1

Acidic content of common food substances

Food substance

pH

Apples

2.9–3.5

Grapes

2.9–3.4

Lime

1.8–2.4

Oranges

2.8–4.0

Pineapples

3.3–4.1

Strawberries

3.0–4.2

Coffee

2.4–3.3

Black tea

4.2

Wines

2.3–3.3

7Up®

3.5

®

2.7

®

2.7

Pepsi Coke

Vinegar

2.4–3.4

Ketchup

3.7

Fruit jam

3.0–4.0

Source: Adapted from Clark et al (1990) and Gandara et al (1999).

Hellwig and Lussi (2006) described the effects of oral hygiene products and acidic medicines. Acidic or EDTAcontaining oral hygiene products and acidic medicines have the potential to soften dental hard tissues. Chewable acetyl salicylic acid tablets and chewable hydrochloric acid tablets for treatment of stomach disorders can cause erosion of teeth. Chewable forms of vitamin C supplements have also been known to cause erosion.

Erosion Related to Deleterious Habits Areca nut chewing habit Apart from the mechanical wear of tooth surface, chewing betel quid may have the potential to cause erosion of teeth. It is believed that the betel quid can cause a change in salivary pH and its buffering capacity. Rooban et al (2006) studied the effect of habitual areca nut chewing on resting whole mouth salivary flow rate and pH. The mean pH of saliva in non-chewers in their study was 6.77; whereas the salivary pH was 6.27 in individuals who chewed betel quid along with lime. It is believed that in habitual betel quid chewers, lime probably reacts with bicarbonate buffering system by the loss of bicarbonate, turning saliva more acidic. Lime (calcium oxide in aqueous form—calcium hydroxide) could cause a free radical injury or the high alkaline content of lime may react with the salivary buffering system and alter the pH. However, Reddy et al (1980) observed no difference in salivary pH between the chewers and non-chewers. These

contrasting results could be explained with the different patterns of betel quid chewing habit and the amount of lime and other constituents that have been used in the betel quid. Chronic alcoholics Harris et al (1997) studied the effects of alcohol on oral and dental health in 107 patients. They found a high incidence of tooth wear and trauma to the dentition. Robb and Smith (1990) studied the prevalence of pathological tooth wear in 37 chronic alcoholics. These patients had more tooth wear compared to age and sex matched controls. The erosion was more commonly seen in males and those who consumed alcohol regularly than those who had alcohol in episodic binges. Almost 40% of the patients exhibited erosion on the palatal surfaces of the upper anterior teeth. Mandel (2005) suggested that the acidity of wine can contribute significantly to dental erosion.

Occupation-related Dental Erosion Wine tasters Wines primarily contain tartaric acid and to a lesser extent malic acid, lactic acid and citric acid. Minute amounts of succinic acid, citramalic acid, galacturonic acid and mucic acid may be found in some wines. Carbonic acid is usually added in champagne to produce the sparkling. The pH of wine is approximately 3.0–4.0. It is a common fact that teeth that are softened after drinking wine are highly vulnerable to attrition or abrasion. It is also believed that wine alters the inherent salivary protection mechanism. In studies involving wine tasters by Ferguson et al (1996), Chaudhry et al (1997), Gray et al (1998), the erosion of teeth was primarily confined to the maxillary incisors. Most of the wine tasters evaluated about 20–30 wines per day and most of these tasters had been in the profession for about 10–23 years. Chikte et al (2005) reported that wine tasters kept the wine to be tasted in the mouth for 10–30 seconds. In their study, wine tasters exhibited almost three times higher risk for dental erosion compared to non-taster controls. Mok et al (2001) in their in vitro study stated that the erosive potential of wine increased with increasing temperature of the wine. Various in vitro studies have shown that red wine, white wine and champagne have the potential to cause erosion of teeth. White wine and champagne are said to cause relatively more erosion than red wine. Piekarz et al (2008) showed that dentin is more susceptible to wine erosion than enamel. This finding supports the hypothesis that erosion progresses much more rapidly once the dentin is involved. 463


Professional swimmers Centerwall et al (1986) studied the extent of enamel erosion among professional swimmers at a gas-chlorinated swimming pool. In their study, the pool water sample had a pH of 2.7. Although the recommended pH for swimming pools is 7.2–8.0. They used the term ‘swimmer’s erosion’ for the acid erosion of dental enamel caused by inadequately maintained gas-chlorinated swimming pools.

Occupations Associated with Exposure to Acidic Fumes Workers of battery and galvanizing factories, galvanizing, pickling, plating and chemical manufacturers are constantly exposed to sulfuric acid and hydrochloric acid and to some amount of phosphoric, nitric and hydrofluoric acids. Inhalation of acidic fumes leads to the erosion of the incisal and labial surfaces of anterior teeth. Elsbury et al (1951) reported erosion of teeth in tin factory workers who are exposed to 11 mg/m3 tartaric acid dust for 30 hours a week. Ten Bruggen Cate (1968) reported dental erosion in individuals involved with the preparation of sanitary cleansers. Individual studies have also shown dental erosion in workers of silicone producing units. Management Piekarz et al (2008) studied the role of Tooth Mousse (GC Corporation) in preventing erosion of teeth in wine tasters. Tooth Mousse contains an anticariogenic remineralizing agent CPP-ACP (a casein phosphopeptide that stabilizes amorphous calcium phosphate nanocomplex) and has superior remineralizing properties compared to fluoride. Studies have shown that Tooth Mousse reduces tooth wear from attrition in both acidic and neutral environments. It has also been shown that Tooth Mousse can minimize erosion of enamel caused by citric acid. Studies have shown that Tooth Mousse can reduce enamel, dentin and cemental erosion. Dentinal hypersensitivity caused by erosion can be managed with desensitizing agents. Larger erosive lesions can be restored.

ABFRACTION Abfraction may be described as the microstructural loss of tooth substance in areas of stress concentration caused by tooth flexure. Theoretically it is believed that occlusal forces create stresses in the cervical area of the enamel and dentin thereby predisposing the tooth to abrasion and erosion.

464

Parafunctional habits, malocclusion, excessive masticatory load and use of dental appliances are some known causes for abfraction. Abfraction commonly occurs in the cervical region of teeth, where flexure may lead to the fracture of the slender layer of enamel rods, as well as microfracture of cementum and dentin. Morphologically they appear as crescent-shaped lesions along the cervical margin of the tooth. It often affects a single tooth with adjacent unaffected teeth. It commonly affects the mandibular dentition because of the lingual orientation and increased susceptibility to concentration of tensile stresses in the cervical region.

CLASSIFICATION OF TOOTH WEAR Bell et al (2002) in their study to assess tooth wear in children with Down syndrome, classified the severity of tooth wear as follows:

Classification of Severity of Tooth Wear ❍

Group A—No tooth wear or mild tooth wear – Small degree of physiological wear present on 1–2 teeth – Tooth wear that requires no clinical intervention ❍ Group B—Moderate level of tooth wear – Higher than physiological level of wear on two or more teeth that have not affected function or esthetics – Tooth wear that requires clinical intervention ❍ Group C—Moderate-severe tooth wear – Pathological wear on four or more teeth, defined as teeth with approximately two-thirds to one-half of the clinical crown remaining – Tooth wear that requires immediate and aggressive clinical intervention ❍ Group D—Severe tooth wear – Pathological wear on four or more teeth, defined as teeth with one or more of the following features: • Less than one-third of the clinical crown remaining • Wear to the gum-line • Severely scooped dentin – Tooth wear of a severity rarely seen in this age group – Tooth wear that requires immediate and aggressive clinical intervention.

Classification Based on Clinical Presentation ❍ ❍ ❍

Group A—no wear Group B—well-defined facet (indicating attrition) Group C—ill-defined facet (indicating multifactorial etiology)


Table 2

Tooth wear index criteria

Score

Surfaces of tooth involved

Criteria

0

Buccal, lingual, incisal

No loss of enamel surface characteristics

1

Buccal, lingual, occlusal, incisal

Loss of enamel surface characteristics

2

Buccal, lingual, occlusal

Loss of enamel, visible dentin for ⬍1/3 of the surface

3

Buccal, lingual, occlusal incisal

Loss of enamel, visible dentin for ⬎1/3 of the surface Loss of enamel just exposing dentin

4

Buccal, lingual, occlusal incisal

Complete loss of enamel, or pulp exposure, or secondary dentin Pulp exposure or exposure of secondary dentin

9

Buccal, lingual, occlusal, incisal

Excluded from analysis missing tooth, partially erupted, orthodontic band, composite restoration, any crowns, tooth fracture, and fissure sealant

Source: Proposed by Smith and Knight, modified by Millward et al.

❍

Group D—well-defined areas of dentin or pitting of dentin (indicating erosion).

Tooth wear index criteria are given in Table 2. Bartlett et al (2008) proposed a new scoring system for erosive tooth wear which can be used both for scientific and clinical purposes. They termed this scoring system as Basic Erosive Wear Examination (BEWE). In this system, all teeth in every sextant are assessed and the most severely affected tooth in every sextant is scored and the cumulative score will guide the dental practitioner in choosing the best treatment modality. Criteria for grading erosive wear ❍ ❍ ❍

Score 0—No erosive tooth wear Score 1—Initial loss of surface texture Score 2—Distinct defect, hard tissue loss ⬍50% of the surface area ❍ Score 3—Hard tissue loss ⱖ50% of the surface area. The buccal/facial, occlusal, and lingual/palatal surfaces are examined. Once all the sextants have been assessed, the sum of the scores is calculated. BEWE scores ❍ ❍ ❍ ❍ ❍ ❍

Sextant (17–14)—record the highest score Sextant (13–23)—record the highest score Sextant (24–27)—record the highest score Sextant (37–34)—record the highest score Sextant (33–43)—record the highest score Sextant (44–47)—record the highest score

The sum of the highest scores for each sextant is taken as the indicator for treatment planning.

❍

Score between 3 and 8: Oral hygiene and dietary assessment, and advice, routine maintenance and observation, Repeat at 2-year intervals. ❍ Score between 9 and 13: Oral hygiene and dietary assessment, and advice, identify the main etiological factor(s) for tissue loss and develop strategies to eliminate respective impacts. Consider fluoridation measures or other strategies to increase the resistance of tooth surfaces. Ideally, avoid the placement of restorations and monitor erosive wear with study casts, photographs or silicone impressions. Repeat at 6- to 12-month intervals. ❍ Score 14 and over: Oral hygiene and dietary assessment, and advice, identify the main etiological factor(s) for tissue loss and develop strategies to eliminate respective impacts. Consider fluoridation measures or other strategies to increase the resistance of tooth surfaces. Ideally, avoid restorations and monitor tooth wear with study casts, photographs or silicone impressions. Especially in cases of severe progression consider special care that may involve restorations. Repeat at 6- to 12-month intervals.

RESORPTION OF TEETH It is defined as a condition or pathologic process resulting in the loss of dentin, cementum and/or bone. Types of resorption 1.

Management strategies ❍

Score ⱕ2: Routine maintenance and observation, repeat at 3-year intervals.

2.

Internal resorption a. Internal replacement b. Internal inflammatory i. Transient ii. Progressive External resorption a. External surface resorption

465


Figure 7

Intraoral periapical radiograph showing external resorption of the root apex in a long-standing periapical abscess. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

3. 4.

b. External inflammatory c. Ankylosis d. Replacement resorption Combined internal and external Transient apical breakdown.

Internal resorption can occur due to various causes like chronic pulp inflammation, trauma, pulpotomy, restorative procedures, herpes zoster, hereditary, cracked tooth syndrome, invaginated cingulum and orthodontic tooth movement. External resorption can be caused due to replantation of tooth, orthodontic forces, eruption of neighboring teeth, root fracture, trauma, necrotic pulp, chronic periapical inflammation or infections (Figure 7), root planing, citric acid treatment and other pathological conditions like cysts (Figure 8), ameloblastoma (Figure 9), giant cell tumor, fibrous osseous lesions, hereditary conditions, bleaching (especially causes cervical external resorption) and orthognathic surgery. Diagnosis is often misinterpreted. External resorption can be described as internal or vice versa. Often the diagnosis can be simplified by a careful assessment of the history, particularly if it is trauma. A pink appearance of the crown is indicative of a highly vascular tissue which has removed sufficient enamel and dentin to allow it to be visible through the overlying tooth substance. Although earlier descriptions of a pink tooth as being internal is incorrect as it may be either internal or external in origin. In the absence of history of trauma, it is more likely that the pink spot will indicate an external origin. 466

Figure 8

External root resorption of the second molar secondary to the dentigerous cyst associated with the impacted third molar. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 9

External root resorption of the mandibular first molar secondary to ameloblastoma involving the body and ramus of the mandible. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Clinical assessment of the mobility may be of use in differential diagnosis. A tooth displaying no mobility or held in infraocclusion indicates ankylosis or replacement resorption. Percussion test will also produce a resonant sound.


The key diagnostic tool is a good radiograph. The margins of internal resorptive defect are smooth and well defined; in contrast to that of external are rough and has ‘moth-eaten’ appearance. Most internal resorptive defects are symmetrical and external resorptive defects are usually asymmetrical. The anatomic configuration of the root canal is altered and increased in size with internal resorption. In external resorption, the canal is unaltered, and its outline can be followed through the resorptive defect. Radiographs exposed at different horizontal beam angles can aid in distinguishing internal from external resorption. If the defect is internal, the relationship of the canal to the defect will remain the same, regardless of the angles. If the defect is external, the relationship of the defect to canal will shift as the horizontal angle of the beam is altered. Key cells involved in resorption are monocytes, macrophages, osteoclast, odontoclasts, dentinoclasts and cementoblasts.

Flowchart 2 Traumatic injury

Intrapulpal hemorrhage

Organizes to granulation tissue

Compresses the dentinal wall

Predentin formation stops and odontoclasts differentiate

Internal resorption

Systemic regulatory factors Parathyroid hormone increases osteoclastic activity by activation of osteoclasts to increase the production of carbonic anhydrase and promotion of fusion of marrow cells to produce multinucleated giant cells. 1,25-Dihydroxy vitamin D increases the activity of osteoclasts without increase in number and calcitonin inhibits resorption by suppressing the osteoclastic cytoplasmic motility and producing cell retraction.

Events in resorption of teeth

structure has no relationship with the normal bone forms of tooth, hence termed as metaplastic tissue. Radiographically, it appears as an enlargement of the pulp space. The pulp space thus enlarged is less radiodense giving the appearance of partial canal obliteration.

Neuronal regulatory factors

Events in resorption of teeth (Flowchart 2)

Neuropeptides released by the terminal nerve endings such as substance P (SP), calcitonin gene related peptide (GRP), neurokinin A, vasoactive intestinal polypeptide (VIP), etc. increase vasodilatation, thus an increase in macrophages and an increased osteoclastic activity, remove mechanism of resorpion.

Treatment consists of pulp tissue removal and canal cleaning and shaping, followed by scaling the canal system.

Internal resorption It is also called chronic perforating hyperplasia of pulp, internal granuloma, odontoclastoma and pink tooth of Mummery. Resorption of internal type occurs from pulp space/root canal space and is asymptomatic. It is usually discovered during routine radiographic evaluation. A pink colored discoloration is visible if extensive internal resorption occurs in the coronal portion of the tooth, as described by Mummery. Most cases are found in the anterior region. Etiological factors are mainly trauma and caries. Internal resorption can be of two types: internal replacement (metaplastic) and internal inflammatory. Internal replacement type occurs as a result of lowgrade irritation of the pulp such as chronic irreversible pulpitis or pulp necrosis. This can occur because of trauma or application of extreme heat to the tooth. There is concomitant resorption of hard tissue with frequent deposition of hard tissue resembling bone or cementum. The resultant

External resorption External resorption is the one which occurs primarily from the periodontal space affecting the root surface. Four categories of external resorption have been described based on the clinical and histological manifestations: ❍ ❍

External surface resorption External inflammatory resorption – Cervical – Apical ❍ Ankylosis ❍ External replacement resorption. External surface resorption is a transient phenomenon in which the tooth undergoes spontaneous destruction and repair. It is found in all the teeth and considered to be a normal physiologic response. It is a self-limiting process and does not require any treatment. External inflammatory root resorption is described as a bowl-shaped defect which penetrates the dentin. This occurs following irritation or injury of the periodontium due to trauma, periodontal infection or orthodontic treatment. Based on location it can be cervical and apical. Cervical 467


resorption occurs following injury to the epithelial cervical attachment apparatus. It can occur because of physical insult like trauma, surgical procedures, orthodontic treatment, bruxism and periodontal root planing. Chemical injury as a result of 30% hydrogen peroxide can cause cervical resorption. Apical resorption occurs because of traumatic injury (luxative and intrusive movements), periradicular periodontitis and orthodontic procedures. Ankylosis is primarily associated with luxation injury, especially avulsion. It is the union of tooth and bone with no intervening connective tissue following extensive resorption. Ankylosis can be further categorized as transient or progressive in nature. External replacement resorption is caused due to luxative injury. This is a continuous process by which the tooth is gradually resorbed and replaced by bone. It differs from ankylosis in which it exhibits the presence of intervening inflamed connective tissue.

Regressive Alterations of Dentin Secondary dentin Physiologic dentin deposition proceeds throughout life. It is a protective response and can be differentiated from primary dentin by the sharp bending of tubules producing a line of demarcation. It has incremental patterns of deposition. The tubular structures are less regular than those of primary dentin. The deposition occurs in greater quantities in the floor and roof of pulp chamber than on walls; so, there is reduction of pulp chamber and pulp horns as the tooth ages. Reparative dentin It is also known as irregular or tertiary dentin. It is a protective response to noxious stimuli such as caries operative procedures, restorative materials, abrasion, erosion or trauma. It is deposited at the rate of 1.5 ␮m per day, produced by replacement odontoblasts. Reparative dentin has less tubules and less mineralized. There is a definite demarcation between secondary and reparative dentin which is called ‘calcitraumatic line’. Dentinal sclerosis It is a regressive alteration in tooth surface that is characterized by calcification of the dentinal tubules. It is also called transparent dentin. The causes for dentinal sclerosis includes aging caries and tooth wear. Exact mechanism of deposition of calcium salts is not understood. Most likely source is dentinal fluid within the tubules. Initially, only sporadic hydroxyapatite crystals are deposited which gradually fill the tubules. This makes it to appear transparent in transmitted light and dark in reflected light. It decreases the permeability of dentin and slows the carious process. It decreases the conductivity of odontoclastic process. Dead tracts When the odontoblasts disintegrate completely, their empty tubules are filled with air, so they appear black 468

Figure 10

Dead tracts and reparative dentin. Courtesy: Department of Oral Pathology, MCODS, Mangalore

in transmitted light and white in reflected light (Figure 10). The causes for dead tracts include caries, attrition, abrasion and erosion. These are seen more in narrow pulpal horn areas, because of crowding of odontoblasts. More commonly these are seen in older individuals.

Regressive Alterations of Pulp Reticular atrophy of pulp change is seen in older individuals. Clinically asymptomatic, responds normally to vitality tests. Histopathologically, large vacuolated spaces in pulp are seen with decreased cellular elements. Degeneration and disappearance of odontoblast is also seen. Pulp calcifications Pulp calcifications (pulp stones, denticles) are nodular calcified masses appearing in either or both the coronal and radicular portion of pulp (Figure 11). These are usually asymptomatic until they impinge on nerves or blood vessels. Pulp stones are classified as true denticles or false denticles according to microscopic appearance. True denticles are rare and resemble dentin structurally with dental tubules and odontoblastic processes and are usually seen close to the apical foramen. False denticles do not resemble dentin. These do not exhibit dentinal tubules but have concentric layers of calcified tissue. Flowchart 3 describes the formation of pulp stone. Pulp stones can be either free, attached or embedded according to the mode of attachment. Free dentricles are not attached to walls of pulp space; attached stones are attached to wall of pulp cavity, and embedded dentricles are attached and become an integral part of dentin. Various causes of formation of pulp stones are aging, systemic causes like cholelithiasis, cardiac, renal lithiasis, arteriosclerosis, gout, acromegaly, and diseases such as dentin dysplasia type II, pulpal dysplasia, tumoral calcinosis, calcinosis


universalis and Ehlers–Danlos syndrome. It may cause problem during endodontic therapy. Radiographically, it appears as radiopaque masses in pulp space (Figure 12).

Regressive Alterations of Cementum Cementum is the mineralized dental tissue that overlies the anatomic roots of teeth. It provides the site for attachment

of the periodontal ligament fibers that anchor the tooth to the surrounding structures. It is avascular. The inorganic component of cementum consists of hydroxyapatite and fluoride. It is interesting to note that the fluoride content in cementum is the highest compared to all mineralized tissues. Cellular cementum (presence of cementocytes) is generally seen at the apical one-third of the root; whereas the rest of the root surface is covered by acellular cementum (lack of cementocytes).

Figure 11 Figure 12

Radiograph revealing well-defined radiopacities in the pulp chamber of first and second molars suggestive of pulp stones. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Histologic appearance of a free pulp stone. Courtesy: Department of Oral Pathology, MCODS, Mangalore

Flowchart 3 Process of formation of pulp stone

Local metastatic dysfunction

Trauma

Hyalinization of injured wall

Vascular damage (thrombosis)

Fibrosis Mineralization (nidus formation)

Grows with time

Pulp stone

Process of formation of pulp stone

469


Figure 13

Bulbous roots evident in extracted teeth specimen. Courtesy: Department of Oral Pathology, MCODS, Mangalore

The thickness of cementum overlying the root varies based on the location. The thickness of the cementum at the cementoenamel junction is the thinnest and it measures 20–50 ␮m at the apex. The thickness of cementum is roughly 150–200 ␮m.

Figure 14

Intraoral periapical radiograph showing thickening of the roots. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Figure 15

Hypercementosis Hypercementosis is a non-neoplastic deposition of excessive cementum which is continuous with the normal radiographic cementum. It is asymptomatic and seen in adulthood. The incidence of hypercementosis increases with age. It may appear in one tooth or involving multiple teeth (Figure 13). Hypercementosis is frequently seen in relation to the premolars. The cause for hypercementosis can be either due to local factors like abnormal occlusion, inflammation, nonfunctional tooth, tooth repair, root fracture, and cemental tear or systemic factors like Paget’s disease, hyperpituitarism (acromegaly and gigantism), arthritis, calcinosis, rheumatic fever, thyroid goiter, idiopathic. Radiographically, thickening or blunting of root is seen. Enlarged root is surrounded by the radiolucent periodontal ligament space and intact radiopaque lamina dura (Figures 14 and 15). Histological section reveals deposition of cellular or secondary cementum in concentric layers over the existing thin layer of acellular or primary cementum. This cellular cementum has also been referred to as osteocementum owing to its histological resemblance to bone. Treatment is not required but it may pose problem during extraction. 470

Radiograph revealing bulbous roots with intact lamina dura. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Cementicles Small foci of non-neoplastic calcified tissue, which lie in periodontal ligament along the lateral and apical root areas are called cementicles. Calcification of epithelial cell rest of Malassez, aging and cemental tears undergoing remodeling have all been implicated in the formation of cementicles. These present as circular laminated structures. When attached to root, cementum shows roughened globular outline on the root surface.

SECTION

System Review

VII

18 19 20 21 22 23

Systemic Disorders and their Clinical Implications Bone Diseases and Fibro-osseous Lesions Autoimmune Disorders Granulomatous Diseases Sexually Transmitted Diseases Nutritional and Metabolic Disorders

473 568 590 605 625 633

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Systemic Disorders and their Clinical Implications

CHAPTER

Arshiya Ara, Ceena Denny, Gajendra Veeraraghavan, Seema Patil, Vishwananth R, Sarat Gummadapu, Veena KM, Ranganath Ratehalli, Sandeep Deshpande

Cardiovascular Disorders ➧ Symptoms Suggestive of Cardiovascular Disease Chest Pain Breathlessness or Dyspnea ➧

Common Cardiovascular Disorders and their Dental Considerations

➧

➧

➧

➧

Cyanotic Acyanotic

➧

Platelet Disorders

➧

Thrombocytopathic Disorders

➧

Thrombocytopenic Disorders

➧

Rheumatic Fever ➧ Infective (Bacterial) Endocarditis Clinical Conditions that Warrant Use of Antibiotic Prophylaxis Treatment Needing Antimicrobial Prophylaxis in Patients at Risk of Infective Endocarditis ➧

Idiopathic Thrombocytopenic Purpura Thrombotic Thrombocytopenic Purpura ➧

Disorders of Coagulation

➧

Inherited Coagulation Disorders Hemophilia A Hemophilia B and C Von Willebrand’s Disease

Heart Failure Classifications of Heart Failure Oral Disease Aspects

Hematological Disorders ➧ Red Blood Cell Disorders ➧ Polycythemia ➧ Anemia Iron Deficiency Anemia Paterson–Kelly Syndrome (Plummer–Vinson Syndrome) Anemia due to Vitamin B12 and Folic Acid Deficiency Aplastic Anemia Glucose-6-phosphate Dehydrogenase Deficiency Sickle Cell Anemia

➧

Thalassemia White Blood Cell Disorders ➧ Qualitative Disorders

Respiratory Disorders ➧

Classification of Respiratory Tract Disorders

➧

Common Symptoms of Respiratory Diseases Cough Sputum Hemoptysis Chest Pain Breathlessness or Dyspnea Wheezing

➧

Non-neoplastic Disorders Leukopenia Reactive Leukocytosis

Upper Respiratory Tract Infections Viral Infections Allergic Rhinitis Pharyngitis and Tonsillitis

Chediak–Higashi Syndrome ➧

Acquired Coagulation Disorders Liver Disease Vitamin K Deficiency Disseminated Intravascular Coagulation

➧ ➧

Vascular Disorders (Vessel Wall) Hereditary Hemorrhagic Telangiectasia Ehlers–Danlos Syndrome Marfan’s Syndrome Scurvy

Ischemic or Coronary Heart Disease Myocardial Infarction Congenital Heart Disease

Bleeding Disorders Classification of Bleeding Disorders

Angina Pectoris ➧

Neoplastic Disorders Leukemia Lymphomas Multiple Myeloma

Hypertension ➧

18

➧

Lower Respiratory Tract Infections Asthma

473

Section VII – System Review

Chronic Obstructive Pulmonary Disease or Chronic Obstructive Airway Disease Cystic Fibrosis ➧

Granulomatous Diseases

➧

Malignant Disorders

➧

Categories of Disturbances of Endocrine Function Pathophysiology of Hypothalamic–Pituitary Axis ➧

Other Respiratory Diseases Legionnaire’s Disease (Legionellosis) Obstructive Sleep Apnea Syndrome

Renal Disorders ➧ Renal Diseases Chronic Renal Failure Uremic stomatitis

Gastrointestinal Disorders ➧ Gastroesophageal Reflux Disease ➧ ➧ ➧ ➧ ➧ ➧

Inflammatory Bowel Disease Ulcerative Colitis Crohn’s Disease Hiatal Hernia Peptic Ulcer Disease Eating Disorders Anorexia Nervosa Bulimia Nervosa

➧

➧

➧

General Overview of Functional Mechanisms of Endocrine System Hormones

CARDIOVASCULAR DISORDERS Cardiovascular disease is quite common, though more frequent and severe in later life, can also affect young individuals. It is one of the leading causes of death in the world. A thorough knowledge of cardiovascular diseases is necessary because of its implications in dentistry and also the initial measures taken by the dentists in case of certain emergency conditions can be lifesaving. 474

Thyroid Gland Pathophysiology of Hypothalamic–Pituitary–Thyroid Axis

➧

Disorders Associated with Thyroid Gland Hypothyroidism Hyperthyroidism

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Parathyroid Glands Hyperparathyroidism Hypoparathyroidism Tetany

➧

Hypothalamus–Pituitary–Adrenal Axis Cushing’s Syndrome Endocrinopathic Pigmentation Adrenal Insufficiency Aldosteronism Disorders of Adrenal Medulla Sex Hormones

Jaundice Hepatitis

Endocrinal Disorders

Disorders of Posterior Pituitary (Neurohypophysis) Diabetes Insipidus

Liver Diseases

Neuromuscular Disorders ➧ Bell’s Palsy ➧ Epilepsy ➧ Parkinsonism ➧ Multiple Sclerosis ➧ Muscular Dystrophy ➧ Oromandibular Dystonia ➧ Myasthenia Gravis

Growth Hormone Growth Hormone Deficiency Growth Hormone in Children—Dwarfism Adult GH Deficiency Growth Hormone Excess Gigantism Growth Hormone Excess in Adults

Bronchogenic Carcinoma ➧

General Overview of Disorders of Endocrine System

➧

Pregnancy Multiple Endocrine Neoplasia Type III (Multiple Mucosal Neuroma Syndrome)

➧

Saliva and Monitoring of Hormone Levels

Mental Health and its Relevance to Dentistry ➧

Concepts of Mental Illness and its Classification

➧

Diagnostic Criteria and Screening Questions

➧

Interesting Interface between ‘Dentistry’ and ‘Psychiatry’

➧

Management of Psychiatric Disorders

Cardiovascular history taking Clinicians must assess the status of cardiovascular system within the context of the patient’s overall health. These associated conditions can heighten cardiovascular risk during dental care. Consequently, an initial medical history should be obtained from all patients and it must be reviewed with the patient at each appointment to identify serious cardiac conditions. The clinicians should also note history of cerebrovascular disease, renal dysfunction, chronic pulmonary

Chapter 18 – Systemic Disorders and their Clinical Implications

disease, diabetes mellitus, anemia, dyslipidemia, peripheral vascular disease, orthostatic intolerance and anemia. Further an accurate record of current medication taken by the patient, use of tobacco products, alcohol and over-thecounter and recreational drugs should be documented.

– The functional capacity can be expressed in terms of metabolic equivalent (MET) values. Functional capacity can be classified as: ❍ 1 MET or more – Do light work around the house – Walk a block on level ground at 3.2–4.8 km/ hour ❍ 4 METs or more – Climb a flight of stairs or walk up a hill – Walk on level ground at 6.4 km/hour – Run a short distance – Do heavy work around the houses (scrubbing floors, lifting or moving heavy furniture) ❍ 10 MET or more – Participate in strenuous sports (swimming, singles tennis, football, basketball or skiing)

SYMPTOMS SUGGESTIVE OF CARDIOVASCULAR DISEASE Chest Pain It is the common presentation of cardiac diseases, though can be a manifestation of disease of the lungs, musculoskeletal system or gastrointestinal system. Pain is usually felt behind the sternum, radiates across the chest and down the arms, it may also radiate to the back or to the mandible.

The functional capacity can be graded as:

Breathlessness or Dyspnea It is a major symptom of many cardiac disorders, particularly left heart failure. Dyspnea may vary in severity from an uncomfortable awareness of breathing to a frightening sensation of fighting for breath. There are three forms of dyspnea: ❍

Orthopnea: Lying flat causes a steep rise in left atrial pressure in patients with heart failure resulting in pulmonary congestion and severe dyspnea. A semirecumbent position helps such patients. ❍ Paroxysmal nocturnal dyspnea: Frank pulmonary edema on lying flat awakens the patient from sleep with distressing dyspnea. Symptoms are corrected by standing upright. ❍ Exertional dyspnea: Exercise causes a sharp increase in left atrial pressure resulting in dyspnea. Fatigue Exertional fatigue is an important symptom of heart failure and is more severe toward the end of the day. Palpitation Awareness of the heartbeat is common during exertion or heightened emotions. However, it may be indicative of an abnormal cardiac rhythm. Dizziness and syncope Cardiovascular disorders produce dizziness and syncope by transient hypotension resulting in abrupt cerebral hypoperfusion. Recovery is usually rapid. Lower limb pain or discomfort A tight or cramping pain in lower limb muscles on exercise may be present. Edema of legs Bilateral swelling of the legs due to edema is a common feature of chronic heart failure. The history should also determine the patient’s functional capacity. ❍

Functional capacity – Functional capacity refers to an individual’s capacity to perform a spectrum of common daily tasks.

❍ ❍ ❍ ❍

Excellent (if 10 MET) Good (7–10 MET) Moderate (4–7 MET) Poor ( 4 MET).

Patients are at an increased cardiac risk when unable to meet a 4 MET demand during normal daily activity. Physical examination The general appearance of the patient can provide valuable information related to his/her physical and emotional state. Pallor, cyanosis, peripheral edema, dyspnea, tremors, Cheyne–Stokes respiration, obesity and anxiety are clues that suggest the presence of cardiovascular disease. Cyanosis It is defined as the blue color of the skin and mucous membranes due to the presence of excessive amount of deoxygenated hemoglobin in these tissues. It is seen in heart failure, cyanotic congenital cardiac disease and chronic cardiac disorders. Finger clubbing It is the obliteration of the angle between nail base and adjacent skin of the finger. Clubbing is characterized by the thickening of the nail bed secondary to hypervascularity and opening of the anastomotic channels in the nail bed. It is seen in congenital cardiac disease and infective endocarditis. Distended neck veins Systemic fluid retention and inability of heart to pump blood into the lungs may be seen as distention of the veins in the neck. Swelling of legs due to peripheral edema Bilateral swelling of both the legs may be due to chronic heart failure. Edema is detectable by fingertip pressure over the tibial bone for about 30 seconds, a pit due to physical displacement of excessive tissue fluid is observed. Blood pressure Determination of the blood pressure provides a useful clue that will confirm or rule out significant cardiovascular disease. It should be recorded on all new 475


patients at the time of initial appointment and at all subsequent appointments on all patients with a history of hypertension, cardiovascular disease, diabetes mellitus, thyroid disorders, adrenal disease, renal dysfunction and significant use of tobacco, alcohol or coffee. The auscultatory method of measurement of BP is recommended. In patients older than 50 years, elevated systolic pressure may predict the potential for cardiovascular morbidity and mortality. Pulse rate and rhythm The pulse pressure closely correlates with systolic pressure and is a reliable cofactor that will provide us with information on cardiovascular disease. Rate below 60 or above 100 in adults and if associated with symptoms such as sweating, weakness, dyspnea and chest pain should be considered as a risk factor in association with non-cardiac procedures. Further abnormalities in the normal rhythm of the pulse should provoke a search for any underlying cardiac diseases.

COMMON CARDIOVASCULAR DISORDERS AND THEIR DENTAL CONSIDERATIONS Hypertension Hypertension is a disorder characterized by an abnormal elevation of arterial pressure, which if sustained and untreated, is associated with a significant increase in morbidity and mortality. The systolic or diastolic pressure or both are elevated in hypertension. It may be asymptomatic for long periods but ultimately leads to damage with resultant symptoms in several organs including kidney, heart, brain and eyes. It is generally accepted that a sustained systolic blood pressure of 140 mmHg or more and a sustained diastolic blood pressure of 90 mmHg or more is abnormal. Etiology Majority of the patients with hypertension have no cause for their disease. These patients are diagnosed to have primary, idiopathic or essential hypertension. Essential hypertension is seen in elderly, obese and individuals who are tensed and fearful. Genetic factors also play a role. However, a few patients have underlying systemic diseases that produce hypertension, which is known as a secondary hypertension. Systemic diseases causing secondary hypertension ❍ ❍ ❍ ❍ ❍ 476

Renal disease (renal parenchymal disease, renal artery stenosis) Adrenal abnormalities (primary aldosteronism, Cushing’s syndrome, pheochromocytoma) Coarctation of aorta Hyperthyroidism Pregnancy (eclampsia)

❍

Central nervous system (CNS) disorders (head injury, infection, hemorrhage and brain tumors) ❍ Autonomic hyperactivity ❍ Sleep apnea ❍ Drug-induced (cyclo-oxygenase [COX-1 and COX-2] inhibitors, sympathomimetics, steroid hormones, cyclosporine and tacrolimus). Lifestyle risk factors increasing the chances of a person becoming hypertensive are: ❍ ❍ ❍ ❍ ❍ ❍

Obesity High dietary salt intake Excess alcohol Smoking Physical inactivity Stress/anxiety.

Signs and symptoms A patient with hypertension is usually asymptomatic for quite a few years. The early symptoms include occipital headache, vision changes, ringing ears, dizziness, weakness and nose bleeding. Odontalgia due to hyperemia or congestion of dental pulp has also been reported. Untreated hypertension reduces the life span by 10–20 years. Even mild hypertension that has not been treated for 7–10 years increases the risk of complications. Sustained hypertension results in arterial damage (atherosclerosis) and the onset of these vascular changes in the kidney, cardiovascular system, cerebrovascular system and eyes can cause complications such as renal failure, coronary insufficiency, myocardial infarction, congestive cardiac failure, cerebrovascular accident (stroke) and blindness in patients. Malignant hypertension develops in 1% of hypertensives. The chief complication is severe ischemic damage to kidney and renal failure. In the absence of treatment, it can be fatal within 1 year of diagnosis. Blood pressure is measured by the use of a sphygmomanometer, an instrument that indirectly records the diastolic and systolic pressure. Food, exercise, alcohol and smoking should be avoided for 30 minutes before measurement of BP and also the patient should be at rest for at least 5 minutes. Faulty BP readings involve using improper size cuffs or applying the cuffs too loosely or too tightly. Classification of blood pressure Classification

Systolic BP (mmHg)

Diastolic BP (mmHg)

Normal

120

80

Pre-hypertension

120–139

80–90

Stage 1 hypertension

140–159

90–99

Stage 2 hypertension

160

100


Malignant hypertension It is a highly elevated blood pressure associated with organ damage (eyes, brain, lungs and kidneys are affected). The systolic and diastolic blood pressures are usually more than 240 mmHg and 120 mmHg respectively. White coat hypertension It is a phenomenon in which patients exhibit elevated blood pressure in a clinical setting but not when recorded by themselves at home or when ambulatory. White coat hypertension is believed to be secondary to anxiety, some individuals may experience during their visit to a hospital.

Therapeutic goals and pharmacologic strategies for hypertension Therapeutic goal

Pharmacologic strategies

Reduce volume overload Block beta-1 adrenergic receptors Dilate blood vessels Reduce sympathetic outflow from the central nervous system

Diuretics Beta-1 adrenergic receptor antagonists ACE inhibitors Angiotensin II receptor antagonists Calcium channel blocking agents Alpha-1 adrenergic receptor antagonists Alpha-2 adrenergic receptor antagonists

General management

Oral side effects of antihypertensive medicines

❍ ❍

Drugs

Side effects

Diuretics

Dry mouth, lichenoid reactions

Beta blockers

Dry mouth, lichenoid reactions, taste change

ACE inhibitors

Loss of taste, dry mouth, ulcerations, angioedema

Calcium channel blockers

Gingival enlargement, dry mouth, altered taste

Alpha blockers

Dry mouth

Direct-acting vasodilators

Facial flushing possible, increased risk of gingival bleeding and infection

Central-acting agents

Dry mouth, taste changes, parotid pain

Angiotensin II antagonists

Dry mouth, angioedema, sinusitis, taste loss

Acute emotions should be avoided. In patients with secondary hypertension, manage the primary cause. ❍ Patient should practice the following for a lifetime: – Weight loss—maintaining ideal bodyweight lowers systolic BP reading by 5–20 points. – Reduction in salt intake less than 2.4 g/day – Restricting alcohol and caffeine – Stop smoking – Exercise (lowers BP by 5–9 mmHg) – Intake of fruits, vegetables and low fat dairy products. Specific management Antihypertensive therapy ❍

❍

❍ ❍

❍ ❍

❍

Direct-acting vasodilators: Nitroglycerin and minoxidil directly relax vascular smooth muscle. Methyldopa and clonidine act in the CNS to decrease sympathetic nervous system output. Angiotensin II receptor blockers: Losartan and telmisartan prevent angiotensin II from binding on smooth muscle sites in arteries, promoting vasodilatation. Diuretics: Frusemide and hydrochlorothiazide reduce blood volume and decrease vascular resistance. Beta blockers: Propranolol and sotolol reduce heart rate, and force of contraction. Selective beta blockers are preferred. Non-selective beta blockers are contraindicated in patients with asthma, because their beta agonist action is blocked. ACE inhibitors: Captopril, ralopril retard renin–angiotensin system leading to vasodialatation. Calcium channel blockers: Amlodipine, nifedipine, decrease the calcium influx in smooth and cardiac muscles, reduce total peripheral resistance and decrease force of contraction. Alpha blocking agent: Prazosin, terazosin prevent norepinephrine from binding to receptors in arterioles leading to vasodialatation.

Dental considerations Patients with controlled hypertension can receive dental care in short appointments. Anxiety and pain should be avoided since endogenous epinephrine release in response to pain or fear may induce dysrhythmias. Preoperative reassurance and sedation with 10 mg temazepam or 5 mg diazepam may be helpful. Raising patients from supine position may cause postural hypertension and loss of consciousness if patient is using thiazides, calcium channel blockers. Aspirating syringe should be used to give local anesthesia to avoid intravenous entry of epinephrine. Epinephrine in local anesthesia is not contraindicated unless systolic pressure is over 200 mmHg or diastolic pressure is over 115 mmHg. Epinephrine containing local anesthesia should not be given in large doses in patients taking non-selective beta blockers since interaction may induce hypertension and cardiovascular complications. Gingival retraction cords containing epinephrine should be avoided. 477


Administration of two to three cartridges of local anesthesia with epinephrine 1:100,000 will not cause cardiovascular changes. Epinephrine should be used with caution in patients taking tricyclic antidepressants and diuretics since acute hypertensive changes and dysrhythmias, respectively may occur.

ISCHEMIC OR CORONARY HEART DISEASE It is one of the most common medical problem in general population. Coronary heart disease is an inflammatory disease affecting the large and medium sized arteries of heart resulting in inadequate or decreased coronary blood flow. Atherosclerosis and hypertension are the major contributory factors. Atherosclerosis basically refers to the formation of fibrofatty lesions in the walls of arteries. These may increase in size to cause stenosis of the vessels reducing the blood flow to the heart on exercise. This is known as angina. In the later stages, the atherosclerotic plaque ruptures and exposes the arterial blood to the plaque contents and stimulates the formation of hemostatic plug. This occlusive thrombus may cause myocardial infarction. It is related to a variety of risk factors. Knowledge about the risk factors will help the dentist to assess the risk of cardiac problems in patients with no coronary problems. Risk factors Non-modifiable factors 1. Family history: Presence in patient’s parents, increases the risk of occurrence in patients at an early age. 2. Gender: Men between 25 and 65 years of age are more prone and women at post-menopausal age. Modifiable factors 1. Total cholesterol of more than 240 mg/dl is associated with ischemic heart disease. Elevated LDL, decreased HDL, increased total to HDL cholesterol and hypertriglyceridemia also contribute. Statins and fibrates correct lipid abnormalities. 2. Hypertension: Systolic pressure more than 140 mmHg or diastolic pressure more than 90 mmHg increases the chances of ischemic heart disease. 3. Smoking: Women who smoke more than 19 cigarettes per day are likely to have ischemic heart disease. 4. Other risk factors are diabetes mellitus, obesity, lack of exercise, lack of fruits and vegetables in the diet, alcohol use, stress, elevated levels of C-reactive proteins.

Angina Pectoris It is the most common clinical presentation of ischemic heart disease and is infrequent before the age of 40 years. 478

It may be defined as a temporary inability of the coronary arteries to supply the myocardium with the sufficient amount of circulated blood. Atherosclerotic narrowing of the coronary arteries is an important cause of this imbalance in oxygen supply. It is rarely caused by spasm of the blood vessels. Initially, the atherosclerosis does not lead to any symptoms. However, the obstruction becomes large over a period of decades to cause pain. The pain of angina is described as a sense of choking, tightness, heaviness, or compression of the chest, sometimes radiating to the left arm or jaws. The common precipitating causes include physical exertion and emotions. Levine’s sign is characteristic of ischemic chest pain. It is seen in angina pectoris and myocardial infarction. This sign described by Dr Sam Levine who observed many of his patients suffering from chest pain hold their fist over the chest. Variants of angina Stable angina Pain only on exertion and relieved by rest within 10 minutes. Stable angina is caused by fixed atheromatous plaque in one or more coronary arteries. Unstable angina Angina at rest, angina appearing more frequently, appearing at lower level of exertion, requiring larger doses for relief or relief taking longer. It is caused by dynamic obstruction of coronary artery due to plaque rupture with superimposed thrombosis and spasms. Prinzmetal’s angina Angina at rest and occurs commonly at night caused by coronary artery spasm. Management Pain is relieved by nitroglycerin. Nitroglycerin lowers peripheral vascular resistance and lowers oxygen demand of the heart. Drugs such as aspirin are used to inhibit platelet function. Beta adrenergic blockers prevent the effects of cardiac sympathetic stimulation and reduce myocardial oxygen demand by decreasing the heart rate, ventricular systolic pressure and peripheral arterial pressure. Calcium channel blockers prevent calcium from entering muscle cells (arterial or cardiac muscles) thus preventing contraction leading to vasodilatation. When angina does not respond to drugs, coronary angioplasty, percutaneous coronary arterioventral procedures or bypass grafts are indicated. Dental considerations Preoperative nitroglycerin can be given prophylactically before dental therapy. Effective local anesthesia is a must. Long-acting local anesthesia with bupivacaine can be used with vasoconstrictor to prolong the effect of local anesthesia. Aspirating syringe is a must.


Increased heart rate and blood pressure during long appointments indicate need to conclude dental care. If a person develops angina during dental treatment, the procedure should be terminated and the patient should be seated in semi-inclined position and the patient should be given nitroglycerin 0.3–0.6 mg sublingually. If pain persists even after 3 minutes, additional doses (up to 3 mg) every 5 minutes should be given and medical help should be sought. If pain persists, 300 mg of chewable aspirin is given. Moreover, morphine sulfate (IV) relieves pain and anxiety. Nausea, bradycardia, hypertension indicating myocardial infarction may occur. Tricyclic antidepressants are contraindicated. Conscious sedation and general anesthesia should be deferred for 3 months in patients with recent onset angina or unstable angina.

MYOCARDIAL INFARCTION It is a severe form of coronary artery disease. An anginal pain lasting longer than 30 minutes is considered to be a myocardial infarction. The pain may be accompanied by nausea and vomiting, tachycardia, grossly irregular pulse, pallor and difficulty in breathing, sweating, and restlessness. About 10% have painless infarctions. Diagnosis The diagnosis of acute myocardial infarction is based on the presence of two of the following three criteria: (1) signs and symptoms compatible with myocardial ischemia, (2) typical ECG changes—ST segment elevation at the end of the PR segment, (3) measurement of creatinine kinase (CK) and myocardial-bound CK (CK-MB). Elevations in the serum troponin T and troponin 1 levels, which are sensitive markers for myocardial injury, have also been used to test for acute myocardial infarction. Therapeutic goals and pharmacologic strategies for coronary heart disease Therapeutic goals

Pharmacological strategies

Inhibit progression of atherosclerosis

Lipid-lowering agents HMG-Co-A reductase inhibitors

Improve circulation in coronary arteries

Nitrated calcium channel blockers

Reduce workload

Beta-1 adrenergic receptor antagonists

Prevent thrombus formation

Antithrombotic agents

Prevent coagulation

Anticoagulants

2.

3. 4. 5. 6.

Patients within 6 months of an MI (recent MI) are at the risk of further complications, hence, elective dental care should be deferred. However, the first 6 weeks is more critical, and with the physician’s consent, simple emergency dental treatment under LA may be done during the first 6 months. Anxious patients may be given preoperative glyceryl nitrate. Effective local anesthesia is important. Aspirating syringes must be used. Use of epinephrine impregnated gingival retraction cords should be avoided.

Management of myocardial infarction Same as that of angina. Additionally, patients are on platelet inhibitors. Care should be taken to prevent significant bleeding. Local hemostasis should be promoted (procoagulant materials such as collagen or topical thrombin should be used). Local pressure should be applied for a longer duration. Injecting vasoconstrictor containing local anesthesia directly into surgical site and using sutures is not required.

CONGENITAL HEART DISEASE It is a common heart disease among children, present in 1% of live births. Congenital defects involving heart or adjacent vessels may be associated with other congenital anomalies. These congenital anomalies can be cyanotic or acyanotic in nature.

Cyanotic Transposition of great vessels, tetralogy of Fallot, Eisenmenger’s syndrome. Cyanotic defects are lethal.

Acyanotic Atrial and ventricular septal defects, patent ductus arteriosus, coarctation of aorta, pulmonary stenosis, mitral valve prolapse, aortic stenosis. Causes ❍ ❍

Idiopathic Acquired (congenital rubella, maternal drug misuse).


Dental aspects 1.

Physician’s consent is necessary before treating the patient.

Most striking feature in some congenital heart disease is cyanosis (more than 5 g reduced hemoglobin per deciliter of blood) ❍ Causes severely impaired development and often gross clubbing of fingers and toes 479


❍ ❍

Eventually polycythemia develops Cyanosis due to right to left shunt leading to chronic hypoxia ❍ Shunt from left to right leads to pulmonary hypertension, direction changes later leading to cyanosis ❍ Patients with congestive heart disease liable to infective endocarditis and others are pulmonary edema, polycythemia, bleeding tendency, growth retardation, fatigue and brain abscess. Dental considerations ❍ ❍

Antimicrobial prophylaxis Bleeding tendencies due to platelet dysfunction and excessive fibrinolytic activity ❍ Dental bacteria may cause cerebral abscess ❍ Aspiration during local anesthetic procedure is a must due to epinephrine in local anesthesia ❍ Gingival retraction cord containing epinephrine should be avoided. Oral manifestations associated with congenital heart diseases ❍ ❍ ❍ ❍

Delayed eruption of both the dentitions Greater frequency of positional anomalies Enamel hypoplasia Teeth have bluish white skimmed milk appearance and gross vasodilatation in pulp ❍ Greater incidence of caries and periodontal activity.

RHEUMATIC FEVER Rheumatic fever is the most common cause of cardiac valve disorders. The mitral valve is affected more frequently. It results from an altered immunologic response to a group A beta hemolytic streptococcal pharyngitis, leading to formation of Aschoffs nodules in the myocardium which develops 1–3 weeks after the streptococcal infection. Though, only 3% of cases of beta hemolytic pharyngitis resulting in rheumatic disease, there is no way to forecast which individuals will have rheumatic heart disease (RHD). Common manifestations include new onset murmur, carditis, polyarthritis, chorea, erythema marginatum, fever and subcutaneous nodules (modified Jones criteria). The beta streptococcal infection is confirmed by increased serum antistreptolysin O (ASO) antibody titer or positive throat culture. RHD resulting in valvular injury is confirmed by echocardiography for any patient with a history of rheumatic fever, it is imperative to determine whether the infection resulted in RHD. Dental considerations ❍ 480

Consult with the physician

❍

All rheumatic heart lesions are at the risk of infective endocarditis and hence precautions and treatment similar to infective endocarditis should be carried out ❍ Local anesthesia can be given ❍ General anesthesia should be avoided.

INFECTIVE (BACTERIAL) ENDOCARDITIS Infective endocarditis (IE) is a rare, potentially lethal infection, predominantly affecting heart valves. The endocardium can also be affected. It results from bacteremia originating from any site and representing almost any species. It is caused mainly by bacteria as well as fungi. Bacterial endocarditis can be defined as an infection that affects the endocardium in valvular, mural and septal defects, as well as in arteriovenous and arterioarterial shortcircuits. It usually occurs in older individuals, peak prevalence is 6th or 7th decade. It is less frequent in the young, except in intravenous drug users. It occurs predominantly in males. Most patients have pre-existing cardiac disease. The mitral valve is more frequently affected followed by aortic valve and tricuspid valve. Sterile vegetations, i.e. comprising of platelets and fibrins accumulate over the damaged valves and these get readily infected during bacteremias resulting in infective endocarditis. Main groups affected by infective endocarditis

Approximate percentage of all cases of infective endocarditis

No obvious cardiac valve disease

40%

Chronic rheumatic heart disease

30%

Congenital heart disease

10%

Prosthetic cardiac valves

10%

Intravenous drug abuse

10%

Oral microorganisms could play an important role in the pathogenesis of infective endocarditis. Some oral microorganisms pass into the blood stream and colonize areas of valvular endothelium on a previous sterile incipient vegetation. Staphylococcus aureus usually produces an acute infection, whereas Streptococcus viridans, enterococci, certain gram-positive and gram-negative bacteria and fungi may produce subacute infection. Dental treatment precedes infective endocarditis only in 5–10% of cases though a number of oral manipulations can cause bacteremia. It is estimated that the prevalence of bacteremia following scaling and root planing is about (0–25%), with single tooth extraction (25–50%) and almost 50–80% with multiple extractions. The prevalence of bacteremia is about 25–50% with periodontal surgery. It has been reported that some cases of infective endocarditis have been associated with oral infections in the absence of dental manipulations and hence a synergistic


effect between the presence of periodontal or periapical infections and dental manipulations could favor the development of infective endocarditis. Moreover, a number of studies have reported that brushing teeth, chewing gum or eating may provoke bacteremia and that the prevalence of IE increases when these acts are performed by patients with intraoral infections. Because of the high morbidity and mortality associated with IE, antibiotic prophylaxis has been advised. Though, antibiotic therapy has not proven to prevent endocarditis and it also carries with a risk of adverse reactions (anaphylaxis), it is still advised prophylactically for certain treatment procedures.

Clinical Conditions that Warrant Use of Antibiotic Prophylaxis Cardiac conditions ❍ ❍ ❍ ❍ ❍ ❍ ❍

Previous history of bacterial endocarditis Prosthetic cardiac valves Complex cyanotic congenital heart diseases Acquired valvular dysfunction Surgically constructed systemic pulmonary shunts Hypertrophic cardiomyopathy Mitral valve prolapse with regurgitation.

Neurosurgical shunts Shunts are placed in patients with hydrocephaly to help in the drainage of cerebrospinal fluid. The ventriculoatrial shunt allows drainage of the CSF from the lateral ventricles to the venous circulation. The ventriculo-peritoneal shunt helps drain the CSF into the abdominal cavity. Indwelling catheters and stents Antibiotic prophylaxis is indicated only in instances where the catheters are on the right side of the heart. Only the first 2 weeks are critical and indicated for antibiotic prophylaxis when stents are placed in cardiac patients. The risks of developing a superinfection are very minimal after the first few weeks as an epithelial layer develops over these stents. Patients with renal diseases undergoing hemodialysis Patients receiving peritoneal dialysis do not require antibiotic prophylaxis. However, patients who have an arteriovenous shunt (made up of autogenous tissue or a silastic tube) implanted for dialysis require antibiotic coverage during dental procedures, as these shunts are vulnerable to infection.

Patients undergoing chemotherapy are prone to develop infections as the chemotherapeutic agents suppress the inherent immune system. Invasive dental procedures such as extraction of teeth, subgingival scaling and periodontal surgeries that might cause significant bleeding warrant antibiotic prophylaxis in these patients. Patients inflicted with HIV/AIDS generally do not require antibiotic cover; nevertheless it is always wise to perform dental procedures such as extraction of teeth and periodontal surgeries under antibiotic cover as it might minimize the risk of the patient acquiring a superinfection. Patients with uncontrolled insulin-dependent diabetes mellitus (IDDM) are vulnerable to infections. Invasive dental procedures that involve significant amount of bleeding may require antibiotic cover.

Treatment Needing Antimicrobial Prophylaxis in Patients at Risk of Infective Endocarditis ❍ ❍ ❍ ❍ ❍ ❍ ❍

Extractions Subgingival procedures (probing, cord placement or scaling) Oral/periodontal/implant surgery or raising mucogingival flaps Endodontics beyond root apex Sialography Intra-ligamental local anesthesia Rubber dam, matrix or wedge placement.

Procedures for which antimicrobial prophylaxis is not required ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍

Dental radiography Endodontics not beyond apex Exfoliation of primary teeth Impression taking Non-surgical procedures that do not induce bleeding Abscess incision and drainage Suture removal Orthodontic band removal.

Prophylactic antibiotic regimen Patient category

Oral medications

Adults, not allergic to penicillin

2.0 g amoxicillin 1 hour before procedure

Adults, penicillin allergic

600 mg clindamycin 1 hour before procedure or 2.0 g cephalexin 1 hour before procedure or 500 mg azithromycin or clarithromycin 1 hour before procedure

Children, not allergic to penicillin

50 mg/kg amoxicillin 1 hour before procedure

Patients with compromised immune status These patients are more prone to develop an overwhelming septicemia from a relatively harmless transient bacteremia because of their compromised immune status.

481


Patient category

Non-oral medications

Adults, not allergic to penicillin

2.0 g ampicillin IM or IV within 30 minutes before procedure

Adults, penicillin allergic

600 mg clindamycin IV within 30 minutes before procedure or 1.0 g cefazolin IM or IV within 30 minutes before procedure

Children, not allergic to penicillin

50 mg/kg ampicillin IM or IV within 30 minutes before procedure

Chlorhexidine hydrochloride and povidone–iodine mouthrinses may reduce the incidence and magnitude of bacteremia before dental treatment. Moreover, patients should be encouraged to maintain meticulous oral hygiene. It has been suggested by some authors that in patients with poor oral health, antibiotic coverage should be given for all dental procedures.

Stage D: Patients with end stage disease requiring specialized treatment such as mechanical circulatory support, continuous ionotropic infusion or cardiac transplantation. 2. The New York Heart Association Class one: Asymptomatic patients Class two: Patient symptomatic with moderate exertion Class three: Patient symptomatic with mild exertion Class four: Patient symptomatic at rest. Clinical manifestations Left heart failure manifests as tachycardia, fatigue on exertion, dyspnea on mild exercise, intolerance to cold, paroxysmal nocturnal dyspnea and nocturnal cough. Right heart failure is characterized by fatigue, jugular venous distention, fullness in the abdomen, with an enlarged liver and tenderness in the upper right quadrant. In advance cases ascites and pitting edema of lower extremities is seen. Management

HEART FAILURE Heart failure is a clinical syndrome defined as chronic inadequate contraction of the heart muscle, resulting in insufficient cardiac output. It is basically an inability of the heart to pump blood at a rate required by the body tissues. It occurs frequently in the elderly population. It is a manifestation of one or more underlying conditions including: ❍ ❍ ❍ ❍ ❍ ❍ ❍

Systemic or pulmonary hypertension Myocardial infarction Cardiomyopathy Congenital heart disease Rheumatic fever Cardiac dysrhythmias Pericardial disease and other infections.

Heart failure reflects impairment of either the left or right ventricle. Left ventricular failure commonly develops in patients with coronary artery disease, hypertension and congenital heart disease. Right ventricular failure is mostly caused by left ventricular failure which increases pulmonary venous pressure and leads to pulmonary arterial hypertension. Heart failure leads to hypoperfused tissues and congested organs.

Classifications of Heart Failure 1. American Heart Association Stage A: Patients at risk of failure without any structural disorder Stage B: Patients with a structural disorder of heart, without symptoms of heart failure Stage C: Patients with present or past symptoms of heart failure and structural disorder 482

Reduction in physical activities, stress reduction, fluid restriction, dietary sodium restriction, weight loss, subcutaneous heparin administration, supplemental portal oxygen, medications prescribed include diuretics, cardiac glycosides, vasodilators, ACE inhibitors and sympathomimetic drugs. Dental considerations ❍ ❍

❍ ❍ ❍ ❍ ❍

❍ ❍ ❍

❍ ❍ ❍

Physician’s consent is a must. Patient should avoid heavy meals just before their dental appointment since digitalis may cause nausea and vomiting if the doses are high. The dentist should avoid stimulating gag reflex. Rubber dam should be used cautiously. Patient should not be in supine position because dyspnea is worsened. Dental treatment may precipitate dysrhythmias and angina in uncontrolled patients. Anxiety must be minimized and patient’s pain control should be effective. Patients should be treated in late morning, because endogenous epinephrine peaks during early morning and cardiac complications may arise. Aspirating syringe should be used since epinephrine can theoretically increase hypertension. Bupivacaine is cardiotoxic. Epinephrine in local anesthesia should be avoided in patients taking beta blockers, since hypertension may be induced. For patients in whom significant bleeding is expected, monitor protrombin time. During the course of treatment, vital signs should be monitored. Medications such as diuretics may cause orthostatic hypotension.


❍

NSAIDs other than aspirin should be avoided in patients taking ACE inhibitors, since there is a risk of renal damage.

Special considerations Appointment timing Most sudden cardiac arrests may come during peak endogenous epinephrine levels (08:00– 11:00 hours) and so appointments are best for late morning or early afternoon. Preventive strategies Dental management plans for patients with cardiovascular diseases should include appropriate preventive strategies. Toothbrush The use of electromechanical brushes have been shown to be more effective than conventional brushes in reducing plaque and gingivitis and hence should be recommended in all patients with cardiovascular disease. Topical rinses and fluorides The use of topical agents, such as chlorhexidine gluconate is useful to combat gingivitis and other periodontal pathosis that result from plaque accumulation. For patients with xerostomia and a high incidence of dental caries, preventive modalities such as dietary analysis and counseling, and prophylaxis combined with home fluoride use should be implemented. A topical fluoride, 1.1% sodium fluoride in the form of a brush-on gel, may be preferred to a topical solution. Sialagogues Xerostomic patients, in whom the salivary glands respond to stimulation benefit from dietary measures such as carrots, celery, or from chewing xylitol containing gums. Drugs such as pilocarpine hydrochloride 2.5–5 mg in 2–6 increments per day and cevimeline hydrochloride can be used to treat drug-induced xerostomia. However, in patients with no residual salivary gland function, salivary substitutes, oral moisturizer, and artificial saliva provide some relief. Local hemostatic agents They are used for surface dressing for wounds and over extraction sockets. They arrest bleeding by creating a mechanical matrix which facilitates blood clotting when the absorbable hemostatic agent is applied directly to the hemorrhagic site. Examples include absorbable gelatin sponge, microfibrillar collagen hemostat and oxidized regenerated cellulose. Adverse drug events Dentists must have an awareness of the potential for adverse drug events since patients with cardiovascular diseases are frequently treated with multiple drugs. Hence, a rational approach should be developed toward the use of pharmacotherapeutic agents in the management of odontogenic problems.

Oral Disease Aspects Periodontal disease Demmer and Desvarieux (2006) in their article titled ‘Periodontal Infections and Cardiovascular Disease: The Heart of the Matter’ suggest that there is still some evidence

that supports the association between periodontal infections, atherosclerosis and vascular disease. They further recommend that irrespective of whether there is an association between periodontal diseases and cardiovascular lesions or not, periodontal treatment must be recommended on the basis of the value of its benefits for the oral health of patients, recognizing that patients are not healthy without good oral health. Lichenoid stomatitis Cardiovascular drugs such as diuretics, beta-1 blockers, ACE inhibitors may cause development of lichenoid lesions. Lichenoid lesions are indistinguishable from oral lichen planus. The diagnosis is confirmed when condition resolves after the offending drug is discontinued. Xerostomia Cardiovascular drugs with xerostomic side effects include diuretics, beta-1 blockers and centrally acting sympathetic agonists. Xerostomia is usually caused due to the drug’s parasympatholytic or antimuscarinic effects. Xerostomia can lead to complications such as high incidence in dental caries. Moreover, it can contribute to difficulties in mastication, swallowing, speech. The dryness of the oral mucosa if persistent can lead to atrophy and susceptibility to candidiasis and other superinfections. Gingival hyperplasia Calcium channel blockers such as nifedipine can cause gingival enlargement primarily affecting the labial or facial interdental papilla and it is firm and painless. However, it is usually associated with erythema and edema resulting in pain, bleeding, and difficulty in mastication. Patients on antithrombotic agents An increasing number of cardiovascular patients are prescribed antithrombotic, anticoagulant, and thrombolytic agents and hence special precautions need to be taken in such patients. Aspirin is one of the commonly prescribed antithrombotic agents. It irreversibly acetylates cyclo-oxygenase resulting in inhibition of thromboxane A2 mediated platelet aggregation. However, it is relatively a weak antithrombotic agent, since the action of other mediators of platelet aggregation are not inhibited, hence the effect of aspirin therapy on intra- and post-operative surgical and periodontal procedures are minimal. If the patient is also taking oral anticoagulant, significant synergism may mandate modifications of drug regimen. Measurement of patients bleeding time can be helpful to determine the degree of antithrombotic effect and its impact on invasive dental procedures. Considerations for patients on anticoagulant agents For any patient taking anticoagulant the dentist and physician must assess the risk for altered bleeding after an invasive dental procedure. Assessment includes magnitude of invasive procedure, patient’s bleeding history, patient’s 483


bleeding profile which includes prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratio (INR). Oral anticoagulants are commonly prescribed for arterial or venous thromboembolism. This therapy is usually monitored by prothrombin time which is converted to INR. For most clinical indications, a moderate–intensity anticoagulant effect with a target INR of 2.0–3.0 and PT of 1.5– 2.5 is appropriate. Warfarin is the commonly prescribed oral anticoagulant. Most patients can undergo minor oral surgical procedures such as extraction and alveolectomies without alteration of their warfarin regimen. However, to prevent serious bleeding the preoperative assessment of the patient’s level of anticoagulation is necessary. Warfarin has plasma half-life of 36–42 hours, hence any change in dosage requires at least 2 days to be reflected in INR value. Once an acceptable range is achieved local anesthesia (LA) can be administered with caution to minimize hematoma formation and using meticulous local measures such as minimal trauma, application of gelfoam and placement of sutures to ensure hemostasis. Heparin therapy For a patient on heparin therapy requiring an oral surgical procedure, the drug should be discontinued approximately 4 hours before the procedure. Surgery is performed using local anesthesia, atraumatic surgical technique, application of local hemostatic agents and careful suturing. Postoperatively heparin therapy may be re-instituted the same day if there is no active bleeding. Local anesthesia The use of local anesthetic agents with vasoconstrictors in patients with cardiovascular disease is controversial. The two most commonly used vasoconstrictors are epinephrine and levonordefrin. Patients receiving LA without vasoconstrictor have impaired pain control compared to those receiving LA with epinephrine. Hence, patients with cardiovascular disease may be at greater risk of experiencing massive endogenous epinephrine release secondary to poor LA than they are from the small amount of vasoconstrictor used in LA. Some studies have found that infiltration anesthesia containing 3.6 ml of lignocaine with 1–80,000 epinephrine can be given safely in CVS patients who have an exercise capacity of more than 4 MET. Most studies have shown no significant changes in BP or heart rate in patients with mild to moderate cardiovascular system (CVS) disease after dental injection of 1.8–5.4 ml of 2% of lignocaine with 1–100,000 epinephrine. Hence, it is recommended that patients with mild to moderate CVS disease receive the smallest amount of LA needed to provide anesthesia with an aspirating syringe. Moreover, use of conscious sedation to decrease stress to minimize endogenous release of epinephrine may help in ensuring hemodynamic stability than avoiding small 484

amount of epinephrine in LA. However, vasoconstrictors in LA may be contraindicated in patients with severe CVS disorders such as unstable angina, recent MI or bypass surgeries, uncontrolled dysrhythmias, severe hypertension and severe congestive heart failure. Intraligamentary injection of LA with vasoconstrictor is generally contraindicated in patients with significant CVS disease. Pacemakers It is a small implanted electronic device that stimulates the heart to beat and pace the heart rate when it is too slow (bradycardia). Pacemakers have pulse generators and electrode leads and these are powered by lithium batteries. Modern pacemakers are bipolar, implanted transvenously in the subclavian or cephalic vein and typically located in right ventricle or on the chest wall, either with the pectoral muscle or underneath the skin or in abdominal wall. Dental apparatus/instruments with no known effect on cardiac pacemakers ❍ ❍ ❍

Electric toothbrushes Electronic apex locators Piezoelectric ultrasonic scalers.

Dental apparatus/instruments with likely effects on cardiac pacemakers ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍

Diathermy units Electronic dental analgesia units Electrosurgical units Ferromagnetic seaters Lithotripsy units MRI (magnetic resonance imaging) units TENS (transcutaneous electric nerve stimulation) units Ultrasonic instrument baths.

Interference with pacemakers/defibrillators High frequency external electromagnetic radiation can interfere with pacemaker sensing function. Pacemakers can be disrupted by ionizing radiation, ultrasonic and electromagnetic interference from a wide range of sources. Digital phones, TV transmitters may pose interference, but the risk is small and only used in close proximity to the pacemaker. Electrical appliances like remote controls, electric blankets, heating pads, shavers, sewing machines and microwave ovens are safe.

HEMATOLOGICAL DISORDERS Hematological diseases include abnormalities involving RBCs, WBCs and platelets. As platelet abnormalities lead


to defective coagulation mechanism. They will be discussed in the section pertaining to bleeding and clotting disorders. RBCs and WBCs perform many of the vital functions of the body. Their qualitative or quantitative defects can lead to derailment of internal homeostasis. The oral cavity is equally affected and demonstrates a plethora of manifestations. These are sometimes specific for a particular disease and many of the times, non-specific. The oral manifestations of the hematological diseases have to be identified, underlying systemic cause treated and consideration should be given for a patient, while undertaking a particular dental procedure. Hematological diseases can be broadly classified as qualitative and quantitative defects. Qualitative disorders Cells affected

Disorder

WBCs

Chediak–Higashi syndrome Enzyme deficiencies e.g. G-6-P dehydrogenase deficiency, pyruvate kinase deficiency

RBCs

Hemoglobinopathies e.g. Sickle cell anemia, thalassemia Abnormal shape e.g. Hereditary spherocytosis, hereditary elliptocytosis

Quantitative defects Cells affected

Disorder Increase in number e.g. Leukocytosis, leukemia, lymphoma

WBCs

RBCs

Decrease in number e.g. Granulocytopenia, agranulocytosis, cyclic neutropenia

POLYCYTHEMIA Polycythemia is an abnormal increase in the erythrocyte count. Polycythemia is of three types: (1) primary proliferative polycythemia (polycythemia rubra vera), (2) secondary polycythemia, and (3) apparent polycythemia. Polycythemia rubra vera (PRV) is an idiopathic myeloproliferative disorder seen after 5th decade of life. PRV is not only characterized by proliferation of erythrocytes, but also granulocytes and platelets. While secondary polycythemia results from increased erythropoietin concentration, apparent polycythemia results from decrease in plasma fluids rather than any increase in RBC concentration. RBC levels may reach up to 6–12 million cells/mm3 leading to increased blood viscosity and thrombosis. Cyanosis of the face and extremities (due to deoxygenated blood), and hemorrhagic tendency may be seen in the later stages of the disease. Oral manifestations Polycythemia rubra vera will exhibit oral manifestations such as petechiae, purpura, spontaneous bleeding of the gingiva owing to hemorrhagic tendency and purple red discoloration on tongue, mucosa owing to cyanosis. Leukemic manifestations may also be seen if PRV progresses to acute myeloid leukemia, due to the proliferation of leukocytes. Secondary polycythemia also exhibits petechiae, ecchymosis and purple red discoloration of tongue and mucosa. Apparent polycythemia, which does not affect the quantity of RBC, does not exhibit any appreciable oral changes. Dental considerations Bleeding tendency during dental treatment procedures warrants adequate hemostasis measures. Cytotoxic chemotherapy should be administered prior to dental treatment procedures if hemoglobin levels are not controlled.

Increase in number e.g. Polycythemia

Treatment

Decrease in number e.g. Anemia (sickle cell anemia, thalassemia and anemia due to deficiency of vitamin B12, folic acid and iron)

The type of polycythemia should be diagnosed first and treated accordingly. Phlebotomy and chemotherapeutic agents like busulfan and chlorambucil are the common treatment options.

RED BLOOD CELL DISORDERS Red blood cell precursors, the pluripotential stem cells, give rise to erythroid progenitor cells on stimulation by various growth factors. These progenitor cells are further stimulated by erythropoietin, a hormone produced by kidney, leading to their differentiation and maturation into erythrocytes.

ANEMIA Anemia is defined as a reduction in the oxygen carrying capacity of the blood. It is not a disease but rather a symptom complex due to either reduction in number of circulating RBCs or due to an abnormality in the hemoglobin contained within RBCs. RBCs with a normal range of 5–6 million cells/mm3 may dwindle due to loss of blood or due to decreased production or increased destruction. 485


Anemias can be classified in many ways. They can be classified based on their etiology or size of the RBC with hemoglobin concentration in two. Classification based on etiology ❍ ❍

Blood loss anemia: Iron deficiency anemia Anemia due to decreased production: Aplastic anemia, anemia due to folic acid and vitamin B12 deficiency ❍ Anemia due to increased destruction (hemolytic anemia): Thalassemia, sickle cell anemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency. Classification based on size and hemoglobin concentration ❍

Microcytic hypochromic anemia: Iron deficiency anemia, thalassemia. ❍ Macrocytic normochromic anemia: Anemia due to folic acid and vitamin B12 deficiency. ❍ Normocytic normochromic anemia: Sickle cell anemia. Patients suffering with any type of anemia will have depleted oxygen carrying capacity manifesting as pallor, weakness and difficulty in breathing (dyspnea). Hemoglobin levels below 13.5 g/dl in adult males and less than 11.5 g/dl in adult females is considered anemic. Anemias due to increased destruction (hemolytic anemia) are further classified based on the etiology as following:

❍

Extracorpuscular factors causing hemolysis, e.g. autoimmunity, infections, liver disease and Rh factor incompatibility. ❍ Intracorpuscular factors causing hemolysis, e.g. hereditary spherocytosis, G6PD deficiency, sickle cell anemia, thalassemia and paroxysmal nocturnal hemoglobinuria.

Genitourinary causes like menstruation, malignancies, etc. ❍ Trauma/surgery. Blood loss from various sources is the most common cause of iron deficiency. Menstruation is the most likely cause in women between the age of 15 and 45 years. In adult and postmenopausal women, chronic GI tract losses should be the first consideration. In addition to clinical manifestations common to all anemias such as fatiguability, pallor and dyspnea, iron deficiency anemia patients exhibit spoon-shaped, cracked and split nails (koilonychia). Oral manifestations Iron deficiency can contribute to impaired cellular immunity, deficient bactericidal activity of polymorphonuclear leukocytes, inadequate antibody response, and epithelial abnormality that may cause high prevalence of oral candidiasis, angular cheilitis, and atrophic glossitis in patients. Characteristic oral manifestations of tissue iron depletion are glossitis and glossodynia, angular cheilitis, papillary atrophy of tongue (Figure 1), paresthesia, pallor and dysphagia due to esophageal strictures. Dental considerations Increased bleeding tendency might be a problem while treating anemic patients with hemoglobin levels less than 10 g/dl. This tendency is exhibited due to altered rheologic interactions between cells when hemoglobin level falls below a critical level. General anesthesia is also contraindicated in severe anemia, as oxygen carrying capacity is severely impaired. Therfore, patients presenting with typical features of anemia should be thoroughly investigated and referred to a physician for further investigations and treatment.

Iron Deficiency Anemia

Diagnosis

Iron is an essential element in which it participates in hemoglobin synthesis, electron transport for cellular respiration, DNA synthesis and other vital enzymatic reactions. Iron deficiency anemia is one of the most common diagnoses in the world, affecting both pediatric and adult population with a variety of etiologies.

Following are the list of investigations for iron deficiency anemia:

Causes Inadequate ingestion/increased requirements Infants, children and in pregnancy. Decreased absorption or utilization malabsorption syndrome.

Partial gastrectomy,

Blood loss ❍ ❍ 486

❍

Gastrointestinal (GI) tract causes like peptic ulcer Respiratory causes like infections, malignancies, etc.

❍ ❍ ❍ ❍ ❍

Blood count: Decreased RBC and hemoglobin Peripheral smear: Microcytic hypochromic anemia Serum iron: Decreased Serum iron binding capacity: Increased Mean corpuscular volume: Decreased.

Hypochromic microcytic anemia alone is also seen in other conditions like thalassemia and sideroblastic anemia. Other mentioned investigations should be done to effectively rule out these latter two conditions. Treatment Once the diagnosis of iron deficiency has been made, the cause of iron deficiency should be sought and treated. The best treatment of iron deficiency is an iron salt by mouth


Figure 1

Bald tongue and angular cheilitis in a patient with iron deficiency anemia. Courtesy: Dr Sarat Gummadapu

(ferrous sulfate 200 mg twice daily). Oral iron may need to be given for 3 months or more to replenish marrow iron stores.

Paterson–Kelly Syndrome (Plummer–Vinson Syndrome) Paterson–Kelly syndrome presents as a classic triad of dysphagia, iron deficiency anemia and esophageal webs. Dysphagia is due to muscular degeneration in the esophagus leading to esophageal strictures or webs. The patients are commonly females in the age range of 4th to 7th decade and complain of ‘spasm in the throat’ or ‘food sticking in the throat’. Symptoms resulting from anemia (weakness, pallor, fatigue, tachycardia) may dominate the clinical picture. Additional features are glossitis, angular cheilitis and koilonychia. The most important etiologic factor is iron deficiency. Paterson–Kelly syndrome can be treated effectively with iron supplementation. Since this syndrome is associated with an increased risk of squamous cell carcinoma of the pharynx and esophagus, patients should be monitored closely.

Anemia due to Vitamin B12 and Folic Acid Deficiency Vitamin B12 (cyanocobalamin) and folic acid are needed for the maturation of RBCs in bone marrow. A deficiency in the daily intake or absorption of these can result in anemia. Vitamin B12 deficiency can occur due to pernicious anemia, gastrectomy, tropical sprue, alcoholism, scleroderma and drugs such as colchicine. The most common of

all these is the pernicious anemia, which is due to atrophy of gastric mucosa resulting in a lack of intrinsic factor secretion. The intrinsic factor binds to vitamin B12 and is necessary for its absorption. Autoimmunity was considered as an etiological factor for destruction of gastric parietal cells or the intrinsic factor. Pernicious anemia is commonly seen in adult life with patients being susceptible to gastric carcinoma, rheumatoid arthritis and neuromuscular abnormalities. Folic acid deficiency causes severe anemia but does not cause neurological abnormalities seen in pernicious anemia. It is prevalent in alcoholics, drug users and in patients whose diet is devoid of leafy vegetables. Anticancer drugs such as methotrexate are known to cause folate deficiency by interfering with DNA synthesis. Anemia due to deficiency of vitamin B12 and folic acid is also called megaloblastic anemia because of the presence of large RBCs with small immature nuclei. Oral manifestations Patients with pernicious anemia exhibit glossitis, sore or burning tongue, angular cheilitis, papillary atrophy, recurrent oral ulcerations and taste abnormalities. The glossitis can either be atrophic or Moeller’s, where a pattern of red lines may be seen without depapillation. Atrophic tongue occurs not only in anemias such as vitamin B12 deficiency, folic acid and iron deficiency, but also due to diabetes, xerostomia and candidiasis. Several hypotheses regarding the pathogenic role of nutrient deficiencies in atrophic glossitis have been proposed. Because cells of the tongue papilla have a high rate of turnover, deficiencies in micronutrients needed for cell proliferation or cell membrane stability may lead to depapillation. Nutrient deficiencies may also contribute to oral pathology by altering the pattern of microbial flora. Burning mouth sensation can be also encountered due to neuropathy or candidosis, which may be precipitated by anemia. Neuropathy can be explained by the fact that defective myelin synthesis is seen in patients with vitamin B12 deficiency. Oral manifestations of folic acid deficiency include angular cheilitis, aphthous stomatitis and pharyngitis. Diagnosis Diagnosis of pernicious anemia requires the demonstration that megaloblastic hemopoiesis is present, vitamin B12 deficiency is present and intrinsic factor is missing. Diagnostic tests performed and would be indicative of either vitamin B12 deficiency or folic acid deficiency are: ❍ ❍ ❍ ❍ ❍

Blood count: Decreased RBCs and hemoglobin Peripheral smear: Macrocytic normochromic anemia Mean corpuscular volume: Increased Serum B12 assay: Decreased (in vitamin B12 deficiency) Serum folic acid assay: Decreased (in folic acid deficiency) 487


❍ ❍

Schilling’s test: Positive (in vitamin B12 deficiency). Antibodies to parietal cells or intrinsic factor: Present (in pernicious anemia).

Treatment Since oral changes would appear to precede many of the systemic indicators of vitamin B12 deficiency, it is hoped that the recognition of these will lead to early diagnosis and institution of therapy. Regardless of the etiology of vitamin B12 deficiency, high dose oral supplementation (1,000–2,000 mcg daily for 2 weeks), followed by 1,000 mcg daily for maintenance is currently recommended. Historically pernicious anemia was treated with intramuscular vitamin B12 supplementation. However, several studies have demonstrated that high doses of oral vitamin B12 are just as effective as, and are better tolerated than intramuscular cyanocobalamin in patients with vitamin B12 malabsorption. Management for folic acid deficiency consists of administration of oral folic acid (5 mg/day), which is given for a period of 4 months. The differentiation of vitamin B12 deficiency and folic acid deficiency is crucial as folic acid supplements may correct the anemia but will not stop the neurological manifestations.

Aplastic Anemia Aplastic anemia is a rare, potentially life-threatening failure of hemopoiesis characterized by pancytopenia and bone marrow aplasia. Although most cases are acquired (drugs, viruses, chemicals, toxins and radiation), some are inherited. The pathophysiology of acquired aplastic anemia is immune mediated in most cases; autoreactive lymphocytes mediate the destruction of hemopoietic stem cells. Fanconi’s anemia is an inherited aplastic anemia that manifests in early childhood. The term ‘anemia’ in aplastic anemia is a misnomer, since all the three cellular elements of the bone marrow are often involved (pancytopenia), i.e. granulocytes, erythrocytes and platelets. Clinical manifestations are proportional to the peripheral blood cytopenias and include dyspnea, fatigue and pallor (effects of anemia), petechiae and easy bruising (effects of thrombocytopenia) and susceptibility to infections (effects of neutropenia).

Oral manifestations Oral manifestations like gingival bleeding, pallor, petechiae, ecchymosis; neutropenic ulcers and delayed healing are observed in patients with aplastic anemia (effects of anemia, thrombocytopenia and neutropenia). Petechial hemorrhages were the most common intraoral finding in patients with aplastic anemia. These petechiae might be due to minor trauma from normal deglutition and mastication rather than due to thrombocytopenia. Rapidly progressing severe periodontitis, which is a feature of several quantitative and qualitative neutrophil defects like cyclic neutropenia, agranulocytosis and leukocyte adhesion deficiency (LAD), is also evident in aplastic anemia. Bacterial sepsis and fungal infections represent the most frequent cause of death in this condition. Dental considerations Thorough oral examination should be carried out in a patient with aplastic anemia as bleeding tendency and infections pose a serious problem. Local hemostatic measures such as pressure pack application and systemic antifibrinolytic agents such as aminocaproic acid and tranexamic acid should be considered. Tranexamic acid is given in a dosage of 20 mg/kg body weight 4 times a day starting 24 hours before oral procedures and continuing for 3–4 days afterwards. Chlorhexidine mouthrinses will reduce the microbial load in the oral cavity. Antibiotic prophylaxis, typically with amoxicillin or clindamycin, and platelet transfusion of thrombocytopenic patients, when necessary, should be adequate to prevent serious sequelae for all dental procedures. However, intramuscular injections and nerve block anesthesias are to be avoided because of risk of thrombocytopenia and bleeding tendency. Management Cause should be identified and removed. Patients with asymptomatic cytopenias probably need no treatment. Treatment for patients with severe cytopenias includes bone marrow transplantation, immunosuppressive therapy and high dose cyclophosphamide without transplantation of bone marrow.

Diagnosis A complete blood count, leukocyte differential, reticulocyte count, and a bone marrow aspirate and biopsy can establish the diagnosis. Peripheral blood flow cytometry can be done to rule out paroxysmal nocturnal hemoglobinuria. Patients younger than 40 years should be screened for Fanconi’s anemia by the use of clastogenic agents, diepoxybutane or mitomycin, which test for increased chromosomal breakage seen with this disorder. A family history of cytopenias should raise suspicion of an inherited disorder even when no physical abnormalities are present. 488

Glucose-6-phosphate Dehydrogenase Deficiency Glucose-6-phosphate dehydrogenase is an enzyme in the RBC needed for the glucose metabolism. Deficiency of this enzyme leads to accumulation of oxidants in the RBCs. These substances, which produce methemoglobin and denatured hemoglobin, precipitate to form Heinz bodies. The Heinz bodies cause alteration of cell membrane by attachment, thus leading to hemolysis of cell. Beans, drugs and infection commonly trigger the hemolysis and lead to acute intravascular hemolysis. Clinical features such as dyspnea,


palpitations, weakness and jaundice may be seen. Oral manifestations common to other anemias may be encountered. Dental considerations

which is possibly stimulated by parvovirus, leading to rapid onset of anemia. Stroke, which is the most dreaded complication of sickle cell disease, is also a result of vasoocclusive event in the brain. Hemolysis in patients with sickle cell anemia leading to jaundice.

Avoidance of triggering drugs such as dapsone and sulfasalazine. Blood transfusion can be considered prior to dental treatment if anemia is very severe.

3.

Treatment

Manifestations of oral cavity reflect the systemic features:

Hemolytic episodes are self-limited many of the times and most patients with drug- or infection-induced hemolysis recover fully following treatment. Oxidant drugs should be avoided.

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Oral manifestations

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Sickle Cell Anemia Sickle cell anemia and thalassemia are described as hemoglobinopathies due to the defective globin portion of the hemoglobin molecule. While sickle cell anemia is due to a qualitative defect in the globin chains (valine replaces glutamic acid), thalassemia is due to a quantitative defect. The minor alteration in the globin chain renders the hemoglobin susceptible to low oxygen tension, low temperature or decreased pH. In the presence of latter factors, hemoglobin forms a sickle-shaped crystal within the erythrocyte and leads to stasis, vascular occlusion and ultimately hemolysis of the red cells in end-capillary circulation. Sickle cell disorders, which are inherited as autosomal recessive, are of two types: sickle cell trait and sickle cell anemia. While in sickle cell trait (heterozygous), only one of the beta chains is abnormal, both the beta chains are abnormal in sickle cell anemia (homozygous). These patients with sickle cell trait are relatively asymptomatic unless they are subjected to extremely low oxygen tension (15 mmHg), such as in an unpressurized aircraft.

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Delayed eruption secondary to their general underdevelopment. Pallor. Susceptibility to osteomyelitis due to compromised blood supply: This is a result of intravascular sickling leading to ischemic infarction and necrosis of bone that creates a favorable environment for bacterial growth. Uncommon manifestations include anesthesia of mandibular nerve and asymptomatic pulpal necrosis. Anesthesia and pulpal necrosis are caused by restriction of the microvascular blood supply. Dental radiographs demonstrate step ladder trabecular pattern due to hyperplasia and widening of marrow spaces (as body tries to compensate for anemia). Lateral skull radiographs demonstrate thickening of diploe with ‘hair-on-end’ appearance due to perpendicular arrangement of trabeculae (Figure 2). Areas of radiopacity demonstrated on the radiograph are suggestive of previous infarction and calcification.

Diagnosis ❍ ❍ ❍

Peripheral smear: Normocytic normochromic cells Complete blood count: Decreased hemoglobin Hemoglobin electrophoresis: Demonstrates abnormal hemoglobin.

Treatment Clinical manifestations Manifestations of sickle cell anemia are divided into three categories. 1.

2.

Systemic manifestations including impaired growth and development and increased susceptibility to infections: Significant delay in sexual maturity, weight and height achievement is observed. Increased susceptibility to infection might be due to impaired splenic function or because, macrophages are involved in phagocytosis of the defective RBCs and may not be available for killing bacteria. Vaso-occlusive events and organ damage: The stasis of sickled red cells lead to vascular occlusion and infarction of the end organ. This vaso-occlusive phenomenon leads to multiple crises. These crises are painful crises in chest and abdomen, splenic sequestration crises due to infarction and fibrosis of spleen, and aplastic crisis,

Patients with sickle cell anemia need regular monitoring of their hematological state. Sickle cell anemia can only be symptomatically treated, as there is no cure. Prompt and adequate relief of pain is of prime importance. Vigorous hydration, analgesics and appropriate antibiotics best achieve management of the painful vaso-occlusive crisis, if there is any evidence of infection. Dehydration is common due to the patient’s inability to produce concentrated urine. Blood transfusion is advised in case of severe anemia and bone marrow transplantation was found to be successful in a patient with homozygous sickle cell disease. Folic acid supplements were also found to be beneficial as patients exhibit folic acid deficiency due to the rapidly proliferating bone marrow. Dental considerations The main principles are to prevent trauma, infection, hypoxia, acidosis or dehydration as these can precipitate 489


Figure 2

Oral manifestations ❍ ❍ ❍ ❍

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Lateral skull radiograph reveals ‘hair-on-end’ appearance in sickle cell anemia. Courtesy: Dr Sarat Gummadapu

sickle cell crises. Hemoglobin concentration of at least 7 g/dl must be ensured for adequate oxygen delivery during general anesthesia for dental and other surgeries.

Developmental and growth abnormalities leading to malocclusion, spacing and occlusal abnormalities Pain and swelling of parotid glands due to deposition of iron Deciduous and permanent teeth may be discolored due to the deposition of iron Some cases might also show teeth with short roots, thin lamina dura and prominent premaxilla (Chipmunk facies) Radiographic changes include generalized rarefaction of alveolar bone, chicken-wire appearance of enlarged marrow spaces and coarse trabeculation. In the skull, proliferation of marrow may completely erode the cortex, leaving only periosteum, and produce a ‘hair-onend’ radiographic appearance.

Diagnosis ❍ ❍

Peripheral smear: Normocytic normochromic cells Complete blood count: Decreased hemoglobin and decreased RBC ❍ Hemoglobin electrophoreses: Demonstrates abnormal hemoglobin. Treatment

THALASSEMIA Thalassemias are a group of congenital hemoglobinopathies characterized by a reduced rate of production of one or more of globin chains (alpha or beta) in the hemoglobin molecule. Alpha chain is reduced or deficient in alpha thalassemia and beta chain is reduced or deficient in beta thalassemia. Beta chains are commonly involved, when compared to alpha chains. If affected individuals are heterozygous for beta chains, it is called as beta thalassemia trait or beta thalassemia minor. If affected individuals are homozygous for beta chains, then it is called as beta thalassemia major or Cooley’s anemia. In thalassemia, imbalance in globin chain production leads to hemolysis thus resulting in microcytic, hypochromic type of anemia. The hemoglobin levels can even reach up to 2–3 g/dl. While, beta thalassemias are most frequently found in Mediterranean and black populations, alpha thalassemias are found more frequently in South East Asia, Middle East and Mediterranean populations. Clinical manifestations Systemic manifestations are mildly similar to sickle cell anemia, which are indicative of severe anemia. Growth and development of the child is retarded with ashen gray skin color due to pallor and jaundice. Patients may also present with cardiomegaly, splenomegaly and hepatomegaly. 490

Treatment of thalassemia major includes multiple blood transfusions and the primary complication of the treatment is iron overloading leading to deposition in liver, spleen, pancreas and thyroid. Another complication is chronic active hepatitis due to viral infection. Folic acid is also advised to offset the increased demand associated with chronic hyperactivity of the bone marrow. Splenectomy was indicated previously, to decrease the sequestration of RBC. Dental considerations A patient who has had a splenectomy is at risk of massive infection following bacteremia. It has been suggested that these patients receive prophylactic antibiotics like oral penicillin or erythromycin prior to dental treatment. Hepatitis risk to the patients due to transfusion should also be considered and universal precautions taken. Poor healing is also a complication of the dental treatment. Surgery for facial deformities has been used successfully.

WHITE BLOOD CELL DISORDERS White blood cells (WBCs) or leukocytes originate from pluripotent hematopoietic stem cells in either bone marrow or lymphoid tissue. These cells are responsible for the protection of the body against foreign invaders such as fungi, bacteria, viruses and parasites. Leukocytes are of three types: granulocytes, monocytes and lymphocytes.


While, the granulocytes and the monocytes protect the body against invading organisms by phagocytosis, the lymphocytes function by boosting the immunity. White blood cell disorders can also be classified as follows:

Oral manifestations ❍ ❍ ❍ ❍

Gingival and periodontal disease Increased caries incidence Oral ulcerations Early loss of teeth.

Classification Qualitative disorders Chediak–Higashi syndrome

NON-NEOPLASTIC DISORDERS

Non-neoplastic disorders ❍ Leukocytosis ❍ Leukopenia

The number of circulating WBCs is expressed as the number of cells found in a cubic millimeter of blood, which normally ranges from 4,500 to 11,000/mm3 in adults. The differential WBC count is an estimation of the percentage of each cell type per cubic millimeter of blood. A normal differential count is as follows: neutrophils, 50–60%; eosinophils, 3%; basophils, less than 1%; lymphocytes, 20–30%; and monocytes, 3–7%. The term leukocytosis is defined as an increase in the number of circulating WBCs to more than 11,000 cells/mm3, and leukopenia as a reduction in the number of circulating WBCs (usually to 4,500 cells/mm3).

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Neoplastic disorders Leukemia Lymphoma Multiple myeloma.

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WBCs released by the bone marrow, circulate in peripheral blood forming two pools of cells, a marginal one and a circulating one. Cells in the marginal pool adhere to vessel walls and are readily available. When infection threatens the body, the storage and marginal pools can be called on to help fight the invading organisms. Growth promoting substances called colony-stimulating factors (CSFs) are responsible for the growth of committed granulocytemonocyte stem cells. In response to infection, there will be local release of CSFs leading to increased production of granulocytes and monocytes in the bone marrow.

QUALITATIVE DISORDERS Since leukocytes play a central role in host defense, it is not surprising that defects in leukocyte function, both genetic and acquired, lead to increased vulnerability to infections. These qualitative defects can be: ❍

Defects in adhesion: Leukocyte adhesion deficiency (LAD type I) ❍ Defects in microbicidal activity: Chronic granulomatous disease ❍ Defects in phagolysosome function: Chediak–Higashi syndrome.

Leukopenia A decrease in the peripheral WBC count may occur because of decreased numbers of any of the specific types of leukocytes, but most often it involves the neutrophils (neutropenia). A reduction in the number of granulocytes in blood is known as neutropenia or sometimes, when severe as agranulocytosis. Affected persons are extremely susceptible to infections, which may be severe enough to cause death. Patients may also exhibit fever, weakness and marked fatigability. Causes for neutropenia Inadequate or ineffective granulopoiesis ❍ ❍ ❍

Aplastic anemia Leukemia Due to cancer chemotherapeutic agents.

Accelerated removal or destruction ❍ ❍ ❍ ❍

Idiopathic Drugs such as aminopyrine Splenomegaly Overwhelming bacterial or fungal infections.

Chediak–Higashi Syndrome It is a rare autosomal recessive disorder characterized by abnormal granules in the granulocytes. This abnormality results in neutrophils with decreased chemotactic and bactericidal ability. Patients develop severe neutropenia as a result of ineffective granulopoiesis and most die in childhood from infections or advanced lymphoproliferative syndrome. Patients exhibit neuropathy, hypopigmentation, recurrent bacterial infections and hepatosplenomegaly.

Oral manifestations Ulcerations and necrotizing lesions may be seen on the gingiva, floor of the mouth, buccal mucosa, pharynx or other sites within the oral cavity (agranulocytic angina). Ulcers lack the surrounding inflammation and are characterized by necrosis and foul smell. All of these lesions often show massive growth of microorganisms, with a relatively poor leukocyte response (minimal swelling and pus). 491


Treatment Cause must be identified and all drugs should be discontinued. Infections must be prevented or treated, if present. Current treatment efforts also include administration of recombinant hematopoietic growth factors, such as granulocyte CSF, which stimulate neutrophil production by the bone marrow. Dental considerations Oral infections in patients with severe neutropenia should be considered potentially life-threatening because they can lead to bacteremia and septicemia. Ulcers can be treated with topical anesthetics and antiseptic mouthrinses. In severe pulpal and periodontal infections, broad-spectrum antibiotics can be advised until culture reports are available. Cyclic neutropenia It is a rare disorder that occurs secondary to a periodic failure of the stem cells in the bone marrow. It is characterized by transient severe neutropenia that occurs approximately every 21 days. Neutrophil count is at its bare minimum for a period of 3–7 days during which the clinical manifestations pertaining to neutropenia are observed. The most common signs are fever, stomatitis, pharyngitis and skin abscesses. Severity of infection is directly proportional to the severity of neutropenia. Treatment and dental considerations are similar to that of neutropenia.

Reactive Leukocytosis An increase in the number of WBCs is a common reaction in the variety of inflammatory states caused by microbial and non-microbial stimuli. Leukocytosis is relatively nonspecific and can be classified on the basis of particular white cell series affected. In response to increased demand, increased number of immature neutrophils called ‘bands’ enters the circulation, a process called a ‘left shift’. This is called as leukemoid reaction, which is often secondary to viral infections. This reaction can be distinguished from acute leukemia, as there is an orderly maturation and proliferation of all normal myeloid elements in the bone marrow. Causes of leukocytosis Physiologic ❍ ❍ ❍

Exercise Pregnancy Stress

Pathologic ❍

492

Neutrophilic leukocytosis – Acute bacterial infections – Burns

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Eosinophilic leukocytosis – Allergic diseases – Parasitic infestations – Drug reactions – Certain malignancies ❍ Basophilic leukocytosis – Malignancies ❍ Monocytosis – Chronic bacterial infections such as tuberculosis, systemic lupus erythematosus, etc. ❍ Lymphocytosis – Infections due to hepatitis A, cytomegalovirus and Epstein–Barr virus. Oral manifestations are seen as a consequence of underlying disease process rather than the elevated leukocyte levels. For example, in infectious mononucleosis, there is lymphocytosis and patients complain of sore throat, petechiae and fever. Patients exhibiting these clinical signs must be evaluated and investigated as these clinical findings can be confused with leukemia.

NEOPLASTIC DISORDERS Leukemia Leukemia is a heterogeneous group of hematological disorders that arise from a hematopoietic stem cell characterized by a disordered differentiation and proliferation of neoplastic cells. This neoplastic proliferation in marrow results in diminished production of normal erythrocytes, granulocytes and platelets in leukemia. These neoplastic cells ultimately infiltrate various organs like spleen, CNS, lymph nodes, skin and gingiva. Leukemia is categorized according to its clinical behavior: acute or chronic; and histogenic origin: lymphocytic or myelocytic. The classification is called as FAB (French, American, and British) and is widely accepted. The etiology is unknown but genetic factors, irradiation, viruses, chemicals such as benzene and some drugs have been implicated. All types of leukemia are more common in males compared to females.

Acute Leukemia About 50% of all leukemias are in the acute form. Acute leukemias are divided into two major groups: acute lymphocytic leukemia (ALL) and acute monocytic leukemia (AML). While, ALL is more commonly seen in children, AML is frequently seen in the adults. ALL is frequently derived from B-lymphocytes or their precursors. The acute leukemias have increased number of immature cells called blasts in the peripheral circulation. As blasts accumulate in the marrow, they suppress normal hematopoietic stem cells.


Clinical features The major manifestations of acute leukemia result from the paucity of normal RBCs, WBCs and platelets. They have the following characteristics: ❍ ❍

Abrupt stormy onset. Symptoms related to depression of normal marrow function: Fatigue, owing mainly to anemia, fever, reflecting infections due to granulocytopenia and bleeding, secondary to thrombocytopenia. ❍ Generalized lymphadenopathy, splenomegaly and hepatomegaly due to dissemination of leukemic cells. ❍ CNS manifestations such as palsies, vomiting and headache due to meningeal spread. These features are more common in children and in ALL. ❍ Localized tumors or chloromas, which turn green on exposure to sunlight, due to local infiltration of leukemic cells. Laboratory diagnosis Laboratory findings show WBC count sharply elevated, sometimes reaching 100,000 cells/mm3. Platelet count is usually depressed below 100,000 cells/mm3 and numerous blast cells can be identified. Bone marrow aspirate reflects the peripheral circulatory changes. Treatment Therapeutically, the aim is to reduce the population of leukemic clone enough to allow reconstitution with the progeny of remaining normal stem cells. Chemotherapy satisfies the above requirement and is conveniently divided into three phases. The purpose of the first phase (induction) is to hit hard and induce a state of remission by killing tumor cells with cytotoxic agents. The purpose of the second phase (consolidation) is to consolidate the killing of remaining leukemic cells. The purpose of the third phase (remission) is to provide maintenance treatment to prevent any remaining leukemic cell mass from expanding. Patients are cured when no leukemic cells remain. Chemotherapeutic agents commonly used are vincristine, cytarabine, daunorubicin and methotrexate. Long-term survival occurs when the leukemic cell mass is greatly reduced and kept from increasing over a long period. If a patient relapses, remission again is difficult to induce and bone marrow transplantation is then advised. There are some regions in the body where the leukemic cells migrate and are not acted upon by the chemotherapeutic agents. These regions are called sanctuaries (CNS in ALL). In these patients, radiation along with intrathecal methotrexate can be tried.

Chronic Leukemia Onset of chronic leukemia is insidious with the course (untreated) of the disease running up to 2–6 years. So

in effect, the chronic leukemias have a slower onset of symptoms, a better prognosis, and more mature WBCs than do acute leukemias. The two major types of chronic leukemia are chronic granulocytic or myelocytic leukemia (CML) and chronic lymphocytic leukemia (CLL).

Chronic Myelocytic Leukemia Chronic myelocytic leukemia accounts for about 14% of all leukemias, is almost exclusively a disease of adults with the peak of presentation being at 40–60 years and is characterized by the presence of Philadelphia chromosome, an acquired genetic defect resulting from translocation of genetic material from chromosome 22 to chromosome 9. CML has two phases: chronic and blastic. While malignant cells with normal function are present in chronic phase, cells with further malignant transformation are found in blastic phase. Patient often survives for years before the disease enters blast phase. Clinical features Some of the patients are asymptomatic and some exhibit the following: ❍ ❍ ❍ ❍

Shortness of breath due to anemia Abdominal discomfort due to splenomegaly Weight loss and fever Bleeding tendency in the later stages.

Laboratory diagnosis ❍ ❍

Complete blood count: Increased WBC count. Bone marrow aspirate: Demonstrates increased cellularity and Philadelphia chromosome.

Treatment Control of chronic phase is often successful when compared to blastic phase. Imatinib, a tyrosine kinase inhibitor is the first line of treatment in the chronic phase. As the disease enters blastic phase, other treatment options have to be explored. Allogenic hemopoietic stem cell transplantation can cure approximately 70% of chronic phase CML patients but with risk of complications and death due to graft-versus-host disease (GVHD) and opportunistic infections.

Chronic Lymphoid Leukemia Chronic lymphoid leukemia is one of the most common leukemia, occurring predominantly in later life and increasing in frequency with advancing years. It is almost invariably B-lymphocytic in origin. In many patients it is a chance finding with no symptoms, while others present with features of bone marrow failure or immunosuppression. 493


Clinical features

Figure 3

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Recurrent infection because of (functional) leukopenia and immune failure (reduced immunoglobulins) ❍ Anemia due to hemolysis or marrow infiltration ❍ Painless lymphadenopathy ❍ Splenic discomfort. Laboratory diagnosis ❍

Complete blood count: Increased WBC count, platelets and normal or reduced RBC ❍ Blood film: Lymphocytes increased ❍ Bone marrow aspirate: Reflects peripheral blood, infiltrated with lymphocytes. Treatment Supportive treatment involves treatment of hemolytic anemia with steroids, infection with antibiotics and infiltrations with chemotherapy. Specific treatment involves administration of chlorambucil to reduce blood count and to decrease lymphadenopathy and splenomegaly and thus successfully palliating the disease. Fludarabine alone or in combination with cyclophosphamide had a much greater impact on the bone marrow and can induce complete remission. Oral manifestations of leukemia Leukemic patients are prone to the development of variety of oral conditions associated with the malignancy and treatment. The oral manifestations of acute leukemias reflect the systemic complications. The manifestations are: Signs and symptoms related to depression of marrow function Pallor, owing to anemia; petechiae, ecchymosis and gingival bleeding owing to thrombocytopenia (spontaneous if platelet level falls below 20,000 cells/mm3); and infections, owing to neutropenia. The latter can manifest as ulcerations and can be bacterial, viral or fungal. Neutrophils are known to play a crucial role in protective host response to colonization. In patients with leukemia, neutropenia is compounded by the chemotherapy thus increasing the risk of different opportunistic fungal infections. Among the opportunistic infections present in the oral cavity, the most frequent is candidiasis. Mucormycosis also occurs commonly in pulmonary and rhinocerebral sites and can become widely disseminated to other organ systems. Viral infections are also common in leukemia, with herpes simplex being the most common. Signs and symptoms related to infiltration of leukemic cells Gingival and salivary gland enlargement (Figure 3), neural and developing tooth crypt involvement, and painless cervical lymphadenopathy. Signs and symptoms related to treatment of leukemia Oral ulcerations and mucositis due to chemotherapy and/or radiation, craniofacial and dental anomalies in children 494

Gingival enlargement and bleeding in patient suffering from acute myeloid leukemia. Courtesy: Dr Sarat Gummadapu

(result of radiotherapy for cranial involvement), and lichenoid lesions, desquamative gingivitis due to graft-versus-host reaction. The oral mucosal cells due to their high mitotic index are frequently compromised, due to their susceptibility to chemotherapeutic agents, predisposing the patients to mucositis and xerostomia. The dental anomalies encountered are microdontia, dental agenesis and arrested root development. Radiographic findings Most children with leukemia had detectable radiographic changes of the jaws. These changes include loss of lamina dura, displacement of teeth, loss of the crypt outline around unerupted teeth, widened periodontal ligament and loss of cancellous bone trabeculation. The latter leads to an appearance of generalized rarefaction. There are other reports that mention generalized bone loss, increased mobility and protrusion of teeth in leukemic patients. Periodontal destruction, which is severe, may have been due to infiltration of leukemic cells into alveolar bone. The patients of chronic leukemia also exhibit oral hemorrhage, petechiae, ulcerations and gingival swellings. Dental considerations Dental treatment should only be carried out after consultation with the physician, as various aspects of management and the probable life expectation may affect it. Preoperative precautions should include screening for hepatitis B and HIV. Preventive oral healthcare is essential and where indicated, conservative dental treatment may be possible. Management of chronic dental infections in patients with hematologic malignancies ideally should be based on data that correlates examination findings with outcomes of treatment. One result of compromised hematologic status


among dental patients with hematologic malignancy, idiopathic or drug-induced blood dyscrasias and sickle cell anemia is that certain clinically relevant laboratory values have been proposed as important in management protocols. When oral surgical procedures are anticipated, a platelet count of at least 50 109/l and absolute neutrophil count of at least 0.5 109/l are sought by the provider to comfortably assure effective hemostasis and reduce the risk of postoperative bacterial infection. But, in smokers, dental extractions should not be used as a means of controlling chronic asymptomatic periodontal and pulpal diseases, as these patients are prone to fungal infections. Oral ulcerations in leukemic patients should be managed by topical antibacterials along with analgesic and anesthetic rinses. Removing irritants, applying local pressure and hemostatic agents such as absorbable gelatin or collagen sponges should be used to manage bleeding tendency. If the patient does not respond, then platelet transfusions might be warranted.

features of HD include Pel-Ebstein fever, a cyclic spiking of high fever, and generalized severe pruritis. Pruritis is a well-known cutaneous, paraneoplastic manifestation of HD. As the disease progresses, signs and symptoms arise from pressure and obstruction caused by enlarging nodes. Diagnosis is made from nodal biopsy or bone marrow aspirate.

Lymphomas

Non-Hodgkin’s Lymphoma

The lymphomas represent seventh most common malignancy worldwide. These encompass a group of entities that vary widely in terms of their clinical presentation and behavior. These originate in lymph nodes or in extranodal tissue in any part of the body, and from any type of lymphocyte. Three types of lymphomas can be considered: Hodgkin’s, nonHodgkin’s and Burkitt’s. Multiple myeloma also needs a special mention, though it is not a lymphoma, as it is a malignancy of plasma cells, which arise from B-lymphocytes.

Non-Hodgkin’s lymphoma (NHL) is a lymphoproliferative disorder of unknown cause that can occur in all races and age groups. Unlike HD, which often begins with a single focus of tumor, NHL is usually multifocal when first detected. Ninety percent are of B-cell derivation. NHL has been reported in association with AIDS and is classified based on patterns of distribution (diffuse or nodular), cell type (lymphocytic, histiocytic and mixed) and degree of differentiation of cells (well, moderate and poor).

Hodgkin’s Disease Hodgkin’s disease (HD) is a disorder of unknown etiology involving primarily the lymphoid tissue. It arises almost in a single node or chain of nodes and spreads characteristically to the anatomically contiguous nodes. There are two peaks of incidence, one in early adulthood and one around fifth decade of life, and males have increased incidence when compared to females. Four subtypes are recognized based on histologic features (Rye system): lymphocyte predominance, nodular sclerosis, mixed cellularity and lymphocyte depletion. The lymphocyte predominance has the best prognosis and lymphocyte depletion, the worst. HD is also staged into four stages based on the clinical features (Ann Arbor classification). Prognosis becomes worse as the stage increases. Histologically, HD shows multinucleated Reed– Sternberg cells.

Treatment The outlook after aggressive radiotherapy and chemotherapy for patients with this disease, including those with disseminated disease, is generally very good. With current modalities of therapy, the histologic picture has very little impact on the prognosis; instead clinical stage appears to be an important prognostic indication. However, long-term survivors of combined chemotherapy–radiotherapy protocols are at much higher risk of developing acute leukemia. Currently, combination chemotherapy of doxorubicin, bleomycin, vincristine and dacarbazine is used for most patients.

Clinical manifestations The most common presentation of NHL is a painless persistent enlargement of lymph nodes (Figure 4). Unlike HD, extranodal lesions can occur in GI tract, Waldeyer’s ring, spleen, skin and bone marrow. Signs and symptoms include fever of unknown cause, weight loss, malaise, sweating, and abdominal or chest pain. The clinical differences between HD and NHL are outlined below. Clinical differences between HD and NHL HD

NHL

Extranodal involvement uncommon

Extranodal involvement seen

More often localized to a single axial group of nodes

More frequent involvement of multiple peripheral nodes

Orderly spread by contiguity

Non-contiguous spread

Pel–Ebstein fever

Non-specific fever

Clinical manifestations Hodgkin’s disease usually presents as a painless enlargement of the lymph nodes (rubbery). Extranodal involvement is rare. The signs and symptoms include fever, weight loss, sweating, pruritis and fatigue. Characteristic clinical

Treatment Non-Hodgkin’s lymphoma is radiosensitive and the treatment may include a combination of radiotherapy and chemotherapy. High dose chemotherapy with autologous stem 495


Figure 4

Enlargement of the accessory group of lymph nodes on the right side of the face in a patient suffering from non-Hodgkin’s lymphoma. Courtesy: Dr Sarat Gummadapu

cell transplantation is the treatment of choice for relapsed disease. Commonly used drug protocols include cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP and CVP).

Burkitt’s Lymphoma Burkitt’s lymphoma (BL) is a B-cell neoplasm endemic in some parts of Africa and sporadic in other areas, including the United States. The tumor is the human cancer most closely linked with a virus (Epstein–Barr virus). The tumor is considered as the fastest growing human tumor as it doubles in 1–3 days. Clinical features Both the endemic and non-African cases mainly affect children or young adults. In both the forms, the disease rarely arises in lymph nodes. In African patients, involvement of maxilla or mandible is the common mode of presentation, whereas abdominal tumors are more common in North America. Treatment Majority of patients can be cured with aggressive chemotherapy. BL was found to be responsive to cyclophosphamide, methotrexate, vincristine and cytarabine. Oral manifestations and dental considerations Painlessly enlarged cervical lymph nodes are the initial complaint in many of the cases. Suspicion of lymphoma 496

should arise if lymphadenopathy appears without signs of infection or more than one lymph node chain is involved, or a lymph node of 1 cm or more in diameter persists for more than 1 month. A lymphoma may form in the oral cavity or oropharynx but this is rare except in NHL. HD may exhibit inflammatory gingival overgrowth, root resorption and bone loss, which are thought to be paraneoplastic. The most common site for non-Hodgkin’s extranodal lymphomas is the GI tract. In the head and neck region it occurs within soft tissues or bone; the salivary gland, cheek, paranasal sinuses and gingiva are the most common sites. Maxilla is more commonly involved when compared with the mandible. The radiographic methods used for diagnosis of malignant lymphoma include MRI, CT scanning and ultrasound. Ceysens et al noted that the CT appearance of extranodal NHL might often mimic other malignant and inflammatory lesions. Further, 67Ga scintigraphy and bone scintigraphy may also be useful for evaluating malignant lymphoma. NHL is more commonly seen in HIV patients presenting as a slow-growing, painless, bluish, soft masses on the palate. Numb chin syndrome, which is the mental neuropathy and facial and oral numbness restricted to the distribution of the mental nerve, is also found to be frequently associated with malignant lymphoma. This might be either due to direct invasion of tumor cells into the nerve or the compression of the nerve by metastatic mandibular tumors, or the involvement of the trigeminal nerve root by metastatic meningeal tumors. More commonly, dental complications result from radiotherapy or chemotherapy administered in children with HD during tooth development. These include agenesis, hypoplasia and blunted or thin roots. Patients with lymphoma sometimes complain of burning mouth symptoms that may be related to drug toxicity, xerostomia, candidiasis or anemia. Patients who have received more than 3,000 rad (cGy) are susceptible to xerostomia and would benefit from salivary substitutes or pilocarpine. Radiation also can damage taste buds, cause trismus of masticatory muscles, and stunt craniomandibular growth and development.

Multiple Myeloma Multiple myeloma (MM) is a relatively uncommon malignant neoplasm of the plasma cells (which arise from the B-lymphocytes) that often appears to have a multicentric origin within bones. The cause of the condition is unknown, although sometimes a plasmacytoma may evolve into multiple myeloma. This disease makes up about 1% of all malignancies and 10–15% of hematologic malignancies. The abnormal plasma cells in the bone marrow proliferate from a single malignant precursor (monoclonal) and produce immunoglobulins that are not normal or functional. This monoclonal nature of plasma cells can be differentiated from polyclonal nature of plasma cells seen in chronic inflammation.


Clinical and radiographic features Multiple myeloma is typically a disease of older adults (4th to 5th decade), with men being affected slightly more often than women. The manifestations commonly seen are anemia, thrombocytopenia and leukopenia due to suppression of other cells originating in the bone marrow. This may lead to pallor, fatigue, infections and bleeding tendency. Bone pain, due to motion or pressure against bony tumor masses and pathological fractures. Renal failure and amyloidosis due to deposition of abnormal proteins in kidney and various parts of the body. Bence Jones proteins, which are the light chains of immunoglobulins, are excreted in the urine. Hypercalcemia, due to destruction of bone: Radiographically, multiple well-defined ‘punched-out’ radiolucencies or ragged radiolucent lesions may be seen. Oral manifestations Macroglossia, gingival and soft tissue enlargement due to deposition of amyloid. Pallor, petechiae, ecchymosis and increased bleeding tendency. The elevated serum monoclonal antibody can act directly as a thrombin inhibitor or inhibit the interaction of von Willebrand factor (vWF) with platelets or interfere with fibrin polymerization and lead to excessive bleeding tendency. Jaw swelling, jaw pain, tooth mobility and paresthesia due to tumor growth: Multiple myeloma can have three different radiographic manifestations in the jaw bone: (i) normal findings, when there is non-detectable or mild bone resorption, (ii) multiple punched-out radiolucencies from the focal proliferation of plasma cells inside the bone marrow and (iii) generalized bone rarefaction and osteoporotic changes resulting from diffuse or total replacement of the bone marrow by malignant cells. Treatment Chemotherapy constitutes the main modality with radiation therapy as palliative modality of treatment for painful bone lesions. Alkylating agent, such as melphalan or cyclophosphamide, is often used in conjunction with prednisolone, and approximately 60% of patients respond initially to this regimen. Complete remission is never attained and all patients will relapse without further treatment. The prognosis is variable, but the survival of treated patients averages 3 years. Dental considerations Dental treatment can be complicated by anemia, infections, hemorrhagic tendency, renal failure and corticosteroid therapy. Bleeding may result from several causes, including thrombocytopenia, abnormal platelet function, abnormal coagulation or hyperviscosity.

BLEEDING DISORDERS The integrity of circulation is maintained by blood flowing through intact vessels lined by endothelial cells. Efficient mechanisms have evolved to maintain the circulation as a transport system, which both prevent blood loss from a damaged vessel by securing hemostasis, and also prevent the cessation of flow due to thrombosis. Hemostasis depends upon interactions between vessel wall, platelets and clotting factors. There are two phases of hemostasis: primary and secondary. In the initial primary phase, the damaged vessel constricts and platelets aggregate at the site of damage to form a plug to arrest hemorrhage within a few minutes. This is followed by activation of the coagulation system with secondary deposition of a fibrin mesh to secure the platelet plug. These two phases are interlinked; damaged endothelium and the subendothelial matrix activates platelets, which then provide the optimal surface for the binding of the clotting factors and generation of insoluble fibrin. Fibrinolysis is the major means of disposing of fibrin after its hemostatic function has been fulfilled, and it can be considered the rate limiting step in clotting. The protagonists of the hemostasis are as follows: Vessel wall After tissue injury, serotonin and other vasoactive substances are released, which mediate the immediate reflex vasoconstriction. This alone might be sufficient to arrest bleeding from small vessels. Platelets If the defect in the blood vessel is very small—and many small holes develop in the vasculature each day—it is often sealed by a platelet plug rather than by a blood clot. Platelets are minute round or oval disks, which circulate in the blood. When these circulating platelets are exposed to damaged vascular surfaces (in the presence of normal vWF and endothelial cells), they are activated to produce physical and chemical changes. These changes produce an environment that causes the platelet to aggregate and release ADP and platelet factors, which cause further platelet aggregation and promotes clotting mechanism. Clotting mechanism Coagulation involves a series of enzymatic reactions leading to conversion of soluble plasma fibrinogen to fibrin clot. This process involves multiple proteins, many of which are synthesized by liver (fibrinogen, prothrombin, factors V, VII, IX, X, XI and XII) and many are vitamin K dependent (factors II, VII, IX and X). The scheme of reaction is a bioamplification in which, the precursor is altered to an active form, which, in turn, activates the next precursor in the sequence. Beginning with an undetectable biochemical 497


reaction, the coagulation mechanism results in the formation of insoluble fibrin. The clotting of blood also requires calcium and phospholipids. The mechanism initially proceeds by two separate pathways (intrinsic and extrinsic) that converge by activating a third (common) pathway. The extrinsic pathway is initiated by release of tissue thromboplastin and does not require contact activation. Tissue thromboplastin binds to factor VII in the presence of calcium, and this complex is capable of activating factor X to Xa. The intrinsic pathway is initiated when factor XII is activated by surface contact (e.g. with collagen or subendothelium), and it involves the interaction of factors XII and XI. The activated factor XI with the help of divalent cation (calcium) and phospholipids converts factor X to Xa. The factor Xa heralds the initiation of common pathway. Factor Xa converts prothrombin to thrombin, which further converts fibrinogen, a soluble plasma protein, to insoluble fibrin. Finally, fibrin polymerizes to form a gel, stabilizing the platelet plug. The clot thus formed has to be broken down after or else it may lead to thrombosis. This critical function is carried out by TPA (tissue plasminogen activator), which converts plasminogen to plasmin. The plasmin thus formed degrades fibrinogen and fibrin into fibrin degradation products (FDPs). This phase is the fibrinolytic phase, which forms the rate limiting step of hemostasis. Laboratory investigations A number of procedures that are performed in dentistry may cause bleeding. Under normal circumstances, these procedures can be performed with little risk to the patient; however, the patient whose ability to control bleeding has been altered by drugs or disease may be in grave danger unless the problem is identified before undertaking any dental procedure. An alert clinician will get suspicion based on the history offered by the patient, which underscores the importance of meticulous history taking. The most commonly used laboratory screening tests for bleeding disorders are bleeding time, platelet count, prothrombin time and activated partial thromboplastin time. In addition to this, capillary fragility test can also be conducted. Platelet count This is usually obtained as a part of complete blood count. Normal platelet count is 150,000– 450,000 cells/mm3. Decrease in the number of platelets is called as thrombocytopenia. If the platelet count falls below 50,000 cells/mm3, then hemorrhage may result due to trauma or minor surgery. Spontaneous clinical hemorrhage is usually not observed with platelet counts above 10,000–20,000. Bleeding time (BT) This is a functional test of primary hemostasis. The ivy template method is performed using a special device that produces two small wounds keeping the cuff of a sphygmomanometer constantly inflated at 498

40 mmHg. A piece of filter paper is used to dry the borders of the tiny cuts every 30 seconds until no more oozing is present. Normal ivy bleeding time is between 1 and 6 minutes and is prolonged if it is more than 15 minutes. Increase in bleeding time could be caused by platelet defects— quantitative or qualitative—or by blood vessel defects. But its use as a predictive screening test for oral surgical procedures has been discouraged as it is a poor indicator of clinically significant bleeding at sites other than skin. Prothrombin time (PT) The normal range of PT is 11–13 seconds. The screening test examines the efficiency of extrinsic and common coagulation pathways. Increase in PT can be due to vitamin K deficiency, fat malabsorbtion, coumarin therapy, liver disease or disseminated intravascular coagulation (DIC). Because different laboratories use different types of reactives derived from different tissues (lung and brain) and different species (rabbit, bovine and human), it is necessary to standardize the PT. This has been done using the international normalized ratio (INR). The normal coagulation profile is reported as an INR of 1.0. Activated partial thromboplastin time (aPTT) The normal range is 22–36 seconds. The aPTT tests the coagulation factors involved in the intrinsic coagulation pathway (factors VIII, IX, XI and XII). It is therefore elevated in conditions like hemophilia and von Willebrand’s disease, which are a result of deficiency of one of these factors. It is also elevated in heparin anticoagulant therapy. Tourniquet test The tourniquet test for capillary fragility, which assesses the Rumpel–Leede phenomenon, is useful in identifying disorders of vessel wall integrity or platelet disorders. After inducing stasis by inflating the sphygmomanometer cuff around the arm for 5 minutes, petechial hemorrhages are visible on the volar aspect of the arm.

Classification of Bleeding Disorders Bleeding disorders can be broadly classified as: 1. 2. 3.

Vascular disorders (vessel wall) Platelet disorders Disorders of coagulation.

VASCULAR DISORDERS (Vessel Wall) Infections, chemicals, collagen disorders or certain types of allergy can alter the structure and function of the vascular wall to the point at which the patient may have a clinical bleeding problem. The vascular phase in the hemostasis begins immediately following injury and involves vasoconstriction of arteries and veins in the area of injury. Retraction of arteries that have been cut, and build up of extravascular pressure by blood loss from cut vessels aids


in collapsing adjacent capillaries and veins leading to cessation of bleeding. The various vascular disorders that may lead to excessive bleeding tendency are: Vessel wall disorders 1. Congenital a. Hereditary hemorrhagic telangiectasia b. Connective tissue disorders • Ehlers–Danlos syndrome • Osteogenesis imperfecta • Marfan’s syndrome • Cushing’s syndrome 2. Acquired disorders a. Severe infections b. Allergic manifestations c. Drugs • Steroids d. Others • Scurvy • Senile purpura

Hereditary Hemorrhagic Telangiectasia It is a rare disorder with autosomal dominant inheritance. Dilatation of capillaries and small arterioles produce characteristic small red spots that blanch on pressure in the skin and mucous membranes, particularly the nose and GI tract. Recurrent epistaxis and chronic GI tract bleeding are the major problems and may cause chronic deficiency anemia. Perioral and intraoral angiomatous nodules or telangiectasia are common with progressive disease, involving areas of the lips, tongue and palate that may bleed with manipulation during dental procedures. Diascopy test is positive unlike petechiae or ecchymoses. Mucocutaneous lesions may bleed profusely with minor trauma or occasionally spontaneously. Iron deficiency anemia has to be treated with iron supplements, and persistently bleeding lesions may be treated with cryotherapy, laser ablation, electrocoagulation or resection.

Ehlers–Danlos Syndrome Ehlers–Danlos disease is a congenital disorder of collagen synthesis in which there is joint hyperextensibility, skin extensibility and tissue fragility such that capillaries are poorly supported by subcutaneous collagen leading to ecchymosis. Oral findings include bleeding after toothbrushing, hypermobility of TMJ, fragility of oral mucosa and gingiva, stunted teeth and pulp stones on dental radiograph.

Marfan’s Syndrome The connective tissue disorder is inherited as an autosomal dominant trait and is caused by mutations in the fibrillin

gene on chromosome 15. It is characterized by skeletal disproportion (arm span more than height), arachnodactyly (long, thin spider-like fingers), generalized hypermobility of joints and CVS anomalies like mitral valve prolapse, aortic incompetence, etc. The oral manifestations are: high arched palate, bifid uvula, malocclusion and multiple odontogenic cysts of the maxilla and mandible. TMJ dysarthrosis is also reported.

Scurvy Ascorbic acid (vitamin C) is the most active reducing agent in the aqueous phase of living tissues and is involved in the hydroxylation of proline in protocollagen to hydroxylproline in mature collagen. It has been suggested that high dose of vitamin C improves immune function (including resistance to common cold) and cholesterol turnover, but such effects remain unproven in controlled trials. The scurvy, i.e. deficiency of vitamin C, leads to defective formation of collagen. This impairs healing of wounds, and causes capillary hemorrhage and reduced platelet adhesiveness (normal platelets are rich in ascorbic acid). Hemorrhage can occur in the muscles, joints, nail beds and gingival tissues. Gingival involvement may include swelling, bleeding, secondary infection and loosening of teeth. For treatment, a dose of 250 mg vitamin C, 8-hourly by mouth should saturate the tissues quickly. The general deficiencies of the patient’s former diet also need to be corrected and other vitamin supplements given if necessary. Investigations for vascular disorders ❍ ❍

Bleeding time: Elevated. Tourniquet test: Positive.

PLATELET DISORDERS Platelet numbers or function may be impaired by many diseases or drugs. Decrease in the number of platelets is called as thrombocytopenia, which can occur either due to impaired production or excessive destruction. Defect in the function of platelets is called as thrombocytopathy, which can occur due to drugs, liver disease or can be inherited. For convenience, thrombocytopenic disorders and thrombocytopathic disorders are again divided into congenital and acquired.

THROMBOCYTOPATHIC DISORDERS Disorders of the platelet function are usually associated with excessive bruising and gingival bleeding and, in 499


some of the acquired forms, with thrombosis. The platelet count is normal or increases and the bleeding time is prolonged. Platelet function is abnormal due to a defect either in the adhesion, aggregation or release of active substances. Inherited platelet disorders like Glanzmann’s thrombasthenia and Bernard-Soulier syndrome are deficient in platelet membrane glycoprotein resulting in failure of platelet aggregation. Bernard-Soulier syndrome is also characterized by large platelets resulting in epistaxis, menorrhagia and prolonged bleeding from tooth extractions. Storage pool disease is also an inherited thrombocytopathic disorder, which shows lack of storage pool of platelet dense bodies, causing poor platelet function. Medications can also reduce absolute number of platelets or interfere with their function, resulting in post surgical hemorrhage. Drug related platelet disorders are reversible within 7–10 days of discontinuation of drug. Aspirin activates an enzyme called prostaglandin synthetase, resulting in inactivation of cyclo-oxygenase and decreasing biosynthesis of prostaglandin and thromboxane that are needed to regulate interactions between platelets and endothelium. A single 100 mg dose of aspirin provides rapid complete inhibition of platelet cyclo-oxygenase activity and thromboxane production. Most NSAIDs have similar but less significant antiplatelet effects compared with aspirin. Congenital

Acquired

Storage pool disease

Drug-induced (e.g. Aspirin)

Bernard–Soulier syndrome

Renal and liver disease

Glanzmann’s thrombasthenia

Myeloproliferative disorder

THROMBOCYTOPENIC DISORDERS These are caused by reduced platelet production in the bone marrow or excessive peripheral destruction of platelets. The underlying cause may be revealed by history and examination but a bone marrow examination will show whether the platelets are reduced, normal or increased and will provide essential information on morphology as well. In patients with thrombocytopenia due to failure of production, no specific treatment may be necessary but the underlying condition should be treated if possible. If the platelet count is very low or the risk of bleeding is very high, then platelet concentrate administration is indicated. Idiopathic thrombocytopenic purpura (ITP), which is due to increased destruction of platelets and thrombotic thrombocytopenic purpura are the commonly acquired thrombocytopenic disorders. May–Hegglin anomaly is a rare hereditary condition characterized by the triad of thrombocytopenia, giant platelets and inclusion bodies in leukocytes. Clinical features and the pathogenesis of bleeding of these are poorly defined. 500

Congenital

Acquired

May–Hegglin anomaly

Impaired production • Bone marrow failure • Leukemia • Aplastic anemia (drugs, chemicals) Excessive destruction • Immune • Idiopathic thrombocytopenic purpura Dilutional • Massive transfusion Others • DIC • Thrombotic thrombocytopenic purpura

Idiopathic Thrombocytopenic Purpura Idiopathic thrombocytopenic purpura (ITP) is due to immune destruction of platelets. The antibody-coated platelets are removed following binding to receptors on macrophages. The condition is seen in both children and adults. In children, it is usually acute but self-limiting and may follow a viral infection or immunization. In adults, it is usually less acute than in children. It is characteristically seen in women and may be associated with other autoimmune disorders such as SLE, thyroid disease and autoimmune hemolytic anemia and also after infections with viruses such as HIV. Platelet autoantibodies are detected in about 60–70% of the patients, and are presumed to be present, although not detectable, in the remaining patients. Easy bruising, purpura, epistaxis and menorrhagia are common. In severe ITP, oral hematomas and hemorrhagic bullae may be present. Children do not usually require treatment. If treatment is necessary on clinical grounds, high-dose prednisolone is effective, given for a very short course. Intravenous immunoglobulin (IV IgG) should be reserved for very serious bleeding or for urgent surgery. Adults with ITP having platelet counts more than 30,000 cells/mm3 require no treatment unless a surgical procedure is being carried out. Otherwise, first-line therapy consists of oral corticosteroids, 1 mg/kg body weight but IV IgG is useful where a rapid rise in platelet count is desired, especially before surgery. Second-line therapy involves splenectomy, to which the majority of patients respond.

Thrombotic Thrombocytopenic Purpura Thrombotic thrombocytopenic purpura (TTP) is a rare, but very serious condition, in which platelet destruction leads to profound thrombocytopenia. It is a characteristic symptom complex of fever, florid purpura, fluctuating cerebral dysfunction and hemolytic anemia often accompanied by renal failure. The underlying cause is not fully understood but TTP seems to be due to endothelial damage associated


with the presence in the circulation of very high molecular weight multimers of vWF. TTP is associated with pregnancy, metastatic malignancy, drugs such as mitomycin C and infections. Microvascular infarcts occur in gingival and other mucosal tissues in about 60% of the cases. Treatment includes plasma exchange, using cryoprecipitate depleted FFP (cryo-poor supernatant). Most patients are also treated with prednisone, 1 mg/kg daily. Oral manifestations and dental considerations Oral manifestations Oral manifestations of vessel wall disorders and platelet disorders are similar in which they exhibit small pinpoint hemorrhages, called petechiae and larger patches called ecchymosis. Platelet disorders with severely altered hemostasis can lead to spontaneous gingival bleeding. Continuous oral bleeding over long periods of time fosters deposits of hemosiderin and other blood degradation products on the tooth surfaces, turning them brown. Patients with disorders of coagulation mechanism will exhibit bleeding due to trivial injuries, severe hemophiliacs experience bleeding into the joints (hemarthrosis) and soft tissue hematomas. Oral bleeding occurs from sites that are susceptible to trauma like labial frenum, tongue and buccal mucosa. Though hemarthrosis is a common complication in hemophiliac’s weight-bearing joints, it rarely occurs in the TMJ. Dental considerations Basic management principles for patients with severe defects: When severe bleeding is expected to result from dental treatment, the goal of management is to restore the hemostatic system preoperatively to within the requisite parameters and to support coagulation with adjunctive medications or local measures. For reversible coagulopathies, removal of the causative agent or treatment of the primary illness or defect may allow the patient to return to normal for the dental treatment period. For irreversible coagulopathies, however the missing or defective element may need to be replaced from an exogenous source. Because of the risks and expense of blood products, dental treatment plans should be arranged to maximize the benefit from the transfusion by completing all procedures likely to induce bleeding at one treatment visit, when possible. Preventive and periodontal therapy Preventive dental care and the maintenance of a healthy periodontium are especially important for the patient with severe bleeding disorder. Gingivitis can predispose the patient to spontaneous gingival bleeding. Instructions in thorough brushing and flossing, diet and nutrition, fluoride use, and semiannual examination with gentle probing and prophylaxis are emphasized as with normal patients. Calculus can be removed atraumatically in stages with an ultrasonic scaler or hand instruments to reduce hyperemia. The periodontal

patient requiring deep subgingival scaling and root planing in areas of inflammation may require medical management before a comprehensive initial therapy appointment. Restorative and prosthodontic therapy Restoring carious teeth and preparing and cementing fixed prosthesis usually produce minimal bleeding. The risk of gingival bleeding can be reduced by the use of a thin rubber dam and selection of an atraumatic, stable clamp or hemostatic gingival retraction cord. Wedges and matrices can be used with gentle handling. Removable appliances can be constructed conventionally. Attention should be paid to removal of rough areas in trays and final prostheses that might produce traumatic ulceration and bleeding. Endodontic therapy Endodontic treatment of infected teeth is especially important in the coagulopathy patient because it may avert the need for extraction. Generally, there are no contraindications to root canal therapy, provided the instrumentation does not extend beyond the apex. Pulpotomies, pulpectomies and root canal therapies can be generally performed without bleeding complications. The minimal bleeding during pulp extirpation can be controlled intrapulpally with epinephrine or formocresol. Orthodontic therapy There is no contraindication to orthodontic treatment. Properly managed fixed appliances are preferred over removable and functional ones that reposition the mandible because they are less likely to provoke bleeding both intraorally from tissue irritation and within the TMJ. Archwires should be secured with elastic bands rather than free wires with sharp edges that cut the mucosa. Careful adaptation and cementation of bands and placement and removal of archwires are encouraged. Pediatric dental therapy Pediatric dental patient occasionally presents with prolonged oozing from exfoliating primary teeth. Administration of factor concentrates and extraction of the deciduous tooth with curettage may be necessary for the patient’s comfort and hemorrhage control. Pulpotomies can be performed without excessive pulpal bleeding. Stainless steel crowns should be prepared to allow minimal removal of enamel at gingival areas. Pain control/local anesthesia The administration of local anesthetics in bleeding disorder patients requires certain precautions to prevent hematoma formation. Although patients with mild-to-moderate disease are at low risk, those with severe disease, especially severe hemophilia A, have been shown to have 11% rate of hematoma formation following inferior alveolar nerve blocks. Hematoma spread to the lateral pharyngeal, retropharyngeal and submandibular/ sublingual spaces may cause respiratory obstruction and death. Hence, block anesthesia and some infiltration anesthesia in the patient with a severe coagulopathy (including many mild-to-moderate hemophiliacs with factor levels below 20%) should be avoided until the hemostatic defect is 501


corrected. For acute treatment of a forming hematoma, application of pressure and ice are useful adjuncts to systemic correction of the hemostatic defect. Use of periodontal ligament injections in mild-to-moderate hemophiliacs may be effective for restorative procedures. Intrapulpal anesthesia is safe and effective following access for pulp extirpation. An alternative to local anesthesia is nitrous oxide/oxygen sedation which raises pain threshold and reduces anxiety. Intramuscular injections should be avoided unless the coagulation defect has been corrected. Postoperative pain is controlled with acetaminophen and narcotics. Aspirin and other NSAIDs are contraindicated. When general anesthesia is considered, oral intubation is preferred over nasal intubation, which may induce a difficult-to-control nasal bleeding.

INHERITED COAGULATION DISORDERS

Oral surgery Surgical procedures impose the highest risk of bleeding in the coagulopathy patient. Though primary importance is placed on systemic preoperative management such as plasma product infusion, local measures are also extremely important in assisting clot formation and maintenance. Surgical technique should be atraumatic, with care taken to remove osseous fragments and granulation tissue, reappose buccal and lingual plates, and smooth bony margins. Although having no direct effect on hemostasis, primary closure protects the blood clot, makes the postoperative period more comfortable, and decreases the risk of postoperative bleeding. Placement of absorbable hemostatic agents such as bovine collagen in the apical third of extraction sites promotes stable clots. Topical buffered thrombin solution also has potent hemostatic properties. It directly converts fibrinogen to fibrin and can be applied to the bleeding site on an oxidized cellulose product, such as oxycel or surgical. Antibiotics should be considered when absorbable hemostatic agents are used or signs of active infection exist because postoperative infection can lead to resumed bleeding. The antifibrinolytic epsilon-aminocaproic acid (EACA) is an extremely useful adjunct to prevent postsurgical bleeding without the need for subsequent transfusions and to treat gingival oozing following deep scaling and root planing. EACA prevents premature destruction of the fibrin clot by virtue of its ability to inhibit plasminogen activation. The usual adult dosage is 50 mg/kg body weight every 6 hours for 7–10 days. A 25% oral solution used topically and systemically is preferred over the tablet form or intravenous route.

Hemophilia A

DISORDERS OF COAGULATION Coagulation disorders may be inherited or acquired. The inherited disorders are uncommon and usually involve deficiency of one factor only. The acquired disorders occur more frequently and almost always involve several coagulation factors. The coagulation disorders can be classified as follows. 502

The inherited disorders can result from deficiency of factors essential in the clotting cascade or deficiency of vWF. Of the inherited coagulopathies, von Willebrand’s disease is the most common. It results from the deficiency of von Willebrand’s factor (vWF). Hemophilia A, caused by coagulation factor VIII deficiency, is the next most common coagulation disorder, followed by hemophilia B, a factor IX deficiency. Clinical bleeding can vary from mild to severe, depending on the specific clotting factor affected and the level of factor deficiency.

Hemophilia A is due to defective factor VIII (antihemophilic factor, AHF). This is a glycoprotein of several components, including factor VIII C (procoagulant that participates in clotting cascade), VIII K:Ag (vWF, which binds to platelets and is the carrier for factor VIII C) and VIII R:Rco (Ristocetin cofactor, which supports platelet aggregation). In hemophilia A only factor VIII C is reduced. Inherited as an X-linked recessive trait, hemophilia affects males. Females are carriers as the normal X chromosome suppresses the effect of abnormal X (females have XX chromosomal disposition). Hemophilia is denoted as severe if factor VIII is less than 1%, moderate if factor VIII is 1–5% and mild if factor VIII level ranges between 5% and 25%. Hemophilia typically becomes apparent in childhood when bleeding into muscles or joints (hemarthroses) follows injuries. Hemarthroses can cause joint damage and cripple the patient, but bleeding after dental extractions is sometimes the first or only sign of mild disease. Bleeding into the cranium, bladder and other sites can cause severe or fatal complications. Hemorrhage in hemophiliacs is dangerous either because of loss of blood, or because there may be damage to joints, muscles and nerves or pressure on vital organs if hemorrhage is internal. This compression of the pharynx and larynx following hematoma formation in the neck can be fatal. Investigations ❍ ❍ ❍ ❍ ❍ ❍ ❍

Bleeding time: Normal Prothrombin time: Normal Platelet count: Normal Activated partial thromboplastin time: Elevated Factor VIII C: Deficient Factor VIII R: Ag—Normal Factor VIII R: Rco—Normal.

Management Bleeding is treated by administration of factor VIII concentrate by IV infusion. Factor VIII concentrate is freeze-dried


and may be stored in domestic refrigerators at 40C. This allows it to be administered by the patient immediately after bleeding has started, reducing the likelihood of chronic damage to joints and the need for in-patient care. The majority of severely affected patients are given prophylaxis 3 times per week from early childhood in an attempt to prevent permanent joint damage. Synthetic vasopressin (desmopressin)—IV or SC or intranasal—produces a rise in factor VIII C proportional to the initial level of factor VIII. It avoids the complications associated with blood products and is useful for treating bleeding episodes in mild hemophilia and as prophylaxis before minor surgery. It is ineffective in severe hemophilia.

Hemophilia B and C Christmas disease (factor IX deficiency) is clinically identical to hemophilia A and inherited in the same way, but it is about one-tenth as common as hemophilia A. Factor IX replacement is needed before surgery and desmopressin is not used. Concentrates used to treat factors VIII and IX deficiencies are specific for each state, and therefore a correct diagnosis must be made to ensure effective replacement therapy. Factor XI deficiency (PTA deficiency) is one of the more common among other congenital coagulation defects and is sometimes known as hemophilia C. It is transmitted as an autosomal dominant trait. Bleeding symptoms do occur but are usually mild. In the event of major surgery or trauma, hemorrhage can be controlled with infusions of fresh frozen plasma.

Von Willebrand’s Disease Von Willebrand’s disease is due to the inherited deficiency in vWF, which is a component of factor VIII. It affects females as well as males and is usually inherited as an autosomal dominant condition, but a severe form of the disease may be inherited as a sex-linked recessive trait like the hemophilia. vWF is responsible for platelet adhesion to damaged endothelium and also acts as a carrier for factor VIII, protecting it from proteolytic degradation. Thus both bleeding time and activated partial thromboplastin time are elevated in von Willebrand’s disease. Clinical features Von Willebrand’s disease causes bleeding that has features similar to that caused by platelet dysfunction. But if severe, it can resemble hemophilia. Three types of von Willebrand’s disease have been identified. Type I and type II patients usually have mild clinical features. Bleeding follows minor trauma or surgery, and epistaxis and menorrhagia often occur. Hemarthroses are rare. Type III patients have more severe bleeding but rarely experience the joint and muscle bleeds seen in hemophilia A.

Investigations ❍ ❍ ❍ ❍ ❍

Bleeding time: Elevated Platelet count: Normal Activated partial thromboplastin time: Elevated Factor VIII C: Decreased vWF: Decreased.

Management Treatment depends on the severity of the condition and may be similar to that of mild hemophilia, including the use of desmopressin where possible. Intermediate purity factor VIII or vWF concentrates should be used to treat bleeding or to cover surgery in patients who require replacement therapy. Cryoprecipitate should be avoided because of greater risk of transfusion transmitted infections. Aspirin and other NSAIDs should also be avoided.

ACQUIRED COAGULATION DISORDERS Liver Disease Liver disease may result in a number of defects in hemostasis. The defects are: ❍ ❍ ❍ ❍

❍

Vitamin K deficiency: Occurs due to intrahepatic or extrahepatic cholestasis Reduced synthesis: Reduced synthesis of coagulation factors may be due to severe hepatocellular damage Thrombocytopenia: Results from hypersplenism due to splenomegaly Functional abnormalities: Functional abnormalities of platelets and fibrinogen are found in many patients with liver failure Disseminated intravascular coagulation (DIC): May occur in acute liver failure.

Vitamin K Deficiency Vitamin K is necessary for carboxylation of coagulation factors II, VII, IX, X, without which these factors cannot bind calcium. Deficiency of vitamin K may be due to inadequate stores, malabsorption and oral anticoagulants (vitamin K antagonists). PT and aPTT are prolonged and there may be bruising, hematuria and gastrointestinal or cerebral bleeding. Deficiency may be treated by phytomenadione (vitamin K) 10 mg IV. Newborn babies have low levels of vitamin K, and this may cause minor bleeding in the first week of life (classic hemorrhagic disease of the newborn).

Disseminated Intravascular Coagulation There is a widespread generation of fibrin within blood vessels, owing to activation of coagulation by release of 503


procoagulant material, and by diffuse endothelial damage or generalized platelet aggregation. There is a consumption of platelets and coagulation factors and secondary activation of fibrinolysis leading to production of fibrin degradation products (FDPs), which may contribute to coagulation defect by inhibiting fibrin polymerization. The consequences of these changes are a mixture of initial thrombosis followed by a bleeding tendency due to consumption of coagulation factors and fibrinolytic activation. DIC may be caused by malignant disease, septicemia, hemolytic transfusion reactions, trauma, burns, surgery and liver disease. The clinical presentation of DIC varies from no bleeding at all to profound hemostatic failure with widespread hemorrhage. Bleeding may occur from oral cavity, nose and venepuncture sites. The underlying condition is treated and this may be all that is necessary in patients who are not bleeding. Transfusion of platelet concentrates, cryoprecipitate and red cell concentrates is indicated in patients who are bleeding. Anticoagulant therapy Anticoagulation with warfarin is frequently used as a preventive measure for embolic phenomenon related to several conditions. Some of the most common ones are atrial fibrillation, dilated cardiomyopathy, systolic congestive heart failure, valvular heart disease and deep vein thrombosis. Warfarin inhibits production of vitamin K-dependent factors II, VII, IX and X. The injudicious use of coumadin on occasion can lead to spontaneous bleeding that can be severe or even fatal.

RESPIRATORY DISORDERS The lungs, with their combined surface area of more than 500 m2, are directly open to the external environment. Thus, structural functional, or microbiological changes within the lungs can be closely related to epidemiological, environmental, occupational, personal, and social factors. Primary respiratory diseases are responsible for a major burden of morbidity and ultimately deaths and lungs are often affected in mouth system diseases. Respiratory infections are commonly encountered among dental patients. The anatomic proximity of respiratory tract with the oral cavity lead to much interplay between oral and respiratory infections and there is a growing body of literature pointing to a direct association between oral pathogens and respiratory diseases. Recent studies have reported an oral bacteria as a causative pathogen in respiratory diseases and conditions associated with significant morbidity and mortality and furthermore some respiratory illnesses may have an effect on orofacial morphology and even on dentition.

504

This section provides an overview of the more common respiratory disorders and explores the relationship between these conditions and oral health. A dentist with adequate knowledge and skills to collect information pertaining to those conditions which are likely to place these patients at a higher risk of developing complications by receiving invasive dental treatment, can suitable modify dental treatment to meet the needs of these patients.

Classification of Respiratory Tract Disorders Respiratory tract disorders can be grouped as: I.

Upper respiratory tract infections 1. Viral respiratory infections 2. Allergic rhinitis 3. Pharyngitis and tonsillitis 4. Sinusitis II. Lower respiratory tract infections 1. Pneumonia 2. Asthma 3. Chronic obstructive pulmonary disease (COPD) or chronic obstructive airway disease (COAD) 4. Cystic fibrosis 5. Pulmonary embolism III. Granulomatous disorders 1. Tuberculosis 2. Sarcoidosis IV. Malignant disorders 1. Bronchogenic carcinoma (lung cancer) 2. Nasopharyngeal T and NK cell lymphomas V. Other respiratory disorders 1. Legionnaire’s disease (legionellosis) 2. Lung abscess 3. Bronchiectasis 4. Obstructive sleep apnea syndrome (OSAS) 5. Occupational lung disease.

Common Symptoms of Respiratory Diseases Cough, production of sputum, hemoptysis, chest pain, breathlessness and wheeze are common symptoms associated with respiratory diseases. Cough Cough is defined as an explosive expiration that provides normal protective mechanism for clearing of tracheobronchial tree of secretions and foreign materials. Origin of the cough

Common causes

Nature/characteristics

Pharynx

Post-nasal drip

Usually persistent

Larynx

Laryngitis, tumor

Harsh, barking


Trachea

Tracheitis

Painful

Bronchi

Bronchitis

Dry or productive

Asthma

Dry or productive, worse at night

Bronchiectasis

Productive. Changes in posture induce sputum production

Sputum Sputum is matter (mucus, phlegm) that is expectorated from the respiratory tract (usually lower respiratory tract), that is mixed with saliva, which can then be spat from the mouth. It is usually associated with diseases of the lower respiratory tract.

mediastinal tumors), and pain associated with the chest wall (rib fractures, direct invasion of chest by tumor, spinal nerve root involvement). Breathlessness or dyspnea It is the unpleasant subjective awareness of the sensation of breathing. The common respiratory causes for breathlessness include: acute severe asthma, chronic asthma, chronic obstructive pulmonary disease, pneumonia, and pneumothorax. Occasionally other respiratory conditions may also predispose to dyspnea such as laryngeal edema, inhalation of foreign object, extreme cases of pleural effusion, bronchial carcinoma and acute respiratory distress syndrome. Wheezing

Type

Appearance

Cause

Serous

Clear, watery, may be frothy and pink

Acute pulmonary edema

Mucoid

Clear, gray, white and occasionally black

Chronic bronchitis, asthma, chronic obstructive pulmonary disease

Purulent

Yellow, green, brown

All types of bacterial infection

Rusty

Rust colored sputum or golden yellow

Pneumococcal pneumonia

Hemoptysis Hemoptysis is the expectoration of blood or of bloodstained sputum from the bronchi, larynx, trachea, or lungs. Causes for hemoptysis Common causes

Uncommon causes

Others causes

Pulmonary infarction

Mitral stenosis

Foreign body inhalation

Bronchial carcinoma

Aspergilloma

Chest trauma

Tuberculosis

Bronchial adenoma

Iatrogenic

Lung abscess

Metastatic pulmonary

Bronchoscopy Transbronchial biopsy

Acute bronchitis

Malignant disease

Chronic bronchitis

Laryngeal tumors

Chronic obstructive pulmonary disease

Chest pain Chest pain is commonly associated with anxiety, cardiac diseases, respiratory diseases, and disorders of the musculoskeletal and gastrointestinal system. Chest pain associated with the respiratory system can manifest as pleural pain (pneumonia, pulmonary infarction, tuberculosis, malignant disease), retrosternal pain (tracheitis,

It is a continuous, coarse, whistling sound produced in the respiratory passages during breathing. The primary causes for wheezes to occur are either narrowed or obstructed respiratory passages or increased velocity of airflow within the respiratory passages. Wheezes may occur at various stages in the inspiratory and expiratory respiratory cycle. Diseases involving the brochioles may exhibit a wheeze that occurs in the expiratory phase of respiration. Tumors, hypersensitivity pneumonitis and foreign body obstructions may produce a monotonal wheeze throughout the inspiratory phase. Partial collapse of the lungs may lead to production of wheeze that occurs at the termination of both the expiratory and inspiratory phases. Such a wheeze usually signifies the periodic opening of deflated alveoli. Stridor is a term used for a harsh, high-pitched, vibrating sound that is heard in respiratory tract obstruction. Obstructions in the upper airway passages (trachea, larynx, epiglottis) may produce stridor that occurs in the inspiratory phase, whereas lower airway obstructions will produce a stridor in the expiratory phase of respiration. Clinical causes for wheeze ❍ ❍ ❍ ❍ ❍ ❍ ❍

Infections (croup [laryngotracheobronchitis], whooping cough, laryngitis) Laryngo-, tracheo- or bronchomalacia Laryngeal or tracheal tumors, mediastinal masses Tracheal stenosis Emotional laryngeal stenosis Foreign body aspiration Asthma

Chronic obstructive pulmonary disease ❍ ❍

Bronchorrheal states (chronic bronchitis, cystic fibrosis) Bronchiectasis

505


❍ ❍ ❍ ❍

Interstitial fibrosis, hypersensitivity pneumonitis Pulmonary edema Forced expiration in normal subjects Medications (many asthmatics wheeze following intake of aspirin).

Oral manifestations and dental considerations

Respiratory diseases and their dental significance are listed below.

The soft palate may reveal the presence of well-defined minute erythematous macular lesions. Use of antihistamines for the management of upper respiratory tract infections may result in xerostomia.

UPPER RESPIRATORY TRACT INFECTIONS

Diagnosis

Viral Infections Main causes for upper respiratory tract infections (RTI)

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Rhinoviruses Respiratory syncytial viruses Parainfluenza virus Coxsackie viruses Echoviruses Adenoviruses Influenza viruses Epstein–Barr viruses Beta-hemolytic streptococci

Common cold

Tonsillitis and pharyngitis

Majority of the upper respiratory tract infections are caused by Rhinoviruses (Picornaviridae family). Other viruses that are commonly implicated include the respiratory syncytial viruses (Paramyxoviridae family), influenza viruses (Orthomyxoviridae family) and coxsackie viruses (Picornaviridae family). As rhinoviruses are the major causative factors for upper respiratory tract infection, only they will be discussed. Rhinoviruses spread via aerosols of respiratory droplets and contaminated surfaces and direct person to person contact. Once the virus enters the upper respiratory tract it binds to intercellular adhesion molecule-1 (ICAM-1) receptors on the respiratory epithelial cells and begins to replicate within 15 minutes of entering the host’s respiratory tract. The infected cells release chemokines and cytokines. These substances activate the inflammatory mediators of the host. Following an incubation period of about 10 hours the first symptoms begin to appear. Rhinoviruses rarely cause lower respiratory tract disease probably because they grow poorly at 37C. Clinical features The common clinical features seen in rhinovirus infections include non-specific signs and symptoms such as fever, sneezing, malaise, myalgia, headache, cough, rhinorrhea with discharge (serous or purulent), nasal congestion and oro-nasal-pharyngeal irritation. As a consequence sinusitis and earache (obstruction of the pharyngotympanic tube by edema or by bacterial 506

infection of middle ear) may be present. Maxillary sinusitis may result in facial pain.

Laboratory tests are not really necessary for the diagnosis of upper respiratory tract infections. However, the virus may be isolated by culture or rapid diagnostic assay. A complete hemogram may reveal increased numbers of mononuclear cells, lymphocytes, and monocytes. Management Most of the infections are self-limited. The treatment is aimed at managing symptoms. Patient should be adequately hydrated. Antihistaminics are used to manage the rhinorrhea. Analgesics and antipyretics are used to treat fever and myalgias.

Allergic Rhinitis Rhinitis is the recurrent inflammation of the nasal membranes and is characterized by a symptom complex that consists of a combination of any of the following: sneezing, nasal congestion, nasal itching, and rhinorrhea. The eyes, ears, sinuses, and throat may also be affected. When the conjunctiva is also affected the term allergic rhinoconjunctivitis is used. It is estimated that almost 20% of the population suffer from allergic rhinitis. Seasonal, perennial, sporadic/vasomotor and occupational allergic rhinitis are some of the types of allergic rhinitis. Environmental triggers such as pollen, dust mites, animal dander may incite a type I allergic hypersensitivity reaction. In susceptible individuals, exposure to certain foreign proteins leads to allergic sensitization, which is characterized by the production of specific IgE directed against these proteins. This specific IgE coats the surface of mast cells, which are present in the nasal mucosa. When the specific protein (pollen/dust mite, spore) is inhaled, it can bind to the IgE on the mast cells, leading to immediate and delayed release of a number of mediators such as histamine, chymase, kinins and heparin, which in turn produce the symptoms of rhinorrhea. Rhinits is present in two phases: the early or immediate phase and the late phase. The early phase is seen within a few minutes of exposure to the allergen and characterized by nasal congestion, sneezing, itching, redness, tearing, and


post nasal drip. The late phase usually occurs about 6 hours after the early phase and patients present with reduction in the frequency of sneezing and itching. However, congestion and increased mucus production is more common. This phase may last for a few days. Fatigue, malaise, drowsiness or sleepiness are common systemic effects of rhinitis. It is believed that allergic rhinitis may often occur along with asthma or atopic dermatitis. Orofacial features and dental considerations The readily visible facial features in allergic rhinitis are ‘allergic shiners’, transverse nasal crease and Dennie–Morgan lines. ‘Allergic shiners’ is the term used to describe the dark circles around the eyes due to vasodilation or nasal congestion. Rhinorrhea prompts individuals to frequently rub the nose in an upward direction with the palm. This is classically referred to as ‘allergic salute’. Repeated rubbing of the nose causes the formation of a transverse crease at the tip of the nose. Dennie–Morgan lines are prominent infraorbital creases. These are also seen in atopic dermatitis. The typical intraoral findings include tonsillar hypertrophy and streaks of lymphoid tissue on the posterior part of the oropharynx which gives rise to a cobble-stone appearance. Other symptoms include itching sensation in the palate and tongue protrusion. A study by Elad et al (2006) showed the patients with allergic rhinitis had lower salivary flow rates compared to healthy individuals. Gingival inflammation Matsson and Möller (1990) studied the degree of gingival inflammation in children with rhinoconjunctivitis due to birch pollinosis. Their study showed that during the pollen season, children with allergic rhinoconjunctivitis exhibit an enhanced degree of gingival inflammatory reaction. Dental and skeletal abnormalities Trask et al (1987) analyzed the effects of perennial allergic rhinitis on dental and skeletal development. The allergic subjects were characterized by deeper palatal vault height, retroclined mandibular incisors, increased total anterior facial height and lower facial height, a larger gonial angle, and greater SN, palatal, and occlusal planes to mandibular plane angles. Also, the allergic subjects had smaller SNB and SN-pogonion angles and an increased overjet compared to normal controls. Martínez Esteinou and Omaña Vidal (1988) showed that the patients with history of allergic rhinitis and nasopharyngeal obstruction (may result in mouth breathing) of allergic origin exhibited a high palatal vault, retroinclinable maxillary incisors and increased total anterior facial height.

Posture and allergic rhinitis Hasegawa (1994) studied the effects of supine and lateral recumbent positions in patients with allergic rhinitis. Their investigations showed that posture induces complete nasal obstruction in the supine or lateral recumbent positions in some patients with allergic rhinitis. Diagnostic tests Blood tests will reveal an elevated serum IgE and eosinophil count. Radioallergosorbent test (RAST) may be employed to test sensitivity to specific allergens. Alternatively a skin prick test is performed. A drop of a known allergen extract is placed on the forearm and a lancet is used to make a small prick on the skin through the drop. If the patient is allergic to the test substance a small lump is seen in 15–20 minutes time. Dental considerations Use of first generation antihistamines may result in dry mouth. Long-term use of steroid based inhalers may cause oral candidiasis.

Pharyngitis and Tonsillitis Inflammation of the pharynx is referred to as pharyngitis. It is usually caused by the direct infection of the pharynx, primarily by viruses or bacteria. Group A beta-hemolytic Streptococcus (GABHS) pharyngitis accounts for 15–30% of cases in children and 5–15% of cases in adults. Pharyngitis may also be caused due to post nasal drip secondary to rhinitis, gastroesophageal reflux, thyroiditis, allergies, a foreign body, chronic mouth breathing and smoking. It is estimated that approximately 1.1% of the visits to the primary care center are for acute pharyngitis. It usually occurs in late winter and early spring. Transmission of typical viral and GABHS pharyngitis occurs mostly by hand contact with nasal discharge, rather than by oral contact. The first symptoms are seen after an incubation period of 24–72 hours. Viral pharyngitis The viral form of pharyngitis is characterized by the presence of rhinorrhea, cough, conjunctivitis, coryza, malaise or fatigue, hoarseness, and low-grade fever. The common viral causes for pharyngitis include Ebstein–Barr infection (infectious mononucleosis), coxsackie virus infection (herpangina). Patients present with fever, malaise and fatigue, exudative tonsillopharyngitis, generalized lymphadenopathy and hepatosplenomegaly. Almost 90% of the patients present with a classic maculopapular rash. Coxsackie virus infection is characterized by the presence of tonsillopharyngitis and discrete minute ulcers (2–3 mm) on the anterior tonsillar pillars, uvula and soft palate. 507


Bacterial pharyngitis Patients with bacterial pharyngitis generally do not have rhinorrhea, cough, or conjunctivitis. GABHS (mainly Streptococcus pyogenes) is the most common bacterial cause of pharyngitis. Other less common bacterial causes include Corynbacterium diphtheriae, Neisseria gonorrheae, Chlamydia and Mycoplasma pneumoniae. Pharyngotonsillitis caused by GABHS is characterized by pharyngeal erythema and swelling, tonsillar exudate, edematous uvula, palatine petechiae, and anterior cervical lymphadenopathy. The infections last for about one week when left untreated. Scarlet fever is associated with GABHS pharyngitis and usually presents as a punctate, erythematous, blanchable, sandpaper-like exanthem. The rash is found in the neck, groin, and axillae, and is accentuated in body folds and creases (Pastia’s lines). The pharynx and tonsils are erythematous and covered with exudates. The tongue may be bright red with a white coating (strawberry tongue). The complications of GABHS infection are rheumatic fever, peritonsillar abscess and poststreptococcal glomerulonephritis. Peritonsillar abscess occurs in fewer than 1% of patients treated with antibiotics. Patients with peritonsillar abscess typically have a toxic appearance and may present with a ‘hot potato voice’, fluctuant peritonsillar mass, and asymmetric deviation of the uvula. Clinical scoring system for validation of Streptococcal infection Symptoms and points ❍ ❍ ❍ ❍

Fever (subjective or measured in office): 1 point Absence of cough: 1 point Tender anterior cervical adenopathy: 1 point Tonsillar swelling or exudates: 1 point.

streptococcal infections especially in the course of acute rheumatic fever. Management Viral pharyngitis runs a short course and usually treated symptomatically. Patients may be advised to use antiseptic and analgesic mouthrinses. Acute streptococcal pharyngitis is treated with oral penicillin V or erythromycin or IM injections of benzathine penicillin G or oral cephalosporins. Dental considerations GABHS may be persistent on toothbrushes and removable orthodontic appliances, thus patients with GABHS infections should be instructed to thoroughly clean their toothbrushes and removable orthodontic and acrylic appliances daily and also to change to a new toothbrush after the acute stage of any oropharyngeal infection. Amoxicillin and ampicillin should be avoided in treatment of GABHS as they tend to cause rashes, especially if the sore throat in glandular fever is misdiagnosed as a streptococcal sore throat.

LOWER RESPIRATORY TRACT INFECTIONS Of the various lower respiratory tract infections, some of those which have significant dental considerations will be discussed below.

Asthma Asthma is a dynamic condition characterized by chronic airway inflammation and bronchial hyperactivity resulting in symptoms of paroxysmal wheeze, cough, chest tightness and dyspnea.

Age ❍ ❍ ❍

Younger than 15 years: 1 15–45 years: 0 Older than 45 years: 1.

Scoring ❍ ❍ ❍

0 or 1 points: streptococcal infection ruled out (2%) 1 to 3 points: order rapid test and treat accordingly 4 to 5 points: probable streptococcal infection (52%), consider empiric antibiotics.

Diagnosis Along with the clinical findings, blood smear examination, estimation of liver enzymes, culture for group A Streptococcus and detection of antigen will aid in the diagnosis. Antistreptolysin ‘O’ titers raise about 150 U within 2 weeks of acute infection. They are useful for documenting recent 508

Predisposing/risk factors Asthma originates from the interaction of multiple genetic and environmental factors. Asthma is known to run in families. Childhood asthma usually occurs in atopic individuals who express elaborate amounts of IgE when exposed to common allergens/antigens. Environmental factors are: house dust mites, automobile exhausts, industrial gaseous wastes, climatic changes, tobacco smoke, airborne irritants (including acrylic and aerosolized dental materials) and pollen. Other factors that predispose to asthma are infections (viral and bacterial infections), drugs (-blockers, salicylates/NSAIDs cause bronchoconstriction) and anxiety. Extrinsic asthma is precipitated by allergens in house dust, feathers, animal fur, molds, milk, eggs, fish, fruits, nuts and NSAIDs; whereas intrinsic is related to mast cell instability and hyperresponsive airways.


Pathophysiology It generally is believed that both genetic and environmental factors, as well as allergens, are important in the initiation and continuation of the airway inflammation. Airway inflammation in asthma has been characterized as acute, subacute or chronic. The acute state of inflammation is caused by the release of chemical mediators from activated resident cells, such as local airway mast cells undergoing histamine degranulation. Subacute inflammation is marked by early cellular infiltrates, especially eosinophils that release mediators with direct toxic effects on the respiratory epithelium. The airway inflammation is described as chronic when lymphocytes and eosinophils mediate a persistent, ongoing inflammation, thus resulting in a continuous cycle of damage and repair. Long-standing chronic inflammation can lead to irreversible airway obstruction in some patients. Bronchial smooth muscle contraction contributes markedly to the airway obstruction seen in asthma, while vasodilation, diapedesis and vascular permeability account for the edematous changes. These changes are attributed to cellderived mediators. Mucus hypersecretion is also observed and can result in the development of mucus plugs and associated dyspnea. Clinical symptoms and signs Cough, shortness of breath, chest tightness, wheezing, tachypnea and tachycardia, are usually noticed. Typically these symptoms show ready reversal when bronchodilators are used. In acute asthmatic attacks patients are extremely distressed, flaring of the nares, sweating, central cyanosis, use of accessory respiratory muscle, pulsus paradoxus and silent chest may be seen. Orofacial features Asthmatic patients are known to have an increased incidence of carious lesions, reduced salivary flow, an increased prevalence of oral mucosal changes, increased levels of gingivitis and related orofacial abnormalities. It is believed that the prolonged use of 2-agonists, which is associated with diminished salivary production and secretion results in increased caries development. This reduction in salivary flow (26% drop in whole saliva) is accompanied by concomitant increase in lactobacilli and Streptococcus mutans in the oral cavity. Anti-asthmatic medications containing fermentable carbohydrate and sugar may also add to the bacterial build-up. The use of corticosteroids via nebulizers leads to dysphonia, dryness of mouth and oropharyngeal candidiasis. Linder et al (1995) reported tongue hypertrophy associated with inhaled corticosteroid therapy in premature infants. Since most of the asthmatics are habitual mouth breathers, gingival enlargement is routinely encountered. Use of

inhaled steroids has also been linked to increased levels of gingivitis. Mandel et al (1969) and Wotman et al (1973) have shown that asthmatic children exhibit more calculus than do healthy children. It was found that the children suffering from asthma have increased levels of calcium and phosphorus in submaxillary and parotid saliva. For many years the association between asthma and dentofacial morphology has been evaluated and discussed. It is suggested that the reason for the abnormalities is due to the impaired nasorespiratory function. Various dentofacial abnormalities seen in asthmatics are increased upper anterior and total anterior facial height, higher palatal vaults, greater overjets, higher prevalence of posterior crossbites, long and tapered facial form, increased lower facial height and narrow maxillary arch. Management Patients should be educated to avoid all known allergens. For patients with mild, intermittent asthma, the occasional use of an inhaled short-acting 2-agonist (albuterol, terbutalin) is indicated. Bronchospasm can be managed with aerosolized bronchodilator containing methylxanthines such as theophylline and oxtriphylline. Steroids such as betamethasone and triamcinolone and mast cell inhibitors (cromolyn sodium) are also used effectively. Dental considerations For dental considerations see Table 1.

Chronic Obstructive Pulmonary Disease or Chronic Obstructive Airway Disease Chronic obstructive pulmonary disease (COPD) is caused by chronic bronchitis and emphysema. Chronic bronchitis is defined as the excessive production of mucus and persistent cough with sputum production for more than 3 months in a year over 2–3 consecutive years. Emphysema is dilatation of air spaces distal to the terminal bronchitis with destruction of alveoli and reduction in the alveolar surface area available for respiratory exchange. Etiopathogenesis The main etiological agent is tobacco smoke. Other etiological agents include industrial dust, automobile exhaust, smoke emitted from traditional cooking using firewood. The contents of smoke produce a severe inflammatory response. The respiratory epithelium is damaged and the enzymes necessary for respiratory metabolism are impaired. The oxygen carrying capacity of RBCs is diminished. 509


Table 1

Dental considerations for asthma

Do’s

Don’ts

Fluoride supplements for those taking 2-agonist

Barbiturates and narcotics should be avoided because they can cause bronchospasm and reduce respiratory functions

Instruct patient to rinse mouth with water after using inhalers. Oral hygiene measures to reduce gingivitis and periodontitis

Avoid antihistamines (promethazine, diphenhydramine) as they can cause a drying effect and increase risk of forming tenacious mucus in acute attack

Schedule patient’s appointments for late morning or later in the day, to minimize the risk of an asthmatic attack

Dental materials such as methyl methacrylate that precipitate attack are best avoided. Ensure that acrylic appliances are cured prior to insertion

Antifungal medications should be prescribed in patients on inhalational corticosteroids

Drug interactions with theophylline are common (macrolide antibiotics increase the level of theophylline, phenobarbitals may reduce the level, tetracycline have been associated with more accentuated side effects when given together with theophylline)

Steroid prophylaxis should be advised in patients who are on long-term systemic corticosteroids

Avoid aspirin and other non-steroidal anti-inflammatory agents as they might cause allergic reactions

Use stress-reducing techniques, Conscious sedation should be performed without bronchoconstrictions (hydroxyzine)

Oxygen and bronchodilators should be available in case of an exacerbation of asthma

Nitrous oxide can be used in mild cases

In severe asthmatics, nitrous oxide may irritate the airways

Local anesthetics containing epinephrine may be used. However, preservatives such as sodium metabisulfite should be avoided as they may exacerbate an asthmatic attack

In some asthmatic patients there may be an interactions between epinephrine and 2-agonists that may producing increased blood pressure and arrhythmias

Judicious use of rubber dams prevents reduced breathing capability Care should be taken in the positioning of suction tips as they may elicit a cough reflex During an acute asthmatic attack, discontinue the dental procedure, remove all intraoral devices, place the patient in a comfortable position, make sure the airway is opened, and administer a 2-agonist and oxygen and if there is no improvement, administer epinephrine subcutaneously (1:1,000 concentration, 0.01 mg/kg of body weight, up to a maximum of 0.3 mg) and avail medical assistance

Clinical features Early morning productive cough, dyspnea and orthopnea are common clinical features. Dyspnea leads to reduced oxygen saturation, carbon dioxide build-up and respiratory failure or cor pulmonale (right sided heart failure). Some patients with emphysema try their best to maintain normal levels of blood gases by hyperventilating. These patients are referred to as ‘pink panters or pink puffers’. However, patients suffering from chronic bronchitis cannot hyperventilate and become hypoxic and hypercapneic (high levels of carbon dioxide in blood). Such a state of hypoxemia results in central cyanosis in association with elevated jugular venous pressure giving rise to a blue bloated appearance. These patients are referred to as ‘blue bloaters’. Dental considerations Patients suffering from emphysema may present with xerostomia. Occasionally, tobacco related mucosal lesions may be seen.

510

Patients should ideally be seated upright for the treatment. Rubber dam should be avoided as it can further compromise breathing. Drugs to be avoided include IV barbiturates, diazepam and midazolam as they cause respiratory depression. General anesthesia is best avoided. Wherever possible all treatment should be performed under local anesthesia without epinephrine. Bilateral mandibular nerve blocks should be avoided. Management Patients should be advised to abstain from exposure to smoke. Expectorants and humid environment will hasten the recovery process. Bronchodilators (methylxanthines— theophylline, aminophyline), sympathomimetic agents (isoproterenol, ephedrine, salbutamol) and corticosteroids are effectively used. Acute infective phases can be managed with antibiotics. Digitalis and diuretics are used for cor pulmonale.


Cystic Fibrosis Cystic fibrosis (CF) is an autosomal recessive genetic disorder that affects the functioning of nearly all of the body’s exocrine glands. The pulmonary manifestations are characterized by repeated endobronchial infections, an exaggerated inflammatory response, airways obstruction, and bronchiectasis. It is estimated that the incidence of CF is approximately 1 in 3,500 live births. Pathogenesis of cystic fibrosis Felix (2009) describes the current concept in the evolution of cystic fibrosis. The CF gene defect leads to an absent or malfunctioning cystic fibrosis transmembrane conductance regulator (CFTR) protein, which results in abnormal chloride conductance on the apical membrane of the epithelial cell. In the lung, this results in airway surface liquid depletion and, since airway surface liquid is essential to support ciliary stability and functioning, ciliary collapse and decreased mucociliary transport. The consequence of this is a vicious circle of phlegm retention, infection, and inflammation. Clinical features specific to respiratory system Patients present with a chronic or recurrent cough, which can be dry at the beginning and can produce mucoid (early) and purulent (later) sputum. Prolonged symptoms of bronchiolitis occur in infants. Paroxysmal cough followed by vomiting may occur. Recurrent wheezing, recurrent pneumonia, atypical asthma, pneumothorax, hemoptysis, and digital clubbing are all complications and may be the initial manifestation. Dyspnea on exertion, history of chest pain, recurrent sinusitis, nasal polyps, and hemoptysis may occur. These patients may have a sweat sodium concentration in excess of 70 mmol/l. Spirometry can be used to assess the lung function. Dental considerations Swelling of submandibular gland or parotid gland may be seen. Tooth eruption may be delayed. Enamel hypoplasia is a common feature. Pancreatin, which is used in the treatment of CF can cause oral ulcerations. Extensive use of antibiotics and steroids can predispose to oral candidiasis. The low fat, high carbohydrate diet will lead to carious teeth.

GRANULOMATOUS DISEASES Clinical features and oral manifestations of tuberculosis and sarcoidosis have been described in Chapter 21 on Granulomatous Diseases.

MALIGNANT DISORDERS Bronchogenic Carcinoma It is estimated that almost 95% of all primary lung tumors are bronchogenic carcinomas. These carcinomas may arise from the bronchial epithelium or the mucous glands. Cigarette smoking is considered as the single most important etiological factor in the production of lung cancer. Other predisposing factors include: occupation related exposure to asbestos, chromium and cadmium, and exposure to radiation. Clinical features The earliest clinical signs and symptoms include: cough, breathlessness, pleural pain and hemoptysis. Local infiltration of the tumor leads to pleural effusion, brachial neuritis and recurrent laryngeal nerve palsy (produces bovine cough). When the superior vena cava is obstructed facial cyanosis and edema is seen. Esophageal obstruction may cause dysphagia. Distant metastasis is characterized by symptoms of lassitude, anorexia and weight loss. A wide spectrum of clinical features is appreciated based on the site of metastasis. Common metastatic sites include bones, liver, adrenal glands, lymph nodes, brain and spinal cord. Palpable lymphadenopathy, particularly in the supraclavicular fossa, suggests metastasis. Hepatomegaly is seen when there is hepatic metastasis; cerebral metastasis leads to epilepsy, hemiplegia and disturbed vision. Bone metastasis results in pain, swelling and in severe cases pathological fracture of the bone affected. Dental considerations Metastasis to the jaw bones is relatively rare. On rare occasions, the metastatic lesion may appear as a soft tissue swelling or pigmented lesion of the oral mucosa. Abraham et al (2003) described facial pain as the presenting symptom of lung carcinoma. They reported 31 cases with a symptom of unilateral facial pain, although there was no metastatic lesion in the mandible. The most frequent locations of pain were the ear, the jaw and the temporal region, 61% occurring on the right and 39% on the left side. The pain resolved or partially remitted in most patients following treatment of the carcinoma. They suggested that this pattern of referred pain from the chest to the face presumably involves either direct tumor invasion or compression of the vagus nerve by malignant lymph nodes. The vagus nerve, which contains motor, visceral and somatic afferent and parasympathetic fibers, innervates both thoracic and cranial structures. General anesthesia is best avoided as the respiratory function is compromised.

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OTHER RESPIRATORY DISEASES Legionnaire’s Disease (Legionellosis) Bacteria of the Legionella species are small gram-negative rods that belong to family Legionellaceae. These intracellular pathogens develop in the alveolar macrophages, and less frequently in other macrophages, monocytes and leukocytes. Legionella commonly occurs in natural and artificial water reservoirs, less often in soil and organic matter. Its proliferation is favored by the water temperature of 25–42C, the presence of algae or protozoa, and calcium or magnesium salt-containing sediments. The source of infection may be air-conditioning systems, showers, fountains, dental unit waterlines and other sources producing water mist. Infection occurs by the inhalation of bacteria-laden water droplet aerosol or dust. Incubation time is 2–10 days. The Legionellaceae comprises more than 45 species but Legionella pneumophila is isolated from 90% of culture proven clinical cases of Legionnaire’s disease. Infection with the Legionella rod causes legionellosis. Three clinical types of legionellosis can be distinguished: 1. 2. 3.

Sporadic or epidemic infection in the form of legionellosis pneumonia, described as Legionnaire’s disease Pontiac fever—a flu-like form having a mild course An extra-lung form in immunosuppressed patients, often taking a severe clinical course, with the septic syndrome, coagulation disorders, acute cardiovascular deficiency and nephritis.

Diagnosis Legionellosis diagnostics is based on serological studies of the blood serum to indicate the level of antibodies, on the patient’s urinalysis to determine the presence of a specific antigen with the immunoenzymatic ELISA and radioimmunological (RIA) tests and on the bacteriological examination of the bronchial tree secretion, bronchoalveolar washings, lung biopsy material and sputum. Dental considerations High- and low-speed handpieces, ultrasonic instruments and air–water syringes produce air-water aerosols, which may be source of infection. Both the dental team and the patient are exposed to the infected aerosols via inhalation. By inhaling them and choking, the air–water aerosol with the droplets of 0.2–5.0 m in diameter, can contain Legionella.

Obstructive Sleep Apnea Syndrome Obstructive sleep apnea syndrome (OSAS) is a disorder that derives from the intermittent and repetitive occlusion of the upper airway during sleep. This occlusion is due to the 512

inspiratory collapse of the walls of the pharynx, which determines the complete closure (apnea) or partial closure (hypopnea) of the airway. Apneas or hypoapneas are of varying duration and have distinctive effects on cardiorespiratory homeostasis. Its repetition during sleep, sometimes several hundred times in one night, and day after day for years, ends up producing significant alterations in the central nervous system, in myocardial and cerebral circulation and in pulmonary and systemic circulation. Clinical manifestations Snoring is the most common symptom. It occurs due to the narrowing of the pharynx and vibration of the soft parts of the upper airway (the pharyngeal walls, the veil of the palate and the uvula). The main daytime manifestations are xerostomia, gastroesophageal reflux, impotence, irritability, depression, decreased libido, non-restorative sleep, concentration difficulties and headaches. While nocturnal manifestations include diaphoresis, xerostomia, salivation, altered sleeppatterns, awareness of apnea and sensation of suffocation or panting. These patients are usually associated with neuropsychiatric and cardiorespiratory disorders (arterial hypertension, cardiac insufficiency, bradycardia and nocturnal arrhythmias, dilated myocardiopathy, pulmonary hypertension and ischemia). Orofacial features and management The most common mouth and facial characteristics found include retrognathic jaw, a narrow palate, a wide neck, a deviated nasal septum and relative macroglossia. Orthognathic surgery and uvuloplastopharyngoplasty may be useful. The treatment of choice for OSAS is with continuous positive upper airway pressure (CPAP). This can be achieved using a nasal mask at night. A specific level of pressure is applied in the upper airway, preventing its collapse providing a mechanical widening of the upper airway. Medroxyprogesterone acetate, almitrine, protriptyline and theophylline are some of the pharmaceuticals tested so far. However, these are not very effective. Intraoral appliance was first used in the 1980s. The mandibular advancement devices (MAD) in their two versions (fixed advancement and adjustable advancement) are really efficient for managing obstructive problems of the upper airway. The MADs carry out an anterior and inferior movement of the jaw generating anatomical variations in the upper airway facilitating an increase in the pharyngeal area.

RENAL DISORDERS ‘Homeostasis’, a term introduced by WE Cannon, which means the maintenance of constant internal environment.


The internal environment in the body is the extracellular fluid in which the cells live. This fluid is present outside the cell and it constantly moves throughout the body. It includes the blood which circulates in the vascular system and fluid present in between the cells which is called interstitial fluid. This fluid should be maintained relatively constant in composition for the normal functioning of the cells, since changes in the extracellular fluid are reflected in changes in fluid within the cells and in the cell function. Homeostasis is essential to maintain the normal physiological activities in the body. So, whenever there is threat to alter the physiologic activities, various systems of the body try to regulate and adjust the functions in such a way that the condition is brought back to normal. The human kidney which is an important excretory organ, situated on the posterior wall of the abdomen, one on each side of the vertebral column, plays a significant role in the maintenance of body homeostasis through its various functions.

Functions of Kidney 1. 2. 3. 4.

5. 6.

It excretes waste products, especially the nitrogenous and sulfur containing end products of protein metabolism. It helps to maintain the normal hydrogen ion concentration of body fluids and electrolytes. It eliminates drugs and various toxic substances from the body. Regulations of arterial pressure by renin–angiotensin system, renin secreted by juxta glomerular apparatus converts angiotensin I to angiotensin II which brings about elevation of blood pressure by vasoconstriction. It helps in the regulation of erythropoiesis through the formation of erythropoietin secreted by glomerular cells. It plays an important role in vitamin D metabolism, as it brings about hydroxylation of inactive form of vitamin D and converts to active metabolite which helps in calcium absorption by intestine.

Nephrons that are about 1 million per kidney are the functional unit of the kidney that helps to filter wastes from blood, modulate excretion of salts and water from the body and allow the kidney to perform its excretory, metabolic and endocrine functions. Since, the nephrons are incapable of regeneration, renal function is maintained until approximately half of the nephrons are destroyed. When the kidney’s compensatory mechanisms are overwhelmed, signs and symptoms of renal failure begins to manifest.

RENAL DISEASES 1. 2. 3. 4. 5.

Acute renal failure Chronic renal failure Hypertensive kidney disease Nephrotic syndrome Specific tubular abnormalities.

Renal failure is defined as the stage of renal function in which the kidney is no longer able to maintain the integrity of the internal environment of the organism. Chugh (1999) defined renal failure as the deterioration of renal function resulting in decline in glomerular filtration rate and rise in urea and non-nitrogenous substances in the blood.

Acute Renal Failure Any condition that interferes with kidney function can cause acute renal failure. In this condition, the kidney stops working entirely or almost entirely. In chronic renal failure large numbers of nephrons are destroyed progressively until the kidney simply cannot perform normal function. Vascular or glomerular lesion cause hypertension but not renal failure is referred to a hypertensive kidney disease. In nephrotic syndrome, glomeruli have become more permeable than normal so that large amounts of protein are lost into the urine. Specific tubular abnormalities are characterized by abnormal reabsorption or lack of reabsorption of certain substances by the tubules. Many diseases which affect the kidney are associated with alterations in the mouth or influence the course of the common dental disease or affect the mode of treatment or can cause complications. Severe renal disease especially chronic renal failure can play havoc with the skeletal structure including the maxilla and mandible.

Chronic Renal Failure Physicians earlier used to use the diagnostic term ‘chronic Bright’s disease’ for common end point of diffuse, severe renal parenchymal disease. However, now the term ‘chronic renal failure’ or ‘end-stage renal disease’ (ESRD) is preferred. Davidson (1994) stated that chronic renal failure is irreversible deterioration in renal function. Scott (1996) defined ESRD as a chronic, progressive disease that is characterized by the destruction of nephrons, the kidney’s functional unit. Chugh (1999) defined chronic renal failure as slow insidious irreversible deterioration of renal functions resulting in the development of clinical syndrome of uremia manifested by excretory, metabolic, neurological, hematological and endocrinal abnormalities. Etiology Chronic renal failure may be caused by any condition which destroys the normal structure and function of the kidney. Harrison (1983) stated that glomerulonephritis, tubulointerstitial disease, diabetic nephropathy and nephro-sclerosis are among the most common cause of chronic renal failure. Guyton (1991) has given the causes for chronic renal failure as: ❍ ❍

Chronic glomerulonephritis Traumatic loss of kidney tissue 513


❍ ❍

Congenital absence of kidney tissue Congenital polycystic disease (in which large cysts develop in the kidney and destroy surrounding nephrons by compressions) ❍ Urinary tract obstruction resulting from renal stones ❍ Pyelonephritis and disease of the renal vasculature.

2.

Pathogenesis The various by-products of protein and amino acid metabolism in a patient with uremia exert toxic effect on every organ systems in the body. As the kidney fails, the nephron population falls. If this progresses the glomerular filtration rate falls, and the blood urea nitrogen (BUN) rises, which results in mild azotemia (abnormal retention of nitrogen products in blood), impaired ability to concentrate urine, nocturia and mild anemia. If this continues, frank renal disease follows with its associated polyuria. The anemia may become severe and hypocalcemia, hyperphosphatemia and metabolic acidosis may occur. When azotemia is associated with adverse clinical signs and symptoms, it is called uremia. Advanced uremia is associated with derangement of function in many major organ systems. Mirahamadi et al stated that the prolongation of life in patients with end-stage uremia by the use of maintenance hemodialysis has resulted in the occurrence of a number of clinical syndromes that may be related to the persistence of certain biochemical abnormalities associated with impaired renal function. According to Harrison, urea represents some 80% or more of the total nitrogen excreted into urine in patients with chronic renal failure maintained on diets containing 40 g or more of protein per day. Creatinine may cause adverse effects in uremic subjects following conversion to more toxic metabolites such as sarcosine and methyl guanidine. Davidson has said that disturbances in water, electrolyte and acid–base balance undoubtedly contribute to the clinical picture in patients with chronic renal failure, but the exact pathogenesis of the clinical syndrome of uremia is unknown. Almost any substance present in abnormal concentration in the plasma has been suspected of being a ‘uremic toxin’. It is most likely that the syndrome is caused by accumulation in body fluids of a number of substances, among which phosphate, parathyroid hormone, urea creatinine, guanidine, phenols and indoles must be included. Scott stated that uremic syndrome primarily results from the retention and accumulation of excretory products and the diminished endocrine and metabolic functions of the kidney. He has given the following laboratory findings in progressive renal disease. Systemic manifestations of renal failure Systemic manifestations: 1.

514

Gastrointestinal a. Anorexia

3.

4. 5.

6.

b. Hiccups c. Nausea d. Vomiting e. Uremic gastroenteritis Neuromuscular a. Drowsiness b. Lack of concentration c. Insomnia d. Loss of memory e. Mild behavioral changes f. Errors in judgment g. Neuromuscular irritability h. Seizures and coma i. Peripheral neuropathy Hematologic a. Normochromic–normocytic anemia b. Bleeding Immunologic a. Infection Endocrine–metabolic a. Loss of libido b. Decreased thyroid function c. Amenorrhea Cardiovascular a. Hypertension.

Gastrointestinal The GI tract is extensively affected by chronic renal failure. Anorexia, hiccups, nausea and vomiting are common and early manifestations of uremia. ‘Uremic fetor’, a uriniferous odor to the breath, derives from the breakdown of urea in saliva to ammonia and was associated with unpleasant taste sensation. Mucosal ulcerations leading to blood loss can occur at any level of GI tract in very late stage of chronic renal failure—so-called ‘uremic gastroenteritis’. Neuromuscular Subtle disturbances of CNS function including inability to concentrate, drowsiness and insomnia are among the earliest symptoms of uremia. Mild behavioral changes, loss of memory and errors in judgment soon follows and are associated with signs of neuromuscular irritability, including hiccups, cramps and fasciculation and twitching of large muscle groups. Asterixis, myoclonus and chorea are common in terminal uremia, as are stupor, seizures and coma. Peripheral neuropathy may also be a common complication of advanced chronic renal failure. Cohen stated that neuromuscular signs and symptoms were secondary to hypertensive encephalopathy, electrolyte disturbances and hypocalcemia. He observed that along with neurological hyperirritability, peripheral neuropathy can occur as a result of disturbance of the conduction mechanism rather than a loss of nerve fiber. He noticed that the predominant patient complaint was ‘burning feet’ or paresthesia that may progress to muscle weakness, atrophy and finally paralysis.


Hematologic Patients with chronic renal dysfunction will often have hematologic problems, most commonly anemia and bleeding. Normochromic–normocytic anemia occurs regularly in chronic renal failure and contributes to fatigability and listlessness in these patients. Erythropoiesis may be depressed due to the effects of retained toxins on bone marrow and diminished biosynthesis of erythropoietin by the diseased kidney. Hemolysis occurs because of hypertension, retention of waste products, altered body fluid pH and electrolytes composition which create an unsuitable environment for erythrocytes. Abnormal hemostasis, i.e. bleeding into GI tract, pericardial sac and intracranial vault, in the form of subdural hematoma or intracerebral hemorrhage, has been attributed to intrinsic coagulation defect, a deficiency of platelet factor III or the anticoagulants used in conjunction with dialysis.

up to 90% of renal patients will show oral symptoms. With renal insufficiency and uremia, patients may complain of a bad odor and metallic taste in the mouth. This is due to high urea content in saliva and its subsequent breakdown to ammonia. Patients also complain of dry mouth and often are prone to retrograde parotitis. These complications are believed to result from a combination of direct gland involvement, chemical inflammation, dehydration and mouth breathing. Frerichs (1851) was the first to describe the oral manifestation of uremia. He stated that the condition was not found in acute renal failure but developed slowly when chronic uremia has been present for months or years. Lancereaux (1887) was the first to mention that uremic stomatitis was a complication of uremia. Jones and Mason (1990) mentioned the oral lesions which can occur in renal failure as follows:

Immunologic Enhanced susceptibility to infection occurs in chronic renal failure due to defect in leukocyte formation and function. Mucosal barrier to infection may be defective. Anti-inflammatory steroids and immunosuppressive drugs add further risk of infection. Cohen has quoted reduced immune capacity in uremic patients due to uremic intoxication and protein caloric malnutrition. He stated that uremic plasma suppresses lymphocyte responses such as granulocyte dysfunction and suppressed cell-mediated immunity. He suggested, together these impairments place uremic patient at a high risk of infection.

1. 2. 3. 4 5. 6. 7.

Endocrine-metabolic Number of hormonal abnormalities including loss of libido in both the sexes, are due to the associated hyperprolactinemia. Thyroid function was diminished. Amenorrhea was common in female. Cardiovascular Hypertension develops in 80–90% of patients during the course of chronic renal failure. The hypertension contributes to the development of cardiomyopthy, atherosclerosis and progression of the renal failure itself. Pericarditis was very common in untreated end stage renal failure. Vascular calcification may develop and be sufficiently severe to cause inadequate perfusion of the limbs. Dermatologic Severe pruritus was one of the important manifestations of the clinical syndrome of hyperparathyroidism in patients with advanced uremia. The skin of the uremic patients may be dry and there may be ecchymosis resulting from bleeding tendencies. Pruritus has been attributed to calcium and phosphate deposition in the skin and high circulating PTH levels. In advanced uremia a white, uremic ‘frost’ may evaporate on the skin surface with a fishy scale odor. The patient frequently complains of brittle nails. Oral manifestations Several changes occur in the oral cavity that is associated with chronic renal failure and uremia. It was estimated that

Erythematopultaceous stomatitis Ulcerative stomatitis Hemorrhage Hyperkeratosis and generalized pallor Poor taste perception Infection Peripheral giant cell lesion.

Several mechanisms have been postulated for the pathogenesis of each form of uremic stomatitis. The oral lesion may be a reaction to toxins in the tissues or to the action of ammonia or to irritating ammonium compounds formed by the action of bacteria on urea. The manifestation of uremia in the mouth and GI tract may also be caused by the hemorrhagic diathesis common in uremia. Local hemorrhage may cause a decrease in vitality and viability of the affected tissues allowing bacterial infection. These infections result in ulceration and psuedomembranous formation. Wysocki et al presented a case of primary hyperoxaluria with oxalosis (accumulation of related deposits in various extra-renal sites) involving oral tissues, including bone, gingiva, dental pulp, periodontal ligament and dentin in a 27-year-old male patient. Goldstein (1990) quoted Baries classification of uremic stomatitis as follows: Type I Erythematopultaceous, initially manifests as a red thickening of the buccal mucosa, which later includes a gray, thick, pasty, gluey exudate and pseudomembrane which covers the gingiva, fauces and the oral mucosa. When the psuedomembrane is removed with tongue blade, a swollen, dry, red but not ulcerated mucosa is found. Associated manifestations include fetor oris, dry burning sensation, excessive saliva and perversion of taste. Type II Ulcerative form which is similar to type I but includes loss of integrity of the mucosa with frank ulceration. The ulcers can be superficial or deep and frequently 515


involve the gingiva. Purpura and anemia may be seen on the mucosa. Excessive salivation is again noted. Parotid and submandibular gland swelling may be seen in patients with chronic renal failure without accompanying uremic stomatitis. Ziccardi stated that restricted fluid intake results in xerostomia, the most common oral manifestation in CRF (circulating recombinant form) patients. McCreary et al reported lesion mimicking oral hairy leukoplakia in a case of uremic stomatitis in a 48-year-old male with an extensive white lesion involving dorsal, lateral and ventral surfaces of the tongue and buccal, labial and retromolar mucous membrane and suggested that oral manifestation of uremia should be considered in the differential diagnosis of oral hairy leukoplakia. Wysocki et al reported a case of 31-year-old male suffering from chronic renal failure with oxalosis in which they found tooth resorption, mobility, dental pain and eventual tooth loss as significant clinical problems. Sowell stated that uremia present during development of the dentition results in teeth with enamel hypoplasia and brownish discoloration. Altered maxillary and mandibular growth and resulting malocclusion may occur because of impaired skeletal growth. Woodhead et al (1982) in a review article of Clark (1987) found that enamel hypoplasia was the most common finding in chronic renal failure. They observed the anatomical location of enamel hypoplasia on the teeth correlated well with the age of onset of advanced renal failure. Other less frequently observed changes included discoloration and hypocalcification of the enamel. Scott stated that some patient may have severe erosion of the dentition due to frequent regurgitation, resulting from the nausea associated with hemodialysis treatments. Other dental findings include tooth mobility and drifting without appreciable pathological periodontal defects and abnormal bone healing following dental extraction.

to balance the systems, thus creating the skeletal lesions. This increase in parathyroid activity is secondary to altered serum calcium and phosphate levels and is therefore known as secondary hyperparathyroidism. The skeletal changes occurring secondary to chronic renal failure consist of bone remodeling, osteomalacia, ostitis fibrosa cystica and osteosclerosis. Kelly (1980) quoted Lucas (1883) who stated that abnormalities of the skeletal system can occur in children with renal disease and he used the term ‘renal rickets’ to describe the condition. Parsons (1927) described first radiographic interpretation of secondary hyperparathyroidism. He noted osteoporosis, bending and fracture of long bones, cortical thinning and subperiosteal resorption. The skeletal changes of primary and secondary forms of hyperparathyroidism are indistinguishable from each other. But ‘brown’ tumors which appear as well-circumscribed unilocular or multilocular radiolucencies are rare in secondary hyperparathyroidism. Kelly et al (1980) reported that decreased density of bone, thinning and absence of cortices and fractures and deformities of the weight bearing skeleton, periarticular, soft tissue and vascular calcification are common in secondary hyperparathyroidism. They suggested that alterations of the trabecular pattern (Figure 5) have led to qualitative terms such as ‘chalky’, ‘ground glass’, ‘granular’ and ‘salt and pepper’ to describe the appearance of the bone. Dental manifestations Radiographic alterations of the jaw bones in chronic renal disease are not uncommon and often represent one of the

Figure 5

Radiographic manifestations Liu and Chu (1943) coined the term ‘renal osteodystrophy’, which denotes osseous changes that occur in patients with ESRD. Skeletal changes are caused by the disorders in calcium and phosphorus metabolism, abnormal vitamin D metabolism, and increased parathyroid activity. In chronic renal failure, intestinal absorption of calcium is reduced because the kidneys are unable to convert vitamin D into its active form 1,25-dihydroxycholecalciferol which is required for absorption of calcium from the digestive tract. Impaired absorption of calcium because of defective kidney function and corresponding retention of phosphate causes a decrease in the serum calcium level. This is associated with a compensatory hyperactivity of the parathyroid glands. The parathyroid hormone then extracts calcium from bone 516

Intraoral periapical radiograph showing altered trabecular pattern. Courtesy: Dr Veena Hegde


earliest detectable signs. Subperiosteal bone resorption may be seen as a partial or complete loss of the lamina dura, thinning of the mental foramen, inferior alveolar canal resorption and destruction of condylar process of the mandible and maxillary sinus floor. In addition, the trabecular pattern of the affected bone assumes a ‘ground glass’ or ‘salt and pepper’ appearance. Infrequently, radiolucent brown tumors may be seen. Fordham and Franklin (1963) reported the first case associated with ESRD in a 2-year-old boy with a brown tumor of maxilla which is clinically, chemically, radiologically and according to parathyroid findings consistent with secondary parathyroid hyperplasia. They observed these changes mostly in the lower molar area superior to the mandibular canal. Spolnik et al found 73% of their dialysis patients’ dental radiographs were abnormal. He found altered bone density as the most common abnormality and suggested its diagnostic value in the evaluation of bone disease. Maxwell et al examined 30 male chronic hemodialysis patients using panoramic and periapical radiographs and found 22 patients with abnormal jaw radiographs. They reported pulpal narrowing and calcification in half of dialysis patients. They concluded that dental radiography was as good a screening technique for evaluating renal osteodystrophy as hand radiography and in many cases, was superior to axial skeleton radiography. Scott et al stated that the manifestations of metabolic renal osteodystrophy and compensatory hyperparathyroidism of the mandible and maxilla include bone demineralization, decreased trabeculation, ‘ground glass’ appearance, loss of lamina dura, radiolucent giant cell lesions and metastatic soft tissue calcifications. He further suggested that with such bone loss, it was not uncommon for patients to have spontaneous fractures of the jaws from trauma as well as to be at risk of fracture during oral and periodontal surgical procedure. Dental considerations Dental treatment for patients with chronic renal disease and transplants is recognized as an essential health service. Dental management is complicated because of the oral disease and the medical problems seen in this population. These patients survive under narrowly controlled conditions of intake and activity as well as under great physiologic and psychologic stress with medications, diet, invasive treatments, limited lifestyle and dependency on others. Dental treatment, even minor dental procedures can present major problems and should be considered particularly stressful when superimposed on such situation. Hemodialysis (Figure 6) is the most prevalent therapy for chronic renal disease. Hemodialysis refers to the removal of nitrogenous and toxic products of metabolism from the blood by means of a dialysis system. Exchanges occur

Figure 6

Photograph showing a patient undergoing hemodialysis. Courtesy: Dr Veena Hegde

between the patient’s plasma and dialysate (the electrolyte composition of which mimics that of extracellular fluid) across a semi-permeable membrane that allows uremic toxins to diffuse out of the plasma while retaining the formed elements and protein composition of blood. The usual dialysis system consists of a dialyzer, dialysate production unit, roller blood pump, heparin rate, and pressure of dialysate and to detect blood leaks and arterial and venous pressures. The typical patient undergoes hemodialysis 3 times per week, with each treatment lasting approximately 4 hours. During treatment anticoagulants are administered. It was estimated that 60% of hemodialysis patients need dental treatment to prevent the complications caused by infection or dietary difficulties. Comprehensive oral evaluation and dental treatment are part of the basic healthcare of the chronic renal failure patients. As the technology and medicine advance, the number of patients with chronic renal disease who require dental care is also increasing. The following considerations are important when evaluating and treating the dental patient with renal disease: 1. Timing Disagreement exists over the ideal time for dental treatment of hemodialysis patients. Carl and Wood indicated that the dental treatment should be performed first before hemodialysis, when the patient is free of anticoagulant. Any problems arising from medications given by the dentists will be removed later by dialysis. Sowell, Manton, Ziccardi, and Scott all recommend that dental treatment should be timed so that the effects of dialysis are present, but the effects of heparin have worn off. This enables clotting to be well established before the next dialysis session, when heparin will again be administered. They suggested treatment midway between dialysis 517


sessions ideally about 12 hours post dialysis is the ideal time. Because at this time, the toxins are low in the blood, the effect of the heparin is minimal, and the patient is best able to respond to the stress of treatment. 2. Asepsis Scott stated that because patients undergoing dialysis are exposed to a large number of transfusions and blood exchanges, as well as renal failure related immunosuppression, they are at greater risk of infections such as hepatitis B and C and HIV infection. He suggested that these patients should be encouraged to undergo periodic testing for hepatitis infectivity and HIV antibody. The presence of these infections do not contraindicate dental treatment, but rather indicate the need for special care and meticulous techniques. 3. Hematologic and physiologic status Clinical and laboratory evaluation for anemia, bleeding disorders and leukocyte disorder may be indicated, depending on the status of renal disease or therapeutic modality and the type of dental treatment advised. Evaluation and stabilization of fluid and electrolyte balance should be accomplished before dental treatment. The arteriovenous site should never be jeopardized. That arm should never be used for injection of medication, either intramuscularly or intravenously, nor should the access site be used as an injection site. It is also essential to avoid any factor that may occlude the arteriovenous shunt such as a blood pressure cuff, constricting clothing or cramped arm position. If the device is in the leg, the patient should be allowed to stand or walk occasionally during long procedure. Dental procedures should be delayed for at least 2 weeks after placement or revision of a vascular access and should be avoided during periods of infection or thrombosis of the access. 4. Immunosuppression and corticosteroid medication Many renal transplant patients are on a regimen of antiinflammatory and immunosuppressive medications. Because infections are the major cause of morbidity and death in the renal transplant patient and a majority of septicemic infection have been attributed to oral diseases such as periodontitis, pulpal infection and oral ulceration along with dental treatment which provide a convenient portal of entry for microorganism into the circulatory system. Scott stated that the patients with chronic renal failure who receive hemodialysis have an increased susceptibility to the development of infective endocarditis. They suggested antibiotic prophylaxis should be given prior to dental care to prevent infective endocarditis, vascular access infection and bacteremia in both renal transplant and patient undergoing hemodialysis. Topical antifungal agents are recommended for control of localized oral infections. Long-term systemic steroid administration suppresses the patient’s ability to respond to stress by causing adrenal 518

atrophy. Supplemental steroids should be considered before stressed dental procedures. 5. Medications and drug therapy for dental purposes The practitioner prescribing or administering medications to patients with compromised renal function must be familiar with the metabolism and excretion of each of the agents involved and the functional status of the individual patient’s kidneys. To provide safe yet effective drug therapy, modification of the usual dosage regimen may be necessary. For drug administration for dental purposes, two dosage categories are sufficient: (i) patients with mild to moderate renal failure or renal insufficiency and (ii) patients with severe renal failure or who are functionally anephric. One of the commonly used drug in dentistry is penicillin, which exists as either a sodium or potassium salt. Potassium salts should be avoided due to the potential of hyperkalemia. Other alternative drugs such as clindamycin or erythromycin, which are metabolized by the liver, can be considered. NSAIDs should be avoided because of their nephrotoxic effect. However, NSAIDs can be used once these patients progress to ESRD and no longer have any residual renal function. 6. Local anesthesia The kidney is the main excretory organ for all the local anesthetics commonly used in dentistry and their metabolites. The use of cocaine is contraindicated since it is excreted entirely unchanged in the urine. Goldstein recommended that slow administration of LA not more than 25% of the maximum total recommended dosage for the normal patient, is a practical and safe guideline for local anesthetic injections for dental purposes in the medically controlled patient with absent renal function.

Uremic Stomatitis Uremic stomatitis has become relatively rare, seen mostly in cases of undiagnosed and untreated chronic renal failure. Painful plaques and crusts are distributed predominantly on the buccal mucosa, the floor or dorsum of the tongue, and the floor of the mouth. The incidence has decreased because of readily available dialysis centers throughout the country. The most commonly accepted mechanism behind the development of uremic stomatitis is irritation and chemical injury of mucosa by ammonia or ammonium compounds formed by the hydrolysis of urea in saliva by urease. This occurs when the intraoral concentration of urea exceeds 30 mmol/l. Hemorrhagic diathesis from inhibited platelet aggregation may also play a role due to local hemorrhage, resulting in decreased vitality and viability of the affected tissues, thus allowing bacterial infection. There are two predominant types of uremic stomatitis. In Type I, there is a generalized or localized erythema of the oral mucosa and a thick gray pseudomembranous exudate which does not leave a bleeding or ulcerated base when removed. Additional findings may include pain, burning, xerostomia, halitosis, gingival bleeding, dysgeusia, or


candidal infection. Type II leaves ulceration if the pseudomembranous film is removed. This type may indicate a more severe form of stomatitis, secondary infection, anemia or underlying systemic hematologic disturbances caused by renal failure. Histologically, both types of uremic stomatitis show evidence of an intense inflammatory process with heavy polymorphonuclear leukocytic infiltration and necrosis of the oral mucosa. Bacterial colonization is most commonly associated with Fusobacterium, Spirochaeta or Candida.

GASTROINTESTINAL DISORDERS GASTROESOPHAGEAL REFLUX DISEASE Gastric esophageal reflux is defined as the passage of gastric contents into esophagus. It is believed that Helicobacter pylori, a spiral shaped bacterium located in the mucous layer of the stomach, may inhibit or exacerbate acid reflux. The symptoms that develop when the esophageal mucosa is exposed to the gastric reflux are referred to as gastroesophageal reflux disease (GERD). It is a common, chronic gastrointestinal disorder that affects approximately 30% of the population. Predisposing factors and pathophysiology Genetic factors, smoking, lower esophageal sphincter abnormalities, hiatal hernia, defective esophageal peristaltic activity (common in esophagitis) and defective gastric emptying, increased abdominal pressure (pregnancy and obesity), and dietary behavior (diet consisting of fat, coffee, alcohol and chocolate relax the lower sphincter and incite symptoms). Clinical features Gastroesophageal reflux disease is more common in adults in their third decade of life. The common symptoms are heartburn (mimics anginal pain, burning sensation spreading upward from the epigastrium to the neck) and regurgitation. Water brash is also a very common complaint in patients. It is the presence of a sudden burst of salivation in the mouth due to reflex salivary gland stimulation in response to presence of acid in the gullet. Other clinical findings are chest pain, cough, laryngitis and laryngeal polyps. In severe recurrent reflux episodes, aspiration and pulmonary fibrosis may occur. Oral considerations Bargen and Austin (1937) first described the association between GERD and erosion of teeth. In the initial stages enamel may exhibit subtle changes. As the condition progresses, complete loss of tooth structure may be seen. The teeth typically affected are the palatal aspect of the upper anteriors and premolars.

Patients may complain of dentinal hypersensitivity and foul taste (dysgeusia). In chronic cases pulpal exposure may be seen. Exposure of the oral mucosa to the acidic reflux may result in atrophy and erythema. Complications It is estimated that approximately 50% of patients with reflux develop esophagitis. Based on the severity, esophagitis is divided into four grades: 1. 2. 3. 4.

Grade I—erythema Grade II—linear non-confluent erosions Grade III—circular confluent erosions Grade IV—Barrett’s esophagus.

Barrett’s esophagus is characterized by replacement of normal squamous epithelium with columnar epithelium. It has been linked to the development of adenocarcinoma of the esophagus. Long-standing esophagitis results in significant amount of blood loss and subsequently resulting in iron deficiency anemia. Herbst triad, consists of finger clubbing, hypoproteinemia and iron deficiency anemia associated with gastroesophageal reflux. Investigations Gastroesophageal reflux disease is best diagnosed based on the symptoms of water brash, heartburn and regurgitation. Only 30% of the patients have positive esophageal findings on endoscopy. Barium esophagographs can be used to diagnose hiatal hernia and esophageal strictures. Management Patients should be encouraged to consume small frequent meals along with antacids instead of large meals. They should be educated not to go to bed immediately after a heavy meal. It has been suggested that the raising of the head of the bed by about 4 inches will minimize regurgitation of the acid contents. H2 blockers (cimetidine 400 mg, q.i.d. for 4 weeks; ranitidine 150 mg b.i.d. up to 8 weeks), proton pump inhibitors (omeprazole 20 mg once daily for 4 weeks; lansoprazole 30 mg once a day for 4 weeks). To reduce dysgeusia associated with acidic reflux, about half teaspoon of baking soda (sodium bicarbonate) can be added to 250 ml of water and this solution can be used as mouthrinse. Fluoride application will aid in remineralization of teeth.

INFLAMMATORY BOWEL DISEASE Inflammatory bowel disease (IBD) encompasses a group of diseases with poorly defined etiology that affect the digestive 519


tract which includes Crohn’s disease (CD) and ulcerative colitis (UC). A significant number of individuals develop extra-intestinal manifestations (hepatic manifestations and primary sclerosing cholangitis). Nucleotide oligomerization domain (NOD2) and human leukocyte antigen (HLA) genes are the most extensively studied genetic regions (IBD1 and IBD3, respectively) in IBD. Mutations of the NOD2 gene are associated with CD and several HLA genes are associated with UC and CD.

ULCERATIVE COLITIS Ulcerative colitis is an IBD affecting part or whole of the large intestine frequently lower colon and rectum. It was first described by a physician, Sir Samuel Wilks from London in 1859. The precise etiology of ulcerative colitis is not well understood. A current hypothesis suggests that primary dysregulation of the mucosal immune system leads to an excessive immunologic response to normal microflora. Clinical features Ulcerative colitis is most common between the 2nd–4th and 5th–8th decades of life. Males and females are equally affected. The characteristic symptoms and signs include bloody diarrhea, rectal urgency and difficulty to pass stools. The frequency of bowel movements and the amount of blood present reflect the activity of the disease. The diarrhea is severe, possibly five to eight bowel movements in 24 hours. Patients usually complain of pain that is in both abdominal quadrants and that is crampy in nature and exacerbated prior to bowel movement. Along with the change in the pattern of bowel movements, the patient may have nocturnal diarrhea. The extraintestinal manifestations include osteoporosis, arthritis, primary sclerosing cholangitis, uveitis, pyoderma gangrenosum, deep venous thrombosis, pulmonary embolism. The most serious complication of ulcerative colitis is carcinoma of the colon.

Differential diagnosis of ulcerative colitis

520

Disease

Clinical characteristics

Crohn’s colitis

Perianal lesions common; bleeding less common than in ulcerative colitis

Infectious colitis

Sudden onset; pathogens present in stool; pain may be a predominant feature

Ischemic colitis

Affects older age groups; vascular disease often present; sudden onset, often painful

Pseudomembranous colitis

Recent antibiotic use; clostridium toxin detectable in stool

Oral manifestations and dental considerations Aphthous ulcers may result from nutritional deficiencies of iron, folic acid and vitamin B12 due to poor absorption in the gut and/or blood loss directly related to the ulcerative colitis. Anti-inflammatory medications such as the 5-aminosalicylates, which often represent the mainstay of therapy for IBD patients and which are excreted in saliva, are known to cause aphthous ulcers. Pyoderma gangrenosum may occur in the form of deep ulcers that sometimes ulcerate through the tonsillar pillar. Pyostomatitis vegetans, a purulent inflammation of the mouth, may also occur. These oral lesions are characterized by deep-tissue vegetating or proliferative lesions that undergo ulceration and then suppuration. These lesions disappear with a total colectomy. Ulcerative colitis patients also can develop hairy leukoplakia, a lesion more commonly associated with AIDS. Drugs to be avoided include NSAIDs, antibiotics, including amoxicillin–clavulanate and clindamycin which could aggravate diarrhea. Surgical treatment is contraindicated until the disease is under control because of the risks associated with anemia (such as delayed healing, an increased risk of infection, the side effects of narcotic analgesics, and depression of respiration). Long-term use of steroids can also result in adrenal suppression. Patients undergoing surgery require increased doses of steroids before and after the procedure because their own adrenal response to stress is blunted.

CROHN’S DISEASE Crohn’s disease was first observed by the German surgeon Wilhelm Fabry in 1623, and was later described by and named after physician Dr Burril B Crohn from New York. It is an idiopathic, relapsing chronic inflammatory disease of the GI tract categorized as IBD and is an important cause of morbidity in children and adolescents. The prevailing hypothesis regarding the pathogenesis of CD is an interaction between environmental factors and an altered immune response in genetically predisposed children, leading to chronic inflammation of the GI tract. In CD there is a disordered regulation of mucosal and systemic immune response resulting in the perpetuation of the inflammatory cascade. A dysregulated Th1 response (T helper 1) seems to be crucial in the conversion of physiologic to pathologic inflammation. The immunological profile in CD is predominantly a cell-mediated response. Active mucosal inflammation of the small and large intestine results in diarrhea, protein-losing enteropathy, bleeding, abdominal pain and stricture formation. Proinflammatory cytokines and eicosanoids increase vascular permeability and cause electrolyte secretion, and augment smooth muscle contraction. Many cytokines promote the recruitment and activity of collagen forming cells leading to fibrous tissue proliferation and


thereby resulting in bowel wall thickening and stricture formation. The causal role of TNF- in the etiopathogenesis of CD has gained importance. Clinical presentation It can occur in all age groups and follows the same bimodal pattern of age distribution as IBD. Early onset IBD (EOIBD), i.e. presentation before the age of 5 years, is a unique subgroup constituting 4% of pediatric IBD. In this subset, it is difficult to differentiate between ulcerative colitis (UC) and CD. In UC there seems to be a preponderance of CD in boys, whereas in India it was more prevalent in girls. CD depends upon the site of involvement of the GI tract. It affects the ileocecal region, typically with ulceration, fissuring and fibrosis of the wall, but can affect any part of the GI tract. Abdominal pain and systemic symptoms are generally more severe in CD than in UC. A dyspeptic type of epigastric pain is seen in children with gastroduodenal involvement. Diarrhea occurs in two-thirds of affected children. In children with predominantly ileal involvement, constipation may be a rare presentation. Gross blood in the stools is unusual with isolated small bowel disease and more common when the colon is involved. Fever occurs in approximately 50%. Fatigue, anorexia, weight loss and diminution in growth velocity are other presenting symptoms in children. Perirectal involvement fistulae, fissure and skin tags are important clues to the diagnosis. CD is subcategorized as predominantly inflammatory, fistulizing or stricturing disease based on the clinical phenotype. Crohn’s disease could represent a persistent infection with a fastidious organism or an abnormal and prolonged response to a common pathogen. Various organisms have been linked with CD but none of them are evident in the etiopathogenesis. In genetically susceptible individuals the microvascular injury caused by these infections could result in a granulomatous vasculitis of the mesenteric vessels, leading to microvascular thrombosis, multifocal gastrointestinal infarction, and finally gross pathologic sequelae such as ulcerations, fistulas, fibrosis and strictures. Complications Hemorrhage, obstruction, perforation, abscess and fistula formation are well known in CD. Perianal disease may present with abscess formation, perirectal and perianal fistulization and can precede the intestinal manifestation by years. Perforation with internal fistula is another serious complication. Carcinoma of the colon is a long-term complication of IBD. The two well-accepted risk factors for cancer are duration and severity of the disease. Extraintestinal manifestations include skin manifestations like erythema nodosum and pyoderma gangrenosum. Ocular manifestations such as episcleritis and anterior uveitis are less common. Arthritis is the most common extraintestinal manifestation in children and may occur

years before the intestinal symptoms. Hepatobiliary complications such as chronic hepatitis, sclerosing cholangitis, cholelithiasis and elevated aminotransferase may precede the active disease. The renal manifestations of IBD include nephrolithiasis, hydronephrosis and enterovesical fistula. Other extraintestinal manifestations are thromboembolic manifestations, vasculitis, pancreatitis, interstitial pneumonitis and pericarditis, others include weight loss, growth failure, bone disease (due to malnutrition). Delay in sexual maturation seen in some children with CD may have a significant effect on self-esteem and socialization. Oral manifestations Aphthous ulcerations are the most common oral manifestation of CD. The oral manifestations may occur along with intestinal disease or precede it and may be the primary presentation. Cobble stone appearance of the oral mucosa, oral epithelial tags and folds, gingivitis, persistent lip swelling, lichenoid mucosal reactions, granulomatous inflammation of minor salivary gland ducts, candidiasis, and angular cheilitis. Some patients may have asymptomatic intestinal disease. Melkersson–Rosenthal syndrome (facial swelling, facial palsy and fissured tongue) and cheilitis granulomatosa may also be incomplete manifestation of CD. High prevalence of caries and periodontitis in CD has also been reported. Differentiating CD from ulcerative colitis can be challenging, particularly early in the course of the disease, but it is an important step because appropriate treatments and potential complications vary for these two conditions (Table 2). Table 2

Comparison of ulcerative colitis and Crohn’s disease

Feature

Ulcerative colitis

Crohn’s disease

Sites mainly affected

Ileum

Colo-rectum

Abdominal pain

Variable

Common

Depth of inflammation

Mucosal

Transmural

Distribution

Diffuse, contiguous spread; always involves rectum; spares proximal gastrointestinal tract

Segmental, non-contiguous spread (’skip lesions‘); less common rectal involvement; occurs in entire gastrointestinal tract

Iron deficiency

Common

Common

Other complications

Vitamin B12 deficiency

–

Diarrhea

Severe

Less severe

Fistula and sinus tracts

Rare

Common

Colonic carcinoma risk

Present

High

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Investigations The small bowel has been defined for many years as the ‘black box’ of the gastrointestinal system due to its inaccessibility to endoscopic exploration. The conventional radiological methods, i.e. small bowel enteroclysis (SBE) and small bowel follow-through (SBFT), have long been the only imaging methods providing information on the morphological features of the small bowel valuable in the diagnosis and management of Crohn’s disease. Typical small bowel changes which can be observed by means of these techniques include irregular thickening and distortion of the valvulae conniventes, loops adhesions (mass-like effect) or separated loops because of wall thickening and mesenteric inflammatory infiltration. Transverse and longitudinal distribution of ulcerations can separate islands of thickened internal wall, resulting in the typical cobble stone appearance. Strictures are often separated by healthy bowel tracts (skip lesions); impaired small bowel peristalsis is commonly observed within rigid stenotic tracts. Extrinsic compression may be observed, due to mesenteric lymph node enlargement. Barium meal series is useful to identify small bowel involvement and lesions such as strictures, fistulas and ulcerations may be identified. Bowel ultrasonography The main ultrasonography findings in CD are represented by thickening and stiffness of the gut wall, modifications or lack of its echo stratification, reduction of peristalsis, mesenteric fibro-fatty proliferation, lymph node enlargement; in case of complications, narrowing of the intestinal lumen, abscesses and fistula are usually easily detectable. The use of power Doppler methods and of oral (polyethylene glycole, PEG) and/or intravenous (Levovist) contrast media, have been suggested to improve the diagnostic accuracy of ultrasonography, particularly in discriminating inflammatory from fibrotic strictures and in better defining the presence of internal fistulas. Computed tomography Computed tomography (CT) has been utilized for the detection of extra-enteric complications of CD, mainly intra-abdominal abscesses, but is also suitable in the evaluation of strictures, prestenotic dilatations and fistulas. Non-enhanced CT scan is also used in the diagnosis of post-surgical complications (intra-peritoneal abscesses, anastomotic dehiscence, extra-abdominal abscesses and fistulas, incisional hernias, ascites, volvolus, bowel adhesions, etc). The main findings at CT scan observed in CD patients, are small bowel wall stratification and/or thickening (‘target’ or ‘double halo’ appearance), with or without contrast enhancement, edema of the mesenteric fat, engorged ileal vasa recta (‘comb sign’), submucosal fibrofatty infiltration and mesenteric adenopathy. Video capsule endoscopy Video capsule endoscopy (VCE) is a potentially safe and painless endoscopic method

522

to evaluate the entire small bowel and was found to be superior in detecting CD lesions in patients with mild clinical suspicion and negative traditional imaging studies. Other possible applications of VCE have been suggested in a pediatric setting, in the evaluation of post-surgical recurrence and in the surveillance of mucosal healing after biologic therapy. The major limitations of the use of VCE in CD are an incomplete evaluation of the small bowel, occurring in 20–35% of patients, and by the possibility of capsule retention, occurring in about 7% of patients with CD. Double balloon endoscopy Double balloon enteroscopy (also called push and pull enteroscopy) was described for the first time by Yamamoto et al in 2001. The principle of the double balloon technique allows not only a complete endoscopic evaluation of the small bowel but also makes it possible to take biopsies and to carry out therapeutic interventions along the whole small bowel in patients suspected of CD and negative upper and lower endoscopy. Management Apart from a total proctocolectomy for UC, there is no cure for IBD. Medications, however, aid in the induction and maintenance of remission, and target various points along the disordered immune pathway implicated in IBD. Aminosalicylates remain the standard induction and maintenance therapies for UC but have a more equivocal role in CD. Antibiotics are also commonly used in CD, especially with colonic and perianal disease. Budesonide is effective as a first-line agent for ileal and/or right colonic CD although maintenance benefits remain to be proven. Conventional steroids induce remission for both CD and UC but are reserved for patients with moderate-severe disease or for those who have failed more first-line therapy. New therapies include anti-TNF antibodies; recombinant cytokines and growth factors. Immunomodulators such as 6-MP and azathioprine, as well as methotrexate, are effective steroid-sparing and maintenance therapies. Cyclosporine or tacrolimus can be effective for severe or refractory UC. Anti-TNF agents have been effective for patients with moderate-severe UC and CD, independent of concomitant medications.

HIATAL HERNIA Hiatal hernia is the herniation of part of the stomach into the thoracic cavity through the esophageal hiatus in the diaphragm. Hiatus hernias affect anywhere from 1 to 20% of the population. It is estimated that about 9% present with symptoms. Hiatal hernia is usually seen in the elderly although people of any age can be affected.


Etiology

PEPTIC ULCER DISEASE

It is believed that insufficient dietary fiber and the use of the unnatural sitting position for defecation (need for straining at stool) may cause increased intra-abdominal pressure thereby pushing the stomach through the esophageal hiatus in the diaphragm. Other contributing factors causing increased pressure within the abdomen include: lifting heavy weights or frequent bending over, frequent or hard coughing, hard sneezing, violent vomiting and obesity (extra weight pushes down on the abdomen increasing the pressure). Other etiological factors are hereditary, smoking, stress and drug abuse (cocaine).

Peptic ulcer disease of the GI tract is characterized by mucosal damage secondary to pepsin and gastric acid secretion. It usually occurs in the stomach and proximal duodenum; less commonly, it occurs in the lower esophagus, the distal duodenum, or the jejunum, as in unopposed hypersecretory states such as Zollinger–Ellison syndrome, in hiatal hernias (Cameron ulcers), or in ectopic gastric mucosa (e.g. in Meckel’s diverticulum. It is believed to affect almost 10% of the adults (usually between 25 and 65 years) at least once in their lifetimes.

Clinical features The sign and symptoms include heartburn, belching, chest pain and nausea, which tend to become worse on leaning forward, lifting heavy objects or lying down. In severe cases, dysphagia and painful swallowing may occur. Infants may regurgitate blood stained food and present with difficulty in breathing and swallowing. Occasionally pain may radiate to the jaw and along the arm mimicking anginal pain. Other clinical features are hiccups, dry cough and increase in the contractile force of the heart. There are two major types of hiatus hernia: the sliding hiatus hernia (95%), where the gastroesophageal junction moves above the diaphragm together with some of the stomach. The second rare type is rolling (or paraesophageal) hiatus hernia, when a part of the stomach herniates through the esophageal hiatus beside, and without movement of the gastroesophageal junction. Occasionally, a third type is described, which is a combination of the first and second. Investigations and management Endoscopy is more frequently used than barium studies in the diagnosis and assessment of hiatal hernia. Manometry and esophageal pH testing may provide useful information. Treatment is indicated if symptoms interfere with day to day routine of the patient. Weight reduction, diet modification, raising the head of the bed and reduction of alcohol, caffeine and nicotine intake are all recommended. Routinely, antacids to H2-receptor antagonists and proton pump inhibitors are sufficient. Surgery should be considered in severe and resistant cases of hiatal hernia. Dental considerations Since many of the medications used for treating hiatal hernia can cause xerostomia, cervical caries is common. If reflux into the oral cavity is present, oral manifestations are the same as those of GERD. Patients can be advised to frequently sip water. Salivary substitutes can be recommended. NSAIDs should be avoided.

Etiology H. pylori infection and the use of non-steroidal anti-inflammatory drugs are the most common causes of peptic ulcer disease. Other medications that have been known to cause ulcers include steroids, bisphosphonates, potassium chloride and chemotherapeutic agents (e.g. intravenous fluorouracil). A variety of other infections and co-morbidities are associated with a greater risk of peptic ulcer disease (e.g. cytomegalovirus, tuberculosis, Crohn’s disease, hepatic cirrhosis, chronic renal failure, sarcoidosis, myeloproliferative disorder). Critical illness, surgery or hypovolemia leading to splanchnic hypoperfusion may result in gastroduodenal erosions or ulcers; these may be silent or manifest with bleeding or perforation. Smoking increases the risk of ulcer recurrence and slows healing. Clinical features Typical symptoms of peptic ulcer disease include episodic gnawing or burning epigastric pain; pain occurring 2–5 hours after meals or on an empty stomach; and nocturnal pain is relieved by food intake, antacids or antisecretory agents. A history of episodic or epigastric pain, relief of pain after food intake, and night time awakening because of pain with relief following food intake are the most specific findings for peptic ulcer. Less common features include: indigestion, vomiting (coffee ground vomitus), loss of appetite, intolerance of fatty foods, heartburn and a positive family history. The serious or alarming symptoms that necessitate further investigations and immediate treatment include: anemia, hematemesis, melena (black tarry stools); vomiting suggests obstruction; anorexia or weight loss suggests cancer; persisting upper abdominal pain radiating to the back suggests penetration; and severe, spreading upper abdominal pain suggests perforation. Diagnosis Patients older than 55 years and those with alarming symptoms should be referred for esophago-gastro-duodenoscopy (EGD). It is more sensitive and specific for peptic ulcer

523


disease than upper gastrointestinal barium studies and allows biopsy of gastric lesions. Patients younger than 55 years with no alarm symptoms should be tested for H. pylori infection and advised to discontinue the use of NSAIDs, smoking, alcohol and illicit drug use. Presence of H. pylori can be confirmed with a serum enzyme-linked immunosorbent assay (ELISA), urea breath test, stool antigen test, or endoscopic biopsy.

Anorexia has two subtypes: restricting type and bingeeating/purging type. Diagnostic criteria for anorexia nervosa 1.

Dental considerations Non-steroidal anti-inflammatory drugs and steroids should be strictly avoided. Most patients present with xerostomia secondary to the anticholinergic drugs. Anemia related symptoms and dental considerations have to kept in mind.

2. 3.

Management Treatment of peptic ulcer disease should include eradication of H. pylori in patients with this infection. The recommended duration of therapy for eradication is 10–14 days. Regimen: Omeprazole 20 mg 2 times daily or lansoprazole 30 mg 2 times daily plus amoxicillin 1 g 2 times daily or metronidazole 500 mg 2 times daily (if allergic to penicillin) plus clarithromycin 500 mg two times daily. Surgery is indicated in patients who are intolerant of medications or do not comply with medication regimes, and those at high risk of complications (e.g. transplant recipients, patients dependent on steroids or NSAIDs, those with giant gastric or duodenal ulcer, those with ulcers that fail to heal with adequate treatment).

EATING DISORDERS Eating disorders are associated with various medical and psychologic consequences, including death, osteoporosis, growth delay and developmental delay. Anorexia nervosa and bulimia nervosa are two of the most devastating eating disorders. Eating disorders are most commonly seen among adolescents and young adults of developed nations. They are many times more common in females than in males. These disorders are seen in individuals who participate in activities that promote thinness, such as modeling, movies and athletics, and certain personality traits such as low selfesteem, difficulty expressing negative emotions, difficulty resolving conflict, and being a perfectionist. It is also seen that up to one-third of women with type 1 diabetes may have eating disorders.

Anorexia Nervosa Patients with anorexia use caloric restriction or excessive exercise to control emotional need or pain, and they are terrified of becoming overweight. 524

4.

Refusal to maintain body weight at or above a minimally normal weight for age and height (e.g. weight loss leading to body weight less than 85% of that expected; or failure to make expected weight gain during period of growth, leading to body weight less than 85% of that expected). Intense fear of gaining weight or becoming overweight, even though patient is underweight. Disturbance in the way in which one’s body weight or shape is experienced, undue influence of body weight or shape on self-evaluation, or denial of the seriousness of the current low body weight. Amenorrhea in postmenarchal females (i.e. the absence of at least three consecutive menstrual cycles. A woman is considered to have amenorrhea if her periods occur only following hormone administration.)

Bulimia Nervosa Bulimia also has two subtypes: purging and non-purging. Bulimia is characterized by uncontrollable binge-eating episodes, often followed by purging behaviors such as vomiting or the use of laxatives. Patients with binge-eating/ purging-type anorexia also might binge and purge. Patients who have bulimia may be of normal weight, or they may be under- or overweight, whereas patients with binge-eating/ purging-type anorexia are underweight. Diagnostic criteria for bulimia nervosa 1.

2.

3.

4. 5.

Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following: a. In a discrete period of time (e.g. within any 2-hour period), eating an amount of food that is larger than what most people would eat during a similar period of time and under similar circumstances. b. A sense of lack of control over eating during the episode. Recurrent inappropriate compensatory behavior to prevent weight gain, such as self-induced vomiting; misuse of laxatives, diuretics, enemas, or other medications; fasting; or exercising excessively. The binge eating and inappropriate compensatory behaviors both occur, on average, at least twice a week for 3 months. Self-evaluation is unduly influenced by body shape and weight. The disturbance does not occur exclusively during episodes of anorexia nervosa.


Screening for eating disorders Morgan et al (1999) suggested the use of the SCOFF questionnaire for assessing eating disorders.

Immunological function

Acts as a ‘sieve’ for antigens

Functions of bile juice

Acts as a detergent Emulsifies fat Absorption of fat-soluble vitamin Excretion of hemoglobin by-products Neutralizes any stomach acid Bactericidal potential

SCOFF questions ❍ ❍ ❍ ❍ ❍ ❍

Do you make yourself Sick (induce vomiting) because you feel uncomfortably full? Do you worry that you have lost Control over how much you eat? Have you recently lost more than One stone (14 lb [6.4 kg]) in a 3-month period? Do you think you are too Fat, even though others say you are too thin? Would you say that Food dominates your life? One point for every yes answer; a score 2 indicates a likely case of anorexia nervosa or bulimia nervosa (sensitivity: 100%; specificity: 87.5%).

Oral manifestations Frequent vomiting leads to erosion of the enamel on the lingual surfaces of the maxillary teeth. Palatal ulcerations may be noticed. Parotid enlargement may develop as a sequela of starvation.

LIVER DISEASES The liver has many essential functions, and liver disease presents a number of concerns for the delivery of medical and dental care. A number of conditions that cause liver dysfunction may be related to lifestyle and a variety of diseases. This section of the chapter will deal with two common liver conditions, namely, hepatitis and jaundice, that have important dental implications. Functions of liver Functions of the liver can be categorized as follows: Nutrient metabolism

Carbohydrate Protein Lipids

Protein synthesis

Albumin Coagulation factors Complement factors Hepatoglobin Ceruloplasmin

Storage

Excretion

Iron Copper Vitamin A Vitamin B12 Vitamin D Bile salts Bilirubin Metabolism of drugs

Clinical presentation of a patient with suspected liver disease As a dentist it is very important to look for certain clues in the case history that can take us toward a diagnosis of hepatobiliary abnormality in such patients. Ask your patient for alcohol abuse, intravenous drug abuse, rule out familial history of liver diseases, accidental environmental toxin exposure. Enquire if the patient is on any hepatotoxic medications, recent travel to another country or place and whether he/she has exaggerated reactions to certain medications or chemicals. These clues will not only help in diagnosing any hepatobiliary abnormality but also in deciding an appropriate treatment plan for your patients. The symptoms associated with liver disease include: right hypochondrial pain, abdominal distention, ankle swelling, hematemesis and melena. They can also have pruritus, amenorrhea, breast swellings, confusion and drowsiness. Some important clinical signs are nail changes in the form of clubbing of nails, leukonychia and also smooth nails. Dupuytren’s contracture, palmar erythema and flapping tremors (asterixis), spider nevi, gynecomastia and loss of body hair may be appreciated. Patient may present with ascites, hepatomegaly or spleenomegaly. Investigations ❍ ❍ ❍ ❍ ❍ ❍ ❍

Aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) Gamma-glucosyl transferase 5-Nucleotidase Serum albumin Serum bilirubin (direct and indirect) Prothrombin time Viral markers.

Imaging ❍ ❍ ❍

Ultrasonography CT MRI.

Jaundice Jaundice or icterus is a yellowish discoloration of tissue resulting from the deposition of bilirubin. Tissue deposition of bilirubin occurs only in the presence of serum hyperbilirubinemia and is a sign of either liver disease or less 525


often, a hemolytic disorder. The degree of serum bilirubin elevation can be estimated by physical examination. Slight increases in serum bilirubin are best detected by examining the sclerae, which have a particular affinity for bilirubin due to their high elastin content. The presence of scleral icterus indicates a serum bilirubin of at least 51 mol/l (3.0 mg/dl). The ability to detect scleral icterus is made more difficult if the examining room has fluorescent lighting. If the examiner suspects scleral icterus, a second place to examine is underneath the tongue. As serum bilirubin levels rise, the skin will eventually become yellow in light-skinned patients and even green if the process is long-standing; the green color is produced by oxidation of bilirubin to biliverdin.

Hepatitis Findlay and colleagues in 1939 postulated that the etiology of this particular disease was probably a virus carried in the blood of some apparently by inadvertent inoculation with vaccines contaminated with human serum containing the infectious agent. The term ‘serum hepatitis’ first came into use in the early 1940s as a synonym for post-inoculation hepatitis. The present diseases now labeled hepatitis A and hepatitis B were first described as a single entity, separate from other causes of jaundice, called ‘sporadic and epidemic catarrhal jaundice’ was thought to be infectious, but unknown, causative agent (Cockayne, 1912). MacCallum in 1947 suggested that to avoid confusion in terminology, the two postulated viruses be termed virus A, which produces infectious hepatitis after a short incubation period and virus B, which produces serum hepatitis after a long incubation period. Hepatitis has a number of potential causes, both infectious and non-infectious. Alcohol, prescription medications, and drug abuse are predominant non-infectious causes, while viruses and bacteria are important infectious etiologic factors. Viral and drug-induced hepatitis are examples of primary hepatitis. Secondary hepatitis may occur as a sequela of other disease entities such as mononucleosis, syphilis and tuberculosis.

Hepatitis A Hepatitis A is caused by the hepatitis A virus (HAV), an enterovirus of the Picornaviridae family. HAV is a singlestranded RNA virus surrounded by a protein capsid. Transmission is primarily by the oral-fecal route. Various methods of spread are through contact of an infected person, traveling to an endemic region, and ingestion of contaminated food or water. Hepatitis A is typically a self-limiting disease and usually causes mild illness characterized by sudden onset of non-specific symptoms. In children of age 6 years or younger, it is usually asymptomatic. In adults, infection may present with symptoms such as fever, fatigue, 526

abdominal discomfort, diarrhea, nausea, and/or jaundice. Diagnosis is made based upon signs and symptoms in combination with serologic tests for IgM anti-HAV (positive with recent infection) and IgG anti-HAV. The risk of acquiring HAV infection for healthcare workers is quite low. One effective method of prevention of HAV infection is the administration of HAV immune globulin either before the exposure or within 2 weeks following exposure. Immune globulin provides passive immunity toward HAV. There are currently only two vaccines available that provide active immunization. Those considered to be at increased risk of HAV infection are people traveling internationally, drug users, people with chronic liver disease, and those with occupational risks should be vaccinated. Educating healthcare providers and the public about vaccine availability and efficacy can be effective in preventing HAV outbreaks. Recovery from hepatitis depends on virus replication, the host response and the appearance of antibodies. Greater morbidity and mortality is associated with very young and older patients. Although most patients recover from viral hepatitis, sequelae include persistent infection (or carrier state), dual infection (HDV [a defective virus] with HBV), chronic active hepatitis, fulminant hepatitis, cirrhosis, hepatocellular carcinoma and death. Dual infections increase the risk for fulminant hepatitis, the latter having a mortality rate of about 80%.

Hepatitis B Hepatitis B virus is a 42 nm DNA virus of the Hepadnaviridae family. The DNA genome is circular and comprised of two strands, with one strand being partially incomplete. It is a highly infectious virus that produces three distinct particles during replication: ❍

The Dane particle or complete virus (HBV), composed of an outer shell and an inner core ❍ 22 nm non-infectious spherical particles ❍ Non-infectious filamentous units. The outer shell of the Dane particle carries the hepatitis B surface antigen (HBsAg), which is anchored in a lipid bilayer derived from the host cell. Internally is the inner core that is composed of a protein known as the hepatitis B core antigen (HBcAg), and the hepatitis B early antigen (HBeAg), an antigenic component derived from cleavage of the core antigen. Hepatitis B virus infection remains a serious healthcare problem. There are 350 million hepatitis B virus carriers worldwide, with the highest carrier rates (8–20% of population) in South-East Asia, China and subSaharan Africa. Globally, 1.25 million persons die per year as a result of hepatitis B. In 2000, 6,646 cases of type B hepatitis were reported to the Centers for Disease Control and Prevention (CDC) in the United States. There are over 1.5 million carriers in the United States, and an estimated 6,000 deaths occur annually due to cirrhosis and primary


hepatocellular carcinoma associated with HBV infection. The main causative factor for the prevalence of HBV is its replication pattern. The steps of HBV replication provide therapeutic targets for antiviral therapy. Nucleoside analogs interfere with viral DNA synthesis by blocking further synthesis when incorporated into viral DNA and or competitively inhibiting viral polymerase. Current protocols for treatment of HBV infection use interferon and nucleoside analogs such as lamivudine. Other nucleosides with activity against hepatitis B currently being used are famciclovir and adefovir.

individuals infected with HBV, which may then progress to severe fulminant infection. Transmission of HDV can occur via infected blood or blood products and is primarily seen in intravenous drug users and hemophiliacs. HDV may also be transmitted through sexual activity. Serologic testing for HDV and anti-HDV is used to detect infection. Effective prevention of HBV will protect against HDV infection. The screening of the blood supply for HBV has altered the epidemiology of HDV. There is currently no treatment for HDV infection.

Hepatitis E and G Hepatitis C Hepatitis C virus, previously known as one of the non-A non-B hepatitis viruses, is a small, positive-sense, singlestranded RNA virus of the Flaviviridae family. Six major genotypes of HCV and 40 related subtypes have been identified. The virus has a core protein and two envelope glycoproteins. The prevalence of HCV infection worldwide is between 0.3% and 1.5%, with an estimated 300 million carriers worldwide. The genetic diversity of HCV, and its ability to mutate, allows the virus to avoid neutralization and establish a chronic infection in about 85–90% of infected persons. Eighty-five percent of patients with HCV will develop chronic hepatitis. Chronic HCV infection is the major cause of cirrhosis and hepatocellular carcinoma. Acute HCV infection usually presents with mild flu-like symptoms, while chronic disease is variable in presentation. Patients may experience non-specific symptoms such as fatigue, nausea, and/or abdominal pain. Majority of HCV-infected patients develop chronic active hepatitis that is characterized by persistent and intermittent viremia, fluctuating elevations of serum alanine aminotransferase (ALT) levels and slow but progressive liver damage. The first decade is usually marked by inflammatory cell infiltration of the portal tracts and focal liver cell necrosis. Mild fibrosis ensues that is followed by more severe fibrosis, and bridging between portal tracts and hepatic veins. By the second decade after infection, fibrosis progresses to cirrhosis in at least 20% of patients with chronic HCV infection. Progression is more likely if patients consume excessive amounts of alcohol. Future treatment of hepatitis C may include agents that specifically target the virus rather than current non-specific forms of antiviral therapy. Research is focused on targeting the helicase and polymerase crucial to HCV replication. Other therapeutic targets are the viral proteases and the 59 and 39 strands of HCV RNA.

Hepatitis D Hepatitis D virus (HDV, delta agent) is a defective RNA virus that uses the HBV surface antigen as a viral envelope. HDV can occur as a coinfection or superinfection in

Hepatitis E virus (HEV) is a non-enveloped, single stranded RNA virus that is highly unstable due to the lack of a lipid membrane. Transmission, similar to HAV, is by the oralfecal route. The primary method of spread is through contaminated drinking water and occurs mostly in places with inadequate sanitary precautions. Symptoms of disease commonly include malaise, nausea, abdominal pain, and/or fever. The infection is usually self-limiting, although there have been cases of fulminant hepatitis and chronic disease. In pregnant patients infected with HEV, there is a higher risk of fulminant hepatitis. There is no HEV vaccine available, and treatment is palliative.

Hepatitis G Virus (HGV) Hepatitis G is caused by two isolated viruses that appear to be almost identical. They are single-stranded, positivesense RNA viruses similar to HCV. HGV is transmitted through blood and blood products, sexual activity and perinatal contact. Due to similar transmission routes, HGV may be found in association with other hepatitis viruses, especially HCV. Individuals at risk are organ transplant and blood transfusion recipients, IV drug users, dialysis patients, and healthcare workers with exposure to blood and chronic HCV patients. Diagnosis is based on detection of HGV RNA in serum 1–4 weeks after infection. Serum anti-HGV indicates past infection. Although the rate of remission is low, little evidence exists that HGV causes significant liver damage, even with persistent viremia.

Autoimmune Hepatitis Autoimmune hepatitis is a chronic inflammatory disease. Although the etiology is not clear, it is thought that environmental and viral factors may cause alterations in cellular markers on hepatocytes leading to an autoimmune response in genetically susceptible individuals. The etiology appears to be related to antigen specific and generalized suppressor defects that perpetuate the autoimmune response. The main finding in autoimmune hepatitis is IgG hypergammaglobulinemia, which may be due to chronic infections or alteration in immune response. Autoimmune hepatitis 527


may lead to liver cirrhosis. Treatment protocols for autoimmune hepatitis patients usually include steroid therapy. If remission is not obtained by steroid therapy alone, azathioprine or its metabolite (6-mercaptopurine) may be added to the protocol.

Fulminant Hepatitis Fulminant hepatitis is sudden, severe liver dysfunction which may lead to hepatocellular necrosis as well as hepatic encephalopathy. Signs of fulminant hepatitis include jaundice, hepatomegaly and right upper quadrant tenderness during the inflammatory stage. As necrosis occurs and progresses, the liver becomes atrophic and less readily palpable. With the onset of severe liver failure, liver enzymes, bilirubin, prothrombin time and partial thromboplastin time will be elevated, while hemoglobin and hematocrit will decrease. The prognosis for fulminant hepatitis is poor, and the treatment of choice is liver transplantation. Clinical course of hepatitis B and C Hepatitis B and C virus infections can occur at any age, but are more common after puberty. The incubation period for HBV is 45–180 days and for HCV it is 14–180 days. Hepatitis B and C viruses produce symptoms in 10% and 25–30% of patients, respectively. Symptoms initially are flu-like and include fatigue, fever, loss of appetite, diarrhea, headache, malaise, myalgia, nausea, vomiting and weakness. During acute HBV infection, about 50% of symptomatic persons become icteric within about 10 days of the onset of symptoms. A minority become icteric with HCV infection. Icterus is the stage of infection in which patients demonstrate jaundice in the skin, conjunctiva of the eye, oral mucosa, and urine as a result of serum bilirubin levels rising three- to four-fold above normal levels (0.2–1.2 mg/dl). About 10% of patients infected with HBV also demonstrate serum sickness-like manifestations, including angioedema, arthralgia, and a rash. As the disease progresses, abdominal pain increases and hepatomegaly and splenomegaly develop. Two to eight weeks are required for recovery from symptoms, with hepatomegaly and abnormal liver function persisting for weeks to months. The course of the disease varies with alcohol use and the viral strain and load. The acute infection rarely requires medical treatment other than rest and the avoidance of hepatotoxic drugs. Patients who fail to produce an adequate immune response can develop fulminant hepatitis or a chronic infection. Investigations and diagnosis The diagnosis of acute HBV infection is made by recognition of the clinical features, specific serologic tests for viral antigens and antibodies, and elevated liver enzymes. The hepatitis B surface antigen (HBsAg) is the first detectable specific marker. Hepatitis B surface antigen appears in the 528

blood usually by the 4th week of infection and is followed within a week by the hepatitis B early antigen (HBeAg). Two to four weeks after the appearance of surface antigen, antibodies against the core antigen (anti-HBcAg) appear. Subsequently, antibodies against the hepatitis B early antigen (anti-HBeAg) appear by about the 16th week, and finally the appearance of antibodies against the surface antigen (anti-HBsAg) appear by about 28th week. Clearance of the virus is marked by the disappearance of HBeAg, appearance of anti-HBeAg and the eventual disappearance of HBsAg. Failure to produce anti-HBsAg results in a chronic carrier state. Carriers persistently display HBsAg in their serum for more than 6 months. The presence of the HBeAg in a carrier’s serum indicates virus replication in the liver and an infectious state. Antibody against HCV (anti-HCV) can be detected in 50–70% of patients at the onset of symptoms and in 90% within 3 months after onset of infection. Anti-HCV is commonly detected using an enzyme immunoassay (EIA) that contains HCV antigens from the core and non-structural genes. A supplemental recombinant immunoblot assay (RIBA) and the qualitative reverse transcriptase polymerase chain reaction (RT-PCR) for HCV RNA can be performed for confirmation. The RIBA is often positive after the 3rd week of infection, whereas HCV RNA can be detected in blood as soon as 1 week after initial exposure. Elevation of the serum bilirubin often corresponds with the peak of the icteric phase. During recovery, the transaminase level begins to fall, however, elevations in the bilirubin level regress more slowly. Failure of the PT to return to normal is a significant prognostic sign of extensive hepatic cellular destruction, indicative of a fulminant clinical course or a chronic rather than an acute infection. Oral manifestations The oral cavity may show evidence of liver dysfunction with the presence of hemorrhagic changes, petechiae, hematoma, jaundiced mucosal tissues, gingival bleeding, and/or icteric mucosal changes. HCV has been linked to the onset. Sjogren’s syndrome and chronic hepatitis have been associated with lichen planus in some studies. Glossitis may be seen with alcoholic hepatitis, especially if combined with nutritional deficiencies. Ecchymosis and reduced healing after surgery may also be identified. In some cases, parotid gland enlargement is evident. These oral changes often appear in combination with general signs and symptoms of liver disease such as fatigue, malaise, confusion, weight loss, nausea, vomiting, hepatomegaly, hemorrhagic changes, spider angiomas, edema, ascites, dark urine, and pale/clay-colored stool. Dental considerations Comprehensive and current medical and dental histories should be elicited. Consultation with and/or referral to treating physician prior to dental treatment is also recommended.


Prior to dental treatment appropriate laboratory investigations should be carried pout. These include: ❍

Complete blood count with differential erythrocyte count, leukocyte count, hemoglobin, hematocrit, platelet count, bleeding time ❍ Prothrombin time, partial thromboplastin time, international normalized ratio ❍ Liver function tests. Medications that are metabolized in the liver and/or impair hemostasis should be judiciously used or avoided. Medications that have to be judiciously used include: analgesics (acetaminophen, non-steroidal anti-inflammatory agents, opioids); anesthetics; antibiotics (ampicillin, tetracycline), medication with antiplatelet activity (aspirin) and sedatives (long-acting benzodiazepines, barbiturates). Soft tissue trauma should be as minimal as possible during dental treatment. Universal infection control measures should be practiced such as professional immunization against HBV, disinfection of dental units, proper handling of instruments, sterilization of instruments, good hand washing technique and personnel protective gear.

NEUROMUSCULAR DISORDERS BELL’S PALSY Bell’s palsy is a lower motor neuron disease of the facial nerve (cranial nerve VII) characterized by acute unilateral peripheral facial weakness involving muscles innervated by the facial nerve. Bilateral weakness is very rare and occurs in less than 1% of patients. Bell’s palsy is named after the 19th century Scottish anatomist and surgeon Sir Charles Bell (1774–1842), who first described the condition along with the anatomy and function of the facial nerve. The annual incidence of Bell’s palsy is about 20 per 100,000 persons, with equal numbers of men and women affected and the incidence increases with age. There is no predilection for either side of the face. It occurs more commonly in patients with diabetes and in pregnant women. Patients who have had one episode of Bell’s palsy have an 8% risk of recurrence. About 10% of those with Bell’s palsy have a family history of the condition. Etiopathogenesis Etiology Common condition affecting 15-to 45-year-old age group, both sexes. The cause is unknown, but site of damage is probably the portion of facial nerve lying within the facial canal (stylomastoid). Inflammation of facial nerve in the canal with demyelination and edema further hazards with blood supply. Inflammation of the nerve initially results in a reversible

neurapraxia, but ultimately Wallerian degeneration ensues. Herpes zoster virus shows more aggressive biological behavior than herpes simplex virus type 1 because it spreads transversely through the nerve by way of satellite cells. It is commonly seen in pregnancy, diabetes, influenza, cold or any other respiratory illness. It is immunologically mediated; probably caused by herpes virus, mainly herpes simplex virus type 1 and herpes zoster virus. Clinical features Bell’s palsy is generally considered as a condition based on exclusion. Patients report of no history of trauma, local infection, tumor, or CNS disease. They present with peripheral dysfunction of the facial nerve, involving all distal branches. The onset is usually abrupt and maximal facial weakness is observed at 24–72 hours. Generally, the unilateral facial weakness is complete. However, in about one-third of the patients only partial weakness is noticed. Numbness or pain around the ear on the affected side and reduction in taste on the affected side; altered taste on the anterior two-thirds of tongue are other important clinical findings. Drooping of the corner of the mouth on the affected side with drooling of saliva and loss of facial creases are common findings. About one-third of the patients report of hyperacusis (hypersensitivity to sounds) and inability to close eyelid on the affected side. Differential diagnosis Some of the relatively common conditions that have to be ruled out for before diagnosing Bell’s palsy are Ramsay Hunt syndrome, tumors affecting facial nerve, diabetes mellitus and sarcoidosis and Lyme neuroborreliosis. Investigations Electromyography can confirm the presence and severity of nerve damage. Radiographic evaluation of the cerebellopontine angle, internal acoustic canal and mastoid region can be undertaken to eliminate presence of tumors. Management Spontaneous improvement is generally seen within 6 months in most cases. However, about 15% show incomplete recovery and exhibit residual nerve dysfunction including partial palsy and motor synkinesis (involuntary movement accompanying a voluntary one). It is believed that the treatment is more likely effective before 72 hours and less effective after 7 days. Older patients are less likely to recover completely. The combination of acyclovir 400 mg 5 times/day and prednisolone (40–60 mg daily for a week) is believed to be more effective than steroid alone. Acyclovir (400 mg five times per day for 10 days) helps in limiting the damage to nerve from any associated herpetic infection. 529


Supportive measures include: protecting the cornea with an eyepad or surgical placement of gold weights in the upper lid. Artificial tear substitutes should be used. Bell’s palsy and blepharospasm can be treated with injections of botulinum toxin. Facial exercises can be beneficial in patients with Bell’s palsy. These should be performed while standing in front of a mirror and include trying to raise the eyebrows, opening and closing the eyes, blowing, and whistling.

EPILEPSY The word ‘epilepsy’ is derived from the Greek word ‘epilambanein’ meaning to take or to seize. Epilepsy can be defined as a chronic neurological disorder characterized by frequently recurrent seizures. A seizure manifests as an episodic disturbance of movement, feeling or consciousness caused by sudden synchronous, inappropriate and excessive electrical discharges that interfere with the normal functioning of the brain. Epilepsy usually affects young children (genetic predisposition to epilepsy associated with chromosome 12 anomalies) and elderly individuals who have a history of stroke, tumors and Alzheimer’s disease. Clinical types of epilepsy ❍

Primary or idiopathic epilepsy (70%): Cause of seizures is unknown. ❍ Secondary or acquired epilepsy: Cause of seizure is known such as head trauma (loss of consciousness 30 minutes), metastatic brain tumors, stroke, infections, hypertension and diabetes as well as electrolyte imbalances, dehydration and lack of oxygen. High doses and withdrawal from chronic use of drugs such as heroin, cocaine, barbiturates, amphetamines and alcohol can also lead to seizures.

Generalized seizures There are two basic forms of generalized seizures, namely, tonic-clonic (grand mal) seizures and absence (petit mal) seizures. Grand mal seizures are usually seen in childhood or at teenage. These seizures begin after a brief period of aura (warning signs like irritability, headache, nausea). The seizures begin with abrupt loss of consciousness. The tonic phase is characterized by rigidity of the arm, leg, chest and back muscles. The patient may fall, pupils become dilated and the spine becomes extended (opisthotonos). Following this phase there is a clonic phase characterized by repetitive jerking and twitching movements of the limbs, tongue and lips. Tongue biting, frothy salivation and vomiting may occur. In this phase, bowel and bladder control may also be lost. The seizures usually last for about 2–3 minutes. Following this is the post ictal phase in which the patient is tired and goes to sleep for as along as 12 hours. Status epilepticus When tonic-clonic seizures last more than 5 minutes or recur in a series of three or more seizures without return to consciousness between attacks, a serious neurological emergency called convulsive status epilepticus has developed. Absence (petit mal) seizures Absence (petit mal) seizures are seen in childhood. These are called absence seizures as these are not preceded by aura or warning signs. These seizures last for about 30 seconds and may only present as rapid eye blinking or stare, and brief loss of consciousness. However, these recur very frequently almost up to 100 attacks in a day.

Classification of seizures and clinical features

Diagnosis and dental considerations

Broadly, seizures can be classified as partial or generalized. A seizure is termed ‘partial’ when the electrical discharge causing it occurs in a specific area of the brain or ‘generalized’ when the discharge affects the entire brain cortex.

Apart from a good clinical history, diagnostic tools such as electroencephalography (EEG) and MRI help in diagnosing the type of epilepsy. The number of decayed and missing teeth, the degree of abrasion and periodontal indexes are significantly higher in patients with epilepsy. Patient may present with minor oral injuries such as tongue biting, soft tissue lacerations and fractured teeth; but also frequently lead to tooth injuries. It is believed that enzyme-inducing antiepileptic drugs such as phenytoin, phenobarbital, carbamazepine alter the metabolism and clearance of vitamin D and have been associated with osteopenia and osteomalacia. Such patients have an increased risk of fracture. Hence, these patients should be supplemented with 1,000 mg of calcium and 400 IU of vitamin D per day.

Partial seizures Partial seizures are further subdivided into simple and complex. In simple seizures consciousness is not impaired, whereas in complex seizures there is impaired consciousness. There are several types of simple partial seizures: motor seizures, sensory seizures, autonomic seizures and psychic seizures. Motor seizures may cause patients to clench and grind teeth and facial muscles/muscles of mastication may become stiff. Unpleasant odors and taste disturbances may 530

be seen in sensory seizures. Partial seizures usually last from 30 seconds to 2 minutes. In 30% of patients with partial seizures, the partial seizure evolves into a secondary generalized seizure. In such cases, the excessive electrical activity that starts in a limited area spreads to involve both sides of the brain.


It is estimated that about 50% of the patients using phenytoin exhibit gingival hyperplasia within 12–24 months of initiation of treatment. Xerostomia and stomatitis have been reported rarely as side effects of carbamazepine. Valproic acid can cause direct bone marrow suppression, which can impair wound healing and increase postoperative bleeding and infections. Decreased platelet count is the most common and best recognized hematologic effect of valproic acid. When restoration and replacement of teeth are considered it is best to use a fixed rather than removable prosthesis and inclusion of additional abutments should be planned for fixed partial dentures. Rash is a common side effect of antiepileptic drugs (almost 5–7%). Although most drug-associated rash is benign, serious rashes, including Stevens–Johnson syndrome and toxic epidermal necrolysis do occur. Metronidazole, antifungal agents such as fluconazole and antibiotics such as erythromycin may interfere with the metabolism of certain antiepileptic drugs and render them ineffective for seizure control.

PARKINSONISM Parkinson’s disease is a serious brain disorder characterized by degeneration of the basal ganglia. Patients present with bradykinesia (slow movements), increased muscular tone (rigidity), tremors and loss of postural reflexes. Etiology The exact etiology is still unknown. Though previously no strong genetic basis was considered, it is now believed that genetic factors may have a role to play. Parkinsonism may be caused by head injuries, drug abuse (phenothiazine, valproate, prochlorperazines and methyl phenyl tetrahydropyridine). Environmental exposure to toxins such as carbon monoxide, heavy metals and herbicides/pesticides may have a crucial role in the etiology. This led to the suggestion that many cases of apparently idiopathic toxins such as pesticides, herbicides, manganese, heavy metals and carbon monoxide. Clinical features In the initial stages of the condition patients may complain of fatigue, aching limbs, depression and mental sluggishness. It has also been seen that these patients tend to have a tiny handwriting (micrographia). The unique feature in parkinsonism is a unilateral presentation of the signs/symptoms initially which turns into a bilateral involvement as the condition worsens. Other clinical features are tremors of the hands and feet at rest, tongue tremors, gait becomes slower, muscular tone and rigidity increases (log wheel rigidity) and speech

becomes unclear and softer. Face becomes expressionless with an increased blink reflex. Patients generally tend to hypersalivate and drool. Dental considerations Most of the orofacial findings in parkinsonism are secondary to the medications (levodopa, bromocriptine, catechol O methyl transferase [COMT] inhibitors) used for treating the condition. Local anesthesia is best used without epinephrine. Because the epinephrine can interact with COMT inhibitors and cause hypertension and dysrhythmias. Xerostomia may be seen when anti-muscarinic drugs are used. Levodopa causes taste disturbances and turns the saliva red. The other side effects of these drugs are that they produce dyskinesia such as lip and tongue tremors (fly catchers tongue).

MULTIPLE SCLEROSIS Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS. The etiology is still not clear. It is thought that genetic predisposition together with immunity and environmental factors could trigger the disease. Clinical features Multiple sclerosis is usually seen between the 2nd and 4th decades of life. It is slightly more common in women than in men. MS exhibits a wide variety of symptoms as a result of the demyelination of the CNS, and a later slow down or blocked transmission at the level of axons. Ectopic impulses may also appear, causing paroxysms and convulsions. Multiple sclerosis is categorized into four subtypes: (i) relapsing–remitting (RR), (ii) progressive-relapsing (PR), (iii) secondary-progressive (SP) and (iv) primary-progressive (PP). Almost 85% of the patients belong to the relapsingremitting subtype. Clinically, MS usually appears with a number of symptoms of neurological anomalies which settle in a matter of minutes or hours, and which frequently progress in later days. The most common features are: visual and oculomotor anomalies, optical neuritis, anterior internuclear ophthalmic paralysis, palsies, paresthesia, lack of motor coordination and tonic spasms. Other less common features are genitourinary dysfunction, increased frequency and urge of urination and urinary incontinence, lack of bladder control and episodic retention of urine. In the later stages, paroxysmal ataxia and dysarthria or shaking of upper limbs is frequently seen which indicate brain damage. Dental considerations Patients may be encouraged to sit upright on the dental chair to avoid respiratory embarrassment. Hypothetically, nitrous 531


oxide causes demyelination. Hence, it is best avoided. Facial myokymia or facial hemispasm may be seen. Patients report of perioral paresthesia.

MUSCULAR DYSTROPHY Muscular dystrophy (MD) is a life-threatening recessive neuromuscular disease affecting the short arm of the X chromosome in the p21-2 position. Of the various forms of MD, severe generalized familial muscular dystrophy and mild restricted muscular dystrophy have significant orofacial findings. Severe generalized familial muscular dystrophy is popularly referred to as Duchenne muscular dystrophy (DMD). It is commonly seen in young male children. In the early stages of the disease, muscle enlargement may be seen which becomes atrophic as the disease worsens. The early recognizable symptom is the inability to walk and run. Muscles associated with the lower extremities, pelvis and shoulder girdle rapidly atrophy. Similarly, muscles of the face, larynx and pharynx are affected. Symons et al (2002) carried out a study to assess the dental characteristics of patients with DMD. Their study showed that patients with DMD had high plaque and calculus accumulation, leading to gingival inflammation, due to decreased muscle function. However, the caries experience was low. Disturbances in tooth form, number and eruption of the second premolars were observed in 39% of patients. Anterior and posterior open bites were common, associated with lip incompetence, mouth breathing, macroglossia and tongue thrusting. Maxillary and mandibular arch breadths were significantly larger, on average, in the DMD group than in controls. Rather than a normal parabolic arch form, the dental arches in DMD patients tended to be hyperbolic, with the posterior teeth being displaced buccally, consistent with an imbalance between the lingual and facial musculature. An elevated serum creatinine phosphokinase level is typical for this condition. The disease has no known treatment as of date and usually the affected individuals do not live beyond the 2nd decade of life.

OROMANDIBULAR DYSTONIA Dystonia is an involuntary, repetitive, sustained (tonic) or spasmodic (rapid or clonic) muscle contraction. Few of the dystonias that are of interest to a dental surgeon are cranial-cervical dystonia (CCD) and oromandibular dystonia (OMD). Multiple etiological factors are proposed for OMD, namely, genetic predisposition, injury to the CNS, peripheral trauma, medications, metabolic or toxic states and neurodegenerative disease. It usually affects individuals 532

in the 5th decade of life and women are more prone to develop OMD. CCD is an involuntary, sustained, contraction of the periorbital, facial, oromandibular, pharyngeal, laryngeal or cervical muscles. OMD involves the masticatory muscles, lower facial, and tongue muscles and may result in trismus, bruxism, involuntary jaw opening or closure, and involuntary tongue movement. These involuntary movements may produce inappropriate deviation of the mandible, subluxation, intraoral soft tissue trauma and bone resorption. Dysphagia, dysphonia and difficulty with mastication also often occur with OMD. Brueghel’s syndrome is an association of OMD with blepharospasm.

MYASTHENIA GRAVIS Myasthenia gravis is described in Chapter 20 on Autoimmune Disorders.

ENDOCRINAL DISORDERS The specialty of endocrinology encompasses the study of glands and the hormones they produce. The term ‘endocrine’ was coined by Starling to denote the action of hormones secreted internally in contrast to exocrine glands which secrete into a lumen. The term ‘hormone’ is a Greek word meaning ‘to set in motion’ describing the dynamic actions of hormones as they elicit cellular responses and regulate physiologic processes through feedback mechanisms. The classic endocrine glands—pituitary, thyroid, parathyroid, pancreatic islets, adrenals and gonads—communicate broadly with other organs through the nervous system, hormones, cytokines and growth factors. In addition to its synaptic functions, the brain produces a vast array of peptide hormones, spawning the discipline of neuroendocrinology. The immune and endocrine systems are also intimately intertwined. The adrenal glucocorticoid, cortisol, is a powerful immunosuppressant. Cytokines and interleukins have profound effects on the functions of the endocrine organs. Common endocrine diseases, such as autoimmune thyroid disease and type I diabetes mellitus are caused by dysregulation of immune surveillance and tolerance. Endocrinal disease can present with either overt disease or subtle findings to the oral health clinician. Patients with hormonal dysfunctions caused by endocrinal diseases may be found to have significant abnormalities on head and neck examination. Large pituitary adenomas frequently present with changes in vision and loss of visual field integrity, and the oral health clinician may be the first medical professional to note these diseases. For example, in active Graves’ disease (one of the conditions causing excessive


function of the thyroid), defects in the motor function of cranial nerves III, IV and VI may be observed. In acromegaly and in Cushing’s disease, pituitary adenomas secrete active hormones, causing gradual changes in facial features and orofacial structures. In addition to the changes an oral health clinician can observe and document on physical examination, patients with disease caused by endocrinal dysfunction who often have alterations in the blood levels of several circulating hormones. Notably, abnormal hormone levels may also be the result of previous medical or surgical therapy for underlying disease. Normally, blood levels of hormones secreted by the endocrinal organs are exquisitely regulated. Disruption of their function can produce life-threatening conditions, adversely affecting the safety of patients during all but the most minor clinical interventions. Prompt recognition of endocrinal dysfunction can prevent complications of dental treatment and can provide a safe setting for clinical and therapeutic interventions in these patients. Even after definitive medical or surgical treatment of endocrinal diseases, patients may require lifelong replacement of several hormones. Replacement therapy may be indicated after partial resection or partial destruction of endocrinal tissue. As a result of the destruction of specialized cells, the endocrinal organs may no longer be capable of secreting selected hormones. Replacement hormone therapy may interfere with standard preoperative instructions before dental surgery or treatment and may require the oral healthcare clinician, in consultation with the patient’s physician, to alter the medical regimen or the preoperative instructions to ensure a safe outcome. A general understanding of the pathophysiology, relationship and the regulation of endocrine function will help the clinician recognize new presentations of endocrine disease. Understanding endocrine function and the regulatory role will allow the clinician to avoid complications during the treatment of these patients with complex disease.

General Overview of Functional Mechanisms of Endocrine System The hypothalamic–pituitary–endocrine axes control the major endocrine glands. Peptidergic neurons in the hypothalamus release small peptides into the anterior pituitary. Specialized pituitary secretory cells (Table 3) respond to the small peptides and release larger peptides into the systemic circulation. The specific endocrine glands are the target of specific specialized pituitary peptides. A negative feedback by the hormone product of the target organ has been demonstrated upon the secretory pituitary cell and upon hypothalamic neuronal secretions. The basic functions of the endocrine system include growth and development, sex differentiation, metabolism and adaptation to an ever-changing environment such as

Table 3

Hormones released by the anterior pituitary gland

Cell types of the anterior pituitary gland

Hormones released

Thyrotrophs

Thyroid stimulating hormone (TSH)

Corticotrophs

Adrenocorticotropic hormone (ACTH)

Gonadotrophs

Gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH)

Somatotrophs

Growth hormone (GH)

Lactotrophs

Prolactin

regulation of digestion, use and storage of nutrients, electrolyte and water metabolism and reproductive functions.

Hormones Hormones function as chemical messengers moving through the blood to distant target sites of action (pituitary hormones like growth hormone, thyroid stimulating hormone [TSH] and adrenocorticotropic hormone [ACTH]); act more locally as paracrine or autocrine messengers that incite more local effects (like histamine, bradykinin and eicosanoids). Most are present in body fluids at all times in greater or lesser amounts as needed. Categories of hormones according to structure ❍ ❍

❍ ❍ ❍

Amines and amino acid derivatives—Dopamine, catecholamines and thyroid hormone Peptides, polypeptides—Gonadotropin releasing hormone (GnRH), thyrotropin-releasing hormone (TRH) somatostatin and vasopressin Proteins and glycoproteins—TSH, luteinizing hormone (LH), follicle stimulating hormone (FSH) Steroids—Cortisol and estrogen Vitamin derivatives—Retinoids and vitamin D.

Mechanisms of action of hormones Hormones interact with high-affinity receptors which are linked to one or more effector system in the cell. Some receptors are located on the cell membrane called membrane receptors which bind with proteins and catecholamines. These act through second messenger mechanisms (Table 4). Others are located in the nucleus called nuclear receptors which bind to hormones that can diffuse into the cell like steroids, thyroxine and vitamin D (Table 5). They modulate the synthesis of enzymes, transport proteins or structural proteins. Feedback regulatory system Positive feedback—estrogen mediated stimulation of the midcycle LH surge. Though chronic low levels of estrogen 533


Table 4 • • • • • • • • • •

Glucagon Insulin Epinephrine Parathyroid hormone Thyroid-stimulating hormone (TSH) Adrenocorticotropic hormone (ACTH) Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Antidiuretic hormone (ADH) Secretin

Table 5 • • • • •

Hormone receptor interactions—second messengers like cyclic AMP

Hormone receptor interactions—intracellular interactions

Estrogens Testosterone Progesterone Adrenal cortical hormones Thyroid hormones

are inhibitory, gradually rising estrogen levels stimulate LH secretion. Negative feedback—each of the hypothalamic-pituitary hormone axes is governed by negative feedback maintaining hormonal levels in a narrow range like thyroid hormone on TRH–TSH axis. Types of hormone actions Action at a distant site Released into the bloodstream, the hormones circulate as free, unbound molecules—peptide and protein hormones like TRH and LH usually circulate unbound in the blood or circulate as hormones attached to transport carriers. Steroid hormones and thyroid hormone are carried by specific carrier proteins synthesized in the liver. Paracrine actions Hormones acting locally on cells other than those that produced the hormone, e.g. the action of sex steroids on the ovary; somatostatin secreted from -cells inhibit insulin secretion from -cells of the pancreatic islets. Autocrine actions Hormones exerting action on the cells from which they were produced, e.g. the release of insulin from pancreatic -cells can inhibit its release from the same cells, IGF-I (insulin-like growth factor I) acts on many cells that produce it like chondrocytes, breast epithelium and gonadal cells. Control of hormone levels ❍

534

Affected by diurnal fluctuations that vary with the sleep–wake cycle – GH and ACTH

❍

Secreted in a complicated cyclic manner – Female sex hormones ❍ Regulated by feedback mechanisms that monitor substances such as glucose (insulin) and water (ADH) in the body.

General Overview of Disorders of Endocrine System Endocrinology interfaces with numerous physiologic systems and hence has no standard endocrine history and examination is complete more so as most of the glands are inaccessible. The examination mostly focuses on hormonal excess or deficiency as well as direct examination of palpable glands like thyroid and gonads. It is important to evaluate patients in the context of their presenting symptoms, review of symptoms, family and social history and detecting subtle symptoms and signs suggestive of underlying endocrine disease. Clinical judgment based on knowledge of disease prevalence and pathophysiology is required to decide when to embark on investigative evaluation of these disorders. A biochemical testing for hormonal abnormality with quantitative assessment of their levels and dynamics, imaging tests like CT, MRI, thyroid scan and ultrasonography are used for diagnosis of endocrine disorders.

Categories of Disturbances of Endocrine Function Endocrine diseases can be divided into three major types of conditions: hypofunction, hyperfunction and hormone resistance. Hypofunction An organ is in the state of hypofunction if there is underproduction of hormone. Causes ❍ ❍

Congenital defects Glandular destruction due to infarction, hemorrhage, infection, inflammation, autoimmune responses, neoplastic growth or surgeries ❍ Decline in function with aging ❍ Atrophy as result of drug therapy or unknown reasons ❍ Mutations in a number of hormones, hormone receptors, transcription factors, enzymes and channels can also lead to hormone deficiencies. Autoimmune damage to the thyroid gland (Hashimoto’s thyroiditis) and pancreatic islet -cells (type 1 diabetes mellitus) are prevalent causes of endocrine disease.


Hyperfunction An organ is in the state of hyperfunction if there is excessive hormone production. Causes ❍ ❍ ❍

Autoimmune disorders Hormone-producing tumor of the gland Excess hormone administration.

Hormone resistance Hormone resistance is a state when the production of hormone is optimal but the end organs are resistant to hormonal effects. Causes ❍

Inherited defects in membrane receptors, nuclear receptors, or in the pathways that transduce receptor signals.

These disorders are characterized by defective hormone action, despite the presence of increased hormone levels. Common acquired forms of functional hormone resistance include insulin resistance in type 2 diabetes mellitus. The pathogenesis of functional resistance involves receptor downregulation and post-receptor desensitization of signaling pathways; functional forms of resistance are generally reversible. Endocrine disorders also can be categorized as ❍

Primary disorders—those that originate in the target gland responsible for producing the hormone ❍ Secondary disorders—where the target gland is essentially normal, but its function is altered by defective levels of stimulating hormones or releasing factors from the pituitary system ❍ Tertiary disorders—which result from hypothalamic dysfunction where both the pituitary and target organ are understimulated.

Pathophysiology of Hypothalamic–Pituitary Axis (HPA) The HPA axis can be considered the master of ceremony in regulating the endocrine functions. The secretions of the hypothalamus act on the pituitary which further releases hormones to act on the end organs. Hypothalamic hormones regulating the secretion of anterior pituitary hormones ❍ ❍ ❍ ❍

GH-releasing hormone (GHRH) Somatostatin Dopamine Thyrotropin-releasing hormone (TRH)

❍ ❍

Corticotropin-releasing hormone (CRH) Gonadotropin-releasing hormone (GnRH).

Function of hormones produced by the anterior pituitary ❍ ❍ ❍ ❍ ❍

Body growth and metabolism (GH) Function of the thyroid gland (TSH) Glucocorticoid hormone levels (ACTH) Function of the gonads (FSH and LH) Breast growth and milk production (prolactin).

Disorders associated with hypothalamic and anterior pituitary insufficiency Hypopituitarism is a result of impaired production of one or more anterior trophic hormones or impaired synthesis and secretion of hypothalamic hormone. More often than not the etiology is acquired disease like tumors, inflammation or vascular changes rather than inherited disorders. The clinical manifestations depend on which hormone is deficient.

GROWTH HORMONE The growth hormone (GH), produced by somatotropes in the anterior pituitary is necessary for linear bone growth in children. It stimulates cells to increase in size and divide more rapidly by enhancing amino acid transport across cell membranes; increases the rate at which cells use fatty acids and decreases the rate at which cells use carbohydrates.

Growth Hormone Deficiency Growth Hormone in Children—Dwarfism In children GH deficiency, GHRH receptor mutations, GH insensitivity or nutritional deficiency which interferes with linear bone growth result in Dwarfism. A familial mode of inheritance—autosomal dominant or recessive or X-linked is seen. Isolated GH deficiency is characterized by short stature, micro penis, increased fat, high pitched voice, propensity to hypoglycemia. Etiology of hypopituitarism ❍ ❍ ❍ ❍ ❍ ❍

Developmental/structural—pituitary dysplasia, congenital hypothalamic defects like Kallmann syndrome Traumatic—radiation, head injury, surgery Neoplastic—pituitary adenoma, leukemia, pituitary metastasis Infiltrative/inflammatory—hemochromatosis, sarcoidosis, Langerhans cell disease Vascular—pituitary apoplexy, sickle cell disease Infections—histoplasmosis, toxoplasmosis, Pneumocystis carinii, tuberculosis.

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Causes of short stature

Investigations

❍ ❍ ❍ ❍ ❍ ❍ ❍

Imaging may reveal reduced bone mineral density, structural damage of the pituitary and abdominal scan may show excessive omental adiposity.

Variants of normal Low birth weight Chronic illness and malnutrition Functional endocrine disorders Chromosomal disorders Skeletal abnormalities Unusual syndromes.

Orodental manifestations In pituitary dwarfs eruption rate and shedding of teeth is delayed for 1–3 years for teeth that normally erupt during 1st decade of life and for 3–10 years for teeth erupting in the 2nd decade. Lack of third molar development is a common finding. Clinical crowns are smaller because of incomplete eruption of teeth. The dental arches are smaller resulting in malocclusion. The anatomical crowns are normal in size. The roots of teeth are shorter and supporting structures are retarded in growth. Mandibular growth is more retarded than maxilla.

Evoked GH is less than 3 ng/ml, IGF-I level is low or normal, Concomitant gonadotropin, TSH, ACTH reserves may be deficient, LDL—cholesterol is increased. Managment Replacement therapy with GH at 0.15–0.3 mg/day, maximum 1.25 mg/day to maintain IGF-I levels in the midnormal range for age and gender matched controls. It is contraindicated in the presence of an active neoplasm, intracranial hypertension, uncontrolled diabetes and retinopathy. Replacement with adrenocortical and thyroid hormones in panhypopituitarism may be necessary.

Diagnosis and investigations

Growth Hormone Excess

Assessment of height if short stature, i.e. if a patient’s height is more than 3 SD below mean for age or decelerated growth, final height can be predicted using standard scales (Bayley–Pinneau or Tanner–Whithouse). Radiographic assessment of bone age and skeletal maturation, i.e. degree of growth plate fusion. GH release is pulsatile and is best measured in response to provocative stimuli like exercise, insulin-induced hypoglycemia which normally increases GH to more than 7 g/l in children. Pituitary imaging with MRI may reveal a mass or structural defect.

Gigantism

Management Replacement therapy with recombitant GH (0.02–0.05 mg/ kg per day SC) GH insensitivity and in mutations of GH receptor IGF-I is given which bypasses the dysfunctional GH receptor.

Adult GH Deficiency Growth hormone deficiency in adults is caused by hypothalamic or pituitary somatotrope damage. Infarction of the pituitary leading to hypopituitarism in adults is called Simmond’s disease. Panhypopituitarism, loss of weight, diminished sexual function, reduced basal metabolic rate, atrophic skin, thin eyebrows, loss of eyelash, sharp features; thin lips with immobile expressions are the features. Other clinical features include impaired quality of life, increased body fat mass, central fat deposition, reduced exercise capacity, CVS risk factors with impaired cardiac structure and function, abnormal lipid profile and atherosclerosis. 536

Laboratory findings

Gigantism results if GH excess occurs in children or before the growth plates of bone fuse. This results in increased linear bone growth. McCune–Albright’s syndrome may account for as many as 20% of cases of gigantism. Orodental manifestations The teeth size is proportional to the size of the jaws and the body. Roots may be larger than normal.

Growth Hormone Excess in Adults Acromegaly Growth hormone hypersecretion after the closure of epiphyses characterized by disordered somatic growth and proportion. Excess GH secretion may be a result of pituitary adenomas like GH cell carcinoma, multiple endocrine neoplasia 1, or McCune–Albright syndrome; or due to extra pituitary tumor like pancreatic islet cell tumor. Causes of acromegaly Most common cause (95%) is a somatotrope adenoma. Other causes ( 5%) include excess secretion of GHRH by hypothalamic tumors, ectopic GHRH secretion by nonendocrine tumors such as carcinoid tumors or small cell lung cancers; ectopic secretion of GH by non-endocrine tumors.


Excess GHRH secretion ❍

There central and peripheral causes for excess GHRH secretion ❍ Central—hypothalamic hamartoma, choristoma, ganglioneuroma ❍ Peripheral—bronchial carcinoid, pancreatic islet cell tumor, small cell carcinoma, medullary thyroid carcinoma, pheochromocytoma. Clinical features The condition is insidious in onset and usually occurs between 6.6 and 10.2 years of life. Voice deepening, structural changes like facial and skeletal disfigurement, frontal bossing and cranial ridges, enlarged hand and feet; arthropathy with joint swelling, hypermobility and cartilaginous thickening; periarticular fibrous thickening with joint stiffening or deformities; nerve entrapment; generalized visceromegaly including the tongue, lips, nose, bones, salivary glands, thyroid, heart, liver, spleen; abnormalities of the spinal column like osteophytosis, disk space widening and dorsal kyphosis, carpal tunnel syndrome, hyperhidrosis and oily skin, facial wrinkles, nasolabial pads and heel pads thicken. Skin tags are the markers for adenomatous colonic polyps. The patient is medically compromised due to symptomatic cardiac disease, hypertension and left ventricular hypertrophy. There is an excessive deposition of mucopolysaccharides around heart muscle fibers. Increased GH and decreased glucose tolerance leads to mild-to-moderate diabetes mellitus. Increased blood glucose levels with increased HBA1c (used to assess the efficacy of interventional therapy in DM), accelerated aging of arteries lead to atherosclerosis. Other endocrine complications include: ❍

Increased serum prolactin level with/without galactorrhea ❍ Hypopituitarism with amenorrhea/impotence, secondary adrenal and thyroid failure ❍ Glucose intolerance with diabetes mellitus ❍ Hypertriglyceridemia, hypercalciuria. The oral manifestations include mandibular overgrowth with prognathism in adults, maxillary widening and teeth separation, jaw malocclusion and overbite; enlarged lips, tongue with teeth indentations on the lateral border are common features. Soft palate hyperplasia causes sleep apnea and airway obstruction. Patients usually present for flaring of teeth and orthodontic treatment.

❍

Enlargement of paranasal sinus especially the frontal sinus. ❍ Thickening of the outer table of the skull vault leading to enlargement and deformity. Radiographic features of the jaws ❍ ❍ ❍ ❍ ❍ ❍

Enlargement of the mandible, excess condylar growth and height of the ascending ramus Increased angle between ramus and body of mandible with the loss of antegonial notch Spacing and flaring of anterior teeth with anterior open bite Class III skeletal relationship Increase in thickness and height of alveolar process Radiographic features of the teeth include hypercementosis and supraeruption of posterior teeth to compensate for the growth of mandible.

Investigations Age and gender matched serum IGF levels is increased. Single GH level estimation is not useful. Confirmation is by the failure of GH suppression to less than 1 g/l within 1–2 hour of an oral glucose load. Prolactin levels are increased. CT and MRI play a pivotal role in the evaluation of these patients. MRI is now the investigation of choice in diagnosis of pituitary adenomas. About 80–85% of micro-adenomas are visible on unenhanced T1 weighted MRI and 33–50% are seen as areas of hyperintensity on T2 weighted MRI. MRI is better than CT in assessment of sella in the presence of bony skull base thickening due to fibrous dysplasia as in cases of McCune–Albright’s syndrome. The distinction between pituitary gland and abnormal fibrous bone tissue at skull base is better made on MRI. The combination of pre- and post-contrast images is useful in this regard. However, CT of skull base plays a useful role in some cases for detailing neural foraminal compression, especially if surgery is being contemplated. In one study (Akira Hagiwara et al) on T2-weighted MRI, hypointensity was seen more commonly in adenomas that produced GH than in those which did not; hypointensity was nearly exclusive to densely granulated GH-producing adenomas. Octreotide scintigraphy, in combination with other imaging modalities, is useful in the diagnosis and follow-up of pituitary tumors. It allows scar tissue to be differentiated from tumor recurrence after surgical treatment and ensures better selection of patients who will benefit from medical treatment with somatostatin analogs.

Radiographic features General radiographic features

Management of acromegaly

❍

Synthetic somatostatin analog—octreotide acetate suppress integrated GH levels to 5 g/l in ⬃70% of patients and

Enlargement or ballooning of sella turcica if an enlarged pituitary adenoma is present.

537


2 g/l in ⬃60%. It normalizes IGF-I in ⬃75% of patients. It is given at a dose of 50 g/day 3 times a day up to 1,500 g/day. Lanreotide, a slow-releasing preparation suppresses GH for 10–14 days after 30 mg IM. GH antagonists—pegvisomant at 10 mg/day for 2 weeks reduces IGF-I levels. Dopamine agonists like bromocriptine, cabergoline, high energy stereotactic radiation therapy for tumor mass reduction and trans-sphenoidal surgery are the modalities of treatment.

❍

Primary polydipsia—Secondary deficiency of ADH due to inhibition of secretion by excessive intake of fluids.

Clinical features ❍ ❍ ❍ ❍

Polyuria and polydipsia Urinary output: 5–20 l/day Low specific gravity: 1.010 Low osmolality: 300 mmol/kg.

Investigations ❍

Oral health considerations Patients may seek orthodontic treatment for malocclusion. Bilateral growth of mandible and new onset of diabetes mellitus is suggestive of acromegaly.

Disorders of Posterior Pituitary (Neurohypophysis) The neurohypophysis secretes oxytocin and vasopressin (antidiuretic hormone). Oxytocin is released rendering uterine contraction during child birth and release of milk during breast feeding. The antidiuretic hormone aids in conservation of body water. It acts on permeability of collecting ducts and tubules reabsorbing water. It also causes arteriolar smooth muscle contraction, vasoconstriction and increases arteriolar blood pressure.

Diabetes Insipidus Diabetes insipidus (DI) is caused due to the decreased secretion or action of ADH. It is characterized by production of abnormally large volumes of dilute urine. Etiology Cranial DI—deficient production of ADH. It is caused by genetic defect, such as dominant, recessive DIDMOAD syndrome (DI, diabetes mellitus, optic atrophy, deafness). Hypothalamic or high stalk lesion—histiocytosis X, sarcoidosis, craniopharyngioma, suprasellar pituitary adenoma, basal meningitis, head injury, surgery, encephalitis.

Fluid deprivation test—to distinguish between cranial DI and psychogenic DI ❍ Response to ADH—to distinguish between cranial and nephrogenic DI ❍ Plasma electrolytes, calcium ❍ Investigation of renal tract and suprasellar anatomy. Management ❍

Desmopressin 1–2 mg q day by injection or 10–20 mg b.i.d. intranasally or 100–400 mg b.i.d. orally ❍ Chlorpropamide 125–250 mg/day enhances the renal responsiveness to vasopressin ❍ Thiazide diuretis—only drug therapy for nephrogenic DI.

THYROID GLAND The thyroid produces two hormones, thyroxin (T4) and triiodothyronine (T3). Acting through nuclear receptors, these hormones play a critical role in maintaining thymogenic and metabolic homeostasis; help in cell differentiation influencing growth and development in children and mental development and attainment of sexual maturity. Thyroxin stimulates eruptive movement and tooth size, but has little effect on alveolar growth. After diabetes mellitus, thyroid disease is the most common endocrine problem in the general population and most commonly seen in women with higher rate after the age of 50 years.

Pathophysiology of Hypothalamic–Pituitary– Thyroid Axis It is a classic example of endocrine feedback loop.

Idiopathic causes Nephrogenic DI—renal tubules unresponsive to vasopressin. Causes for nephorgenic DI are: ❍ ❍ ❍

Genetic defect—Sex linked recessive, cystinosis Metabolic—Hypokalemia, hypercalcemia Drug—Lithium, demeclocyline, amphotericin B, aminoglycosides, cisplatin, rifampin, foscarnet ❍ Poisoning—Heavy metals 538

Hypothalamus

TRH +

Anterior pituitary

TSH +

Thyroid

(−) (−)

T4→T3

Thyroid hormone and cortisol provide negative feedback to the pituitary and hypothalamus. A small hypothalamic


peptide most specific to thyroid function thyrotropinreleasing hormone (TRH); TSH, a larger peptide from the pituitary, predominantly associated with thyroid function. Together, these peptides control three major functions of the thyroid: the production of thyroid hormone (T4), the growth and proliferation of thyroid cells, and the production of thyroglobulin (a large protein that acts as a binding, storage and maturation protein for T4). As a consequence of driving thyroid hormone production with TSH, circulating systemic blood levels of T4 are elevated. The increased blood levels of T4 result in decreased pituitary secretion of TSH, forming a negative feedback loop. The negative feedback mechanism causes decrease in the specific releasing and stimulating hormones of the hypothalamus and pituitary. Decreases in the pituitary production of the corresponding stimulating hormones, TSH and ACTH, result in the downregulation of the hormone produced by the specific endocrine gland, T4. Laboratory evaluation Categorized as: 1. 2.

Screening of newborns for congenital hypothyroidism Screening of adult patients seen for non-thyroid related reasons.

❍

Measures of T3, T4, and TSH-TSH immunoradiometric assays followed by measurement of unbound circulating thyroid hormone. TSH should not be used to assess thyroid function in patients suspected or known pituitary disease because secondary hypothalamic pituitary disease is associated with a variable (low-high) TSH level which is inappropriate for the low T4 levels. Radioiodine uptake and thyroid scanning: Thyroid gland selectively transports radioisotopes of iodine (123I, 125I, 131I) and 99mTc pertechnetate, allowing thyroid imaging and quantification of radioactive tracer fractional uptake. Tests to determine etiology of thyroid dysfunction— Autoimmune thyroid disease is detected by measuring circulating antibodies against thyroid peroxidase and thyroglobulin. Resin uptake test. Ultrasonographic scanning and ultrasonographyguided FNA biopsy of a thyroid nodule. CT and MRI scans. Serum or tissue thyroglobulin determination.

❍

❍

❍ ❍ ❍ ❍

Etiology Primary ❍ ❍ ❍ ❍

❍ ❍ ❍ ❍ ❍

Iodine deficiency Autoimmune hypothyroidism: Hashimoto’s thyroiditis, atrophic thyroiditis Iatrogenic: Treatment, subtotal or total thyroidectomy, external irradiation of neck for lymphoma or cancer Drugs: Iodine excess (including iodine—containing contrast media and amiodarone), lithium, antithyroid drugs, p-aminosalicylic acid, interferon- and other cytokines, aminoglutethimide Congenital hypothyroidism: Absent or ectopic thyroid gland, dyshormonogenesis, TSH-R mutation. Infiltrative disorders: Amyloidosis, sarcoidosis, hemochromatosis, scleroderma, cystinosis, Riedel’s thyroiditis Transient hypothyroidism Silent thyroiditis, including postpartum thyroiditis Subacute thyroiditis.

Secondary ❍

Hypopituitarism: Tumors, pituitary surgery or irradiation, infiltrative disorders, Sheehan’s syndrome, trauma, genetic forms or combined pituitary hormone deficiencies ❍ Isolated TSH deficiency or inactivity ❍ Hypothalamic disease: Tumors, trauma, infiltrative disorders, idiopathic. Hypothyroidism in children is termed cretinism and that manifesting in adults called myxedema. Congenital hypothyroidism—cretinism Congenital hypothyroidism if undetected early results in hypothyroidism in children termed cretinism. Congenital hypothyroidism is due to thyroid gland dysgenesis or inborn errors of thyroid hormone synthesis, TSHR antibody mediated. Females have a 2:1 prediliction. The infant appears normal at birth. The condition is diagnosed because of prolonged jaundice, feeding problems, hypotonia, macroglossia, delayed bone maturation, umbilical hernia, sparse and brittle hair and fingers, atrophic sweat glands. Diagnosis is established by heel prick blood estimation of T4. If treatment is delayed permanent neurologic damage occurs. T4 is instituted at a dose of 10–15 g/kg per day with close monitoring of TSH levels.

Disorders Associated with Thyroid Gland

Oral manifestations

Hypothyroidism

Shortened base of the skull leading to retraction of the bridge of the nose with flaring. The face looks wider as longitudinal growth fails. Accumulation of glycosaminoglycans leading to enlarged lips and enlarged tongue with continuous protrusion leading to malocclusion, delayed

Primary hypothyroidism is an intrinsic disorder of the thyroid gland causing low levels of thyroid hormone with raised TSH.

539


eruption, retained deciduous teeth but no impairment of tooth formation. Radiographic features ❍

Hyperthyroidism

In children delayed closure of epiphysis and skull sutures with the production of numerous wormian bones. ❍ Delayed eruption, short roots and thinning of lamina dura. ❍ Relatively small maxilla and mandible.

Hyperthyroidism is the result of excessive thyroid function whereas thyrotoxicosis is a state of thyroid hormone excess the etiology of which is hyperthyroidism.

General signs and symptoms in myxedema

Primary hyperthyroidism

Patient complains of tiredness, weakness, difficulty in concentrating and poor memory. Dryness of skin with hair loss and intolerance to cold. Weight gain with poor appetite, constipation, menorrhagia (later oligomenorrhea or amenorrhea), dyspnea, hoarse voice, paresthesias, impaired hearing are the symptoms. The signs include dry coarse skin; cool, peripheral extremities, puffy face, hands and feet (myxedema), diffuse alopecia, bradycardia, peripheral edema, delayed tendon reflex relaxation, carpal tunnel syndrome, serous cavity effusions, decrease in renal function.

1. 2. 3. 4. 5.

Oral health considerations ❍ ❍ ❍

Delayed eruption of permanent teeth. Myxedema—respiratory depression, CVS depression. Mild hypothyroidism—exaggerated effects of analgesics and sedatives in routine doses. ❍ Increased subcutaneous mucopolysaccharides—decrease the ability of small vessels to constrict—prolonged bleeding. ❍ Decreased metabolic activity in fibroblasts—delayed wound healing. ❍ Drug interactions with lithium, amiodarone, etc. may induce hypothyroid stages. Radiographic features Radiographic features of the teeth include evidence of periodontal disease, loss of teeth, separation of teeth and external root resorption. Treatment Daily replacement dose of levothyroxin 1.6 g/kg (100– 150 g). Thyroxin sodium 1.5 mg/kg, i.e. 100–150 mg/day. Ideal dose restores TSH to normal. Supportive therapy to correct metabolic disturbance. External warming if temperature falls below 30C which can result in cerebral vascular collapse. Correction of hyponatremia and hypoglycemia with hypertonic saline and IV glucose. Hypotonic infusions should be avoided which can lead to water retention. Parenteral hydrocortisone 50 mg

540

every 6 hourly in case of profound hypothyroidism to counter depleted adrenal reserve.

Causes of thyrotoxicosis

6. 7.

Graves’ disease Toxic multinodular goiter Toxic adenoma Functioning thyroid carcinoma metastases Activating mutation of the TSH receptor (autosomal dominant) Struma ovarii Drugs; iodine excess (Jod–Basedow phenomenon).

Thyrotoxicosis without hyperthyroidism 1. 2. 3. 4.

Subacute thyroiditis Silent thyroiditis Other causes of thyroid destruction; amiodarone, radiation, infarction of adenoma Ingestion of excess thyroid hormone (thyrotoxicosis factitia) or thyroid tissue.

Secondary hyperthyroidism 1. 2. 3. 4.

TSH—secreting pituitary adenoma Thyroid hormone resistance syndrome; occasional patients may have features of thyrotoxicosis Chorionic gonadotropin—secreting tumors Gestational thyrotoxicosis.

Clinical features Symptoms Hyperactivity, irritability, dysphoria, heat intolerance and sweating, palpitations, fatigue and weakness, weight loss with increased appetite, diarrhea, polyuria, oligomenorrhea, loss of libido. Signs Tachycardia, atrial fibrillation in the elderly, tremors, goiter, warm, moist skin, muscle weakness, proximal myopathy, lid retraction or lag and gynecomastia. Oral manifestations Alveolar atrophy is seen in advanced cases as a consequence of osteoporosis. Periodontitis and dental caries appear more rapidly. The jaws and teeth development is accelerated and earlier shedding of deciduous teeth and accelerated eruption of permanent teeth is seen. Euthyroid infants of hyperthyroid infants may have natal teeth. Lingual thyroid is sometimes seen. A lingual thyroid if seen


in a euthyroid patient should not be excised unless the presence of the thyroid gland is confirmed with radioactive iodine scanning. Pain associated with subacute thyroiditis radiates to the ear, jaw and occipital region. Horseness of voice and dysphagia are other features.

Graves’ Disease Hyperthyroidism with diffuse thyroid enlargement, ophthalmopathy and dermatopathy. An autoimmune disorder characterized by abnormal stimulation of the thyroid gland by thyroid-stimulating antibodies (thyroid-stimulating immunoglobulins [TSI]) that act through the normal TSH receptors. This is associated with human leukocyte antigen (HLA)-DR3 and HLA-B8. Familial tendency is evident due to immunologically mediated activation of fibroblasts in extraocular muscles and skin with accumulation of lid lag or retraction, proptosis, exophthlamos, diplopia, corneal involvement, periorbital edema, chemosis, optic nerve damage. Dermatopathy in the form of pretibial myxedema, skin appearance appears like orange and clubbing may be seen. Radiographic features In children early development and eruption of teeth with premature loss of primary teeth is seen. In adults generalized decrease in bone density or loss of some areas of edentulous alveolar bone is seen. Investigations ❍ ❍ ❍ ❍

Increased T3 Increased or upper limit normal range—T4 Decreased TSH Non-specific or increased serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase. ❍ Routine thyroid 99mTc radionuclide imaging is helpful in identifying patients with an unsuspected cause of hyperthyroidism other than Graves’ disease. The treatment of Graves’ disease is aimed at 1.

2.

Reducing thyroid hormone synthesis using antithyroid drugs like thionamides—propyl thiouracil 100–200 mg 6–8 hourly, carbimazole and methamizole 10–20 mg 8–12 hourly. Reducing the amount of thyroid tissue with 131I radioiodine or subtotal thyroidectomy.

Thyrotoxic Crisis/Thyroid Storm Thyrotoxic crisis is a medical emergency because of exacerbation of hyperthyroidism precipitated by infection, stroke, trauma, diabetic ketoacidosis or thyroid surgery.

Clinical features Patients present with very high fever, extreme cardiovascular effects (tachycardia, congestive failure and angina) and severe CNS effects (agitation, restlessness and delirium). Management ❍

Propylthiouracil 600 mg initially and 200–300 mg/ 6 hour. Propranolol to reduce tachycardia. ❍ Glucocorticoids and antibiotics if infection present. Orodental treatment evaluation of a patient with thyroid disorder Any patient who is asymptomatic and has had a physical examination and normal thyroid function test within the past 6 months is at low risk for complications during dental therapy. If otherwise the patient is considered as at moderate risk because an asymptomatic hypothyroid patient under thyroid replacement therapy may become hypothyroid again because of lapses in medication or subtle metabolic shifts. Similarly, a hyperthyroid patient on propyl thiouracil or radioactive iodine remain euthyroid only in about 30% of cases or as a complication of radioactive iodine therapy insidiously may become hypothyroid. A hypothyroid patient has pre-existing CNS depression and is acutely sensitive to drugs with CNS depressing side effects. Narcotic analgesics and sedatives can precipitate respiratory and cardiovascular depression. Patients with hyperthyroidism are particularly susceptible to catecholamines (epinephrine as vasoconstrictors) used in local anesthetics and gingival retraction cords. Along with dental stress it can precipitate thyroid storm. Short of thyroid storm it can exacerbate underlying cardiovascular pathology. If no evaluation has been done in the past 6 months the patients have to be referred to the physician and for laboratory evaluation especially when type V and VI procedures are indicated. Patients with hyperthyroidism may have elevated blood pressure and heart rates on the basis of the effects of thyroid hormone on sympathetic nervous system activity. Patients with high arteriolar pressures may require increased attention and a longer duration of local pressure to stop bleeding. Hyperthyroidism patients who are on warfarin (Coumarin) may have an increased metabolism of this drug, leading to decrease in previously therapeutic coagulation indices. Patients with long-standing hypothyroidism may have increased subcutaneous mucopolysaccharides due to decrease in the degradation of these substances. The presence of excess subcutaneous mucopolysaccharides may decrease the ability of small vessels to constrict when cut and may result in increased bleeding from the infiltrated tissues, including mucosa and skin. Local pressure for an extended time will probably adequately control the small-vessel bleeding. 541


PARATHYROID GLANDS Parathormone (PTH) is an 84 amino acid single chain peptide and is the primary regulator of extracellular calcium concentration. It acts directly on bone inducing calcium resorption and on the kidney where it stimulates calcium reabsorption and synthesis of 1,25-dihydroxy vitamin D (1,25(OH)2D) a hormone that stimulates GI calcium reabsorption. Continuous exposure to elevated PTH leads to increased osteoclastic mediated bone resorption. However intermittent administration of PTH, elevating levels for 1–2 hour/ day leads to net stimulation of bone formation rather than breakdown. Thus the effects of PTH are: (i) calcium removal from bone, and (ii) bone remodeling by acting on both osteoblasts and osteoclasts.

Hyperparathyroidism Hyperparathyroidism (HPT) causing bone disease was first described by von Recklinghausen in 1891 and so-called as von Recklinghausen disease of bone. It is a generalized disorder of calcium, phosphate and bone metabolism due to increase in PTH secretion. Hyperparathyroidism occurs in three clinical forms: ❍

Primary HPT is the uncontrolled production of PTH as a result of a parathyroid adenoma (80–90%) or chief cell parathyroid hyperplasia (10–15%) or a parathyroid carcinoma (2%), (multiple endocrine neoplasia I and MEN 2a). Two syndromes are associated with HPT, namely, hereditary hyperthyroid jaw tumor syndrome and familial isolated primary hyperthyroidism with carcinoma. ❍ Secondary HPT is a compensatory mechanism resulting from a primary condition producing hypocalcemia such as rickets, osteomalacia, pregnancy, chronic renal insufficiency, calcium deprivation or maternal hypoparathyroidism. Hypocalcemia prompts increased PTH production with liberation of calcium from bone. Renal osteodystrophy occurs in chronic renal diseases. In the kidney, the hydroxylation of 25-OH vitamin D3 occurs which is necessary for calcium absorption from the gut. Therefore in patient with end stage renal disease active vitamin D is less—less calcium is absorbed from gut—hypocalcemia compensatory PTH production. ❍ Tertiary HPT may occur after long-standing secondary hyperparathyroidism, characterized by the development of a functional parathyroidism adenoma causing increased production of PTH. The most common cause is chronic renal failure. 542

Clinical features It was described by Jackson and Frame (1972) as the tetrad of ‘bones, stones, abdominal groans and psychic moans with fatigue overtones’. Mostly occur after 60 years of age and women are affected 2–4 times more often than men. About 80% of the cases are asymptomatic and the primary involvement is in the kidneys and skeletal system. Stones refer to the increased deposition of calcium in renal parenchyma and a tendency to develop recurrent nephrolithiasis (renal calculi) with resulting complications like urinary tract obstruction, infection, loss of renal function and uremia. Metastatic calcifications are also seen in blood vessel walls, subcutaneous soft tissues, dura and the region around the joints. Band keratopathy, where calcification occurs as a narrow band at the limbic margin of the cornea of the eye is also seen. Bones refer to the distinctive involvement of the bone. Ostetitis fibrosa cystica, bone lesions which on histopathological examination show multinucleated giant osteoclasts in scalloped areas of the bone surface (Howship’s lacunae) and replacement of normal cellular and marrow elements with fibrous tissue. Abdominal groans refer to subtle vague GI disturbances such as nausea, vomiting, anorexia, pancreatitis, duodenal and peptic ulcers. Psychic moans may be due to CNS manifestation ranging from mild personality problems to severe psychiatric disorders due to hypercalcemia. Other manifestations include neuromuscular problems with proximal muscle weakness, easy fatigability and muscle atrophy (differentiated from other neuromuscular disorders by regression after surgical removal of the glands). Orodental manifestations One of the first signs is development of malocclusion because of drifting of teeth. Giant cell tumors and pseudocysts of the jaws are the other possible lesions found. Padbury et al demonstrated a significantly greater incidence of torus/tori in the Caucasian population with the incidence of tori nearly three times higher in HPT patients. HPT leads to a preferential loss of cortical bone and preservation or increase in trabecular bone. It has been proposed that the presence of hypercalcemia in HPT patients is preceded by longer periods of elevated PTH levels. It could be that the tori represent an expansion of trabecular bone at the expense of cortical bone in response to elevated PTH levels with possible contribution from the mechanical forces present in the oral cavity. Furthermore, PTH mediated endosteal resorption has been shown to be compensated by PTH-mediated periosteal apposition with an increase in overall bone size. Periodontal ligament (PDL) width in patients with a torus was higher than those without a torus, and this intriguing


relationship remained when issues of gender and age were taken into account. This is consistent with the HPT patient population having reduced radicular lamina dura density and may reflect the localized impact of PTH in the PDL space to evoke cortical bone loss in the area adjacent to the tooth, whereas compensatory mechanisms are taking place for increased bone growth in the form of the tori more laterally. Radiographic features The classic generalized features: Most important and reliable sign of HPT is subperiosteal erosion along the radial margin of the middle phalanges. Initially, only the outer surface of the cortex appears lace like but then the endosteal surface is also affected. Generalized demineralization shows an unusual radiolucency. Osteitis fibrosa generalisata It is also called as osteitis fibrosa cystica as they appeared cyst-like on radiographs. It refers to the pattern of generalized rarefaction seen in the skeleton in approximately 13% of patients with hyperparathyroidism. It appears as radiolucent area with thin cortices and hazy indistinct trabeculae or a moth eaten image. In regions where the trabeculae are completely missing a cyst-like appearance is seen. Histopathologically a sparse narrow trabeculae scattered throughout a fibrous stroma with few osteoclasts are seen. Brown tumors Peripheral or central tumors of bone are seen in the late phase of the disease in 10% of the cases. Metastatic calcification of soft tissues appearing punctuate or nodular and occur in kidneys and joints. Radiographic features of skull Skull appears osteoporotic and this change may occur before jaw changes. Deossification appears granular caused by loss of diploie and thinning of cortical plates and is prominent in the outer third of the skull termed pepper-pot skull which may be interrupted by one or more cystic areas representing brown tumors. Radiographically, they appear rounded with smooth or irregular borders and with sclerotic reactive bone margins. Radiographic features of jaw bones Generalized demineralization characterized by lack of sharpness of trabecular pattern with a more granular appearance described as ground glass appearance or osteoporosis fibrosa generalisata sometimes may have a mottled or moth-eaten appearance due to variation in density. Subperiosteal erosion at the mandibular angle, resorption of the inferior cortex of the mandible, lining of mandibular canal, mental foramen, walls of antrum and nasal cavities. Resorption of the lamina dura is the first sign of deossification in the jaws. Two relative changes are observed, namely, thickening of PDL space and tapered appearance of roots because the lamina dura provides a definitive edge effect accentuating the

density of the root and is rounded at apex. Some authors feel that the loss of lamina dura occurs only in about 10% case and is the overrated feature of HPT. Metastatic calcification may occur in salivary gland. Brown tumors These occur in pelvis, ribs and femurs but most common in the jaw bones. These are either peripheral or central, monostotic or polyostotic. These may be unilocular or multilocular without marginal scalloping. The borders may be poorly defined and there may be a zone of reactive bone outlining the lesion. Histologically, it is identical to central giant cell granuloma of the jaws. If a giant cell granuloma is found later than the second decade the patient should be screened for serum calcium, PTH and alkaline phosphatase. Teeth The teeth stand out because of the osteopenic nature of the bone. In developing or erupting tooth: (i) loss of crypt wall, (ii) pointed and tapered roots especially at apical third, and (iii) large pulp chambers are seen. In erupted teeth, the pulp chambers appear large in younger people but in adults they are narrower. Pulpal calcifications are seen in pulp chambers. Histopathologic features Brown tumors are characterized by a proliferation of exceedingly vascular granulation tissue with accumulation of hemosiderin pigments giving the lesion a brown appearance. Numerous multinucleated osteoclast type giant cells are seen and some lesions are proliferative showing parallel arrangement of spicules of woven bone set in a cellular fibroblastic background with multinucleated giant cells often associated with secondary HPT related to chronic renal disease. Investigations ❍ ❍

Immunoassay for parathormone. Multiple markers of bone tumors such as formation indices (bone specific alkaline phosphatase, osteocalcin and type I collagen peptides) and bone resorption indices (including hydroxypyridinium collagen crosslinks and telopeptides of type I collagen). ❍ CT and dual energy X-ray absorptiometry (DEXA) of spine produce reproducible quantitative estimates of bone density. Non-invasive imaging like ultrasonography, CT scanning, MRI and parathyroid (PT) scintigraphy may be used. Management Primary HTP: In symptomatic patients removal of hyperplastic/functional tumor is done after PTH assay. 99m Tc-sestamibi/99mTc-pertechnetate subtraction scintigraphy (SS) as initial test for patients undergoing parathyroidectomy and helical CT anatomical detail, such as 543


the relationship with surrounding tissues and detection of concomitant thyroid nodules, guiding the surgical exploration especially in patients with ectopic PT glands. In asymptomatic patients who do not undergo surgery the management is as suggested by Bilezikian et al. Assessment ❍ ❍ ❍ ❍ ❍ ❍

Serum calcium—annually 24-Hour urinary calcium only during initial evaluation Creatinine clearance only during initial evaluation Serum creatinine annually Bone density—annually Abdominal radiographs with or without ultrasonograph at the time of initial evaluation ❍ Secondary HTP ❍ Restriction of dietary phosphate, administration of bisphosphonates and vitamin D metabolite (calcitrol) and renal transplantation.

Hypoparathyroidism Hypoparathyroidism could be hereditary or acquired. Decreased amount of PTH leads to hypocalcemia and hyperphosphatemia.

Hereditary Hypoparathyroidism associated with conditions like DiGeorge syndrome—defective development of thymus and parathyroid glands; and polyglandular syndromes.

Acquired Postoperative hypoparathyroidism Damage to parathyroid gland or inadvertent removal during thyroid surgery. Infantile hypoparathyroidism Transient, associated with maternal hyperparathyroidism or calcium deficiency. Idiopathic hypoparathyroidism Autoimmune disease of adrenal, thyroid or ovary in young people.

❍

Substitution therapy—1 hydroxycholecalciferol or vitamin D 40,000–120,000 g/day (1–3 mg daily) with 1 g elemental calcium.

Oral health considerations It occurs during odontogenesis; pitting enamel hypoplasia and failure of tooth eruption may occur. Presence of persistent oral candidiasis in a young patient may signal the onset of endocrine—candidiasis syndrome.

Tetany Tetany is defined as an increased excitability of peripheral nerves due to hypocalcemia or alkalosis. Causes ❍

Hypocalcemia: Malabsorption, osteomalacia, hypoparathyroidism, acute pancreatitis. ❍ Alkalosis: Repeated vomiting of gastric juice, excess intake of alkalis, hyperventilation, primary hyperaldosteronism. Clinical features Children present with carpopedal spasm, stridor and convulsions. Main d’ accoucheur sign is seen (metacarpophalangeal joints flexed, interphalangeal joints of fingers and thumb extended with opposition of the thumb). Adults present with tingling in hands, feet and around the mouth. Latent tetany is characterized by Trousseau’s sign. When the sphygmomanometer cuff is inflated on upper arm more than systolic BP carpal spasm occurs within 3 minutes. Chvostek sign is seen which is characterized by twitching of upper lip when the facial nerve is tapped below the zygomatic process. Management Tetany is managed with 20 ml of 10% calcium gluconate IV or 10 ml IM. Alkalosis is treated with IV isotonic saline.

Clinical features Calcifications of basal ganglia and extrapyramidal syndromes like choreoathetotic movement and dystonia are more common and appear earlier. Tetany as consequence of hypocalcemia, grand mal epilepsy, psychosis, cataracts, papilledema, increased intracranial pressure and chronic changes in finger nails, hair, alopecia and hypomagnesemia are seen. May be associated with autoimmune polyglandular—candidiasis syndrome. Management ❍

544

Usually asymptomatic—no treatment.

HYPOTHALAMUS–PITUITARY–ADRENAL AXIS The main function of hypothalamus–pituitary–adrenal (HPA) axis is to maintain metabolic homeostasis and to mediate the neuroendocrine stress response. An understanding of the axis is important especially for management of conditions which need long-term corticosteroid therapy and management of patients on long-term corticosteroid therapy and adrenal insufficiency.


Hormone

Released from

Type

Actions

Corticotropin releasing hormone (CRH)

Hypothalamus

Peptide

Controls function of adrenal cortex

Adrenocorticptropic hormone (ACTH)

Anterior pituitary

Pro-opiomelanocortin (POMC)

Controls function of adrenal cortex, controls medullary rennin and aldosterone mineralocorticoid action in controlling blood volume and pressure

Melanocyte stimulating hormone (MSH)

Anterior pituitary


B-endorphins

Anterior pituitary


Mineralocorticoids (aldosterone)

Function in sodium, potassium and water balance

Glucocorticoids (cortisol)

Aid in regulating the metabolic functions of the body and in controlling the inflammation. Essential for survival in stress situations

Adrenal sex hormones (androgens)

Serve mainly as a source of androgens for women

Pathophysiology of adrenal diseases and conditions Acute inflammatory or septic insults activate HPA axis through the integrated actions of proinflammatory cytokines, bacterial toxins and neural signals resulting in cortisol elevation, restraining inflammatory response and providing host protection. Thus, the neuroendocrine stress response reflects the net result of highly integrated hypothalamic, intrapituitary and peripheral hormone and cytokine signals. Disorders affecting the adrenal glands resulting excess or insufficient production of adrenal products. Excess production due to pathophysiologic processes as due to ACTH secreting pituitary tumors (70% of cases) is called Cushing’s disease. Iatrogenic glucocorticoids, adrenal tumors or ectopic secretion of ACTH (malignant tumor of pulmonary origin) and rarely CRH producing ectopic tumor Cushing’s syndrome. Insufficient adrenocortical function may occur primarily due to destruction of adrenal cortex called Addisons’s disease or secondarily due to hypothalamic-pituitary disease or administration of exogenous steroids. In clinical dentistry, cortisol deficiency or excess is overwhelmingly an iatrogenic disease, caused either by treatment of the patient with glucocorticoids—Cushing’s syndrome or by patient withdrawal from previous treatment—adrenal insufficiency. Laboratory evaluation of adrenocortical function Urine levels: A 24-hour urine free cortisol measurement is a reliable screening test. It is higher in the day time (7 AM– 7 PM) than at night (7 PM–7 AM)/urinary creatinine should also be measured to determine the accuracy and adequacy of collection procedure. Stimulation tests: These are useful in hormone deficiency states. ACTH stimulation test is done to determine the functional reserve of adrenal gland for production of cortisol.

Tests for mineralocorticoid reserve and stimulation of renin–angiotensin system is by programed volume depletion such as sodium restriction, diuretic administration or upright posture. Suppression tests are done to document hypersecretion of adrenal hormones by measuring the target hormone response after standardized suppression of its tropic hormone. Examples are the pituitary-adrenal suppressibility and an overnight dexamethasone suppression test as screening test.

Cushing’s Syndrome The diagnosis of the condition presents two great challenges: 1. 2.

To distinguish between pathologic and physiologic/ other cortisol production To determine etiology of cortisol excess.

The condition is commonly seen in the age group of 20–50 years with a 5:1 female predilection. Central obesity, plethoric moon facies, cutaneous atrophy, purple striae with easy bruising, proximal muscle wasting, osteoporosis, hypertension, diabetes mellitus, immunosuppression (including delayed hypersensitivity reaction), psychiatric problems, gonadal dysfunction and hypergonadism. Characteristic central distribution of fat, thin skin with striae and bruising and proximal muscle weakness; osteoporosis in children and young females suggest pathologic causes rather than physiologic causes for excess cortisol production. Actions of cortisol ❍ ❍ ❍

Glucose metabolism Protein metabolism Fat metabolism

545


❍ ❍ ❍

Anti-inflammatory action Psychic effect Permissive effect.

Rapid onset with skin hyperpigmentation with severe myopathy suggests ectopic causes of ACTH secretion. The primary cause of death is cardiovascular disease followed by infections and suicides. Endocrinopathic pigmentation Bronzing of the skin and patchy melanosis of the oral mucosa are signs of Addison’s disease and pituitary-based Cushing’s syndrome. The cause of hyperpigmentation is oversecretion of ACTH, which has melanocyte-stimulating properties. In Addison’s disease, adrenocortical insufficiency evolves as a consequence of granulomatous infection of the cortex or autoimmune cortical destruction. As steroid hormones decrease, the feedback loop is stimulated with excess secretion of ACTH by the neurohypophysis. With a decrease in mineralocorticoids and glucocorticoids, the patient develops hypotension and hypoglycemia, respectively. In Cushing’s syndrome, adrenocortical hyperactivity is observed, and if such activity is caused by a cortical secretory adenoma or cortical hyperplasia of adrenal origin, ACTH secretion will be shut down. Alternatively, if the hypercorticism is the consequence of a pituitary ACTHsecreting tumor that secondarily induces an adrenal hypersecretion, then melanocyte-stimulating effects may evolve. Patients with Cushing’s syndrome may be hypertensive and hyperglycemic and may show facial edema (‘moon face’). In both cases, the skin may appear tanned, and the gingiva, palate, and buccal mucosa may be blotchy. These changes in pigmentation are due to an accumulation of melanin granules as a consequence of increased hormonedependent melanogenesis. Endocrinopathic disease should be suspected whenever oral melanotic pigmentation is accompanied by cutaneous bronzing. Serum steroid and ACTH determinations aid the diagnosis, and the pigment will disappear once appropriate therapy for the endocrine problem is initiated. Dental considerations Patients who are on chronic glucocorticoid therapy have decrease in subcutaneous collagen and the production of other extracellular proteins by fibroblasts, which may explain the tendency of patients with Cushing’s syndrome to bleed and to bruise easily. There may also be related defects in the walls of small blood vessels, resulting in defective constriction of these vessels during bleeding. Wound healing is also impaired, and scar formation is less timely and less vigorous than in a normal subject. Patients who are on chronic glucocorticoid therapy are considered to be immunocompromised and more than normally susceptible to infection. Antibiotic prophylaxis is decided on the basis of the underlying disease, however, 546

and not on the basis of glucocorticoid therapy. Patients with Cushing’s syndrome are also more likely to have Candida and fungal infections, possibly due to abnormal flora on the skin and mucosa. Diagnosis The diagnosis of Cushing’s syndrome is based on laboratory documentation of endogenous hypercortisolism. Hematopoietic features are leukocytosis, lymphopenia and eosinopenia. Radiographic features Primary radiographic feature is generalized osteoporosis which shows a granular pattern. This demineralization leads to pathologic fractures. The skull shows diffuse thinning with mottled appearance. The teeth may erupt prematurely and partial loss of lamina dura may be seen.

Adrenal Insufficiency Primary Adrenal Cortical Insufficiency (Addison’s Disease) Primary adrenal cortical insufficiency is caused by a progressive destruction of adrenal cortex. The etiology is idiopathic or may result from hemorrhage, sepsis, infectious diseases, malignancies, adrenalectomy or drugs leading to deficiency of the major hormones cortisol and aldosterone. The original description of Addison’s disease—general languor and debility, feebleness of heart’s action, irritability of the stomach, and a peculiar change of the color of the skin. Another specific symptom of primary adrenocortical insufficiency is a craving for salt. Although hyponatremia occurs in both primary and secondary adrenal insufficiency, its pathophysiology in the two disorders differs. In the primary condition, adrenocortical insufficiency is mainly due to aldosterone deficiency and sodium wasting, whereas in the secondary form, adrenal insufficiency is due to cortisol deficiency, increased vasopressin secretion and water retention. Signs and symptoms of adrenal insufficiency ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍

Anorexia and weight loss Fatigue and weakness Gastrointestinal symptoms, nausea, diarrhea Myalgia, arthralgia, abdominal pain Orthostatic hypotension Hyponatremia Hyperkalemia Hyperpigmentation Secondary deficiency of select hormones Associated autoimmune conditions.


Secondary Adrenal Cortical Insufficiency This is a more common condition which occurs as a result of hypothalamic/pituitary disease, surgical removal of pituitary gland or administration of exogenous steroids. Withdrawal of glucocorticoids after therapy increases the release of CRH from hypothalamic peptidergic neurons. The pituitary is stimulated to increase ACTH secretion into the blood. After glucocorticoid therapy, however, the adrenal glands may be atrophied and incapable of responding appropriately to increased ACTH. The inappropriate response to the adrenal glands as a consequence of the negative feedback mechanism and suppression of endogenous cortisol production through suppression of ACTH, POMC and CRH resulting in adrenal insufficiency. The production of aldosterone which is independent of ACTH is not appreciably affected.

Acute Adrenal Insufficiency Acute adrenal insufficiency could be a result of fulminating septicemia caused by Pseudomonas and meningococci leading to bilateral adrenal hemorrhage in children called Waterhouse–Friderichsen syndrome. In adults, it could be use of anticoagulants or a coagulation disorder or a chronic insufficiency precipitating to acute stage because of stress or profound infection. Diagnosis of adrenal insufficiency In patients in whom adrenal insufficiency is merely to be ruled out, cortisol can be measured between 0800 and 0900 hours. Hormonal pattern of morning plasma cortisol concentrations of less than 3 g/dl (83 nmol/l) are indicative of clinical adrenal insufficiency whereas concentrations of more than 19 g/dl (525 nmol/l) rule out the disorder. Measurement of plasma corticotropin can be used to differentiate between primary and secondary adrenal insufficiency. In patients with primary adrenal insufficiency, plasma corticotropin concentrations invariably exceed 100 pg/ml (22 pmol/l), even if the plasma cortisol levels are in the normal range. Normal plasma corticotropin values rule out primary, but not mild secondary, adrenal insufficiency. In primary adrenocortical insufficiency, basal plasma aldosterone concentrations are low or at the lower end of normal values, whereas the PRA or concentration is increased because of sodium wasting. Medical management Primary adrenal insufficiency The primary medical needs of addisonian patient are: 1. 2.

Management of adrenal disease—elimination of infectious disease or malignancy Hormonal replacement therapy.

Glucocorticoid replacement equivalent to the normal physiologic output of the adrenals, i.e. in the range of 12.5 to 50 mg. Cortisol 25–30 mg or prednisone 7.5 mg per day would be adequate. In case of emergency inject contents of prefilled dexamethasone (4-mg) syringe should be injected intramuscularly and physicians help sought as quickly as possible. Mineralocorticoid replacement in the form of 0.05–1 mg of fludrocortisone and adequate sodium intake can help addisonian patients lead a normal life. Monitoring lying and standing blood pressure and pulse, edema, serum potassium and plasma renin activity is essential. Secondary adrenal insufficiency During stress in normal individuals, plasma cortisol levels may double, suggesting an inherent ability of the adrenal glands to increase cortisol production by 100%. In the patient with adrenal insufficiency, adrenal function is inadequate to produce adequate cortisol in the face of stress. Secondary adrenal insufficiency due to hypothalamic/ pituitary disease may be managed as an ACTH dependent disorder and replaced with the missing glucocorticoid. The clinical manifestation of adrenal insufficiency usually occurs when a patient on gluococorticoids is being withdrawn from glucocorticoid therapy or when a patient with a previous history of glucocorticoid therapy is challenged by a stressful event. Subnormal cortisol production during acute severe illness has been termed functional or relative adrenal insufficiency. Many patients with chronic inflammatory and autoimmune diseases such as oral lichen planus, pemphigus group of diseases, pulmonary fibrosis, rheumatoid arthritis and severe asthma are on an alternate-day dosage regimen for glucocorticoids. Alternate-day therapy (ADT) is usually reserved for stable chronic disease and permits the reactivation of adrenal and pituitary function on the days during which no oral glucocorticoid is given. For patients on long-acting glucocorticoids, especially the most potent agents, no stimulation of adrenal and pituitary function may occur on the off therapy day because of a long drug half-life. Pituitary ACTH production takes place mainly at night. If circulating glucocorticoid levels are still elevated in the evening hours, the ACTH produced will be insufficient to stimulate the adrenal glands, even during ‘off’ days. This is a particular problem with multiple daily dosing with glucocorticoids such as dexamethasone, which are most potent and which have long half-lives. Alternate-day therapy is a strategy for limiting adrenal insufficiency and cushingoid effect. It is best managed by using a high morning dose (7–8 AM) of prednisone or another short-acting glucocorticoid. Initially, the total dose for the 2 days should be additive; if 20 mg is given every day, then 40 mg will be required on the ‘on’ day. Physicians usually initiate ADT by gradually increasing 547


the ‘on’ day dosage while tapering the ‘off’ day dosage, thus maintaining the total dose as a constant. In patients with recognized adrenal insufficiency, alternate-day dosage can be life-threatening if significant stress occurs on the ‘off’ day. If the patient cannot respond to stress and does not increase the oral glucocorticoid dosage, then severe hypotension, nausea and shock may result. The problem of an adequate response to stress is even more significant in children with severe asthma; in who inhaled glucocorticoid therapy has been shown to cause acute adrenal insufficiency. Hence, three things have to be considered during an ADT: 1. 2.

3.

ADT may be approached through transition schedule that allow the patient to adjust gradually. Supplementary non-steroid medications may be needed on the off day to minimize symptoms of the underlying disease. Symptoms occurring on the off day represent relative adrenal insufficiency rather than exacerbation of underlying disease.

Known severe adrenal insufficiency usually requires the premedication of the patient with 100 mg of hydrocortisone acetate intramuscularly 30 minutes before an invasive procedure. Subclinical adrenal insufficiency may be suspected after as little as 5 days of high-dose glucocorticoid therapy ( 60 mg of prednisone). Salem et al (1994) have recommended the following: 1.

2.

3.

548

Minor surgical stress: 25 mg of hydrocortisone equivalent (refer to Table 5) on the day of surgery. For instance, a patient on 5 mg of prednisone every day may be given 5 mg of prednisone or 25 mg of hydrocortisone or equivalent preoperatively. Moderate surgical stress: 50–75 mg of hydrocotisone equivalent may have to be given for 2 days. For instance, a patient on 10 mg of prednisone daily should be given 10 mg of prednisone (or parenteral equivalent) preoperatively and 50 mg of intravenous hydrocortisone intraoperatively. On the first postoperative day 20 mg intravenous hydrocortisone can be given 8 hourly (60 mg/day). On the second postoperative day, the dosage is then tapered to the preoperative maintenance level. Major surgical stress: 100–150 mg/day of hydrocortisone equivalent may be required for 2–3 days. For instance, a patient on long-term 40 mg of prednisone/ day should receive 40 mg of prednisone (or parenteral equivalent) preoperatively and 50 mg of hydrocortisone intravenously thereafter every 8 hourly for 48–72 hours. But a patient on long-term 5 mg of prednisone/day should receive 25 mg of prednisone (or parenteral equivalent) preoperatively and 25 mg of hydrocortisone

intravenously thereafter every 8 hourly for 48–72 hours. The dosage is then tapered to the preoperative maintenance level. The steroids given are within 2 hours of surgery and readiness to face any post-surgical complications exacerbating adrenal insufficiency, liver dysfunction, sepsis and drugs is warranted. Certain drugs like etomidate (anesthetic), aminoglutethimide (adrenolytic), ketaconazole lower plasma cortisol levels. Inducers of hepatic cytochrome P45 oxygenases like barbiturates, rifampicin and phenytoin accelerate cortisol degradation. Oral anticoagulants can be potentiated by IV high doses of methylprednisolone. Stressful conditions that can precipitate adrenal crisis ❍ ❍ ❍ ❍

Invasive surgical procedure The onset of infection An exacerbation of an underlying disease Serious life event such as the death of a family member.

Orodental treatment evaluation of patient with adrenal dysfunction Before the dental procedure the kind and degree of adrenal dysfunction is to be determined in consultation with the patient’s physician. The risk of blood pressure variation, osteoporosis and peptic ulcers in longterm steroid users should be considered. The BP should be taken at baseline and monitored at every appointment. Fractures are a risk in osteoporotic patients and periodontal bone loss is common. Excessive neck manipulation should be avoided in such patients. Long-term use of NSAIDs to be considered in patients on steroids considering the risk of developing peptic ulcers. Use of appropriate sedation techniques minimizes stress. Antibiotic prophylaxis A short course of antibiotic therapy is useful to prevent infections and delayed wound healing due to immunosuppressive effects of steroids when excessive manipulations of tissues are anticipated. Patients on daily steroid therapy for non-adrenal diseases Patients under these circumstances are usually on a maintenance dose of 5–60 mg of prednisone or equivalent. Oral examination does not require additional steroid supplements. Non-surgical Type II and some Type III and minor surgical procedures Type IV may induce mild to moderate stress for which doubling the maintenance dose to a maximum of 60 mg prednisone or equivalent on the day of procedure tapered back to maintenance dose in 2 days would be adequate. Invasive surgeries Type V and Type VI would require 60 mg of prednisone on the day of surgery, equivalent dose of parenteral hydrocortisone intraoperatively and 50% of the dosage the day after, tapered to maintenance dose over next 2–3 days. Patients on alternate day steroid therapy for nonadrenal diseases Patients under these circumstances have


Table 6

Protocol for supplementation of patients on glucocorticoid therapy who are undergoing dental care Protocol

Dental procedure

Previous systemic steroid use

Current systemic steroid use

Daily alternating systemic steroid use

Current topical steroid use

Routine procedures

If prior usage lasted for 2 weeks and ceased 14–30 days ago, give previous maintenance dose

No supplementation needed

Treat on steroid dosage day; no further supplementation needed


If prior usage lasted 2 weeks and ceased 14–30 days ago, give previous maintenance dose

Double daily dose on day of procedure

Treat on steroid dosage day, and give double daily dose on day of procedure


If prior usage ceased 14–30 days ago, no supplementation needed

Double daily dose on first post-operative day when pain is anticipated

Give normal daily dose on first postoperative day when pain is anticipated

If prior usage ceased 14–30 days ago, no supplementation needed Extractions, surgery, or extensive procedures

comparatively less adrenal suppression than on patients on daily dosage. Operative procedures should be scheduled on the ‘on’ day. No alterations are required for non-surgical Type II and some Type III and minor surgical procedures Type IV. For Type V and Type VI procedures doubling the dose to a maximum of 60 mg prednisone and a single dose the day after may be required followed by resumption of normal schedule. If general anesthesia is indicated an ACTH stimulation test to determine the response of adrenals to exogenously administered steroids (Table 6). Mineralocorticoids The main mineral corticoid is aldosterone; cortisol has primarily a glucocorticoid effect and partially mineralocorticoid effect. Function of aldosterone is to increase renal tubular reabsorption of sodium and secretion of potassium thus regulating the K concentration in ECF, renin–angiotensin system, Na concentration and ACTH.

Aldosteronism It is the hypersecretion of the mineralocorticoid aldosterone.

Primary Aldosteronism (Conn’s Syndrome) Etiology resides within the adrenal gland. It is twice common in women aged 30–50 years. Clinical features include diastolic hypertension, headaches, muscle weakness and fatigue. Other findings include polyuria, polydipsia and absence of edema. Lab findings Hypokalemia less than 2 mEq/l, hypernatremia, metabolic alkalosis and the assessment of ratio of serum aldosterone to plasma renin activity.

Treatment Aldosterone antagonists—spironolactone—25 to 100 mg TDS. Secondary aldosteronism Increased production of aldosterone in response to activation of the renin–angiotensin system. It occurs in association with the accelerated phase of hypertension or on the basis of underlying edema disorder due to overproduction of renin. It may present in many forms of edema—cirrhosis, nephrotic syndrome or cardiac failure and is characterized by hypokalemic alkalosis, moderate to severe increase in plasma renin activity and moderate to marked increase in aldosterone.

Disorders of Adrenal Medulla Pheochromocytoma Tumors of chromaffin tissue that secretes catecholamines, 90% of which are derived from adrenal medulla and rest in sympathetic ganglia. The familial tendency is seen along with MEN type IIA (pheochromocytoma medullary Ca of thyroid hyperparathyroidism) MEN type II B (multiple mucosal neuroma syndrome, von Hippel–Lindau syndrome and neurofibromatosis I. Clinical features Hypertension is the most common sign and hypertensive paroxysms or crises are alarming. It occurs in young to mid adult life. Pallor, palpitations, sweating, headache, anxiety, abdominal and chest pain, vomiting, constipation, weight loss, glucose intolerance are seen. 549


Most important aspect is the precipitation of hypertensive crisis during surgery or trauma or any activity that displaces abdominal contents. Orthostatic hypertension and shock are expected. Any drug is not given unless a thorough review is done. Adverse reactions are seen with opioid, histamines, adrenocorticotropin and glucagons that directly release catecholamine from the tumor; drugs like tricyclic antidepressants that block neuronal uptake of catecholamines, and indirectly acting sympathomimetic drugs like methyl dopa.

Sex Hormones Androgens and estrogens are the essential hormones for sexual development and fertility. The secretion of these hormones is controlled by the H–P axis, GnRH, LH and FSH release. The predominantly male sexual hormone, namely, the androgens and testosterones regulate sexual differentiation, virilization and hormonal changes accompanying puberty, development of testes, ultimately leading to spermatogenesis and puberty. The female sex hormones, namely, the estrogen and progesterone are essential for development of sexual characters, menstrual cycle and ovulation.

Increased metabolic breakdown of folate (a deficiency can inhibit tissue repair).

Estrogen and progesterone ❍

Effect ground substance of connective tissue by increasing fluidity ❍ Concentrations increase in saliva and fluid with increased concentrations in serum. Oral manifestations ❍ ❍ ❍ ❍

Pregnancy epulis Recurrent aphthous ulcers Herpes labialis lesions Candida infections.

Oral changes in menopause ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍

Thinning of the oral mucosa Burning mouth syndrome Gingival recession Xerostomia Altered taste sensation Alveolar bone loss Alveolar ridge resorption Osteoporosis.

Causes of precocious sexual development

Geriatric patient and endocrine related manifestations

❍ ❍ ❍ ❍

❍ ❍ ❍

Idiopathic Gonadal disease Adrenal disease Hypothalamic disease (e.g. Gonadotropin independent/dependent precocious puberty, McCune–Albright’s syndrome).

Hypogonadism, disorders of male reproductive system and sexual differentiation are seen in chromosomal abnormalities like Klinefelter syndrome, Turner syndrome, cryptorchidism among a few. Klinefelter syndrome shows dental anamolies like taurodontism. Effects of estrogen and progesterone on oral tissues Estrogen ❍

Increases cellular proliferation in blood vessels (known in the endometrium) ❍ Decreases keratinization, while increasing epithelial glycogen. Progesterone ❍

Increases vascular dilation, thus increases permeability (result in edema and accumulation of inflammatory cells) ❍ Increases proliferation of newly formed capillaries in gingival tissues (increased bleeding tendency) ❍ Alters rate and pattern of collagen production. 550

❍

Impaired glucose tolerance—diabetes mellitus Reduced thyroxin clearance and production Increased ADH, reduced renin and aldosterone leading to decrease in Na and increased K ❍ Decreased testosterone leading to impotency ❍ Decreased estrogen—burning mouth syndrome and osteoporosis ❍ Decreased vitamin D absorption and activation leading to osteopenia and fractures.

PREGNANCY Pregnancy is one condition where endocrine changes are the most significant alterations due to production of maternal and placental hormones. Dental management guidelines during pregnancy ❍

Developing rapport with the patient thereby reducing anxiety since it is always a very emotional experience for an expectant mother. ❍ Detailed medical history and consultation with the patient’s obstetrician and physician. ❍ Monitoring vital signs and blood examination because of development of anemia and folate deficiency during pregnancy.


❍

❍

❍

❍ ❍ ❍

❍

Patient in the third trimester if positioned in a supine position may suffer from supine hypotensive syndrome due to compression of inferior vena cava by the uterus. A left lateral positioning of the patient in such situation is advisable. Always a short appointment semi-reclined position, often changing of position is advisable. Pregnant patients of abnormal food habits, high sugar diet, high gag reflex and vomiting especially in the first trimester causing high rate of caries and enamel erosion. Preventive program to develop healthy oral environment. Studies have shown that reducing streptococci count in mother reduces incidence of caries in the child. Prenatal fluoride 2.2 mg/day in the second and third trimesters reduces incidence of caries in the child. Odontogenic infections, sepsis and febrility have known to cause miscarriage. Elimination of periodontal irritants reduces chances of pregnancy gingivitis and pregnancy tumor. Moreover, patients with periodontal infections have higher chances of miscarriage, preterm birth and low birth weight. Second trimester is the safest period for elective dental treatment.

Prescription of drugs It is always safe to avoid any drug during pregnancy especially during first trimester when the organs are in the formative stage. The drugs may cross the placental barrier and may be toxic or teratogenic to the fetus since the liver and kidneys are still immature. In unavoidable circumstances the drugs that are approved only may be given. Anesthetics Local anesthetics with adrenaline are relatively safe with required amount eventhough they cross the placental barrier. Lidocaine and prilocaine are safer than bupivacaine, which can cause fetal bradycardia. Analgesics The analgesic of choice is paracetamol. Ibuprofen is the next choice but is best avoided in the second trimester. Other NSAIDs can constrict ductus arteriosus, postpartum hemorrhage and delayed labor especially in the third trimester. Prolonged high dose of opioids leads to congenital abnormalities and respiratory depression. Antibiotics Penicillins, erythromycin (except in etiolate form) second and third generation cephalosporins, metroinidazole and clindamycin are considered safe. However, an increased dose or more frequent administration may be needed as the volume of distribution is increased in pregnancy. Tetracycline is contraindiacated as it chelates to hydroxyapatite of developing teeth and causes enamel hypoplasia.

Anxiolytics Benzodiazepines and barbiturates are best avoided because of cleft palate development on prolonged exposure or neonatal respiratory depression. Nitous oxide is better used only in the second and third trimesters and not more than 30 minutes with at least 50% oxygen to prevent hypoxia. Corticosteroids

Prednisone can be safely used.


Pregnancy gingivitis and pyogenic granuloma mostly in the labial aspect of interdental papilla. It starts around the 2nd month and continues until after parturition and regresses. ❍ Dental caries and enamel erosion and halitosis. ❍ Because of abnormal food habits and gastric regurgitation. ❍ Chloasma gravidarum, pigmented lesion of the skin and mucosa may have to be differentiated from other pigmentation disorders. Radiographs in pregnancy Exposing the patient to X-radiation should be avoided during pregnancy because of the possible stochastic effects (uncertain effects) especially during the first trimester because the developing fetus is susceptible to radiation damage. Under unavoidable circumstances exposing the patient for dental radiographs is considered safe provided precautionary measures in minimizing radiation are established, such as use of F-speed films, digital sensors. Long cone technique (200 mm FSD) filtration and rectangular collimation and use of lead aprons. When a lead apron is used during contemporary dental radiography the gonadal and fetal effective is less than 0.01 Sv (microsieverts). No increase in gross congenital anamolies or intrauterine growth retardation due to exposure during pregnancy has been observed up to less than 5–10 cGy. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also called autoimmune polyendocrine syndrome (APS) type I, is a rare autosomal recessive disease with a complex picture discovered over decades. Chronic mucocutaneous candidiasis (MC), hypoparathyroidism (HP) and adrenocortical failure (AF) are its most common components. To define APS type 1, at least two of the three major components need to be present. 1.

2.

Chronic candidiasis and T cell defect: In most cases of APS type 1, chronic candidiasis is the first manifestation of the disease, often occurring before the age of 5 years. Chronic hypoparathyroidism and parathyroid autoantibodies: In the course of APS type 1, candidiasis is followed by chronic hypoparathyroidism, which usually appears before the age of 10 years and affects 551


3.

70–100% of patients. When chronic hypoparathyroidism develops during the neonatal period, it is important to differentiate this from genetic diseases such as DiGeorge’s syndrome (caused by a 22q11 deletion) Kenney–Caffey disease (locus mapped to chromosome 1q42–q43), or the Barakat syndrome (caused by GATA3 haploinsufficiency). Addison’s disease (AD) and adrenal cortex autoimmunity: In the course of APS type 1, AD tends to be the third disease to appear after chronic candidiasis and/ or hypoparathyroidism, and it develops usually before 15 years of age and affects 22–93% of patients. In most cases the disease is heralded by the presence of adrenocortical autoantibodies (ACA), frequently found at the onset of the other main clinical manifestations of this type of APS (candidiasis and/or hypoparathyroidism).

Systemic lupus erythematosus A hormonal component to SLE is suggested, by its high incidence in women in their child bearing years, the many reports of remission during pregnancy, and the finding of increased estrogen levels in SLE patients suggest an endocrinal role.

Multiple Endocrine Neoplasia Type III (Multiple Mucosal Neuroma Syndrome) Multiple endocrine neoplasia types I to III (MEN I, II, and III) is a group of familial syndromes in which neoplastic change occurs in several endocrine glands in one individual. MEN I involves lesions in some combination of pancreatic islets, adrenal cortex, and parathyroid and pituitary glands; it includes Zollinger–Ellison (or gastrinoma) syndrome, in which multiple primary gastrin-secreting adenomas or adenocarcinomas are located in the pancreas, duodenum, or even extra-abdominal sites such as the parathyroid gland. Stomach ulceration and hyperplasia of the pancreatic islets and parathyroid glands develop secondary to the excess gastrin release and account for the characteristic presenting symptoms. Between one-quarter and one-half of gastrinomas have other features of the MEN I syndrome, which is not associated with any skin or oral phakomatosis. MEN II A which involves medullary carcinoma of the thyroid gland, pheochromocytoma of the adrenal medulla, and parathyroid hyperplasia or adenoma, is not associated with any phakomatosis. MEN II B or MEN III, a subgroup of these patients exhibits multiple neuromas of the commissural mucosa (which is characteristic) lips, tongue, and buccal, conjunctival, nasal, and pharyngeal mucosae, in association with their endocrine neoplasia (this is referred to as multiple mucosal neuroma syndrome). Since these neuromas may 552

occasionally predate any overt endocrine neoplasia, the recognition of these oropharyngeal lesions as possible evidence of MEN III can lead to the early and sometimes successful treatment of the associated malignancies like thyroid carcinoma which has a poor prognosis occurring in 18 to 25-year-old individuals. Thickening of the lip— a characteristic ‘bumpy’or ‘blubbery’ lip appearance is seen. Marfanoid habitus, café au lait spots, lentigines and a history of diverticulosis or lower-bowel surgery are the features. The finding of oral mucosal neuromas in association with a family history of carcinoma of the thyroid or pheochromocytoma clearly indicates a need to search for other evidence of this syndrome. Endocrine abnormalities are also sometimes present in patients who have other inherited syndromes with neoplastic associations, such as neurofibromatosis 1, McCune–Albright’s syndrome and von Hippel–Lindau syndrome. These conditions are usually excluded from the definition of multiple endocrine neoplasias. Diffuse endocrine system This group of widely scattered endocrine tissues consisting of AUPD cells, are called so because of their properties— a high content of amines; the capacity of amine precursor uptake; the presence of amino acid decarboxylase. The cells of these tissue contain characteristic granules and secrete polypeptides and amines. The origin of the tissues is believed to be from the neural crest cells. Neuroendocrinal tumors are rare in the oral cavity. Merkel cell carcinoma or (MCC) or neuroendocrine carcinoma It is a rare but aggressive malignancy of the skin with a rare intraoral occurrence. Only 14 cases of intraoral Merkel cell carcinoma have been reported (Yoshida et al, 2001). Factors strongly associated with the development of MCC are: ❍ ❍ ❍ ❍ ❍

Age more than 65 years Sex predilection—males Fair skin History of extensive sun exposure Chronic immune suppression (e.g. kidney or heart transplantation or HIV) ❍ Association with other premalignant and malignant skin lesions ❍ Common sites in the head and neck region are the cheeks, nose, mouth, eyelids and periocular region. Clinical presentation The common clinical findings include a nodule with or without ulceration. The nodule may be usually firm and erythematous. Pain may or may not be an associated feature. MCC very rarely occurs on mucous membranes of the head and neck region, and it carries a particularly poor prognosis.


SALIVA AND MONITORING OF HORMONE LEVELS Saliva can be analyzed as part of the evaluation of endocrine function. The majority of hormones enter saliva by passive diffusion across the acinar cells. Most of these hormones are lipid soluble (i.e. steroids). Small polar molecules do not readily diffuse across cells and instead enter saliva through the tight junctions between cells. The molecularweight cut-off for ultrafiltration is 100–200. This relatively small molecular size prevents many hormones from entering saliva from serum by means of ultrafiltration. In addition, active transport does not appear to facilitate hormone transfer into saliva. Measurements of salivary hormone levels are of clinical importance if they accurately reflect the serum hormone levels or if a constant correlation exists between salivary and serum hormone levels. For neutral steroids which diffuse readily into saliva, salivary hormone levels represent the free serum hormone levels. Conversely, due to their size, protein hormones do not enter saliva through passive diffusion, but primarily through contamination from serum as a result of outflow of gingival crevicular fluid (GCF) or from oral wounds. Furthermore, some steroid hormones can be metabolized in the salivary epithelial cells by intracellular enzymes during transcellular diffusion, which can affect the availability of these hormones in saliva. Due to their lipid solubility, steroid hormones can be detected in saliva. Salivary cortisol levels demonstrate excellent correlation with free serum cortisol levels. However, the actual salivary cortisol levels are lower than the serum-free cortisol levels, possibly due to enzymatic degradation in the salivary epithelial cells during transcellular diffusion. Salivary cortisol levels were found to be useful in identifying patients with Cushing’s syndrome and Addison’s disease and also for monitoring the hormone response to physical exercise and the effect of acceleration stress. Contrary to cortisol, salivary cortisone, prednisone and prednisolone levels do not accurately reflect serum cortisone levels. Cortisone is a neutral steroid and therefore readily diffuses into saliva; however, cortisol is converted to cortisone by an enzyme present in the salivary glands (11 ß-hydroxysteroid dehydrogenase). Thus, cortisone levels in saliva are higher than in serum and do not bear any diagnostic significance. Salivary aldosterone levels have demonstrated a high correlation with serum aldosterone levels with the use of a solid-phase enzyme immunoassay. Increased aldosterone levels were found in both the serum and saliva of patients with primary aldosteronism (Conn’s syndrome). Testosterone and dehydroepiandrosterone have also been identified in saliva. Salivary concentrations were found to be 1.5–7.5% of the serum concentrations of these hormones with direct radioimmunoassay technique. Monitoring

salivary testosterone levels may also be useful in behavioral studies of aggression, depression, abuse, violent and antisocial behavior. Estradiol can be detected in saliva in concentrations that are only 1–2% of serum concentrations. These concentrations are similar to the serum concentrations of free estradiol, which can diffuse into saliva. Salivary estradiol levels followed the same trends as serum estradiol levels during a menstrual cycle. Furthermore, salivary estriol levels showed a very high correlation with serum levels of free estriol in pregnant women, and salivary estriol levels were suggested as a means for the assessment of feto-placental function. Salivary progesterone levels showed good correlation with serum levels during the menstrual cycle and reflected the free serum progesterone levels. Salivary progesterone levels can be useful for the prediction of ovulation, with serum progesterone levels, and salivary estradiol and progesterone levels can be used for the evaluation of ovarian function. Decreased salivary estriol is suggested as a marker of fetal growth retardation. Furthermore, an increased salivary estriol-to-progesterone ratio may be a predictor of pre-term delivery. In general, serum and salivary levels of protein hormones are not well correlated. These hormones are too large to reach saliva by means of passive diffusion across cells or by ultrafiltration, and the detection of these hormones in saliva is primarily due to contamination from serum through GCF or oral wounds. Therefore, serum levels of protein hormones such as gonadotrophins, prolactin and thyrotropin cannot be accurately monitored by means of salivary analysis (Vining and McGinley, 1986, 1987). Salivary monitoring of hormone levels has many advantages over the more conventional serum analysis. Hormone evaluation often necessitates multiple sample collection in a relatively short time interval, which makes the noninvasive collection of saliva ideal for this purpose. However, it is important to consider the possible limitations of salivary analysis for hormone evaluation. Hormones enter saliva by passive diffusion and ultrafiltration, and active transport of hormones into saliva does not exist. Therefore, mostly lipid-soluble and hormones with small molecular weight can be detected in saliva. Most hormones are protein-bound in serum, and thus salivary hormone levels represent the free hormone levels which are available for diffusion into saliva. This may provide more clinically useful information, since free serum hormone levels are the biologically active fraction of hormone in serum. For accurate results, a constant and predictable correlation must exist between salivary and serum hormone levels. However, different hormones are bound to similar serum carrier proteins, and thus changes in levels of one hormone may affect the free levels of others. For hormones that demonstrate a constant but low salivary-to-serum ratio, a sufficiently large sample volume or a more sensitive analysis 553


method is required. In addition, many hormones exhibit marked circadian variations. Therefore, timing of saliva collection may affect the results. The salivary flow rate can also affect the concentrations of certain hormones. An increase in salivary flow rate will usually result in reduced concentrations of molecules that reach saliva by diffusion. However, the rate of diffusion of steroid hormones, particularly cortisol, is usually high enough to maintain a constant relationship between salivary and serum levels of the hormone regardless of the salivary flow rate. The concentrations of hormones that reach saliva by ultrafiltration, such as dehydroepiandrosterone sulfate, are more affected by changes in salivary flow rate. Changes in salivary flow rate may lead to changes in salivary pH. This may affect the entry into saliva of molecules according to their pKa. The stability of hormones in saliva is important as well for accurate evaluation. Hormones in saliva can be degraded, among other ways, by enzymes native to saliva, enzymes derived from oral microorganisms, and enzymes derived from leukocytes that enter the oral cavity from the gingival sulcus. In addition, molecules that reach saliva by passive diffusion across cells, like unconjugated steroids, may be subjected to enzymatic degradation within the salivary glands, prior to entering saliva. These factors have to be considered when saliva is evaluated as an alternative for the evaluation of serum hormone levels.

MENTAL HEALTH AND ITS RELEVANCE TO DENTISTRY This section aims at equipping the reader with skills to recognize the commonly seen mental illness. In addition to giving a broad overview of mental illness and present day psychiatric practice we intend to focus on the interface between ‘dentistry’ and ‘psychiatry’. We will also give you a broad overview of the treatment options available in psychiatry. In addition to making you confident in recognizing the mental illness to refer them to psychiatry, this section will give you confidence in dealing with the mentally ill when they develop dental problems.

History of Psychiatry Tracing the timeline backwards, in 10,000 BC there was no difference between medicine, magic and religion. Looking at the history of medicine it may seem that Psychiatry as a specialty is relatively new. However the history of Psychiatry dates back to more than 2,000 years when medicine itself had its birth as ‘Science’ in ancient Greece. In the ancient world, Psychiatric illness was believed to come from the Gods and the curse of the devils. People have always been fascinated and puzzled, not being able to understand ‘insanity’. It is interesting to note the varying 554

perceptions of the public, media, arts and the society at large toward the ‘mad’ among us. For centuries mental health problems and their treatments has been the realm of not only ‘physicians’ but also a range of other professionals including ‘faith healers’. Till the 18th century the mentally ill were secluded in ‘institutions’ and ‘asylums’. In the next stage, mid 18th century, some physicians in England and France started recognizing themselves as having a special interest in dealing with mental health. But still there was no treatment available and the mentally ill were ‘chained’ at large. It was Philippe Pinel, a French physician who in 1793 started an initiative toward the ‘moral treatment’ of the mentally ill and ‘liberated’ the insane from their chains. The first half of 20th century saw the accidental discovery of malaria being therapeutic for psychosis in tertiary syphilis. This led to the dangerous practice of injecting milk to induce fever. Inducing seizures by ‘insulin coma therapy’ or injecting ‘camphor oil’ which was considered a successful treatment for ‘schizophrenia’ then is largely ‘barbaric’ this day in age. The biggest breakthrough for Psychiatry came in the 1950s with the discovery of ‘chlorpromazine’ and the First World Congress of Psychiatry at Paris. Since then Psychiatry has probably seen the invention of numerous new medications, perhaps much more than most other branch of medicine. However, present day psychiatry has outgrown the medical model and has incorporated a ‘bio-psycho-social’ model both for understanding and treating mental illness.

Concepts of Mental Illness and its Classification Similar to using the word ‘illness’ loosely in everyday speech, the word ‘mental illness’ is used with little precision in psychiatric practice, and often synonymously with ‘mental disorder’. In this context, ‘mental’ and ‘psychiatric’ are also used interchangeably. A very diverse discussion of the concepts of mental illness can be found in the works of Lazare (1973), Kendell (1975), Hafner (1987) and Clare (1997). It is probably beyond the scope of this discussion to go into the depths of these concepts.

Definitions of Mental Illness There have been numerous attempts to define mental illness but none have been satisfactory and uniformly accepted. One of the common approaches is to examine the concept of illness as in general medicine and to identify any analogies with mental illness. In general medicine there are five types of definitions: ❍ ❍ ❍

Absence of health Disease is what doctor treats Biological disadvantage


❍ ❍

Pathological process Presence of suffering.

Efforts to classify psychiatric disorders have been tried by many over the years. Since there are no definite diagnostic tests such as radiograph for fracture or blood test for malaria we need different tools to provide a conceptual framework to the psychiatric illness. Having a classificatory system helps us to communicate with other professionals and to decide on treatment and prognosis.

The five axes of DSM IV Axis I

Clinical syndrome and ‘conditions not attributable to mental disorder that are the focus of attention and treatment’

Axis II

Personality disorders

Axis III

Physical disorder and conditions

Axis IV

Severity of psychological stressors

Axis V

Highest level of adaptive functioning in the last year

Criticisms of classifications

Current Psychiatric Classifications The two major classificatory systems in use for the psychiatric disorders are the ICD (International Classification of Diseases)-10 and the DSM (Diagnostic and Statistical Manual) IV and it is important to have the basic understanding of both. International Classification of Diseases (ICD)-10, Chapter V The ICD is proposed by the World Health Organization (WHO) as an aid to the collection of international statistics about disease. The system is revised every few years and the current edition is the tenth (ICD-10). It has 22 chapters in it and the fifth chapter is devoted to psychiatry. Main categories of ICD-10 Chapter V (F) F00–09

Organic including symptomatic mental disorders

F10–F19

Mental and behavioral disorders due to psychoactive substance use

F20–F29

Schizophrenia, schizotypal and delusional disorders

F30–F39

Mood (affective) disorders

F40–F49

Neurotic, stress related and somatoform disorders

F50–F59

Behavioral syndromes associated with psychological disturbances and physical factors

F60–F69

Disorders of adult personality and behavior

F70–F79

Mental retardation

F80–F89

Disorders of psychological development

F90–F99

Behavioral and emotional disorders with onset usually occurring in childhood or adolescence

There is no doubt that classification is needed in psychiatry and it helps the clinicians to communicate with one another about the diagnoses given to a patient and it helps to understand the implications of the diagnoses, in terms of their symptoms, prognosis, treatment and sometimes etiology. However, such classifications, on many occasions are criticized as being inappropriate or even harmful. It can be argued that allocating patients to a diagnostic category distracts form the understanding of their unique personal difficulties. It is important to combine the two because these qualities can modify prognosis and these personal difficulties should be taken into account for a holistic treatment of the disorder. It is also worth noting that some conditions could be sub-threshold and resemble the disorders in the classification but do not meet full diagnostic criteria. It is not infrequent to see such patients presenting to a variety of services other than psychiatry. These sub-threshold conditions are however clinically significant and it is important to recognize these conditions to reduce the psychiatry morbidity or comorbidity.

Diagnostic Criteria and Screening Questions We intend to introduce the readers to the common psychiatric illnesses. This section should familiarize you with the brief epidemiological details, diagnostic criteria and screening questions to be used in everyday practice. A functional psychiatric illness should always be diagnosed after ruling out any physical condition that can explain the presentation. For example, a middle-aged lady with hypothyroidism may present with depression as the only symptom. It is important to be aware of this aspect as any psychiatric presentation could be mimicked by an organic condition or by alcohol/illicit drug use.

Diagnostic and Statistical Manual (DSM) The DSM is produced by the American Psychiatric Association (APA). The first edition, DSM-I was published in 1952 as an alternative to the widely criticized ICD-6. It seems that the DSM-I was strongly influenced by the views of Adolf Meyer and Karl Menninger. Its simple glossary reflects the acceptance of the then prevalent psychoanalytic ideas in the United States. The current version is the DSM IV and it has five axes as shown below.

Alcohol and substance use The available epidemiological data suggests a combined 1 year prevalence rate of alcohol misuse and dependence to be 7–10% (Kessler et al, 1994). An understanding of the effects of alcohol and other substances of abuse (tobacco, heroin, cannabis, cocaine) is important for the practice of dentists. When such patients present with oral complications of prolonged substance misuse, in addition to treating the 555


oral condition it becomes important to liaise with the mental health services to treat the dependence. We aim to equip you to diagnose these dependence syndromes with the diagnostic criteria which are common for all substances. Three or more of the following to be present during the previous year 1. Strong desire or a sense of compulsion to take the substance (craving) 2. Difficulty in controlling substance taking behavior (loss of control) 3. Physiological withdrawal symptoms when substance use is reduced, e.g. tremousless, anxiety and lack of sleep with alcohol withdrawal 4. Need to increase the intake over a period of time to get the same effect (tolerance) 5. Neglect of alternative pleasures or interests (salience) 6. Continuing to use despite knowing it to be harmful World Health Organization, 1992.

A commonly used screening tool for alcohol is CAGE which can be administered in a minute or less is shown in the box below. CAGE questionnaire 1. Have you ever felt you should cut down on your drinking? 2. Have people annoyed you by criticizing your drinking?

lasts for more than 2 weeks duration. It has to be differentiated from normal sadness. Such patients have impaired patterns of mood, thoughts and behavior which sometimes lasts for a long period of time. It causes a lot of distress to the person and impairs his/her quality of life. It is also accompanied by a high rate of suicide which is at least 7% in men and 1% in women (Blair-West et al, 1999; Weissman et al, 1996). The 12-month prevalence of depression in the community is between 2 and 5% and the lifetime rate lies between 10 and 20% (Alonso et al, 2004). In 2000, the WHO identified major depressive disorder as the fourth ranked cause of disability and premature death in the world (Murray and Lopez, 1997). WHO has projected that by 2020, major depression will rise in disease burden to be second only to ischemic heart disease. This disorder is very common all over the world with a lifetime prevalence rate of 17% and a recurrence rate of more than 50% (Kessler et al, 1994; Weissman et al, 1996). People with chronic disease have a higher chance of developing depression. It is 40% for people with coronary artery disease and 25% for patients with cancer (Musselman et al, 1998; Patten, 1999). Neurological disorders associated with a higher frequency of depression include multiple sclerosis, Parkinson’s disease, head trauma and stroke (Patten et al, 2000; Poewe and Luginger, 1999). Around one-third of patients with depression develop alcohol or illicit substance misuse in their lifetime (Baker and Dawe, 2005).

3. Have you ever felt bad or guilty about your drinking? 4. Have you ever had a drink first thing in the morning to steady your nerves or to get rid of a hangover (eye opener)?

Most people with depression have five or six of the following:

Each Yes is scored 1 point. Score of 2 suggests significant alcohol problems.

• Feeling sad most of the time (but may feel a little better in the evening) • Lose interest and enjoyment in life (anhedonia) • Feeling tired easily with reduced energy levels

List of commonly misused drugs

• Reduced concentration in day-to-day tasks

• Amphetamines

• Cocaine

• Find it harder to make decisions

• Speedball

• Heroin

• Cannot cope with things that they used to

• Cannabis, hashish

• LSD

• Feel restless and agitated

• Ecstasy, ketamine

• Inhalants

• Lose appetite and weight

• Steroids

• Ether

• GHB

• Glue

• Take 1–2 hours to get off to sleep, and then wake up earlier than usual

• Ritalin, diet pills, rush

• THC, marijuana

• Lose interest in sex

• Barbiturates, Valium, Ativan

• Speed

• Loss of self-confidence

• Opium

• Crack

• Feel useless, inadequate and hopeless

• PCP, Angel dust

• Morphine, methadone

• Avoid other people

• MDA, MDMA

• Crystal meth

• Feeling guilty about trivial issues

• Grass

• Freebase

• Feel irritable • Feel worse at a particular time each day, usually in the morning

Depression Depressive disorder also known as major depressive disorder or unipolar depression is a psychiatric illness which

556

• Having ideas or acts of self-harm or suicide • Have a bleak and pessimistic view of the future World Health Organization, 1992.


Psychoses including schizophrenia and delusional disorders In psychotic illnesses patients suffer from strange and unusual experiences and beliefs that are beyond our understanding. Schizophrenia is a mental disorder that affects around 1 in every 100 people. In one-third of the patients it can can become severe and enduring. The most common symptoms are hallucinations and delusions. A hallucination is a phenomenon where people hear, see, feel or smell something when there is nothing or nobody to account for it. In functional psychotic illnesses the most common is hearing voices that seem to be utterly real and coming from the outer world although other people cannot hear them. These voice/voices can either talk directly to the patient or talk to each other about the patient. The patient might report that he/she is overhearing a conversation. Though the voice can be pleasant they are more often rude, critical and abusive, irritating and sometimes commanding. These commanding hallucinations increase the risk of harm to self and significant others. Delusion is belief that the patient holds with complete convictions although it seems to be based on a misinterpretation or misunderstanding of the situation or event. When we ask the patient why they believe in it, their reasons do not make sense to us or they say that they cannot explain it and ‘they just know it’. So it is customary to define ‘delusion’ as a false unshakable belief, which is out of keeping with the patient’s social and cultural background (Hamilton, 1984). The most common in this category are ‘paranoid’ delusions and delusions of ‘reference’ or ideas of reference. The paranoid delusions or delusional ideas make the patient feel persecuted or harassed. For example, the patient might believe that he/she is being influenced by the neighbours who are using special powers or technology. Another example is where the patient starts to believe that his/her partner is unfaithful. This belief is based on odd details that seem to have nothing to do with sex or infidelity. In such cases other people see nothing to suggest that the belief might be true. Ideas of reference occur when the patients start getting a special meaning in ordinary day-to-day events and believe that they are specially connected to them. For example, radio or television programs are about them or people are communicating to them in odd ways, such as through the color of cars in the street. People with a more severe form of psychosis suffer from ‘thought disorder’ in which their thought process is muddled. Their ideas are disconnected in such a way that it is hard for other people to understand. Some patients experience as if their feelings or actions are controlled by an external agency as if they are being controlled like a puppet or a robot. So people experience as if their thought process is being interfered with. It could be that their thoughts are vanishing as though someone is taking them

out of their mind or as if the thoughts in their mind are not their own, but someone else has put them in their mind. While patients with schizophrenia experience any of the above core psychotic symptoms, delusional disorders are characterized by either a single delusion or a set of related delusions which are usually persistent and sometimes lifelong. These delusions are clearly personal rather than being subcultural and occur in the absence of brain disease. Auditory hallucinations if present are only occasional (WHO, 1992). The delusional disorders are generally more difficult to treat. Though most of the times psychosis is just picked up from the patient’s conversation, the box below gives a list of screening questions. These questions only form a guide to clarify when you suspect something abnormal and only the most relevant questions should be asked keeping in mind the educational and cultural background: Persecution How do you get on with others? Do you believe that people are trying to harm you or make your life miserable? Is there a plot to cause harm to you? Reference Do people talk behind your back? Do things seem specially arranged for you? Do you see any reference to yourself in the TV or newspaper? Grandiosity How do you see yourself compared to others? Do you have any special powers or abilities? Are you specially chosen in any way? Thought disorder Are you able to think clearly? Is there any sort of interference with your thinking process? Do you think people around you can read your mind? Always check for conviction, explanations and coping How do you know this is the explanation? Could it be your imagination or your ‘mind playing tricks’? What do your family and friends think about this problem? What do you intend to do about this problem?

Anxiety, stress-related and somatoform disorders Anxiety is a normal human feeling and we all would have experienced it when faced with situations that we find difficult or threatening. The best example would be an examination or interview. Often people refer to it as ‘stress’ which is confusing and can mean different things. It may refer to things that make one anxious or on the other hand it could be a reaction to being faced with anxiety provoking situations. It is important to differentiate ‘anxiety’ from ‘worry’ and ‘fear’. When anxiety is a result of a continuing problem like financial problem we call it ‘worry’. A sudden response to an immediate threat like looking over

557


a cliff is ‘fear’. Both fear and anxiety can be helpful, helping us to avoid dangerous situations, making us alert and motivating us to deal with problems. However, if it becomes too strong or goes on for too long it can interfere with our daily activities and make our lives miserable. Anxiety causes numerous physiological (in the body) symptoms and cognitive symptoms (in the mind) shown in two separate boxes below. Physiological symptoms of anxiety • Irregular hear beats (palpitations) • Sweating • Muscle tension and pain • Shakes and tremors • Butterflies in the stomach • Tightness in the chest • Breathing heavily • Dizziness • Faintness • Indigestion • Diarrhea

Cognitive symptoms of anxiety • Fear of ‘going mad’ • Fear of ‘passing out’ or ‘imminent death’ • Fear of having a ‘heart attack’ • Fear of a serious physical health problem • Feeling worried all the time • Feeling excessively tired • Unable to concentrate • Feeling irritable • Sleep problems

Phobias and social phobia Phobia is fear of a particular situation or particular things that are not dangerous and which most people do not find it dangerous. We all have fears about things such as height and spiders but, for most of us, these fears do not interfere with the way we lead our lives. These fears are called phobias only when they interfere with things we would otherwise enjoy or do easily. A person with phobia has the same intense symptoms of anxiety described above but these arise only in the particular situations that frighten them. At other times they do not feel anxious. For example, a person with phobia of dogs is comfortable when there are no dogs around. However, phobia makes the person avoid situations in which they know they will be anxious. This ‘avoidance’ actually makes the phobia worse as time goes on. Over time the person’s life becomes increasingly dominated by the precautions he/she needs to 558

take to avoid the fearful situation. This ‘avoidance behavior’ keeps expanding to include more and more situations and circumstances. The sufferer usually knows that there is no actual danger, may feel silly about this fear but still is unable to control it. Such a phobia can start after a distressing or a traumatic experience, many a times in early life. Many of us worry before meeting new people and before going to parties but once we are there we can cope and enjoy the situation. Some people become very anxious about such situations, cannot enjoy them and at worse totally avoid such social situations. This condition is called ‘social phobia’. Such people tend to worry about becoming the center of attention wherever they find themselves among people. They worry that everybody is looking at them and watching what they are doing. At their worst, these feelings of fear and bodily symptoms can end up in a ‘panic attack’. A panic attack lasts for a few minutes during which the person feels overwhelmingly anxious and is terrified of losing control, going mad or dying. These feelings reach a peak and then pass off rapidly leaving the person feeling weak and exhausted. Panic disorder Panic disorder is a type of mental illness with recurrent and unexpected intense episodes of anxiety called as panic attacks. A panic attack is characterized by intense apprehension and terror accompanied by physical symptoms like palpitations, chest pain, dizziness, sweating and difficulty in breathing. These attacks have an abrupt onset and peak in intensity within 10 minutes. These attacks are not associated with any external event or situation and come out of the blue. Such episodes often result in calls to paramedics and visits Accident and Emergency Department. Panic disorder could sometime be a lifelong illness that remains only partially responsive to treatment. Women appear to have more severe form of the disease than men (Yonkers et al, 1998) and is much more commoner in women (Barzega et al, 2001; Kessler et al, 1994). Agoraphobia The term ‘agoraphobia’ means ‘fear of open spaces’. Such people not only fear open spaces but also presence of a crowd. They fear not having an immediate and easy escape to a safe place (usually home). Such patients generally have a fear of leaving home, fear of entering shops, crowds, public places, or of traveling alone in trains, buses, or planes. The severity of anxiety symptoms and the extent of avoidance varies from patient to patient. However, for some people it is the most incapacitating of all phobic disorders and they become completely housebound. Some people are terrified by the thought of collapsing and being left helpless in the public. The lack of an immediately available exit seems to be a key feature in these patients with agoraphobia who tend to be women in early adult life.


Depression and social phobia may also be present but do not dominate the clinical picture. People feel grief-stricken, depressed, anxious and angry after a traumatic experience. A traumatic event is where one is in danger; one’s life is threatened or sees other people dying or being injured. The condition is called posttraumatic stress disorder (PTSD) when one starts re-living the trauma again and again in the form of ‘flashbacks’ during the day or ‘nightmares’ in sleep. In addition, they start avoiding related situations, become emotionally numb and ‘hypervigilant’, unable to relax. The emotional reaction in stress is often accompanied by other symptoms of anxiety listed in the boxes on page 558. The questions in the box below help you to screen for the anxiety disorders. Panic attacks • Have you had spells or attacks when you suddenly felt anxious, frightened, uncomfortable or uneasy, even in situations where most people would not feel that way? Did the spells surge to a peak, within 10 minutes of starting? • Do you feel anxious or uneasy in places or situations where you might have a panic attack or panic-like symptoms, or where help might not be available or escape might be difficult: like being in a crowd, standing in a queue, when you are away from home or alone at home, or when crossing a bridge, traveling in a bus, train or car? Social phobia • Have you been fearful or embarrassed of being watched, being the focus of attention, or fearful of being humiliated? This includes things like speaking in public, eating in public or with others, writing while someone watches, or being in social situations. Post-traumatic stress disorder • Have you ever experienced or witnessed or had to deal with an extremely traumatic event that included actual or threatened death or serious injury to you or someone else? Examples of traumatic events include serious accidents, sexual or physical assault, a terrorist attack, being held hostage, kidnapping, fire, discovering a body, sudden death of someone close to you, war, or natural disaster. • Have you had a dental appointment or a medical intervention in the past which you found significantly traumatic? What was the reason you found it to be traumatic? Was it because you were not adequately prepared due to lack of information as to what was going to happen?

Obsessive compulsive disorder We commonly use phrases like, ‘He’s an obsessive cricket fan’, and ‘She’s a compulsive liar’. We use these phrases when people do things again and again, and others cannot see any reason for it. The essential features of this disorder are recurrent obsessional thoughts and compulsive acts. Obsessions are patient’s own thoughts which are repetitive and intrusive. These thoughts are almost invariably distressing to the patient, because they are violent or

obscene or simply because they are perceived to be senseless. The person often tries to resist these thoughts but is unsuccessful. Obsessional thoughts could be in the form of ideas, images or impulses that enters the individual’s mind again and again in a stereotyped fashion. Compulsive acts are also known as rituals. These are stereotyped behaviors repeated again and again. They are not inherently enjoyable and they do not result in the completion of any useful thoughts. The individual often views the compulsions to be reducing the anxiety caused by the obsessions. Usually these repetitive acts are considered to be pointless and the patient tries to resist them, only to yield to them when the anxiety builds up. However, in very long-standing cases the resistance may be minimal. There is often a close relationship between obsessional symptoms and depression. The most common ritual seen is frequent hand washing as a result of obsessive thoughts that one might be contaminated by germs, dirt or HIV. The other commonly seen compulsion is a checking behavior. About 1 in 50 people suffer from OCD at some point in their lives. Men and women are equally affected. It affects work, relationships and family life of the patient. People with a severe OCD also cause burden on their caretakers. Some people with mild OCD improve without any treatment. Some will slowly get worse and some get worse when they are stressed and depressed. The mainstay of treatment for OCD continues to be talking therapies like exposure and response prevention and guided self-help. Antidepressant medications can be used alone or in combination with talking therapies for moderate to severe OCD. Hypochondriasis Patients with hypochondriasis are preoccupied by a fear of having a serious disease based on the misinterpretation of their bodily symptoms (American Psychiatric Association, 1994). This serious preoccupation persists despite negative investigations and causes distress with impaired functioning of the patient. The central and diagnostic clinical feature is the preoccupation with the idea of having a serious medical condition, usually one which will lead to death or serious disability. The patient usually ruminates repeatedly on this possibility. The minor and insignificant bodily abnormalities, normal variants, normal functions and minor ailments will be interpreted as signs of the serious disease. The patient will consequently seek medical advice and investigation but is unable to be reassured by the negative results. Such patients may be able to accept that their worries are groundless but nonetheless are unable to stop dwelling and acting on them. Such beliefs are more often than not over-valued ideas. However, this belief can be of a delusional intensity when the patient should be treated as for a delusional disorder. Otherwise antidepressants, behavioral therapy and cognitive behavioral therapy (CBT) are the mainstay of the treatment for hypochondriasis. 559


Body dysmorphic disorder Body dysmorphic disorder (BDD) is characterized by ‘devastating’ preoccupation with an imagined defect in appearance and marked distress over the supposed deformity (American Psychiatric Association, 1994). Though the focus of patients with BDD is by definition on physical appearance, data exists on patients with BDD having obsessional concerns with odor (Hollander and Aronowitz, 1999). BDD is also known as dysmorphophobia. It is an intriguing and sometimes difficult to treat condition that often mystifies the clinicians. This disorder is characterized by distressing and impairing preoccupation with a non-existent or slight defect in appearance. Although BDD symptoms may sound trivial the disorder can cause severe distress and can lead to suicide. Individuals with BDD are preoccupied with the idea that some aspects of their appearance is unattractive, deformed or ‘just not right’ in some way. Concerns usually focus on their face or head but can involve any area of the body (Phillips and Diaz, 1997; Phillips et al, 1993). Concerns with bodily asymmetry, for example, ‘uneven’ buttocks are also common. BDD by proxy consists of a preoccupation with supposed flaws in another person’s appearance, which may lead to insistence that the other person should have surgery or dermatological treatment. The majority of BDD patients seek often costly nonpsychiatric treatments (Phillips, 1996) and may also present to the dental practitioners in the first instance for surgical treatment. However, most BDD patients appear dissatisfied with such treatment and many dislike their new appearance even more (Andreasen and Bardach, 1977). Multiple procedures may be received in search for a cosmetic solution to this psychiatric problem before it comes to a psychiatrist. Occasionally, dissatisfied patients sue, or even become violent toward the physician. There are rare reports of patients trying to perform their own surgery, as did one man who cut his nose open and tried to replace his own cartilage with chicken cartilage. The mainstay of evidence based treatments for BDD includes selective serotonin reuptake inhibitors (SSRI) and CBT.

INTERESTING INTERFACE BETWEEN ‘DENTISTRY’ AND ‘PSYCHIATRY’ Disorders on the Psychotic Spectrum Orofacial phantom pain Current day dentists are often faced with challenges when patients present with orofacial pain. In the current day competitive practice there is always an urgency to treat conditions associated with the pain. More often than not the clinical dilemma needs to be resolved quickly and decisively. Such situations impel the clinician to perform procedures designed to eliminate pain such as endodontic therapy or tooth extractions or to construct new and different dentures 560

(Marbach, 1996). Though this urgency is almost palpable, such urgent situations create the potential for failure. It is thus essential to be aware of the three putative neuropathologic facial pain disorders: 1. 2. 3.

Phantom tooth pain Intraoral stump pain Phantom bite syndrome.

1. Phantom tooth pain Reports on tooth pain of obscure origin are relatively recent (Harris, 1974). The term phantom tooth pain was first used in 1978 (Marbach, 1978), and since then the condition has been validated extensively as a clinical entity (Marbach, 1993a, 1993b; Pollmann, 1984; Rees and Harris, 1979). Phantom tooth pain is the most common type of orofacial phantom pain reported. It usually follows dental or surgical procedures such as pulp extirpation or tooth extraction. It is characterized by persistent toothache with no identifiable cause. Neither repeated endodontic treatment nor tooth extraction renders the affected area free of pain. On the contrary, procedures and other surgical interventions such as trigeminal rhizotomy and microvascular decompression frequently exacerbate pain and may even enlarge its distribution. Other terms for phantom tooth pain, such as atypical odontalgia (Brooke and Merskey, 1994), idiopathic odontalgia and atypical facial pain, also are in use (Bates and Stewart, 1991). The pain is described as a constant, dull, deep ache with occasional spontaneous sharp pains. There are no refractory periods. Peripheral stimuli can momentarily exacerbate the pain but have no prolonged influence. Radiographic and laboratory tests are negative. Sleep is undisturbed by pain or other phantom sensations. Many patients report a brief symptom-free period on awakening in the morning. It resembles other phantom pain syndromes that commonly arise following amputation and injury (Marbach, 1996). Phantom tooth pain has only been reported in adults and none in children (Marbach, 1996). 2. Intraoral stump pain Stump pain is a frequent squeal of limb amputations. Davis cited this pain as a major cause of prosthetic limb rejection among amputees (Davis, 1993). Sherman and colleagues suggested that denture pain is the intraoral equivalent of limb stump pain (Sherman, 1989). Stump pain does not disappear with time or with adjustments or replacements of the prostheses (Marbach, 1996). The health and financial conditions of these patients improve on treatment directed toward stump pain which is focused away from mechanically based etiologies (Marbach, 1985). The onset of pain is usually associated with an injury to a peripheral nerve. Pain is often worse at the site of the original trauma, although in chronic cases they have difficulty in localizing the pain. 3. Phantom bite syndrome Phantom bite syndrome is often associated with an inability to adapt to changes in dental occlusion (Marbach, 1978, 1985). Non-painful phantom limb phenomena are common among recent


amputees but usually fade with time (Jensen et al, 1984). Recently orofacial phantom bite syndrome has been viewed as a psychiatric disorder (Bonica, 1991; Jensen et al, 1984; Marbach, 1978, 1985). This interpretation has been revised in light of current research (Jensen et al, 1984; Melzack, 1993; Sherman, 1989). Though phantom bite syndrome can occur at any stage of dental treatment, it is typically associated with the construction of extensive prosthesis in all age groups and the beginning of orthodontic treatment in adolescents (Marbach, 1996). They usually complain of continuous discomfort and are frequently distressed by the lack of familiarity of their own bite (Marbach, 1996). Seeking relief from phantom bite syndrome often becomes an expensive and lengthy effort toward restoration of one’s original but ‘lost’ bite (Marbach, 1978, 1985). Success is rarely if ever obtained. Treatment therefore should be focused on prevention, early detection and patient education. Delusional bad odor Bad breath is also known halitosis; it is a common concern found in millions of people. There seems to be no reliable way to assess breath odor. Some people develop faulty perceptions about having a bad breath. Sometimes it affects their entire life. On the other hand, some people who have halitosis remain unaware of their condition. Every patient has a breath odor self-image. This self-image ranges from little or no distortion to severe psychopathology (Eli et al, 2001). Because these people go to a dentist with a complaint of oral malodor, it becomes the responsibility of dental practitioners to identify this psychopathology. It is important for dentists to consider both psychological and physiological factors while diagnosing and treating such cases. Various researchers have attempted to understand the distortions in self-perception of odors, including oral malodor, in the context of various psychiatric disorders (Davidson and Mukherjee, 1982; Pryse-Phillips, 1971). One relevant example is patients who complain of various body odors (auxiliary, fecal or genital) that appear to have no objective basis. These patients may have somatic delusions or an olfactory reference syndrome (ORS) (Pryse-Phillips, 1971). Causes of ‘delusional halitosis’ were presented in the literature by Davidson and Mukherjee (1982), Iwu and Akpata (1990) and Oxtoby and Field (1994). Halitophobia also may be considered in the context of BDD. Halitophobics often display other psychological phenomenon, such as compulsive toothbrushing and withdrawal from social interactions (Rosenberg, 1996). Olfactory reference syndrome Patients sometimes present with persistent olfactory concerns or preoccupations with personal odor (Malasi et al, 1990; Pryse, 1971; Stein et al, 1998; Videbech, 1966). The term ‘olfactory reference syndrome’ (ORS) has been introduced to differentiate primary olfactory concerns from

those seen as a consequence of other disorders such as schizophrenia, depression or temporal lobe epilepsy (Pryse, 1971). It is still controversial whether ORS is truly a unique disorder or merely a part of the symptomatology of other psychiatric conditions (Lochner and Stein, 2003). However, it has been noted that most patients with primary ORS are young without concurrent psychiatric disorders (Pryse, 1971). Arguably, the principal symptomatology of ORS has sufficient overlap with anxiety and somatic disorders. Case vignette A 22-year-old male presented with the belief that he had malodorous breath (halitosis) and a foul odor emanating from his armpit, feet, and anal region. This persistent preoccupation had begun in early adolescence, but the intensity had increased significantly over the past 7 months. Halitosis was his main concern. But collateral information from his parents confirmed his excessive washing and frequent change of clothes. His embarrassment about the perceived halitosis gradually caused increasing social withdrawal and isolation and also resulted in depressive symptoms. He remained convinced that the halitosis had persisted, despite reassurance to the contrary by his physician and close family members.

Schizophrenia—dental implications Dentists who are familiar with the signs and symptoms of schizophrenia are likely to feel more secure while treating patients with schizophrenia. It makes the dentist more confident while obtaining consultative advice from the patient’s psychiatrist. Dentists can provide the full range of service to such patients and constitute to the psychotherapeutic aspect of management. In addition to being able to communicate effectively with such patients, the dental treatment may need to be modified because of the patient’s impaired ability to think logically. It is very important for all dentists to be aware of the local and systemic effects of psychiatric medications and the adverse interactions between these drugs and medications used in dentistry. Schizophrenia can be conceptualized as a group of disorders, with variable presentations, best described in three different dimensions: positive symptoms, disorganized symptoms and negative symptoms. The positive symptoms are the exaggeration or distortion of normal functions, most commonly delusions and hallucinations which are described earlier in the chapter. ‘Disorganized’ symptoms are inferred from patient’s speech and are also known as ‘thought disorder’. It is manifested as rapid shifts between topics that either have a loose logical association or are completely unrelated. They may also exhibit inappropriate affect manifested by childish silliness and unpredictable agitation. (Andreasen et al, 1995; Marder, 1996). They also exhibit a range of neurocognitive impairments in the areas of memory, attention and executive functions, which in turn impairs their vocational and social adjustment (Green, 1996). Negative symptoms are less dramatic but equally debilitating. They include reduced emotional responsiveness (flat affect); reduced speech output and poor thought content; 561


inability to plan, initiate and persist in goal directed activities (avolition) and poor self-care in terms of washing, bathing and cooking. They also show social withdrawal and loss of pleasure in previously enjoyed activities (anhedonia) (Kaplan, 1994 and Sadock, 1995). Substance abuse frequently accompanies schizophrenia. The prevalence rate of alcohol abuse in schizophrenia is as high as 63% in some studies (Dixon, 1999). Other commonly abused drugs are cannabis and cocaine. Some patients seem to self-medicate their positive symptoms with these illicit drugs which in turn makes the psychosis worse. Abuse of these substances strongly correlates with medical and psychosocial problems like inadequate diet, homelessness, poor compliance with medications and multiple episodes of the disorder (Dixon et al, 1999). More than three-fourths of patients with schizophrenia smoke and this is frequently associated with emphysema, lung cancer, cardiac disease and oral cancer (McEvoy and Brown, 1999). Patients with schizophrenia are often having a disinterest in performing appropriate preventive oral hygiene techniques (Friedlander and Liberman, 1991; Thomas et al, 1996). This in turn leads to the development of advanced oral disease. This is compounded by reduced access to care, prolonged hospitalizations, impaired finances and paucity of clinicians who are comfortable in caring such people. Some antipsychotics, namely, chlorpromazine and thioridazine cause profound hyposalivation through their anticholinergic effects (Sreebny, 1989). This is worsened by the co-administration of antiparkinsonian agents to counteract the extrapyramidal side effects (EPSE) of the conventional (dopamine agonist) antipsychotics. The resultant hyposalivation causes intensification of periodontal disease and rapid caries progression (Gupta et al, 1993). Therefore, a lot of people with schizophrenia have a higher requirement for periodontal treatment, dental restorations and dental extractions (Velasco et al, 1997). The conventional antipsychotics have adverse side effects, especially the movement disorders that mimic neurological diseases. These movement disorders frequently have an orofacial component and are seen to develop in a time-dependent fashion. These movement disorders are caused by the blockade of basal ganglia dopamine D2 receptors in the extrapyramidal system (Holloman and Marder, 1997). Effects of antipsychotic drugs on orofacial movements Acute diagnoses which generally manifest within the first 5 days of starting treatment: • • • • • • •

562

Oculogyric crisis (eye turned upward) Torticollis (head turned sideways) Retrocollis (head turned backward) Trismus (forced closing of the mandible) Laryngospasm Spasm of neck muscles Tongue protrusion

Pseudoparkinsonian side effects generally develop in 1–3 months after therapy: • • • •

Reduced eye blinking Monotonous and soft speech Mask-like face Cogwheel rigidity

Tardive dyskinesia is slow to develop and is generally seen in 7–10 years of antipsychotic use. It is characterized by rhythmical involuntary movements of: • • • •

Mouth (ex, puckering) Face (ex, puffing of cheeks) Jaw (ex, chewing movements) Tongue (ex, protrusion)

Clozapine is another medication to be aware about. It is an atypical antipsychotic used in patients unresponsive to other medications (Breier, Malhotra, Su, et al, 1999). Clozapine has a unique added advantage of reducing the cravings for alcohol and illicit drugs (Volavka, 1999). About 0.5 to 1% of patients on clozapine develop bone marrow suppression causing agranulocytosis and granulopenia (Worrel, Marken, Beckman, et al, 2000). This prevents clozapine from being used as a first-line drug. Thus all patients on clozapine should have periodic WBC count (Hammad, 1998). Although clozapine is a potent anticholinergic agent, it has a unique, unexpected side effect of sialorrhea in 85% of patients (Clark, 1992).

Anxiety and Depressive Disorders Depression and dental implications A depressive disorder may be associated with extensive dental disease (Baker and Dawe, 2005). Patients may seek dental treatment before becoming aware of their psychiatric illness (Gatchel et al, 1996). Depression is often associated with a disinterest in performing appropriate and timely oral hygiene techniques. It can also be associated with a cariogenic diet, diminished salivary flow, rampant dental caries, advances periodontal disease and oral dysesthesias (Friedlander and Mahler, 2001). Side effects of antidepressant medications increase the incidence of dental diseases including xerostomia (Gerber and Lynd, 1998). An appropriate dental management in such patients would include a good dental education, the use of saliva substitutes and anti-caries agents containing fluoride. Special precautions should be taken and every potential drug interaction should be kept in mind while prescribing analgesics and local anesthetics (Callahan, 1996). Depression in chronic facial pain Depressive illness is a common and a serious disorder that affects at least 20% of women and 10% of men during their lifetime (Kessler et al, 1994). Approximately 15% of these


people eventually commit suicide (Angst and Hochstrasser, 1994; Coppen, 1994). Depression has a high comorbity with chronic facial pain, making it important for dental practitioners to be able to identify depressive symptoms in dental patients presenting with facial pain. The rate of depression has been shown to be as high as 40–80% in patients with chronic facial pain (Gallagher et al, 1991; Korszun et al, 1996). More than 40% of patients with chronic facial pain are refractory to treatment (Friedlander and Mahler, 2001). Thus early identification and optimal treatment of co-morbid depressive disorder will have a significant impact on the treatment outcome for these patients. Blumer and Heilbronn (1982) suggested that patients with chronic pain have an underlying depression that is masked and represented only by somatic symptoms that are not accompanied by the usual mood symptoms, making it more difficult for the dental practitioners to recognize depression. On the other hand, some authors have conceptualized depression as a secondary maladaptive response to chronic pain (Dworkin, 1991). As a dental practitioner the most important factor is having awareness of depression as a medical disorder and having an openness to recognize the less obvious presentations of a depressive disorder. If clinicians themselves conceptualize depression as a mental disorder or a character defect and do not understand the neurological basis and treatability of depressive conditions, they will not only fail to recognize this serious condition but will also convey this prejudice to their patients. Patients may also be resistant to even considering a diagnosis of depression particularly when they are consulting a dentist for what they perceive to be a physical condition such as jaw pain. Because of the time constrains in a busy dental practice it might be worth while administering a depression rating scale such as the Beck Depression Inventory (Beck et al, 1961) for all patients presenting with chronic facial pain. Recognizing depressive symptoms in patients with chronic pain is particularly challenging as many symptoms secondary to chronic pain are also prime symptoms of depressive illness. For example, patients with chronic pain have a resulting poor sleep, lethargy, irritability and weight loss due to pain while eating, which are the core symptoms of depression. It is also important to screen for co-morbid alcohol and substance abuse in such patients. A broad multidisciplinary approach to the diagnosis and treatment will improve treatment outcomes of such patients. Antidepressant use—importance for dental practice Many dental patients are prescribed antidepressants for diverse therapeutic reasons such as pain control, insomnia, smoking cessation, substance abuse and eating disorders. However, antidepressants taken with other drugs may increase the risk of complications that require special dental precautions and care. Patients receiving antidepressant therapy commonly complain of decreased salivation and

changes in salivary viscosity (Astor et al, 1999). Xerostomia (Peeters et al, 1998), orthostatic hypotension (Peeters et al, 1998) and cardiotoxicity (Roose et al, 1998) are significant adverse effects of certain antidepressant medications especially when they are taken in combination with other medications (Fox, 1998). Chronic xerostomia can cause oral mucosal changes, increased coronal and root caries susceptibility, candidiasis, partial loss of taste acuity, periodontal disease, and difficulty in swallowing and functional prosthetic problems (Astor et al, 1999). In patients aged 60 years or older, Thomson and colleagues (1995) reported a higher root caries index value for those on antidepressant therapy. Precautions related to orthostatic hypotension include shorter dental interventions, positioning the patient up right in the dental chair, avoiding sudden postural changes, using caution in prescribing medications which cause orthostatic hypotension. The injection of local anesthetics containing vasoconstrictors often causes an increase in blood pressure. A rare paradoxical hypertensive reaction may occur when patients taking drugs with alpha-1 adrenergic blocking activity (such as tricyclic antidepressant) are given with a local anesthetic containing vasoconstrictor (such as epinephrine). This reaction occurs as epinephrine is unable to bind to the blocked alpha-1 receptors, instead interacts with available beta-2 receptors causing vasodilatation and a resultant paradoxical hypotensive reaction (Keene et al, 2003). Dental precautions include using a minimal quantity of local anesthetic with sympathomimetic vasoconstrictor and taking care to prevent intravascular injections. Use of epinephrine containing homeostatic agents is contraindicated. All these precautions are only in addition to routine monitoring of blood pressure and other vital signs (Yagiela, 1999). Eating disorders—dental implications Dentists are likely to encounter patients who have eating disorders and they have an important part to play in the overall care of these patients. There are two major categories of eating disorders namely anorexia nervosa and bulimia nervosa. Anorexia occurs in upper and middle class families while bulimia presents across all social classes (Hugo and Lacey, 1996). Anorexia is aversion to food, which can be conceptualized as resulting from a complex interaction between biological, individual and family factors. This aversion to food leads to severe weight loss and its complications, both physiological and psychological. There are two subtypes of anorexia, ‘restricting’ and ‘binge/purge’ types. The difference between these two sub-categories is based on whether the person regularly engages in binge eating or self-induced vomiting (SIV), excessive exercise or misuse of laxatives, diuretics or enemas. Bulimia is even more common and is characterized by overeating followed by inappropriate compensatory behaviors with normal body weight. 563


Patients with bulimia nervosa often present with bilateral and occasional unilateral parotid gland swelling. The incidence of parotid gland swelling is 10–15% in people with bulimia (Brady, 1985). The submandibular salivary gland is involved infrequently. The exact pathogenesis of these glandular enlargements has not been determined. It is generally accepted that multiple emetic episodes cause an autonomic neuropathy (Ascoli et al, 1993). With sympathetic nerve impairment, individual acinar cells enlarge and lead to clinically visible gland swelling (Ascoli et al, 1993). Such an asymptomatic bilateral parotid enlargement often presents a diagnostic dilemma to the dentists. As these patients with bulimia nervosa and parotid gland swelling are usually secretive about their self induced vomiting (SIV) (purging), the diagnosis will have to be made by conducting a thorough clinical examination and serum electrolyte study. Early recognition and prompt diagnosis when such patients present to the dentists can avoid the later serious medical complications. The need for these patients to seek psychiatric care and discontinue SIV is mandatory. Eating disorders have various orodental adverse effects. Holst and Lange in 1939 coined the term ‘perimylolysis’ to describe the distribution of erosion on the upper palatal surfaces secondary to vomiting, reflux and regurgitation (Holst and Lange, 1939). Several research studies till date have shown that SIV results in increased frequency of erosion on palatal surfaces (Hellstrom, 1977). Whether the caries experience in eating disorder individuals is greater than in normal population remains unclear (Hurst et al, 1977). Salivary flow increases dramatically prior to vomiting because the medullary center that controls vomiting is connected to salivary nuclei (Edgar, 1992). With respect to SIV, the stimulated salivary flow should therefore be altered. Research has discovered reduced bicarbonate in bulimics along with increased salivary viscosity (Edgar, 1992). One study has found increased frequency of periodontal disease in patients with eating disorders (Touyz et al, 1993). Angular cheilitis, candidosis, glossitis and oral mucosal ulceration are possible sequelae of nutritional deficiency. There has not been any report of malignant change associated with SIV (Brady, 1980). The dental care demanded by individuals with eating disorders is very challenging. Although the dentist might suspect vomiting as the cause of erosion, these patients will not readily admit to such behavior because they can be highly secretive and embarrassed by it. The patient’s motivation to reduce the frequency of SIV will increase once the dentist is able to openly relate the progress of dental erosion with the vomiting. Toothbrushing after vomiting is generally regarded as inadvisable because the softened, demineralized surface is more susceptible to toothbrush abrasion (Milosevic et al, 1997; Robb et al, 1995). Patients whose teeth have been damaged as a consequence of an eating disorder are most likely to present first to the dentists. In many cases the dentist is in a position to 564

assist in making the initial diagnosis and can influence progress of the medical and psychological management of the disorder.

MANAGEMENT OF PSYCHIATRIC DISORDERS Broad Principles Some patients who receive psychiatric treatment for mental health problems may be reluctant to admit it. This is most often because of the perceived stigma associated with mental illness. It is important and could be quite tricky for a dentist to overcome such barriers and obtain the necessary information. It always helps to take a supportive and non-judgmental attitude, and advise patients that such information will be held confidential and also that it is indispensable to provide a safe dental care. Patients with mental health problems may be uncooperative and irritable during dental treatment. They may appear unappreciative and may seem to have numerous complaints that are inconsistent with the objective findings (Korszun and Ship, 1997). It is always beneficial to liaise with the patient’s psychiatrist before beginning any dental treatment. Information requested should include at least the latest mental state, risk assessment and the list of psychotropic medications. In addition, a history of alcohol and illicit drug use is always useful. Such patients should undergo a liver function test, full blood count and coagulation profile before commencing the dental treatment.

Importance of Interpersonal Communication Skills with Special Emphasis on Dental Phobia Communication skills—why bother? From personal experience of one of the authors, we state the obvious that dentists should remember that the patient cannot speak with a wide open dry mouth and with dental instruments in their mouth. They should probably ask questions that generate a yes/no type of response. Moreover, at the outset, it is useful to lay down the ground rules such as, ‘if in pain, raise your left hand’. Patients seeking dental treatment have apprehensions about the nature of their problem and the procedure involved. One of the common misconceptions that people have is that all dental procedures are painful. Moreover, the fear of injections and the sound and sight of drills and other instruments keep many patients away. This may lead to patients postponing visits to their dentists or totally avoiding it. The estimates of dental anxiety in general population varies between 6% and 20% (Rouse and Hamilton, 1990). Dentist–patient relationship rests a lot on the interpersonal communication. This also has a significant impact in


allaying dental anxiety. Corah et al (1985) have reported that anxiety during treatment was influenced by patient’s satisfaction with the dentist’s technical competence, understanding and communication skills (Corah et al, 1985). It needs to be stressed that every doctor has to approach his/her patients with warmth and have a basic respect for them and acknowledge the distress that the person seeking help may be going through. Importance of explaining the procedure to the patients Dentists often have to deal with anxious clients. Helping patients overcome such anxiety can reduce the rates of missed appointments and also better compliance on the part of the patient during the treatment session. Various ways of doing it can be employed such as using models, charts or diagrams and video clippings. It is important to check that the patient understands at every step. The very step of explaining the procedure helps patients to be mentally prepared and allays their anxiety. It is also helpful to obtain a verbal consent from the patient ensuring that they are ready for the procedure. In addition, creating a conducive environment for the patient also helps. A survey by Bare and Dundes has shown that a majority of anxious patients found it helpful to have gentle music in the background, magazines and books, adorned walls and a slightly cool temperature in the waiting area (Bare and Dundes, 2004). Dealing with dental anxiety/phobia Bare and Dundes have summarized from past research the reported causes of dental anxiety (Bare and Dundes, 2004). Some of the common ones are: ❍ ❍ ❍

❍ ❍ ❍ ❍ ❍

If patients have had previous painful experiences Belief that painful treatment is inevitable If they feel that they lack control over the situation, including the inability to stop a procedure they find unpleasant Lack of understanding of the procedure that the dentist performs Patients having a general fear of the unknown Media coverage or hearing from acquaintances of frightening tales of dentists or procedures Experienced detached treatment by a dentist Having fears of experiencing ridicule because of how they react to situations arising during their visit.

It is important to provide information to the patients as soon as possible about the nature of the problem and what they can expect during and after the treatment. It is known as ‘informational control’ and it reduces dental anxiety (Levitt et al, 2000). Maggirias and Locker reported that patients who perceive that they have little control over the procedure were

more likely to report pain (Maggirias and Locker, 2002). This again brings us to the fact that explaining the procedure as highlighted in the previous paragraph, gives patients a sense of control and is useful in allaying their anxiety. Study by Eli et al suggests that the level of patient’s anxiety was affected by evaluation of the present dentist by the patient and memories of anxiety from childhood and also by the personality traits of the patient (Eli et al, 1997). Some training centers have communication skills training programs for students in dentistry to teach students micro-skills such as dealing with anxious patients. It has been shown that communication skills training has an effect on the knowledge and a substantial effect on the behavior of the students (van der Molen et al, 2004). Note: ❍ ❍

❍ ❍ ❍

❍

Clear communication involves making simple and short statements asking only one question at a time. Active/attentive listening is a key feature of good communication. It involves making a good eye contact and also by using non-verbal modes of communication (head nodding). Avoid interrupting when the other person is talking. Ask questions to clarify what the person actually meant when unclear. It is important to confirm that the person has understood what the doctor had to say. ‘Have you understood/Am I clear?’, ‘Do you have any questions?’ Reassure, explain that the procedure can be stopped at any time if the patient cannot tolerate it.

Medications Antidepressants Antidepressants are drugs that relieve symptoms of depression. They were first developed in 1950s and have been used regularly since then. There are almost 30 different kinds of antidepressants which belong to the four major categories: tricyclics, mono amine oxidase inhibitors (MAOIs), SSRIs and serotonin noradrenaline reuptake inhibitors (SNRIs). Antidepressants work by increasing the activity of certain neurotransmitters mainly serotonin and noradrenaline. Antidepressants are used to treat moderate to severe depressive illness, severe anxiety and panic attacks, OCD, chronic pain, eating disorders and PTSD. The tricyclic antidepressants such as imipramine, amitriptyline, nortryptiline and dosulepin cause side effects such as dry mouth, slight tremor, tachycardia, constipation, sleepiness and weight gain. In addition to these anticholinergic side effects, men may experience delayed ejaculation and difficulty in getting or keeping an erection. Tricyclic antidepressants are less commonly used as they are dangerous in overdose. 565


SSRIs are the commonly used first line treatment and include drugs such as fluoxetine, sertraline, citalopram and paroxetine. SSRIs are generally well tolerated and less harmful in an overdose which make them the most popular. SNRIs are very similar to SSRIs although venlafaxine should not be used in patients with heart problem and needs monitoring of blood pressure. MAOIs are rarely prescribed these days as they cause dangerously high blood pressure on eating food containing ‘tyramine’ known as ‘tyramine reaction’. It is important to check for the dangerous drug interactions before prescribing if a patient is on MAOIs. It is generally best to taper off the dose of an antidepressant as stopping it suddenly may cause withdrawal such as stomach upset, anxiety, dizziness and flu-like symptoms. The current recommendation is that antidepressant should be continued for at least 6 months after complete remission of symptoms. If one has suffered from two or more episodes of depression then treatment should be continued for at least 2 years.

antipsychotics include risperidone, olanzapine, quetiapine, amisulpiride and clozapine. Risperidone is the only atypical antipsychotic which is available in the form of long acting injection. Clozapine is an atypical antipsychotic medication and the only one that has shown to be more effective for people who do not respond to other sorts of antipsychotics. In addition to the side effects of the atypicals mentioned above, clozapine also produces increased salivation. The main drawback is that it can affect the bone marrow reducing the white cell count causing agranulocytosis which can be fatal. For this reason, patients taking clozapine need weekly full-blood count for the first 6 months, 2 weekly for the next 6 months, and 4 weekly thereafter. Most patients with schizophrenia need to take antipsychotics for a long time. On stopping the treatment, symptoms of schizophrenia usually come back, if not immediately, often within 6 months. It is advisable to reduce the dose of the medication gradually, only in discussion with a psychiatrist who will monitor for early signs of relapse.

Antipsychotics Starting from the mid 1950s several medications were discovered that reduce the symptoms of schizophrenia and other psychotic disorders. They came to be known as ‘antipsychotic’ medications. These older drugs are called ‘typical’ or ‘first generation’ antipsychotics. They work by reducing the action of dopamine in the brain (dopamine antagonist). Some typical antipsychotics are chlorpromazine, haloperidol, pimozide, trifluoperazine and sulpiride. Some of these typical antipsychotics are available in long acting depot injection form which can be administered once in 2 to 4 weeks for people who do not comply with oral medications. The typical antipsychotics have more side effects than atypicals. The side effects include stiffness and shakiness as in Parkinson’s disease along with feeling sluggish and slow in their thinking. Other side effects include uncomfortable restlessness (akathisia) and sexual side effects. A long-term side effect is ‘tardive dyskinesia’—persistent movements generally of the mouth and tongue which is difficult to treat and very disabling. Over the last 10 years, several newer medications have been in use. They work on a different range of chemical messengers in the brain including the serotonin system (serotonin dopamine antagonists). These came to be known as ‘atypical’ or ‘second generation antipsychotics’. These atypical antipsychotics are less likely to cause parkinsonian side effects although they may cause weight gain and problems with sexual functions. They may also help the negative symptoms on which the older drugs have very little effect. They also seem to have much less propensity to cause ‘tardive dyskinesia’. The common side effects of atypicals include weight gain, sexual side effects, glucose intolerance and increased chance of developing Type 2 diabetes and sedation. The commonly used atypical 566

Anti-manic agents Medications used to treat mania include mood stabilizers such as lithium and valproate. Other medications used to treat mania include antipsychotics and benzodiazepines. Medications used to prevent the relapse of manic episodes in manic depression (bipolar disorder), include drugs such as lithium, valproate, carbamazepine and lamotrigine. Lithium has over the last 40 years been the most commonly used drug to prevent relapse. Lithium is a safe drug when taken at the correct dose, however it has a narrow therapeutic window (0.6 to 0.8 mmol/l) and becomes unsafe above this level in the blood. The common side effects include fine tremors, metallic taste in the mouth, tiredness, weight gain and underactive thyroid gland. Long-term treatment with lithium can cause renal impairment. It is thus important to periodically check for serum lithium level, thyroid functions and renal functions including creatinine clearance. Lithium is an ion and is excreted unchanged from the kidneys. Drugs such as diuretics and NSAIDs can dangerously increase the serum lithium levels and so it is very important to check for drug interactions before prescribing for a patient on lithium. Valproate and semi-sodium valproate are becoming widely used treatment for mania and bipolar disorder. The common side effects of valproate include sleepiness, dizziness, increased appetite and weight gain, skin rashes and irregular periods. Very rare side effects include pancreatitis and liver failure. It is again very important to check for drug interactions as valproate is a hepatic enzyme inhibitor and reduces the metabolism of other medications. Carbamazepine is usually used as a second line treatment for bipolar disorder. Unlike valproate, carbamazepine is a hepatic enzyme inducer and increases the metabolism


of other medications and thus reduces their efficacy. Interestingly it reduces its own level and needs bigger doses with longer treatment. Lamotrigine also helps to prevent mood swings particularly of severe depressive episodes. It is however not used as a monotherapy for bipolar disorder. Electroconvulsive therapy Electroconvulsive therapy (ECT) is a treatment used in psychiatry for severe mental illnesses. It was originally developed in the 1930s and was used widely during the 1950s and 1960s for a variety of conditions. Since then its use was declined. ECT remains a controversial treatment, which some people have strong feelings about. There are those who claim it can be a lifesaving procedure, while others feel it should be banned. ECT is a way of causing someone to have a seizure and it is this seizure that is needed for the treatment to work. The seizure is made to happen by passing an electric current across the person’s brain in a carefully controlled way from a specially developed ECT device. The current can be administered to the whole brain when it is called ‘bilateral ECT’ or just to the non-dominant hemisphere called the ‘right unilateral ECT’. The seizure itself is very similar to the seizures that occur in people with generalized epilepsy, but it is caused on purpose in very controlled circumstances using generalized anesthesia and muscle relaxant, just like for a surgical operation. The aim of ECT is to cause a ‘generalized cerebral seizure’ between 10 and 50 seconds long using the right dose of electricity. The current recommendation is to use ECT for treatment resistant severe depression, severe mania and catatonia (NICE, 2003). ECT is used more as a lifesaving treatment for quick resolution of very severe symptoms and is always supplemented with a continuation of the most appropriate pharmacotherapy. Psychological (talking therapies) There are several types of ‘talking treatments’ also known as ‘psychotherapy’. These are different ways of helping people to overcome stress, emotional problems, relationship problems and troublesome habits. The commonality in these treatments is talking to another person and sometimes

doing things together. Behavioral psychotherapy tries to change the behavioral patterns of the patients and helps to overcome fears by spending more and more time in the situation they fear. They are also given homework exercises and are asked to keep a diary to practise the new skills in between the sessions. This type of behavioral psychotherapy is effective for panic, phobias, anxiety, OCD and various kinds of social and sexual difficulties. Results are seen quite quickly. CBT aims at changing the thinking patterns. It emphasizes on how the thinking, behavior, emotions and physiological symptoms are all related in a particular instance and is influenced by the environment. It encourages a discussion on how we think and helps us to get rid of unhelpful ways of thinking. It focuses on the present and not on the past. CBT have achieved particular success in the treatment of certain types of depression. Psychodynamic psychotherapy focuses on the feelings one has about other people, family and those close to the individual. This mode of treatment involves discussing the past experiences and how these may have led to the present situation and affecting the individual’s life. It may involve a brief therapy for a specific difficulty or may be long-standing with daily sessions lasting for many years. Family therapy focuses very clearly on the relationships, boundaries and communication styles in the family of the concerned individual. Marital therapy is for relationship problems in a marriage, partnership or family. In all the above forms of therapy, the therapist may be a psychiatrist, psychologist or the mental health professional who has had an in-depth training in psychotherapy. These therapies are usually done under supervision. When to refer to a psychiatrist As soon as you suspect a mental disorder and realize that the patient is not seeing a psychiatrist, it is good to think about referral. In general the earlier the mental illness is detected the better the final outcome. Always try to reassure and encourage the patient to seek help for the mental health problems. Be non-judgmental and explain to the patient that treatment is available, and it is possible to improve the quality of life with help from the mental health services.

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CHAPTER

19

Bone Diseases and Fibro-osseous Lesions Manish Juneja, Ravikiran Ongole

➧ Fibro-Osseous Lesions

➧

Periapical Cemento-osseous Dysplasia Focal Cemento-osseous Dysplasia Florid Cemento-osseous Dysplasia Gigantiform cementoma Ossifying Fibroma, Cementifying Fibroma and Cemento-ossifying Fibroma Juvenile Ossifying Fibroma (Psammomatoid and Trabecular) Fibrous Dysplasia

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Bone Diseases Osteogenesis Imperfecta Osteopetrosis Cherubism Infantile Cortical Hyperostosis Idiopathic Osteosclerosis Gorham’s Disease Paget’s Disease of Bone

FIBRO-OSSEOUS LESIONS

most fibro-osseous jaw lesions can be assigned with reasonable certainty into one of the several categories:

Fibro-osseous lesions of the jaw comprise a diverse group of conditions which are characterized by replacement of normal bone by a tissue composed of collagen fibers and fibroblasts that contain varying amounts of mineralized substance which may be bone, cementum or both in appearance. These lesions present a wide range of clinical and radiographic patterns. The precise diagnosis of fibroosseous lesions depends on good clinical, radiological and histological correlation. Numerous terminologies have been used to designate these lesions. In 1940s and early 1950s, these lesions were commonly termed as localized osteitis fibrosa, osteofibroma or fibrous osteoma. The lesions in the skull were termed as leontiasis ossea because of its lion-like appearance. With advances in the understanding of these lesions a number of classifications have been proposed by many investigators. Waldron (1985, 1993), Makek (1987), Slootweg (1996), Fowler (2005) are a few among those who have been accepted, although no universally approved classification system has been presented. The classification system that has been considered to be most useful was given by Waldron in 1993. Waldron suggested that with adequate clinical and radiographic data,

I. II.

Fibrous dysplasia Reactive (dysplastic) lesions arising in the tooth-bearing area A. Periapical cemento-osseous dysplasia B. Focal cemento-osseous dysplasia C. Florid cemento-osseous dysplasia III. Fibro-osseous neoplasms: Cementifying fibroma, ossifying fibroma or cemento-ossifying fibroma Another classification which attracted many pathologists was given by Fowler. He classified fibro-osseous lesions as follows: I.

II.

Osseous dysplasia A. Non-hereditary 1. Periapical osseous dysplasia 2. Focal osseous dysplasia 3. Florid osseous dysplasia B. Hereditary 1. Familial gigantiform cementoma Fibro-osseous neoplasms A. Conventional ossifying fibroma B. ‘Juvenile’, ‘active’, or ‘aggressive’ forms of ossifying fibroma

Chapter 19 – Bone Diseases and Fibro-osseous Lesions

III. Fibrous dysplasia A. Monostotic fibrous dysplasia B. Polyostotic fibrous dysplasia C. Polyostotic fibrous dysplasia with endocrinopathy (McCune–Albright) D. Craniofacial fibrous dysplasia.

Periapical Cemento-osseous Dysplasia The term periapical cemento-osseous dysplasia is used to designate a lesion which occurs in the periapical areas and shows cementum-like and osseous areas on histopathologic examination. The term periapical cemental dysplasia which was used earlier to designate these lesions is somewhat incorrect as the lesion shows both cementum-like and osseous areas. The etiology is unknown, but they appear to originate from the periodontal ligament. Clinical features The periapical cemento-osseous dysplasia is a disease which involves the periapical areas of the vital teeth in black female patients who are older than 30 years of age. The lesions are invariably asymptomatic and are discovered on routine radiographic examination. Radiographic features The early lesions show well-defined, circumscribed radiolucent lesions involving the apices of one or several teeth. Individual lesions are seldom more than 1.0 cm in diameter and most are less than 0.5 cm in size. The lesions show an increasing degree of calcification with time, which may appear as mixed radiopaque and radiolucent lesions. The older lesions show radiopaque masses. These lesions do not show any bone expansion. Histopathologic features Not many reports appear that review the histopathologic findings of periapical cemento-osseous dysplasia. The lesions which are misdiagnosed as inflammatory periapical pathologies and are subjected to histopathologic findings have shown to be composed of cementum-like and/or osseous trabeculae in a fibroblastic stroma. As the lesions become older the calcified component appears to be more prominent. Management and prognosis The diagnosis is done mainly on the basis of radiographic presentation and clinical findings. Surgical intervention is contraindicated. Early lesions showing radiolucent areas are often misdiagnosed as periapical cysts or granulomas. Accurate pulp testing should be done to avoid such errors. Isolated lesions involving the apical areas of vital teeth

present greater problems in diagnosis than do multiple lesions, particularly when the solitary lesion is in the premolar area and the patient is male or a white female.

Focal Cemento-osseous Dysplasia The term focal cemento-osseous dysplasia was first suggested by Tomich and Summerlin in 1989. The disease is seen in the edentulous posterior areas of females who are in their 4th and 5th decades of life. Clinical features Focal cemento-osseous lesions are invariably asymptomatic and are discovered on routine radiographic examination. There is no swelling associated with it unless the lesions are old and have caused bony expansion. On surgical exploration the tissue occupying the defect is gritty, hemorrhagic and is removed by curettage in small fragments, often with some difficulty. This helps in differentiating the lesion from ossifying fibroma which is well circumscribed and avascular and easy to enucleate. Radiographic features These are well-demarcated radiolucent or mixed radiolucent/ radiopaque area or highly sclerotic. Most lesions are less than 2 cm but larger lesions may be seen. Simple bone cysts also may occur with focal cemento-osseous dysplasia. Histopathologic features Microscopically areas of cellular fibrous tissue containing numerous small blood vessels, irregular trabeculae of woven bone and/or cementum-like calcifications are seen. Scattered foci of multinucleated giant cells may be seen. Management and prognosis The lesion shows no tendency to recur after removal. Partial removal of the lesion is also advocated in cases where the lesion is very large and limits the total excision. The partial removal does not show any tendency to enlarge or recur and the long-term prognosis seems to be excellent.

Florid Cemento-osseous Dysplasia The term florid cemento-osseous dysplasia (FCOD) was first suggested by Melrose et al in 1976 to describe a condition of exuberant multiquadrant masses of cementum and/or bone in both jaws and in some cases, simple bone cyst-like lesions in affected quadrant. Sometimes familial tendencies have been observed. In past this condition has been designated as sclerosing osteitis, multiple enostoses, diffuse chronic osteomyelitis and gigantiform cementoma. The etiology of florid cemento-osseous dysplasia is unknown. Waldron et al have proposed that reactive or 569


dysplastic changes in the periodontal ligament might be a cause for the disease. Clinical features The disease is seen exclusively in middle aged, black female and has a striking tendency for bilateral occurrence, often presenting symmetrically in the jaws. The disease is limited to the tooth bearing areas of the jaws. Many patients are partially or completely edentulous when the conditions are detected. Many cases are completely asymptomatic and the disease is diagnosed during routine radiographic examination. When the lesions are large, jaw expansion may be noted and symptoms of dull pain or drainage are always associated with exposure of the sclerotic calcified mass to the oral cavity as a result of progressive alveolar atrophy after a denture or after extraction. Laboratory investigations show no biochemical abnormalities. Radiographic features Bilateral densely sclerotic lesions often symmetrically present in various areas of the jaws. These are usually mixed with less well-defined areas of a mixed radiolucent/radiopaque pattern. Majority of the patients are edentulous at initial presentation. If the patient is having remaining anterior teeth, they will often show circumscribed typical lesions of periapical cemento-osseous dysplasia. Well-defined radiolucency representing simple bone cyst is not uncommonly seen with florid cemento-osseous dysplasia. Histopathologic features Microscopically florid cemento-osseous dysplasia shows an admixture of woven bone trabeculae and droplets of cementum-like calcifications in a fibroblastic stroma. The cementum-like calcifications often fuse to form coalescing masses. Management and prognosis The diagnosis of the disease is mainly dependent on the radiographic and clinical presentation. However, the method of treatment is not very satisfactory. In the asymptomatic patient, no treatment should be considered and patient should be kept under observations. In symptomatic patients, where exposure of the sclerotic masses to the oral cavity is seen, biopsy or elective extraction of teeth in the involved area should be avoided. Antibiotic therapy should be instituted. Sequestration of cementum-like masses will occur slowly, followed by healing. Saucerization or surgical excision of the sclerotic masses is not successful.

Gigantiform Cementoma Gigantiform cementoma is a rare, benign fibro-cementoosseous disease of the jaws. It is characterized by formation 570

of massive sclerotic masses of disorganized mineralized material. Both sporadic and familial occurrence has been reported. The etiopathogenetic mechanism of gigantiform cementoma is unknown. The term gigantiform cementoma has been used synonymously with the terms sclerotic cemental masses, florid osseous dysplasia, multiple enostoses and diffuse sclerosing osteomyelitis. It was Norberg in 1930 who first described gigantiform cementoma. In 1971, the World Health Organization (WHO) classified gigantiform cementoma in the category of cemental lesions. Clinical features Gigantiform cementoma is an autosomal dominant disorder having high penetrance and variable expressivity. No sex predilection has been observed. It typically presents as a slow-growing, multifocal/multiquadrant and expansile lesions involving both the jaws. The lesions are usually seen in younger age, although older patients have also been reported. The size of the lesions seen in older patients was comparable to those seen in younger individuals. Thus it has been suggested that these lesions may have plateaued in their growth, probably after cessation of skeletal growth. The characteristic clinical manifestation is of a painless maxillary and mandibular swelling with associated facial deformity. Tooth impaction, malpositioning of teeth and malocclusion are also seen associated with the swelling. The enlargement of the swelling finally stops during the 5th decade. Radiographic features Radiographically, gigantiform cementoma exhibits multiple circumscribed, expansile and lobular mixed radiolucentradiopaque lesions that usually cross the midlines of the jaws. Sometimes large masses are seen in posterior areas of the jaws and the lesions combining in the midline. This suggests that lesions might have started as separate posterior masses; however, with anterior progression they became confluent and crossed the midlines of the jaws. Histopathologic features Microscopically it presents a spectrum of histopathologic features, mainly characterized by variable degrees of cellularity and variation in the amount and size of mineralized deposits. The mineralized component is present as admixture of small and large psammomatoid and spherical hematoxylinophilic, cementum-like calcified deposits and irregular bony trabeculae in a fibroblastic proliferative background. The fibrous stroma may show fascicular or storiform patterns with spindle-shaped or stellate-shaped fibroblasts. The lesions are generally hypovascular, with occasionally focally rich vascular areas exhibiting aggregates of thickwalled small blood vessels. Mitoses, hyperchromatism and pleomorphism are not seen.


Management and prognosis The surgical management of gigantiform cementoma is usually difficult because of the extensive involvement of the jaws with these tumors. Surgical inaccessibility, particularly in the posterior regions of the jaws seems to be responsible for recurrence of the tumors. These lesions seem to have a tendency toward recurrence when they are treated with incomplete surgical removal. It is therefore recommended that these lesions should be managed with conservative but complete surgical excision whenever feasible.

Ossifying Fibroma, Cementifying Fibroma and Cemento-ossifying Fibroma Ossifying fibroma is the most common fibro-osseous neoplasm of the jaw. It is a bone producing, slow growing, asymptomatic, well demarcated, benign lesion common in maxilla and mandible. The tumor is defined as a demarcated and occasionally capsulated lesion consisting of fibrous tissue containing variable amounts of mineralized material resembling bone and/or cementum or both. The term ossifying fibroma is used if the predominant component is bone, while cementifying fibroma is defined by the presence of cementum-like spherical calcifications. The lesions characterized by the presence of bone and cementum are referred to as cemento-ossifying fibroma. The 1972 WHO classification separated the cementifying fibroma which was considered to represent odontogenic tumors, from ossifying fibroma, which was considered to be osseous tumors. However, it has been agreed by all that the two represent the same pathological condition with different histological presentation. Thus, in 1992, WHO classified the lesion as cemento-ossifying fibroma. The origin of the amorphous cementum-like calcifications commonly seen in these lesions is still uncertain. Many of the fibroosseous lesions of the skull which were excised from the regions far away from the jaws showed cementum-like calcifications which make their cemental origin very unlikely. It is also known that bone and cementum cannot be distinguished histologically. Thus, the nomenclature represents only a variation in the histologic presentation. The prognosis and course of the lesion remains the same.

to the tooth-bearing areas of the jaws, although posterior mandibular lesions may extend upward into the ascending ramus. The lesion appears as hard, localized and slow growing, painless mass that may displace adjacent structures and cause root resorption. Exfoliation of teeth may also be seen. Expansion is seen commonly in the inferior border of the mandible, followed by buccal plate expansion. On surgical exploration, the tumor is found to be relatively hypovascular and well demarcated from the surrounding tissue, permitting relatively easy separation from the surrounding bone. This demarcation from the surrounding structure is not seen in fibrous dysplasia and thus can be used to distinguish the two. Radiographic features The lesion appears well circumscribed in contrast to fibrous dysplasia, the borders of which are ill-defined. Initial lesions are radiolucent representing an osteolytic image followed by gradual transformation into a mixed lesion and eventually becoming radiopaque. The periodontal ligament space of the involved teeth is clearly seen unlike fibrous dysplasia. Eversole et al have described two basic radiological patterns: a unilocular radiolucency with or without radiopaque foci, and a multilocular radiolucency. The former presentation is found to be more common. Expansion of the cortical plates is a common finding. Teeth displacement and root resorption may be seen (Figure 1). Histopathologic features Ossifying fibroma shows a range of histologic appearances. It shows fibrous and osseous tissues with the former Figure 1

Etiology Ossifying fibroma occurring in the jaw seems to arise from the periodontal membrane, which contains pluripotential cells capable of forming cementum, bone and fibrous tissue. Clinical features Ossifying fibroma shows a definite female predilection, with the mandible (premolar–molar area) involved more than maxilla in most of the cases. These occur mostly in the 3rd and 4th decades of life. The lesions are restricted

Lateral cephalograph in a patient suffering from ossifying fibroma reveals an extensive expansion of the cortical plate in the mandible. Multilocular radiolucency is evident. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

571


tissue predominating. The fibrous stroma is highly cellular, with spindle-shaped fibroblastic cells arranged in whorls. A fibrous capsule may be seen in some cases. The osseous tissue consists of rounded or lobulated basophilic masses (cementum-like), trabeculae of osteoid, woven or lamellar bone, or combination of the two. Osteoblastic rimming around the trabeculae can be seen. Focal clusters of giant cells (osteoclasts) can be seen to be arranged haphazardly or adjacent to the mineralized material. The histologic differentiation of ossifying fibroma from osteogenic sarcoma may occasionally cause difficulty for the pathologist. Ossifying fibroma shows osseous tissue which is relatively uniform and regularly arranged. On the other hand, in osteogenic sarcoma, the bone spicules and osteoid usually demonstrate irregularity and haphazard arrangement along with significant cellular anaplasia. Management The ossifying fibroma can usually be excised in one piece or removed in several large fragments. Prognosis is excellent and recurrence after removal is seldom seen. There is no evidence of malignant transformation.

Juvenile Ossifying Fibroma (Psammomatoid and Trabecular) Juvenile ossifying fibroma is an uncommon lesion that affects the jaw of children under 15 years of age. Histologically it is composed of cell-rich fibrous tissue containing bands of cellular osteoid, trabeculae of bone and aggregates of giant cells. There are two histologic variants of juvenile ossifying fibroma: psammomatoid and trabecular variants. The lesion is characterized by the early age of onset, the bone pattern, the high tendency to recurrence and the aggressive local behavior. The lesion has been variously described as juvenile ossifying fibroma, active juvenile ossifying fibroma, aggressive ossifying fibroma, reticular desmo-osteoblastoma or active fibrous dysplasia. The term juvenile (aggressive) ossifying fibroma was used in the second edition of the WHO classification of odontogenic tumors to describe a lesion affecting the jaws of children under the age of 15 years. This term is used to describe two distinct histopathologic variants of ossifying fibroma of the craniofacial skeleton. These are referred to here as psammomatoid juvenile ossifying fibroma and trabecular juvenile ossifying fibroma. Psammomatoid juvenile ossifying fibroma was first reported by Benjamins, in 1938, who gave it the designation osteoid fibroma with atypical ossification of the frontal sinus. It was later termed psammomatoid ossifying fibroma of the nose and paranasal sinuses by Gögl, in 1949. The same lesion was later termed juvenile active ossifying fibroma by Johnson et al in 1952. Makek considered the lesion to be a variant 572

of osteoblastoma and termed it psammous desmo-osteoblastoma. Trabecular variant of juvenile ossifying fibroma was described by Reed and Hagy, in 1965. Makek described the trabecular variant as trabecular desmo-osteoblastoma. Etiology Juvenile ossifying fibroma is considered to develop from undifferentiated cells of the periodontal ligament. Clinical features The lesion characteristically occurs under the age of 15 years in 79% of cases. The psammomatoid variant occurs exclusively in the extragnathic craniofacial region especially in the orbital bones and paranasal sinuses (61.6%), and less commonly in the jaws, maxilla (19.7%) and mandible (7%). Few cases have been reported to occur in calvarium, parietal, temporal and frontal bones. In mandible, the tumor occurs more commonly in the ramus than in the body of the mandible. There seems to be no predilection for either sex. Patients often present with symptoms such as exophthalmus, bulbar displacement and proptosis when affecting the orbital bones and paranasal sinuses. In the jaws, the affected region shows a painless expansive swelling of several months. Development of aneurysmal bone cyst in psammomatoid juvenile ossifying fibroma is commonly reported. The cyst tends to occur more commonly in the younger patients in the 1st and 2nd decades of life. The trabecular variant is characterized by a progressive and sometimes rapid aggressive growth. The tumor expands the affected bone, leading to facial asymmetry. It occurs more commonly in maxilla as compared to mandible. Few cases have also been reported in sinonasal region. Slight male predominance has been observed with an average age range of 8.5–12 years. In maxilla, tumor may lead to nasal obstruction, epistaxis and eye displacement. The duration of the lesion is usually a few months. Radiographic features Radiographically, the psammomatoid variant shows welldefined expansion of the affected bone having mixed radiolucent, radiodense and ground-glass appearance. The lesion is partially or completely surrounded with thin, corrugated margins. Sometime multilocular appearance may be seen representing the small cystic spaces. The trabecular variant is expansive, well-defined and unilocular or multilocular with cortical thinning and perforation. The tumor mass is radiolucent with variable calcification-induced radiopacities, occasionally demonstrating fine specks and occasionally producing a ‘groundglass’ appearance. Increase in radiodensity may be observed over time. Root resorption and displacement of involved teeth are also observed.


Histopathogic features Microscopic examination of psammomatoid juvenile ossifying fibroma shows well demarcated but unencapsulated lesion composed of numerous small rounded mineralized collagenous bodies (psammomatoid ossicles) uniformly distributed within a cellular fibroblastic stroma. The cellularity of the fibroblastic stroma varies in different tumors and at different sites within the same lesion. Occasional shrunken cells, representing nuclei of osteocytes, are embedded within the ossicles, and there is usually a collagen outer band to these mineralized bodies. Some of the ossicles may show a basophilic center and eosinophilic fringe. In the periphery of the lesions, some of the ossicles show a transition into small bone trabeculae. The tumor infiltrates and destroys the adjacent bone with focal induction of reactive bone formation. Development of aneurysmal cyst is followed by focal myxoid change in the stroma with hemorrhage and osteoclastic giant cells, with gradual expansion and formation of cysts with thin fibrous walls. The differential diagnosis with other fibro-osseous lesions of the jaw, such as cemento-ossifying fibroma, osteoid osteoma or bone dysplasia, should be made with a mandatory pathological study, and is largely based on the nature of the calcified products of the tumor. The mineralized tissue of central ossifying fibroma is composed of a variable combination of mature and immature bony trabeculae and lobulated basophilic masses of cementum-like material. There may be occasional concentrically laminated particles, called cementicles, but these are not a prominent feature of psammomatoid entity. Microscopic features of trabecular variant of juvenile ossifying fibroma shows an unencapsulated tumor mass infiltrating into the surrounding bone and reactive bone formation at the periphery. The tumors show a characteristic loose structure with cell-rich stroma composed of fibroblastic spindle cells that produce little collagen. Anastomosing trabeculae of osteoid is seen in a pattern that resembles ‘paintbrush’ strokes. The osteoid areas mature into woven bone trabeculae that are rimmed with osteoblasts and show osteocytes embedded in it. Aggregates of osteoclastic giant cells are commonly present and seen in association with the bony trabeculae and in separate foci in the fibrous stroma, usually—but not always—at sites of hemorrhage. Mitotic figures may be observed in the stroma but are never numerous. Cystic degeneration and aneurysmal bone cyst formation have been described in a few cases. Management and prognosis Recurrence after surgical management is common and is reported to range from 30 to 56% in psammomatoid juvenile ossifying fibroma. Recurrence may be attributed to difficulty in proper resection caused by the location of the lesion and the infiltrative nature of tumor borders.

Malignant change has not been reported. Fatal consequences are extremely rare and usually caused by complications arising from direct intracranial extension with resultant encephalitis and meningitis. Trabecular juvenile ossifying fibroma should be conservatively excised in its entirety. Recurrences are seen in 30–50% of cases. More than one excision may be required to achieve cure. No malignant transformation has been reported.

Fibrous Dysplasia Fibrous dysplasia of bone is an uncommon congenital skeletal disorder. It is characterized by the replacement of normal bone and marrow by fibrous tissue, within which irregular trabeculae of woven bone are haphazardly distributed. The maturation of bone is arrested at the woven bone stage. It may affect single (monostotic) or multiple bones (polyostotic) and may be associated with endocrinopathies. A paper by von Recklinghausen in 1891 was probably the first citation of the disease. Albright pointed out two cases that were described by von Recklinghausen as examples of osteitis fibrosa generalisata due to hyperparathyroidism were almost certainly examples of fibrous dysplasia. The term fibrous dysplasia was first suggested by Lichtenstein in 1938 as a designation for multiple bone lesions that were described by Albright et al as osteitis fibrosa generalisata. The lesions of fibrous dysplasia were initially considered to be primarily polyostotic. Lichtenstein and Jaffe later expanded this concept and noted that isolated (monostotic) form of disease also occurred and was by far more common than the polyostotic. McCune and Albright in 1936 and 1937 respectively showed an association of polyostotic fibrous dysplasia with abnormal skin pigmentation, and precocious puberty because of which this association has been termed as McCune–Albright’s syndrome. Jaffe–Lichtenstein described the association of polyostotic fibrous dysplasia with abnormal skin pigmentation; thus it was named as Jaffe–Lichtenstein syndrome. Etiology The molecular mechanism responsible for fibrous dysplasia is a postzygotic activating mutation of the GNAS1 gene that encodes for the Gs␣ subunit of the heterotrimeric G protein complex. The result is constitutive activation of the adenylyl cyclase enzyme and overproduction of 3⬘,5⬘-cyclic adenosine monophosphate. The most common GNAS1 gene mutations are a replacement of arginine by either cysteine or histidine at codon 201 (R201C or R201H), but other mutations have also been identified. The severity of the disease phenotype is thought to depend on when the mutation occurs during embryogenesis. If the mutation occurs during the formation of the inner cell mass, all three germ cell layers will be affected and the phenotype will be 573


McCune–Albright’s syndrome. If it occurs later in development, only one or two germ cell layers will be affected and the phenotype is less severe. Fibrous dysplasia is considered a disease of cells of the mesenchymal stem cell/ osteoblastic lineage in which excess cyclic adenosine monophosphate impairs the ability of the stem cell to differentiate into a mature functioning osteoblast. Clinical features Fibrous dysplasia is mainly diagnosed before the age of 30 years and is equally seen in both the sexes. It occurs both in polyostotic and monostotic forms. Monostotic form is at least six times more common than polyostotic form. In polyostotic form of disease two or more bones are affected generally the long bones, ribs and skull, although any bone may be affected. The lesions are often found unilaterally. Painless expansion of the affected area is most common complaint of the patient. Pathological fracture with resultant pain and bone deformity are other symptoms. Presence of abnormal skin pigmentation with polyostotic fibrous dysplasia is termed as Jaffe–Lichtenstein syndrome. The abnormal hyperpigmentation seen resembles café-au-lait spots which mean coffee with milk. The hyperpigmentation tends to be present on the same side and on the skin overlying the lesions of fibrous dysplasia. The hyperpigmented macules are well-defined and have irregular borders which sometimes distinguish them from the lesions associated with neurofibromatosis. The color can be medium to dark brown. Association of endocrine abnormalities with skin hyperpigmentation and polyostotic fibrous dysplasia is termed as McCune–Albright’s syndrome. A variety of endocrine abnormalities such as accelerated skeletal growth, acromegaly, gigantism, hyperprolactinemia, Cushing’s syndrome, hyperthyroidism, hyperparathyroidism, diabetes mellitus, hypothalamic hypogonadism and hypophosphatemic rickets, gynecomastia, spermatogenesis in young boys and sexual precocity in girls have been associated with the disease. Sexual precocity is the most common endocrine abnormality seen in the affected individual. Male children exhibit enlarged genitalia and advanced secondary sex characteristics. Female children manifest estrogen excess. Monostotic form of the disease is seen in 80–85% of cases. The jaws are the most common areas affected, with the maxillary jaw being more common than the mandibular jaw. The maxillary lesions frequently involve a group of contiguous bones separated by sutures (i.e. maxilla, zygoma, sphenoid and occiput) and thus are not strictly monostotic lesions. Such lesions are more appropriately classified as craniofacial fibrous dysplasia. The craniofacial region is involved in up to 25% of the patients with monostotic fibrous dysplasia, and in approximately 40–60% 574

of those with the polyostotic fibrous dysplasia. Similarly, maxillofacial fibrous dysplasia is the term recently described by Mahajan et al for the lesions which are limited to the facial bones. Painless enlargement of the affected bone is most commonly seen. The patient usually is not able to recall the onset of the swelling. Maxillary and mandibular fibrous dysplasia is associated with significant facial and palatal asymmetries, heterogeneous dental anomalies (rotation, oligodontia, displacement, enamel hypoplasia and hypomineralization, taurodontism, and others), malocclusion, and a high caries index score. Radiographic findings The diagnosis of fibrous dysplasia can be made by radiographs although it is not unusual for bone biopsies to be required because of uncertainty based on radiographs alone. The characteristics, which are somewhat variable, include a ground-glass appearance, which occurs due to superimposition of a myriad of thin, poorly calcified trabeculae. Ground-glass appearance can be best appreciated in a good quality periapical or occlusal view (Figure 2). Early lesions may be radiolucent or mottled. Mandibular lesions sometimes may appear multilocular on the radiograph which is an optical illusion occurring due to endosteal cortical erosion caused by growth of the lesion contrasting with areas of preserved normal cortex. The lesion of fibrous dysplasia is usually ill-defined radiographically;

Figure 2

Mandibular occlusal radiograph showing expansion of the cortical plates and ground-glass appearance in fibrous dysplasia. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore


they tend to blend imperceptibly into the adjacent bone. Foci of irregular or denser calcification may be seen superimposed on ground-glass appearance. Waters’ view of maxillary lesions frequently shows a radiodense area that largely obliterates the maxillary sinus and involves the zygoma and lower rim of the orbit. Most common manifestation of fibrous dysplasia in the skull is the thickening of the occiput and base of skull. Involved dentition shows narrowing of the periodontal ligament space with an illdefined lamina dura that blends with the abnormal bone. Taurodontism of the teeth may also be seen. Involvement of the mandible results in expansion of the cortical plates and bulging of the lower border of the mandible. When long bones are affected in an advanced stage, there may be a Shepherd’s crook deformity of the proximal femur. Computerized tomography (CT) of fibrous dysplasia is useful in demonstrating the ground-glass texture of the lesion and is particularly helpful in defining the extent of craniofacial disease (Figure 3). Magnetic resonance imaging (MRI) does not provide a characteristic appearance of fibrous dysplasia and therefore is a less useful imaging modality.

to be delicate and are not connected to one another. The trabeculae are not sharply defined and along their margins the bone matrix streams out along the collagen fibers that extend from the trabeculae into the neighboring stroma. Under polarizing microscope irregular birefringent fibers of immature or woven bone can be demonstrated. The bone formed is metaplastic in nature thus the trabeculae are not seen to be surrounded by osteoblasts. This form of metaplasia is called a fibro-osseous metaplasia. Older lesions may show lamellar maturation. At the periphery of the lesion pre-existing host lamellar bone may be seen without a clear demarcation between the lesion and the host bone. The fibrous stroma comprises immature appearing small, slender spindle cells in loose and whorled arrangement. Giant cells are usually not seen in lesions of fibrous dysplasia but if seen are usually associated with the pre-existing mineralized tissue. Presumably, they are responsible for spread of the lesion. The microscopic features of macules show excessive deposition of melanin, despite a normal number of melanocytes.


Serum calcium and phosphorus levels are normal. The serum alkaline phosphatase levels may be elevated, roughly corresponding to the extent of the bone lesions. The levels do not increase as seen in Paget’s disease. Urinary hydroxyproline, specific index of bone collagen resorption, can be elevated. In patients with McCune–Albright’s syndrome the various endocrinopathies are associated with elevations of circulating hormones depending on which glands are affected. High levels of growth hormone, prolactin, and thyroid hormones and, less commonly, testosterone, adrenocorticosteroids and parathyroid hormone have been reported. In patients with rickets or osteomalacia, hypophosphatemia and hyperphosphaturia are usually present.

Grossly, the tissue is calcified, firm, gritty or granular. The characteristic microscopic features of fibrous dysplasia comprises a fibrous stroma in which spicules of woven bone are found. The woven bone is present in the form of irregular shaped trabeculae which can be resembled to Chinese script writing (Figure 4). The bone trabeculae tend Figure 3

Laboratory investigations

Figure 4

Computed tomographic image showing expansion of the cortical plate and invasion of the maxillary sinus in fibrous dysplasia. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

The irregular (Chinese letter-shaped) trabeculae of bone in fibrous dysplasia. Courtesy: Department of Oral Pathology, MCODS, Mangalore

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Management and prognosis In most cases, the disease tends to stabilize and essentially stops growing when skeletal maturation is reached. Small lesions, particularly in mandible can be removed by complete resection. However diffuse and larger lesions preclude their removal without extensive surgery. Cosmetic deformity, with associated psychological problems or functional deformity may require surgical intervention. Re-growth of the lesion is seen in 25–50% of the patients after a shave-down procedure. Re-growth after surgical procedures appears to be more common in younger patients suggesting that surgical intervention should be delayed as long as possible. Malignant change in fibrous dysplasia, usually an osteosarcoma rarely has been reported. This risk increases in patients who receive radiation therapy. Thus radiation therapy is definitely contraindicated in fibrous dysplasia. Patients should be kept under long-term follow-up to rule out any malignant changes. Patients with fibrous dysplasia do not have any complications associated with the routine dental care.

BONE DISEASES The bones of the facial skeleton particularly the maxilla and mandible are affected by various diseases. These diseases present with a myriad of clinical features and characteristic oral manifestations. This section will attempt to highlight common bone diseases affecting the maxillofacial skeleton.

Osteogenesis Imperfecta Osteogenesis imperfecta has also been referred to as brittle bone disease, Vrolik syndrome and Ekman–Lobstein syndrome. Osteogenesis imperfecta is an inherited disorder of the connective tissue having an autosomal dominant pattern of inheritance. However, autosomal recessive and nonhereditary types have also been known to occur. The condition is characterized by fragile bones that tend to break easily, often from the mildest of trauma. Pathophysiology The primary pathology in osteogenesis imperfecta is the disturbance in the synthesis of type I collagen (predominant protein of the extracellular matrix of most tissues). In bone, this defect of extracellular matrix causes osteoporosis. The affected bones become weak and fragile thereby making them susceptible to fracture. Type I collagen is also a major constituent of dentin, sclerae, ligaments, blood vessels and skin; therefore, abnormalities of these structures 576

is also seen in individuals suffering from osteogenesis imperfecta. Mutations that interfere with expression of the collagen gene, formation of the triple helix (amino acid sequencing), or procollagen secretion, affect the structure and function of collagen fibrils, resulting in osteogenesis imperfecta. Electron microscopic studies in osteogenesis imperfecta reveals a smaller diameter of the collagen fibril and smaller than normal apatite crystals when compared to that of normal individuals. Mutations in COL1A1 gene on chromosome 17 and the COL1A2 gene on chromosome 7 (genes that encode for the synthesis and/or structure of type I collagen) may cause a combination of production of abnormal collagen and decreased production of normal collagen. The variability in combinations results in the different phenotypic expressions of osteogenesis imperfecta. Milder forms of osteogenesis imperfecta are caused primarily by the decreased production of normal collagen, while more severe forms are caused primarily by the production of abnormal collagen. These abnormalities may be dominantly inherited or the result of sporadic mutation. Classification Dominant or classical osteogenesis imperfecta Majority of the cases of osteogenesis imperfecta (up to 90%) are caused by a dominant genetic defect. These individuals have a 50% chance of passing on the disorder to each of his/her progeny. Though most children in the dominant form inherit the disorder from a parent, some are born with the dominant form of osteogenesis imperfecta even though there is no family history of the disorder. In these children, the genetic defect occurs as a result of a spontaneous mutation. Recessive osteogenesis imperfecta It is believed that approximately 10–15% of cases of osteogenesis imperfecta are caused by a recessive mutation. The parents do not have the disorder but their genes are mutated. To inherit the recessive condition the individual must receive a copy of the mutation from both parents. If one parent has osteogenesis imperfecta because of a recessive mutation, 100% of their children will be carriers of the recessive mutation. Whether any of these children will have the condition will depend on their inheritance from the other parent. Based on the clinical features and molecular studies osteogenesis imperfecta is currently divided into eight types. It is estimated that approximately 85–90% of osteogenesis imperfecta are caused by a dominant mutation in a gene coding for type I collagen. Osteogenesis imperfecta Types I, II, III and IV belong to this category. Types V and VI do not have a type I collagen mutation, but the genes causing them have not yet been identified. Types VII and VIII are inherited in a recessive manner.


Clinical features Type I It is the most common and mildest form of osteogenesis imperfecta. These patients present with normal or close to normal stature. They may have muscle weakness and hypermobility of joints. Since the bones are fragile they tend to fracture easily and most of the fractures occur before puberty. Fragility of the walls of the blood capillaries may be seen. The patients may present with a triangular shaped face. Some authors describe the facies to be similar to that of cleidocranial dysostosis. The skull may be disproportionately large with a temporal bulge thereby causing the ears to be pushed outward and forward. The forehead is broad with frontal bossing giving rise to a mushroom-shaped skull. Hearing loss due to osteosclerosis, may be usually seen in the 2nd and 3rd decades of life. These patients typically present with blue, purple or gray tinted sclera (Figure 5). The sclera in these individuals tends to be extremely thin, therefore allowing the color of the underlying choroid to be transmitted. Most of the patients have normal teeth whereas some may present with opalescent brittle teeth. Histologically collagen has normal structure but the quantity of the collagen present is usually less than normal. Type II It is the most severe and lethal form of this condition. Most infants are still born or die shortly after birth. The death may occur mostly due to respiratory distress or intracerebral hemorrhage. It is estimated that almost 90% of the infants do not live longer than a month. Severe bone deformity and multiple fractures are evident. These individuals have a small stature with underdeveloped lungs. Blue colored sclera is seen. The collagen that is formed is insufficient in quantity and is of poor quality. Dentinogenesis imperfecta may be seen. Based on the radiographic findings of the long bones and ribs, Type II osteogenesis imperfecta is subdivided into groups A, B and C. Type IIA demonstrates broad and short

long bones with broad and beaded ribs. Type IIB shows broad and short long bones with thin ribs that have little or no beading. Type IIC group shows thin and longer long bones with thin and beaded ribs. Type III In Type III osteogenesis imperfecta the bones are extremely fragile and hence have an increased tendency to fracture. Fractures are often present at birth. These individuals are usually short statured. The sclera has a bluish tint. It has been reported that the mortality rate is generally higher at adolescence. Kyphoscoliosis causes cardiopulmonary distress resulting in death. A barrelshaped rib cage is seen. The patients may have a triangular face. Hearing loss can be seen; some patients may present with brittle opalescent teeth. Histologically the collagen is improperly formed. Type IV Individuals suffering from Type IV osteogenesis imperfecta may show mild to moderate bone fragility. It is considered that the severity of this form of the condition is in between the severity of Type I and Type III osteogenesis imperfecta. These individuals may present with a mildto-moderate bone deformity and a slightly shorter than average stature. Bones are fragile and fractures are usually present before puberty. The sclera is generally white (normal) in color. Some patients may present with a faint blue tint. Triangular face and barrel-shaped rib cage is usually seen. Teeth may be brittle and appear opalescent in some patients. Hearing deficits may be encountered. Histologically there is improper formation of collagen. Type V It has a dominant inheritance pattern. Individuals of this form of the condition do not exhibit mutations in type I collagen genes. It mimics the symptoms and signs of Type IV osteogenesis imperfecta. The site of fracture shows hypertrophic calluses. Radiographs of long bones reveal a radiodense band adjacent to the growth plate. The sclera is white and teeth are normal. The characteristic microscopic finding is the presence of ‘mesh-like’ pattern of bone.

Figure 5 Type VI This subtype of osteogenesis imperfecta mimics the symptoms and signs of Type IV. It is believed to be inherited as a recessive trait. The characteristic ‘fish scale’ appearance of bone under a microscope is unique for this type of osteogenesis imperfecta. Blood investigations reveal minimally elevated levels of alkaline phosphatase.

Blue colored sclera. Courtesy: Department of Oral Medicine and Radiology, KLE Institute of Dental Sciences, Bangalore

Type VII It is inherited in a recessive manner. It is believed to originate from mutation to the cartilage associated protein (CRTAP) gene. This type of osteogenesis imperfecta mimics Type IV or lethal Type II. Infants may present with a small head and round face. The sclera are white; other features include short stature, short humerus and femur. Another typical feature is a deformation of the hip joint (coxa vara). 577


Type VIII It is inherited in a recessive manner. It is believed to be caused by the mutation of LEPRE1 gene. The clinical features in this type are similar to those of osteogenesis imperfecta lethal Type II or Type III. However, infants present with severe growth deficiency and white sclera.

of multiple joints usually with flexion deformities, with or without pterygia or webbing at the joints involved) and osteogenesis imperfecta.

Orofacial manifestations

Exercises such as walking, swimming and water therapy, to strengthen bones and muscles are recommended. Patients should be advised to refrain from smoking, alcohol consumption, excessive use of caffeine and use of steroids as these can accelerate the rate of bone depletion. Bisphosphonates such as palmidronate have been used successfully in managing osteogenesis imperfecta. It is believed that palmidronate minimizes the rate of bone loss. It can be administered intravenously in a dosage of 7.5 mg/kg/year at 4–6 month intervals.

Patients suffering from this condition can present with triangular facies as a result of the soft craniofacial bones along with a large and thin calvarium. Osteogenesis imperfecta can be associated with dentinogenesis imperfecta. The color of teeth affected by dentinogenesis imperfecta may vary from blue to gray to brown. The outer enamel may often chip off to reveal the underlying soft dentin. Other skeletal and dental disturbances noted are the frequent presence of a skeletal class III malocclusion (especially in type III and type IV osteogenesis imperfecta) and anterior and posterior crossbites. Radiographic features General radiographic findings The common feature in all forms of osteogenesis imperfecta is osteoporosis. In the milder forms of the disease, the bones exhibit thin cortices and minimal fractures. However, in severe forms of the disease the long bones are stunted and exhibit extensive fractures. The skull is poorly mineralized and exhibits wormian bones. Spinal deformities such as flattened spinal bones (platyspondyly) and S-shaped scoliosis. Other characteristic features associated with osteogenesis imperfecta include cod fish vertebrae, popcorn calcifications in the metaphyseal-epiphyseal region of long bones, especially of the knee and ankle caused due to repeated microfractures at the growth plate, basilar invagination or impression (projection of the tip of the odontoid process above the McGregor line) and Tam O’Shanter skull (caused by large and thin cranium with platybasia). Radiographic findings specific to oral cavity Teeth may have bulbous crowns constricting at the cervical portion and stunted roots. The pulp chamber and radicular portion of the pulp may be partially or totally obliterated. Dental considerations Since most patients especially in the younger age group have high susceptibility for fractures, excessive force should best be avoided during extraction of teeth. Tooth wear may be managed esthetically with restorations or crowns. Syndrome association Datta and others (2005) reported a 34-week pre-term baby suffering from Bruck syndrome, which is a combination of arthrogryposis multiplex congenita (congenital contractures 578

Management

Osteopetrosis Osteopetrosis is also known as marble bone disease and Albers–Schönberg disease. It was first described by Albers–Schönberg, a German radiologist in 1904. Osteopetrosis is a rare disorder of bone that arises from defective differentiation and function of osteoclasts and reduced generation of superoxide by leukocytes. As the osteoclasts fail to resorb bone, the bones become dense and fragile. Bone fragility occurs because very few collagen fibers connect osteons adequately and the remodeling of woven bone to compact bone is defective. This, in turn, will make bones vulnerable to fracture. The actual incidence of osteopetrosis is unknown. However, Beighton et al (1979) reported that the overall incidence of osteopetrosis was approximately one case in 100,000–500,000 population. Pathophysiology The gene for adult osteopetrosis has been mapped to chromosome 1p21 (Van Hul, 1997). Whyte (1999) described few probable reasons for the functional failure of osteoclasts such as abnormalities in the osteoclast stem cell or its microenvironment, osteoblast precursor cells or the mature heterokaryon or in the bone matrix. Other factors that may predispose to altered bone resorption that may influence osteoclastic activity include synthesis of abnormal parathyroid hormone and defective production of interleukin-2 (IL-2). Hofbauer (1999) reported osteopetrosis in cathepsin K (cysteine protease important for osteoclast function) deficient mice. Types Three distinct clinical forms of osteopetrosis are recognized: 1.

Adult form of osteopetrosis (osteopetrosis tarda)—autosomal dominant


2. 3.

Infantile form of osteopetrosis (osteopetrosis congenita)—autosomal recessive Intermediate form of osteopetrosis (marble bone disease)—autosomal recessive.

The other rare varieties of osteopetrosis are transient infantile, lethal and post infectious. Clinical features Adult form of osteopetrosis The adult form of osteopetrosis is usually discovered later in life on radiographic examination. It is believed to be asymptomatic in about 60% of the patients. The usual complaint could be related to bone pain, fractures and osteomyelitis. The typical radiographic finding in osteopetrosis tarda is sclerosis of the axial skeleton. The long bones are generally spared or minimally affected. The adult form has two subtypes: 1. 2.

Type I: Occurrence of fractures is rare, cranial nerve compression, normal serum acid phosphatase levels. Type II: Fractures are commonly seen, cranial nerve is rarely compressed, high levels of serum acid phosphatase levels.

A prominent dental consideration is the susceptibility to develop osteomyelitis following dental extractions. Other oral findings include increased susceptibility to carious lesions, delayed eruption of teeth and/or malformed teeth. Osteopetrosis congenita It is a severe form in which the patient suffers from osteopetrosis at birth or in the first few years of life. This condition is usually fatal due to bleeding, severe anemia or uncontrollable infection. The skeleton reveals generalized sclerosis. Osteopetrosis results in severe bone marrow failure. Subsequently hepatosplenomegaly is seen to compensate for hematopoiesis. Involvement of the cranial foramina results in blindness, deafness and hydrocephalus. The child shows extreme growth retardation. Other orofacial features include frontal bossing, hypertelorism and paranasal sinus malformations. Like other forms of osteopetrosis the jaws are susceptible to osteomyelitis following dental extractions. Marble bone disease The intermediate form of osteopetrosis is not as severe as osteopetrosis congenita. In this form of the disease, bone marrow failure is not seen. These individuals have retarded growth and may present with fractures in the 2nd decade of life. However, they may show intracranial calcifications, macrocephaly and cranial nerve deficits. These individuals also show increased susceptibility to infections. Histopathologic features The presence of remnants of mineralized primary spongiosa that persists as islands of calcified cartilage within mature bone is typical of osteopetrosis.

Other features of abnormal endosteal bone formation are evident such as tortuous lamellar trabeculae replacing the cancellous portion of bone, globular amorphous bone deposition in marrow spaces and osteophytic bone formation. The number of osteoclasts may be increased, normal or decreased, but there is no evidence of functional osteoclasts, as Howship’s lacunae are not visible. In the adult form of osteopetrosis, there is increased amount of osteoid. The osteoclasts are usually few in number and they lack ruffled borders. Occasionally, the osteoclasts may be large in size and may be present in large number. Presence of woven bone may be a common feature. In the infantile form of osteopetrosis, osteoclasts are usually abundant and found at the bone surfaces. Osteoclast nuclei are especially numerous, but the ruffled borders or clear zones that characterize normal osteoclasts are absent and fibrous tissue usually crowds the marrow spaces. Radiographic features There is generalized, homogeneous increase in density throughout the skeleton. The increased density obscures the trabecular pattern such that the cortical bone and cancellous bone cannot be differentiated. Long bones may appear club-like or bone within bone (endobone). The skull shows increased radiodensity, especially at the base. Sinuses are small and not fully pneumatized. The extremely radiopaque vertebrae may exhibit alternating bands which is referred to as known as the rugger-jersey sign. The pelvic bones show subcrestal sclerosis. Radiographic findings of jaws and teeth The maxilla and mandible exhibit increased radiodensity. Owing to the increased radiodensity, internal structures such as teeth and other normal anatomic landmarks are not readily visible. The increased density of bone compromises the vascularity thereby making the jaws susceptible to infections (such as osteomyelitis). Osteopetrosis may cause delayed eruption of teeth. Other dental findings include relatively thickened lamina dura, premature loss of teeth and malformed teeth. Teeth may be susceptible to carious lesions as they are poorly calcified. Management and prognosis Infantile osteopetrosis if untreated will usually result in death in the first few years of life due to bone marrow failure. The only cure for children with severe osteopetrosis is allogenic hematopoietic stem cell transplantation. Askmyr et al (2008) propose the possibility for gene replacement therapy to manage osteopetrosis. In their article, they describe that the hematopoietic stem cell-targeted 579


gene therapy in a mouse model of infantile malignant osteopetrosis has reportedly shown to correct many signs and symptoms of osteopetrosis. Key (1995) conducted a 6-month trial to study the efficacy of recombinant human interferon gamma on osteopetrosis. In the study comprising 14 patients suffering from severe osteopetrosis, they administered subcutaneous injections of recombinant human interferon gamma-1b (1.5 ␮g/kg of body weight per dose) three times per week 6 months. There were no side effects reported. They concluded that long-term therapy with interferon gamma increases bone resorption and hematopoiesis and improves leukocyte function. Corticosteroids have also been used in managing osteopetrosis, though it is not a preferred modality of treatment. Steroids have known to increase the red blood cell mass and platelet count, but they do not improve the bone mass. In another independent study, children suffering from osteopetrosis were administered 1,25-dihydroxy vitamin D. The study showed no improvement in the clinical condition of these children. However, bone biopsies showed evidence of increased osteoclastic bone resorption. Key and others (1984) suggested that large doses of calcitriol (up to 32 ␮g/day) along with the use of calcium deficient diet will stimulate bone resorption by activating the dormant osteoclasts.

Cherubism Cherubism is a non-neoplastic hereditary bone lesion that is histologically similar to central giant cell granuloma. It affects the jaws of children bilaterally and symmetrically, producing the characteristic cherubic appearance. Cherubism has also been referred to as familial or hereditary fibrous dysplasia, bilateral giant cell tumor and familial multilocular disease. Cherubism was first described by Jones in 1933. He termed it familial multilocular disease of the jaws. However, as the cystic nature of the condition was invalidated Jones and others were the first to use the term cherubism. The word ‘cherub’ originally designated a member of the second order within the Christian celestial chorus. These were creatures with severe, staring eyes (including eyes on the wings and the body) and a wheel below the feet. Angels constituted another order within the celestial chorus, and angels with childish, full-cheeked faces, often gazing upward, were widely depicted in baroque art. Thus, the term ‘cherubism’, is actually inappropriate for the disease, because the typical clinical picture does not resemble a classical cherub but a baroque angel. According to the WHO classification, cherubism belongs to a group of non-neoplastic bone lesions affecting only the jaws. It is a rare, benign condition with autosomal dominant inheritance, and it is one of the very few genetically determined osteoclastic lesions in the human body. 580

Genetic basis The locus for the cherubism gene is 4p16. The most reasonable conclusion from the linkage data obtained in a study of four families by Tiziani and others is that the locus for cherubism is located on the telomeric side of D4S1582. Ueki et al detected point mutations causing amino acid substitutions in the SH3-binding protein SH3BP2. Clinical features Cherubism appears to have 100% penetrance in males and only 50–70% penetrance in females. Although the condition is known to be hereditary, in some cases there has been no detectable family history, and although it usually occurs bilaterally, there have also been cases of unilateral involvement, perhaps because of incomplete penetrance or new mutations. Typically, the jaw lesions of cherubism remit spontaneously when affected children reach puberty, but the reason for this remission is unknown. The reduction in osteoclast formation caused by sex steroids and the increase in plasma concentrations of estradiol and testosterone at puberty both suggest that the genetic defect responsible for the localized increase in osteoclasts in cherubism is overridden and normalized by the increased synthesis of sex steroids. Affected children are normal at birth and are without clinically or radiographically evident disease until 14 months to 3 years of age. At that time, symmetric enlargement of the jaws begins. Typically, earlier the lesion appears, the more rapidly it progresses. The self-limited bone growth usually begins to slow down when the patient reaches 5 years of age, and stops by the age of 12–15 years. At puberty the lesions begin to regress. Jaw remodeling continues through the 3rd decade of life, at the end of which the clinical abnormality may be subtle. The signs and symptoms depend on the severity of the condition and range from clinically or radiographically undetectable features to grotesquely deforming mandibular and maxillary overgrowth with respiratory obstruction and impairment of vision and hearing. Cherubism was reportedly fatal in one case, where aspiration occurred because of the grotesque facial deformity. The jaw lesions are usually painless and symmetric swellings, having florid maxillary involvement (Figures 6 and 7). The lesions, which are firm to palpation and nontender, most commonly involve the molar to coronoid regions, the condyles usually being spared, and are often associated with cervical lymphadenopathy. Enlargement of the cervical lymph nodes contributes to the patient’s fullfaced appearance and is said to be caused by reticuloendothelial hyperplasia with fibrosis. The lymph nodes become enlarged before the patient reaches 6 years of age, decrease in size after the age of 8 years, and are rarely enlarged after the age of 12 years. Intraoral swelling of the alveolar ridges may occur. When the maxillary ridge is involved,


Figure 6

Figure 7

Extraoral photograph of a 7-year-old girl with cherubism. Reproduced with permission from editor, JCDA. Ongole R, Pillai RS, Pai KM. Cherubism in siblings: a case report. J Can Dent Assoc 2003;69(3):150–54

the palate assumes a ‘V’ shape. A rim of sclera may be visible beneath the iris, giving the classic ‘eye to heaven’ appearance. Numerous dental abnormalities have been reported, such as agenesis of the second and third molars of the mandible, displacement of the teeth, premature exfoliation of the primary teeth, delayed eruption of the permanent teeth, and transpositions and rotation of the teeth. In severe cases, tooth resorption occurs. Although cherubism was initially described as a familial disease affecting the jaws, cases without any apparent hereditary origin have been reported. In a few cases cherubism has been described as being associated with other diseases and conditions such as Noonan’s syndrome, gingival fibromatosis, psychomotor retardation and obstructed sleep apnea.

Extraoral photograph of the girl’s 14-year-old brother also suffering from cherubism. Reproduced with permission from editor, JCDA. Ongole R, Pillai RS, Pai KM. Cherubism in siblings: a case report. J Can Dent Assoc 2003;69(3):150–54

In order to overcome the limitations of Arnott’s classification, Kalantar Motamedi developed a different classification system, which addresses both the involvement and aggressive behavior of the disease. ❍ ❍ ❍ ❍

❍

Radiographic staging Arnott suggested the following grading system for the lesions of cherubism:

Grade I (divided into five classes): Lesions of the mandible without signs of root resorption Grade II (divided into three classes): Lesions of the mandible and maxilla without signs of root resorption Grade III (divided into five classes): Aggressive lesions of the mandible with signs of root resorption Grade IV (divided into three classes): Lesions involving the mandible and the maxilla and showing signs of root resorption Grade V: Massively growing, aggressive and extensively deforming juvenile cases involving the maxilla and the mandible and which may include the coronoid process and condyles.

❍


Arnott’s staging was not exhaustive and some authors found it difficult to stage their cases.

Cherubism is characterized by bilateral multilocular cystic expansion of the jaws (Figures 8 and 9). Early lesions occur in the posterior body of the mandible and the ascending rami. Maxillary lesions may occur at the same time but escape early radiographic detection because of overlap of the sinus and nasal cavities. Displacement of the inferior alveolar canal has been reported.

Grade I: Involvement of both mandibular ascending rami ❍ Grade II: Involvement of both maxillary tuberosities as well as the mandibular ascending rami ❍ Grade III: Massive involvement of the whole maxilla and mandible except the coronoid process and condyles.

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Figure 8

Orthopantomograph showing bilateral multilocular radiolucencies involving the mandible and displacement of teeth in cherubism in a 7-year-old patient. Reproduced with permission from editor, JCDA. Ongole R, Pillai RS, Pai KM. Cherubism in siblings: a case report. J Can Dent Assoc 2003;69(3):150–54

Figure 9

Orthopantomograph showing bilateral multilocular radiolucencies involving the mandible and displacement of teeth in cherubism in a 14-year-old patient. Reproduced with permission from editor, JCDA. Ongole R, Pillai RS, Pai KM. Cherubism in siblings: a case report. J Can Dent Assoc 2003;69(3):150–54

Destruction of the alveolar cavity may displace the teeth, producing a radiographic appearance referred to as ‘floating tooth syndrome’ (Figure 10). With adulthood, the cystic areas in the jaws become re-ossified, which results in irregular patchy sclerosis. There is a classic (but nonspecific) ground-glass appearance because of the small, tightly compressed trabecular pattern. Histopathologic features Histologic examination of the lesions usually reveals numerous multinucleated giant cells. These multinucleated cells show strong positivity for monoclonal antibody 23c6 582

and tartrate-resistant acid phosphatase, which is characteristic of osteoclasts. The collagenous stroma, which contains a large number of spindle-shaped fibroblasts, is considered unique because of its water-logged, granular nature. The capillaries exhibit large endothelial cells and perivascular capillary cuffing. The eosinophilic cuffing is considered to be a characteristic feature of cherubism. However, these deposits are not present in many cases, and their absence does not exclude the diagnosis of cherubism. Resolving lesions of cherubism show an increase in fibrous tissue, a decrease in the number of giant cells and formation of new bone.


Figure 10

Orthopantomograph showing bilateral multilocular radiolucencies affecting the body and ramus of the mandible in cherubism. The radiograph also shows the lower right second molar appearing to be floating. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore


Treatment

Giant cell granuloma of the jaws, osteoclastoma, aneurysmal bone cyst, fibrous dysplasia and hyperparathyroidism are considered in the differential diagnosis of cherubism. Giant cell granuloma and osteoclastoma are histologically similar to cherubism. However, giant cell granuloma is usually unilateral and usually affects patients between 20 and 40 years of age, whereas cherubism is a symmetric lesion affecting children. Osteoclastoma rarely occurs in the jaws, unlike cherubism. Aneurysmal bone cyst may also exhibit giant cells, but its main feature is a cavity lined with tissue other than endothelium. Both fibrous dysplasia and hyperparathyroidism contain large numbers of osteoclasts. However, histologic examination of the classic form of fibrous dysplasia reveals trabeculae of immature bone resembling Chinese characters within the proliferating stroma. These trabeculae are not rimmed by osteoblasts. Furthermore, polyostotic fibrous dysplasia first presents in the 2nd or 3rd decade of life. Hyperparathyroidism rarely affects the jaw in an isolated manner. Its histologic features differ from those of cherubism in which it does not contain the mononuclear stromal cell population that is characteristic of the latter. Finally, peritrabecular fibrosis is a feature of hyperparathyroidism but not cherubism. Serum concentrations of parathyroid hormone and calcium also help to distinguish these lesions. Levels of serum alkaline phosphatase are generally elevated in cases of fibrous dysplasia. In cases of hyperparathyroidism, levels of serum calcium are elevated, levels of serum phosphorus are decreased and levels of serum alkaline phosphatase are generally within normal levels.

The condition is self-limiting and generally regresses by puberty. Surgery to correct the jaw deformities of cherubism is rarely indicated. If necessary, surgery is usually undertaken after puberty or when severe functional and esthetic problems are reported. Although exacerbation has sometimes been reported after surgery, it is believed that surgery ultimately accelerates the involution process. Liposuction has been used to change the contour of the jaws in a patient with cherubism. The procedure involves removal of the fibro-osseous tissue (consistency of firm Jell-o). This consistency of the tissue makes the removal difficult with bone ronguers and curettes. A blunt suction lipectomy cannula is used to curette the abnormal tissue and then aspirated by a high-suction apparatus. Radiation has been used successfully, but it is discouraged because of possible retardation of jaw growth as well as the risks of osteoradionecrosis and induction of malignancy. The treatment of choice is curettage, but equally good results have been obtained with simple contouring to produce a more cosmetically acceptable appearance. Southgate and others (1998) proposed the possibility of managing cherubism with calcitonin. de Lange et al (2007) report a case of cherubism treated with calcitonin.

Infantile Cortical Hyperostosis Infantile cortical hyperostosis was first described by Caffey (1945) and Silverman. It is also known as Caffey’s disease, Caffey–Silverman syndrome, familial or sporadic infantile cortical hyperostosis. 583


It is a self-limiting, inflammatory process with unknown etiology characterized by hyperostosis or thickening of cortices of various bones in the skeleton. Some authors believe that it is transmitted as an autosomal dominant trait with incomplete penetrance. Other proposed etiological factors include a primary arterial abnormality and an allergic phenomenon. Clinical features As the name suggests the condition is first noticed at birth or in the first few months of life. It has been reported that the average age of onset varies from about 7 to 11 weeks. Infants are usually very irritable and present with tender, deep seated and firm swellings. The swellings are evident on the scalp, face, neck, thorax and extremities overlying the affected bones. Swellings in the mandible may be seen in the ramus and angle of the mandible. Hyperostoses of various bones of the skeleton are seen. The mandible and clavicular bones are reported to be most commonly affected. However, the ribs, skull and long bones have been reportedly involved. Other associated clinical features that have been reported in literature include facial nerve palsy (Challapalli et al, 1998) and Hotlzman (1972) reported Erb’s palsy (form of brachial plexus palsy in which there is paralysis of the muscles of the upper arm and shoulder girdle) in a patient with infantile cortical hyperostosis affecting the scapula. Histopathologic features Initial stages of the condition show periosteal and soft tissue inflammation. In the subsequent stages thickening of the periosteum and immature lamellar bone beneath the periosteum is seen. However, in the advance stage of the disease, no signs of inflammation or subperiosteal changes are evident. Hyperplasia of the lamellar cortical bone is appreciated. Laboratory findings Though laboratory findings are not specific for infantile cortical hyperostosis, elevated erythrocyte sedimentation rate and serum alkaline phosphatase levels are evident. Some patients exhibit leukocytosis and anemia. Kumar et al (2008) reported a patient with Caffey disease having raised immunoglobulins (IgG and IgM) and thrombocytosis. Radiographic features Radiographic evaluation plays an important role in diagnosing infantile cortical hyperostosis. The long bones, clavicle and mandible are most frequently involved. These bones initially reveal periosteal bone formation. With time, the periosteal bone density increases and integrates 584

with the underlying cortical bone. Over time the bone undergoes remodeling to assume normal morphology. The mandible (unilaterally or bilaterally) is affected in almost every patient. The cortices exhibit thickening and sclerosis. Bykov and others (2003) describe a characteristic radiotracer uptake in the mandible in bone scan of a child suffering from localized mandibular Caffey disease. They described the finding as ‘bearded infant’ appearance. Management Caffey disease is almost always self-limiting. It usually regresses without any complications by about 9 months. Literature review shows use of corticosteroids and NSAIDs to manage symptoms and signs of pain and inflammation. Other drugs that have been used with some success are prostaglandin inhibitors such as naproxen and indomethacin.

Idiopathic Osteosclerosis Idiopathic osteosclerosis has also been termed dense bone island and enostosis. It is believed that enostosis is a counterpart of exostoses that occur in the inner surface of the cortical plates within the cancellous bone. It represents a focus of mature compact (cortical) bone within the cancellous bone (spongiosa). The etiology for their occurrence is unknown. These are asymptomatic, benign and usually found on routine radiographic investigations. Greenspan (1995) in a review of enostosis described that enostosis is probably congenital or developmental in origin and represents failure of resorption during endochondral ossification. Characteristic features Idiopathic osteosclerosis have known to occur anywhere in the skeleton. However, the sites that are commonly involved are the pelvis, femur, other long bones, spine and the mandible. McDonnell (1993) in a review of 107 patients reported that the average age at which idiopathic osteosclerosis was discovered was 36 years and women exhibited enostosis twice as much as men. Mandible was most commonly affected. However, he reported the presence of enostosis in the maxilla in a few individuals. The common site of occurrence is the mandibular first molar region. Almost 10% of the enostosis occurring in the mandibular molar region tend to resorb the roots of the mandibular first molar. The typical radiographic appearance is usually a solitary radiopacity with relatively ill-defined or diffuse border. However, occasionally the internal structure of the sclerotic area may show variable radiopacity (Figure 11). Kawai et al (1996) reported a gigantic dense bone island of the jaws. The dimensions of these large enostoses


measured between 2.5 and 7 cm on an orthopantomograph. They concluded that these gigantic dense bone islands were simply larger versions of the dense bone islands seen routinely. Greenspan and Stadalnik (1995) reported that the characteristic findings on a plain radiograph were a homogeneously dense, sclerotic focus in the cancellous bone with distinctive radiating bony streaks (‘thorny radiation’) that blend with the trabeculae of the host bone to create a feathered or brush-like border (Figure 12).

Figure 11

Bone islands are usually ‘cold’ on bone scintigraphy. However, one should be aware of the fact that some harmless bone islands can mimic aggressive lesions on a bone scan. No treatment is required. The clinician should differentiate these dense bone islands from other bone pathologies that may require active treatment.

Gorham’s Disease Gorham’s disease is also called Breschet–Gorham syndrome, Gorham’s osteolysis, Gorham’s syndrome, Gorham– Stout syndrome, massive osteolysis, vanishing bone disease and phantom bone disease. Gilbert Breschet, Lemuel Whittington Gorham and Arthur Purdy Stout were the first few people who described this condition. However, JBS Jackson in 1838 published the first case report. Subsequently Gorham and coworkers (1954) and Gorham and Stout (1955) reported patients suffering from massive osteolysis. Gorham’s disease is a rare condition characterized by proliferation of vascular channels that result in destruction and resorption of the osseous matrix. Etiopathogenesis

Cropped orthopantomograph revealing small radiopaque foci approximating the apices of the mandibular first premolar and second molar. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

In this condition, the normal bone is replaced by an aggressively expanding, non-neoplastic vascular tissue. The aggressively proliferating neovascular tissue causes massive bone loss. In a study by Graham and Stout, they showed an association between vanishing bone disease and the presence of hemangiomatous or lymphangiomatous tissue. However, they were not able to demonstrate osteoclasts in the region of bone resorption.

Figure 12

Orthopantomograph revealing enostoses in relation to the mandibular right second molar, second premolar and mandibular left first premolar. The radiopaque foci are homogeneously dense and blend into the normal trabecular bone pattern producing a brush like border. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

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Many other investigators however demonstrated osteoclasts in the lytic front of the lesion. The role of osteoclasts is supported by the fact that the use of calcitonin and bisphosphonates (inhibitors of osteoclastic activity) to treat patients suffering from Gorham’s disease arrests bone resorption. Devlin and others (1996) proposed that interleukin-6 (IL-6) can be a potential mediator of the massive osteolysis. They found that the levels of cytokine IL-6 increases almost by seven times when compared to the levels in a normal patient. They believe that there are multiple sources of interleukins such as the blood vessels or dilatation of the vascular marrow or the osteoclasts or cells in the bone marrow microenvironment, including monocytes, fibroblasts, and lymphocytes are potential sources of IL-6. Clinical features Gorham’s disease is usually discovered in the first 4 decades of life. However it may affect any age group and exhibits no sex predilection. The disease commonly affects the pelvis and shoulder. Other sites that are affected are the scapula, clavicle, maxillofacial skeleton, ribs, spine, skull and the bones of the extremities. Severe complications include paraplegia, when the spine is involved and respiratory difficulty when the thorax involved. It is believed that the maxillofacial skeleton in involved in about 25 to 30% of the patients. Deformed mandible or maxilla causes malocclusion, mobility of teeth and occasionally results in pathological fracture. Classification of idiopathic osteolysis (Hardegger et al, 1985) Type 1 Hereditary multicentric osteolysis with dominant transmission. Usually seen between the age of 2 and 7 years. Associated with spontaneous pain and swelling beginning in the hands and feet. Carpotarsal osteolysis occurs over the period of a few years. The progression ceases normally in adolescence. Type 2 Hereditary multicentric osteolysis with recessive transmission similar to type 1, but may be associated with severe generalized osteoporosis. Type 3 Non-hereditary multicentric osteolysis with nephropathy. It appears in childhood. There is a gradual disappearance of the carpus with the tarsal bones involved, but to a less degree. Proteinuria is seen. Death occurs usually due to renal failure and malignant hypertension. Type 4 Gorham’s massive osteolysis (Gorham–Stout syndrome). Monocentric occurrence in any part of the skeleton may start at any age. Normally ‘hemangiomatous tissue’ is found in the osteolytic region. It has neither a hereditary 586

pattern nor an associated nephropathy. The disease is benign and the osteolysis usually stops after a few years. Type 5 Winchester syndrome with autosomal recessive transmission. Rare childhood carpotarsal osteolysis in association with contractures, shortness of stature, skin lesions, corneal clouding and osteoporosis without nephropathy. Diagnosis and investigations The typical radiographic features will help in definitive diagnosis of Gorham’s disease. Laboratory tests are generally not diagnostic and usually the blood tests are within normal limits. However, the serum alkaline phosphatase level may be slightly elevated. Plain radiographs, bone scans, CT and MRI can be used to evaluate the osteolysis. The initial changes include radiolucent foci in the medullary portion of the bone with illdefined margins. As the disease progresses these foci coalesce together and involve the cortical plates and subsequently large portion of bone undergo dissolution or ‘disappear’. Orthopantomographs may reveal thinned-out cortical plates and loss of lamina dura. Histologic features Histologically, proliferation of thin walled vessels is seen. As the disease advances, extensive osteolysis is seen. Subsequently the osseous tissue is replaced by fibrous tissue. Management and prognosis The prognosis of massive osteolysis is relatively good unless vital structures are involved. Generally massive osteolysis has poor prognosis when the spine and viscera are affected. The major cause for mortality or morbidity in Gorham’s disease is the development of chylothorax (presence of lymphatic fluid in the pleural space) due to direct extension of the dilated lymphatic vessels into the pleural cavity. Though various treatment modalities have been used in the management of massive osteolysis, no single treatment modality has proven to be effective in controlling the disease process. Various non-surgical methods have been tried such as radiation therapy (40–45 Gy in 2 Gy fractions), anti-osteoclastic drugs (bisphosphonates) and alpha-2b interferon. Surgical management includes resection of the lesion followed by reconstruction using bone grafts. Surgical defects can also be cosmetically masked with prostheses.

Paget’s Disease of Bone Paget’s disease was first described by Sir James Paget in 1877. He called this condition osteitis deformans as he believed it was an inflammatory bone condition. Rhodes and Jawad suggested that as the pathology is now known


to be a disorder in bone turnover and not an inflammatory condition, the term ‘osteodystrophia deformans’ is more appropriate needs wider recognition. Paget’s disease of bone is characterized by excessive osteoclastic bone resorption in a focal area that is accompanied by an increased osteoblastic bone deposition. This abnormal resorption and deposition of bone results in weakened and distorted architecture of bone. Etiology and pathophysiology The etiology of Paget’s disease is still unknown. Some of the well accepted causes include viral infection and genetic predisposition. Helfrich and Hockling (2008) describe that the disease has a genetic basis and mutations in SQSTM1 gene have been associated with familial and sporadic disease in up to 40% of cases. SQSTM1 gene encodes sequestosome 1, also known as p62, which is an ubiquitin-binding protein that is involved in the IL-1, TNF and RANKL signaling pathways. In Paget’s disease, osteoclast precursors have also been shown to be hyperresponsive to the RANK ligand (RANKL), a member of the tumor necrosis factor-alpha superfamily, which promotes osteoclast genesis. One possibility is that increased expression of RANKL contributes to the localized nature of the disease. Macrophage-colony stimulating factor (M-CSF) may play a role in Paget’s disease. M-CSF is a growth factor produced by many cells, including osteoblasts and marrow fibroblasts. Significantly high levels of M-CSF have been found in patients with untreated Paget’s disease. Several genetic theories also suggest that human leukocyte antigen (HLA) on chromosome 6 and the gene on chromosome arm 18q may play important roles in Paget’s disease. The other popular hypothesis for the etiology of Paget’s disease is the action of slow virus (slow viruses are those that produce diseases with extended or prolonged incubation periods). The measles virus messenger RNA sequences have been found in osteoclasts and other mononuclear cells of pagetic bones. Canine distemper virus nucleocapsid antigens have also been found in osteoclasts from patients with Paget’s disease. According to this hypothesis, bone marrow cells (the progenitors of osteoclasts) are infected by a virus that causes an abnormal increase in osteoclast formation. Progression of disease The progression of Paget’s disease passes through three phases, namely, the lytic phase, mixed or intermediate phase and the sclerotic phase. In the lytic phase, there is increased bone resorption. There is increased number of osteoclasts at the site of resorption. These osteoclasts have typically multiple nuclei

(almost around 100 nuclei compared to five to ten in normal osteoclasts). In the intermediate phase, as the bone is rapidly resorbed, there is an increased amount of bone formation with numerous osteoblasts which are morphologically normal. The new bone formed is abnormal with the collagen fibers being laid down in a haphazard manner. In the sclerotic phase bone formation occurs at a rapid pace. The bone thus formed is disorganized (woven bone) which is structurally weak. Fibrous connective tissue and blood vessels invade the woven bone leading to a state of hypervascularity of the bone. As time progresses there is diminished hypercellularity resulting in the formation of a pagetic bone. This state is referred to as burnt-out Paget disease. Clinical features Paget’s disease of bone affects individuals over the 4th decade of life. The incidence increases with the advancing age. It is believed that males are twice as more likely to be affected than females. It is common in Europe, North America, Australia and New Zealand and almost always affects whites. Paget’s disease is rare among Asians and Africans. A series of articles by Joshi et al (2006), Anjali et al (2006), Bhadada et al (2006) studied the prevalence and presentation of Paget’s disease in various parts of India. They reported the mean age at which the condition was diagnosed was in the 5th decade. The male-to-female ratio of occurrence was 2.5:1. Paget’s disease follows a chronic course. It is estimated that about 80% of the patients are asymptomatic and the disease is recognized on routine radiographic examinations. Though the disease affects multiple bones, almost 17% are unifocal (monostotic). The common bones that are involved are the bones of the axial skeleton (spine, pelvis, sacrum, femur and the skull). The common signs and symptoms are bone pain, deformed bones, neurological deficits secondary to compression of the neural tissues. Other patients present with a range of symptoms that may include pathologic fractures, congestive heart failure, hearing loss (compression of eighth cranial nerve), and dysesthesias and weakness from nerve root compression. Patients present with bowed legs and associated abnormalities in the gait. Some authors describe the gait as waddling or simian gait. Spinal deformities such as spinal stenosis or kyphosis are seen. Some individuals exhibit increased size of the skull with or without frontal bossing and enlargement of the middle third of the face, mimicking the face of a lion (leontiasis ossea). Patients generally find the need to change hats to accommodate the growing size of the head. Pathologic fractures are common in Paget’s disease. However, the healing is normal. 587


Oral manifestations The maxilla and mandible can be affected. It is estimated that the maxilla is almost twice as commonly affected than the mandible. The involved jaw will be enlarged. Enlarged maxilla will cause widening of the alveolar ridge and flattening of the palatal vault. Spacing between teeth may be a secondary complication. In advanced cases, the lips fail to cover the enlarging jaws resulting in an open mouth state. Laboratory investigations Patients with Paget’s disease may demonstrate very high levels of serum alkaline phosphatase (helps to estimate bone formation), especially when multiple bones are affected. It is believed that the total alkaline phosphatase levels have only 78% sensitivity of detecting Paget’s disease. Therefore, bone specific alkaline phosphatase levels are more accurate. However, serum calcium and serum phosphorus levels are normal. Other investigations that can help in the identification of the extent and severity of bone turnover include estimating levels of deoxypyridinoline and N-telopeptide of type I collagen (help in estimating amount of bone resorption). Urinary excretion of deoxypyridinoline and N-telopeptide are elevated. Alpha-alpha type I C-telopeptide fragments are sensitive markers of bone resorption for assessing disease activity and monitoring treatment outcome. Radiographic features The radiographic findings in Paget’s disease depend on the phase of the disease. Radiographs may exhibit areas of osteolysis and areas of bone deposition or an intermediate phase. There are very unique radiographic features of Paget’s disease such as osteoporosis circumscripta, blade of grass lesion, brim sign, framed vertebrae and cotton-wool appearance. Osteolytic zones in the skull represented by large circumscribed radiolucent areas are referred to as osteoporosis circumscripta (usually seen in the frontal and occipital bones). In the intermediate phase, as bone deposition occurs, areas of patchy sclerosis are seen in the skull and the jaws, giving rise to the cotton-wool appearance. Hypercementosis and loss of lamina dura around the roots of teeth is usually seen in Paget’s disease. Rarely, root resorption may be seen. Long bones of the skeleton reveal a V-shaped pattern that divides the healthy bone from its pagetic counterpart. This unique finding is termed ‘blade of grass’ lesion. Thickening of the iliopectineal line in the pelvic bone is termed ‘brim sign’. Enlargement of the vertebral bodies with thickened cortices and vertical striations gives rise to the appearance of ‘framed vertebrae’. 588

On radionuclide imaging, the radiopharmaceutical is markedly taken up by the pagetic bone. Extensive involvement of the mandible may occasionally reveal the uptake of the radiopharmaceutical from condyle to condyle giving rise to the Lincoln’s sign or the ‘black beard’ sign. Histologic features The histologic features depend on the phase of the disease process. The pathognomonic feature in Paget’s disease is the presence of the basophilic resting and reversal lines which are indicative of the junction between the resorptive and formative phases of bone that results in the appearance of mosaic pattern or jigsaw puzzle pattern of bone. The bony trabeculae will reveal prominent osteoblastic and osteoclastic activity. Dental considerations During the active phases of the disease process, invasive oral surgical procedures may result in extensive bleeding due the vascularity of the diseased bone. Hypercementosis of teeth may make dental extractions difficult. Patients on treatment with bisphosphonates are more likely to develop chemo-osteonecrosis even with minimal trauma. Dental extractions should be best avoided during the treatment. Similarly, in the advanced phases of the disease, the bone is susceptible to infections and pathologic fracture. Patients may require frequent replacement of oral prosthesis to accommodate for the ever increasing size of the jaws. Management In symptomatic patients, bone pain can be managed with NSAIDs. The drugs routinely used are calcitonin (osteoclast inhibitor) and bisphosphonates (anti-resorptive agents). These drugs minimize the bone turnover rate. New generation bisphosphonates such as pamidronate, etidronate, tiludronate, alendronate and risedronate are preferred over calcitonin. The recommended dosages of these drugs are etidronate (400 mg/day for 6 months), pamidronate (single IV infusion of 60 mg to a maximum of 90 mg per day for 3–4 days diluted in saline or glucose solution for 46 hours), alendronate (given orally 20–40 mg/day for 6 months), tiludronate (400 mg/day for 3 months) and risedronate (30 mg/day for 2 months). All patients treated with bisphosphonates should be given calcium and vitamin D supplements. Keating and Scott (2007) described the efficacy of zoledronic acid, a third generation, nitrogen containing bisphosphonate in the management of Paget’s disease. They describe that a single intravenous dose of zoledronic acid 5 mg is effective and well tolerated in the treatment of Paget’s disease of bone. A single IV dose of zoledronic


acid was associated with a significantly higher therapeutic response rate and a more rapid reduction in bone turnover than that achieved with 60 days of oral risedronic acid. Moreover, biochemical remission was sustained after 24 months of follow-up in zoledronic acid recipients. Cytotoxic drug such as mithramycin (plicamycin) has also been tried where the disease is refractory to bisphosphonates. However, it is seldom used these days.

Surgical management may be required mainly for decompression of the nerves. Prognosis It is believed that about 1% of the patients develop osteosarcoma as a complication of Paget’s disease. Benign and malignant giant cell tumors have also known to occur in these patients.

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CHAPTER

20

Autoimmune Disorders Balaji Rao B, Sumanth KN

➧ Concepts of Immunity and Autoimmunity

Sjögren’s Syndrome Mikulicz’s Disease (Benign Lymphoepithelial Lesion) Aphthous Stomatitis (Aphthous Ulcers, Canker Sores, Recurrent Aphthous Stomatitis) Giant Cell Arteritis Periodontal Disease Rheumatoid Arthritis

Systemic Autoimmune Diseases with Orofacial Manifestations ➧

Pemphigus Pemphigus Vulgaris Pemphigus Vegetans

CONCEPTS OF IMMUNITY AND AUTOIMMUNITY The human body has the ability to resist almost all types of organisms or toxins that tend to damage the tissues and organs. This capacity is termed immunity. A specific type of immunity that arises from general processes, rather than from specific disease organisms is called innate immunity. In addition, the human body has the capability to develop extremely powerful specific immunity against individual invading agents such as lethal bacteria, viruses, toxins, etc. This is called acquired immunity. Acquired immunity is caused by special immune system that forms antibodies and activated lymphocytes that attack and destroy specific organisms or toxins. Two basic forms of acquired immunity occur in the body. In one of them the body develops circulating antibodies, which are globulin molecules in the blood that are capable of attacking the invading agent. This type of immunity is called humoral immunity or B-cell immunity (because B-lymphocytes produce the antibodies). The second type

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Pemphigus Foliaceous Brazilian Pemphigus Pemphigus Erythematosus Paraneoplastic Pemphigus Bullous Pemphigoid Cicatricial Pemphigoid ➧

Epidermolysis Bullosa Acquisita

➧

Systemic Lupus Erythematosus

➧

Autoimmune Polyendocrinopathy– Candidiasis-Ectodermal Dystrophy

➧

Diabetes Mellitus Type I (IDDM)

➧

Systemic Sclerosis

➧

Myasthenia Gravis

of acquired immunity is achieved through the formation of large umbers of activated lymphocytes that are specifically designed to destroy the foreign agent. This type of immunity is called cell mediated immunity or T-cell immunity (because the activated lymphocytes are T-lymphocytes).

Autoimmunity Failure of the immune system to tolerate (antigen-specific immunological unresponsiveness) self-tissues. It is a condition in which structural or functional damage is caused by the action of immunologically competent cells or antibodies against normal components of the body. When the concept of autoimmunity came to be accepted as a pathogenic mechanism, a large number of diseases were suggested to have an autoimmune etiology, based on the finding of autoantibodies in the patients. However, autoantibodies have also been found in the serum or tissues of otherwise normal and healthy elderly individuals. Autoantibodies are also formed following tissue injury and may serve a role in the removal of the products of tissue

Chapter 20 – Autoimmune Disorders

breakdown. This lead to the need to formulate criteria for diagnosing autoimmune diseases.

orofacial region. Sumanth and Balaji Rao have proposed a simpler classification of autoimmune diseases that affect the orofacial region.

Diagnostic criteria for autoimmune disorders

1.

The first criterion for recognizing autoimmune disease was given by Witebsky in 1957. This criterion was extended by many authors. Robert H Waldman documented the following criteria: 1.

2. 3. 4. 5.

a.

Circulating or localized populations of cells sensitized to antigen, or products of immunologically activated cells, active under physiologically conditions should be demonstrated, or b. Circulating or localized populations of cells sensitized to antigen, or products of immunologically activated cells, active under physiological conditions, should be present Sensitizing antigen should be identified and characterized Antibodies or sensitized lymphocytes should be produced in vitro or in animals against the same antigen Pathological events in vitro or in the experimental animal should correspond to those in human disease Transfer of disease from immunized to normal animal by cells or serum.

Classification of autoimmune diseases Fergusson (1995) categorized autoimmune diseases as organ specific and non-organ specific. 1.

2.

Organ specific autoimmune diseases a. Hashimoto’s thyroiditis b. Primary myxedema c. Thyrotoxicosis d. Pernicious anemia e. Autoimmune atrophic gastritis f. Autoimmune Addison’s disease g. Type I diabetes mellitus h. Goodpasture’s syndrome i. Myasthenia gravis j. Sympathetic ophthalmia k. Autoimmune hemolytic anemia l. Idiopathic thrombocytopenic purpura m. Primary biliary cirrhosis n. Chronic active hepatitis o. Sjögren’s syndrome Non-organ specific autoimmune diseases a. Rheumatoid arthritis b. Dermatomyositis c. Systemic sclerosis d. Systemic lupus erythematosus (SLE).

Various classifications in literature do not necessarily group autoimmune diseases that specifically affect the

2.

Autoimmune disorders affecting orofacial region predominantly a. Sjögren’s syndrome (Gougerot–Sjögren syndrome) b. Benign lymphoepithelial lesion (Mikulicz’s disease) c. Aphthous stomatitis d. Periodontal disease e. Giant cell arteritis (temporal arteritis) Systemic autoimmune disorders with orofacial manifestations a. Pemphigus b. Bullous pemphigoid c. Cicatricial pemphigoid d. Epidermolysis bullosa acquisita e. SLE f. Bullous SLE g. Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) h. Myasthenia gravis i. Dermatomyositis j. Systemic sclerosis k. Idiopathic thrombocytopenic purpura.

Sjögren’s Syndrome (Gougerot–Sjögren Syndrome) Described in Chapter 11 (Diseases of Salivary Glands) on page 265.

Mikulicz’s Disease (Benign Lymphoepithelial Lesion) Described in Chapter 11 (Diseases of Salivary Glands) on page 265.

Aphthous Stomatitis (Aphthous Ulcers, Canker Sores, Recurrent Aphthous Stomatitis) Described in Chapter 7 (Vesiculobullous Disorders) on page 174.

Giant Cell Arteritis Giant cell arteritis is a relatively common form of large vessel vasculitis occurring predominantly in elderly individuals. The mean age of onset is 70 years with a 2:1 female-to-male ratio. Temporal artery is the common artery that is involved in cranial arteritis (Figure 1).

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Figure 1

The prominent temporal artery in a patient suffering from temporal arteritis. Courtesy: Dr C Stephen Foster, The Ocular Immunology and Uveitis Foundation, Cambridge, Massachusetts, USA

Muki proposed an autoimmune basis for giant cell arteritis because it occurred more frequently in patients with other autoimmune disorders such as thyroid disease or rheumatoid arthritis. Clinical features ❍ ❍

The temporal artery is extremely tender on palpation. The individual may complain of deep aching or throbbing pain and burning sensation over the muscles. ❍ The pain may radiate to the maxilla, mandible, neck or face. Diagnosis The definitive diagnosis is based on temporal artery biopsy, which demonstrates giant cell arteritis and elevated erythrocyte sedimentation rate. Management The condition once recognized should be treated aggressively with corticosteroids. Approximately 50% of the patients who have not been treated in time may develop blindness.

Periodontal Disease For almost two decades the concept of autoimmune pathogenesis for periodontal disease was considered. Alphonse et al (1981) have detected rheumatoid factor by latex slide agglutination in subgingival plaque,

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inflamed gingival tissue, stimulated pooled saliva and serum of patients suffering from chronic moderate periodontitis. They correlated the presence of rheumatoid factors to the periodontal disease and concluded an autoimmune origin of the disease. Ftis et al (1986) found increased levels of antibodies to type I collagen in patients with periodontal disease than in control subjects. Hirsch et al (1988) used enzyme-linked immuno spot test to enumerate antibody secreting cells to human collagen types I–IV by cells isolated from gingival and peripheral blood of individuals suffering from adult periodontitis. Analysis revealed the presence of high numbers of cells that secreted antibodies to type I collagen when compared to type III. They suggested that autoimmunity may contribute to the pathogenesis of this common disease. Anusaksathien and Dolby (1991) postulated many possible explanations to explain the presence of autoantibodies in periodontal disease. 1.

2. 3.

4. 5. 6.

Enhanced presentation of self-antigens through increased expression of the molecule associated with antigen presentation, namely, Ia antigen. Altered T helper or T suppressor cell function. Polyclonal activation of cells which have the ability, for reasons which may not be clear, to produce autoantibodies. Idiosyncrasies of the antigen-idiotype network. Bacterial or viral cross-reactivity with self-antigen leading to the production of cross-reactive antibodies Genetic predisposing factors.

Rheumatoid Arthritis Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder that may affect many tissues and organs— skin, blood vessels, heart, lungs and muscles—but principally attacks joints, producing a non-suppurative proliferative synovitis that often progresses to destruction of the articular cartilage and ankylosis of joints. Although the cause for RA remains unknown, there is convincing evidence that autoimmunity plays a pivotal role in its chronicity and progression, likening this condition to other so-called connective tissue diseases. RA can affect the TMJ. Pathogenesis It is currently believed that RA is triggered by the exposure of an immunogenetically susceptible host to an arthritogenic microbial antigen. The involved mechanisms in the causation could be: 1.

Genetic susceptibility: Rosenberg and Nuki have shown that 65–80% of the individuals suffering from


2.

3.

4.

RA have human leukocyte antigen (HLA)-DR4 and HLA-DR1 or both. Other haplotypes like DW4, DW10, DW13, DW14 and DW15 have also been implicated. Primary exogenous arthritogen: Roudier et al proposed Epstein–Barr virus as the primary microbial agent for the causation of RA. Other microbial agents like retroviruses, parvoviruses, mycobacteria, borrelia and mycoplasma could also initiate the disease. Autoimmune reaction: Warder in 1940 proposed the presence of rheumatoid factor, which was the first human autoantibody described in association with RA. Although T cells played a primary role in the pathogenesis of RA, B cells were also involved. In 1993, Panayi reported that approximately 80% of patients have rheumatoid factors which were directed against Fc portion of IgG, present in serum and synovial fluid. The presence of rheumatoid factors in the joints is believed to contribute to the inflammatory reaction. Williams in 1996 observed that rheumatoid factors showed principal specificity for structures on C3 and C2 (Fc) domains of IgG, which thus defined rheumatoid factor as an autoantibody associated with RA. Mediators of tissue damage: Panaji in 1993 reported that the rheumatoid synovium was heavily infiltrated with lymphocytes, most of which were CD4 helper T cells. They generate cytokines, which in turn could activate other immune cells and macrophages.

2.

3.

The changes of RA most useful for diagnosis are noted in the hands and wrists. They include swan neck deformity, ulnar deviation, dorsal interosseous muscle atrophy and swelling of wrist. Temporomandibular joint manifestations It is believed that TMJ symptoms develop in more than one-third of the patients during the first year of RA. According to Tegellerg and Kopp (1987) and Votalia (1964), the most characteristic clinical signs of RA affecting the TMJ were palpatory tenderness of the joint, crepitus from the joint and swelling in relation to the TMJ region. Almost 60% of the individuals present with bilateral involvement of joints. Severe RA involving the TMJ can result in a progressive anterior open bite due to bilateral destruction of mandibular condyles. Hugh Ogus described a possible course of rheumatoid involvement of the TMJ. He proposed that the TMJ involvement progresses through three phases: 1.

Clinical features

2.

❍

3.

❍ ❍ ❍ ❍ ❍ ❍

It can occur at any age, but bimodal peaks are seen at 40 and 60 years of age. Women are two-and-half times more likely than men to develop disease. Patients complain of polyarthralgias, fatigue and muscle aches. Prolonged morning stiffness of joints. Joints of the hands, feet, elbows, shoulders, knees and TMJ are affected. Within weeks of affliction, the involved joints become tender and marked swelling is seen. Low-grade fever, malaise, anorexia and weight loss is seen.

1.

Joints that are usually affected—ankles, cervical spine, elbows, hips, knees, metacarpophalangeal joints, metatarsophalangeal joints, proximal interphalangeal joints, shoulders, tarsal joints, temporomandibular joints and wrists.

Active phase (acute symptoms, synovial effusion, destruction of fibrocartilage and erosion of underlying bone) Healing phase (remodeled and flattened articular surface) Secondary osteoarthrotic phase (marginal proliferations and further destruction of the condyle, predominant clinical finding of crepitus).

Radiographic features of rheumatoid arthritis affecting the TMJ 1.

2.

Joint manifestations Katz classified the joint manifestations as:

Unusually affected joints—carpometacarpal joints, cricoarytenoid joint, sacroiliac joints and sternoclavicular joint. Rarely affected joints—distal interphalangeal joints, lumbar spine.

3. 4.

Formation of new bone (marginal proliferation) was described in 1975 by Hugh Ogus. It is reported that the erosions of the articular surface were the most important diagnostic finding of RA in other joints and not the TMJ. Subcondylar cystic destruction and severe destruction of bone eventually lead to complete loss of condyle. Such destruction will give the remaining condylar bone the shape of the mouth piece of a flute. Anterior open bite and reduced joint space (due to destruction of articular cartilage). The most characteristic radiographic signs of RA in the TMJ are erosions of cortical outline and reduced joint space (Figure 2) as proposed by Akerman et al in 1988.

593


Figure 2

Erosions of the cortical outline of the condyle and reduced joint space. Courtesy: Department of Oral Medicine and Radiology, MCODS, Mangalore

Kopps in 1995 stated that the radiographic diagnosis of RA in TMJ was difficult. However, absence of radiographic changes in the TMJ will not exclude the possibility of early RA in TMJ. Extra-articular manifestations of rheumatoid disease A. Systemic manifestations 1. 2. 3. 4.

Fever Weight loss Fatigue Increased susceptibility to infections

1. 2. 3. 4.

Pleural effusions Fibrosing alveolitis Bronchiolitis Caplan’s syndrome

G. Cardiac 1. 2. 3. 4. 5.

Pericarditis Myocarditis Endocarditis Coronary vasculitis Granulomatous aortitis

B. Musculoskeletal manifestations

H. Ocular

1. 2. 3.

1. 2. 3. 4.

Osteoporosis Bursitis Muscle wasting

C. Hematological manifestations 1. 2. 3.

Anemia Thrombocytosis Eosinophilia

Laboratory findings ❍

1. 2. 3.

❍

Visceral arteritis Pyoderma gangrenosum Digital arteritis

1. 2. 3. 4.

Cervical cord compressions Compression neuropathies Peripheral neuropathies Mononeuritis multiplex

Episcleritis Scleritis Scleromalacia Keratoconjunctivitis sicca

I. Amyloidosis.

D. Vasculitis

E. Neurological

594

F. Pulmonary

❍ ❍ ❍

None of the multiple blood, synovial fluid or biopsy studies is specific for RA. These individuals exhibit increased ESR levels and anemia. 50% of the patients show presence of antinuclear antibody (ANA). 80% of patients exhibit significant elevations of rheumatoid factor (not diagnostic). Rheumatoid synovial fluid is generally cloudy and tinged green.


Diagnosis The diagnosis of RA is based on a carefully obtained history and a diligent physical examination to unravel subtle signs of inflammation. One should strive to detect the condition as early as possible to prevent crippling deformities. The American Rheumatism Association diagnostic criteria aid in clinical diagnosis. These criteria were designed principally for research and literary purposes. A. Classical rheumatoid arthritis This category requires seven of the following criteria to match. In criteria 1 through 5, the joint signs or symptoms must be continuous for at least 6 weeks. 1. 2.

Morning stiffness. Pain on motion or tenderness in at least one joint (observed by the physician). 3. Swelling (soft tissue thickening or fluid, not bony overgrowth alone) in at least one joint (observed by a physician). 4. Swelling (observed by a physician) of at least one additional joint (symptom free period between the two joint involvements may not be more than 3 months). 5. Symmetrical joint swelling (observed by a physician) with simultaneous involvement of the same joint on both sides of the body (bilateral involvement of proximal interphalangeal, metacarpophalangeal or metatarsophalangeal joints is acceptable without absolute symmetry). Involvement of the terminal phalangeal joint will also satisfy this criterion. 6. Subcutaneous nodules (observed by a physician) over bony prominences, on extensor surfaces or in juxtaarticular regions. 7. Radiographic changes typical of RA (which must include at least bony decalcification localized to or most marked adjacent to the involved joints and not just degenerative changes). Degenerative changes do not exclude patients from any group classified as RA. 8. Positive agglutination test—demonstration of the ‘rheumatoid factor’ by any method which, in two laboratories, has been positive in not over 5% of normal controls—or positive streptococcal agglutination test (the latter is now obsolete). 9. Poor mucin precipitates from synovial fluid (with shreds and cloudy solution). 10. Characteristic histologic changes in synovium with three or more of the following marked villous hypertrophy, proliferation of superficial synovial cells, often with palisading, marked infiltration of chronic inflammatory cells (lymphocytes or plasma cells predominating) with tendency to form ‘lymphoid nodules’, deposition of compact fibrin either on surface or interstitially, foci of necrosis. 11. Characteristic histologic changes in nodules show granulomatous foci with central zones of necrosis,

surrounded by a palisade of proliferated macrophages, and peripheral fibrosis and chronic inflammatory cell infiltration, predominantly perivascular. B. Definite rheumatoid arthritis This diagnosis requires five of the above criteria. In criteria 1 through 5, the joint signs or symptoms must be continuous for at least 6 weeks. C. Probably rheumatoid arthritis This diagnosis requires three of the above criteria and total duration of joint symptoms must be at least 3 weeks. D. Possible rheumatoid arthritis This diagnosis requires two of the following criteria and total duration of joint symptoms must be at least 3 weeks: 1. 2. 3. 4. 5. 6.

Morning stiffness Tenderness or pain on motion (observed by a physician) with history of recurrence or persistence for 3 weeks History or observation of joint swelling Subcutaneous nodules (observed by a physician) Elevated erythrocyte sedimentation rate or C-reactive protein Iritis (of dubious value as a criterion except in the case of juvenile RA).

Diagnostic criteria for local involvement of TMJ The criteria for diagnosing TMJ involvement with RA were given by Kopp in 1995. 1. 2. 3. 4. 5. 6. 7. 8.

Bilateral joint involvement Tenderness to adaptation of lateral or posterior aspects of the joint Joint crepitus Radiographic signs of erosions of the articular cortical bone of the TMJ Swelling over the TMJ (acute phase) Temperature change in or over the TMJ. Increase in the acute phase and decrease in the chronic phase Anterior open bite Abundance of polymorphonuclear leukocytes in the joint fluid (acute phase) or mononuclear leukocytes (lymphocytes and plasma cells, chronic phase)

The presence of four of those eight criteria should be able to determine the local diagnosis. Differential diagnosis Differential diagnoses include ankylosing spondylitis, psoriatic arthritis, Reiter’s syndrome, arthritis of chronic inflammatory bowel disease, polytendinitis, osteoarthritis and sarcoidosis. Management The successful management of RA lies in a comprehensive multidisciplinary approach. Systemically administered 595


drugs, local injections of corticosteroids, physical therapy, occupational therapy, psychosocial support, patient education, family involvement, surgical intervention and vocational rehabilitation are all part of the routine daily management program of patients with RA.

foliaceous. Oral mucosal involvement is of little consequence in the foliaceous and erythematosus forms.

1.

Non-steroidal anti-inflammatory drugs Piroxicam 20 mg once a day, diclofenac 25–75 mg twice a day, naproxen 250–500 mg twice a day, ibuprofen 400– 800 mg four times a day or ketoprofen 50–75 mg thrice a day. Remittive drugs used in the treatment of rheumatoid arthritis – Antimalarials (chloroquine 250 mg, hydroxychloroquine 200 mg)—one tablet twice a day followed by once a day. – Gold parenterally (sodium aurothiomalate or urothioglucose)—test dose of 10 mg followed by 25–50 mg weekly for 4–6 months. – Gold given orally (auranofin 3 mg)—one tablet twice a day – Methotrexate given orally (2.5 mg)—one tablet thrice a day, once or twice in a week – Penicillamine (125–250 mg)—initial dose of 250 mg once a day, raised by 125 mg increments, every 6–8 weeks as tolerated if active arthritis persists, maximal daily dose 1,500 mg.

Described in Chapter 7 (Vesiculobullous Disorders) on page 174.

Physical and occupational therapy, surgery, occlusal splints, occlusal adjustments, prosthetic treatment can increase the patient comfort and help in mastication.


2.

Pemphigus Vulgaris

Pemphigus Vegetans Described in Chapter 7 (Vesiculobullous Disorders) on page 174.

Pemphigus Foliaceous Described in Chapter 7 (Vesiculobullous Disorders) on page 174.

Brazilian Pemphigus (Fogo Selvagem) Described in Chapter 7 (Vesiculobullous Disorders) on page 174.

Pemphigus Erythematosus (Senear–Usher Syndrome)

Paraneoplastic Pemphigus

SYSTEMIC AUTOIMMUNE DISEASES WITH OROFACIAL MANIFESTATIONS PEMPHIGUS It is an autoimmune disease involving the skin and the mucosa and characterized by intraepidermal bullae formation. It is caused by antibodies directed as the intercellular intercementing substances. Classification ❍ ❍ ❍ ❍ ❍ ❍

Pemphigus vulgaris Pemphigus vegetans Pemphigus foliaceous Pemphigus erythematosus (Senear–Usher syndrome) Brazilian pemphigus (Fogo selvagem) Benign familial chronic pemphigus (Hailey–Hailey disease) ❍ Paraneoplastic pemphigus. Pemphigus vegetans is a variant of pemphigus vulgaris and pemphigus erythematosus is a variant of pemphigus 596


Bullous Pemphigoid Described in Chapter 7 (Vesiculobullous Disorders) on page 174.

Cicatricial Pemphigoid Described in Chapter 7 (Vesiculobullous Disorders) on page 174.

EPIDERMOLYSIS BULLOSA ACQUISITA Epidermolysis bullosa acquisita (EBA) is a chronic subepidermal blistering disease associated with autoimmunity to the collagen within the anchoring fibrils (type VII collagen) that are located at the dermal–epidermal junction. The first diagnostic criterion was putforth by Raenigk et al in 1971.


Figure 3

characteristically seen within the flexural areas and skin folds. Some patients may present with erythema and flat urticarial plaques in the absence of blisters. About 10% of the patients exhibit severe mucous membrane involvement may present a picture clinically similar to cicatricial pemphigoid with erosions and scarring in the oral cavity, conjunctiva, upper esophagus and anus or vagina. Diagnostic criterion for EBA was proposed by Yaoita et al (1981). This is still the most widely followed diagnostic criterion. These criteria, with some updated modifications are as follows: 1. 2. 3. 4.

5.

Extensive erosions over the lower extremity and some areas of healing with scar formation in epidermolysis bullosa. Courtesy: Dr Ajit Auluck

1. 2. 3. 4.

A negative family and personal history for a previous blistering disorder An adult onset of eruption Spontaneous or trauma-induced blisters that resemble those of hereditary dystrophic epidermolysis bullosa The exclusion of all other bullous diseases.

Clinical features Epidermolyis bullosa acquisita may have at least three different clinical presentations: the ‘classical presentation’, ‘bullous pemphigoid like presentation’ and a ‘cicatricial pemphigoid like presentation’. The classical presentation is a non-inflammatory, bullous disease with an acral distribution that heals with scarring and milia formation. It is a mechanobullous disease marked by skin fragility. These patients have erosions, blisters and scars over trauma prone surfaces (back of the hands, knuckles, elbows, knees, sacral area and toes) (Figure 3). A scarring alopecia and some degree of nail dystrophy may be seen. The lesions heal with scarring and frequently with the formation of pearl like, milia cysts within the scarred areas. The bullous pemphigoid like presentation is a widespread inflammatory vesiculobullous eruption involving the trunk, central body, skin folds and the extremities. The bullous lesions are surrounded by inflamed or urticarial skin. The distribution of lesions like bullous pemphigoid is

Bullous disorder with the clinical spectra outlined above No family history of a bullous disorder A subepidermal blister by histologic examination Deposition of IgG deposits within the dermal-epidermal junction (a positive direct immunofluorescence of perilesional skin) Junctional IgG deposits localized to the lower lamina densa and/or sublamina densa zones of the basement membrane when examined by direct immunoelectron microscopy or indirect or direct salt split skin immunofluorescence and/or western blotting.

Histologic features Routine histologic examination of lesion on skin obtained from EBA patients show a subepidermal blister and a clean separation between the dermis and the epidermis with inflammatory infiltrate. Immunologic parameters Patients with EBA have IgG deposits within dermal– epidermal junction of their skin. This is detected by direct immunofluorescence. IgG is the predominant immunoglobulin class, but deposits of complement IgA, IgM, factor B and properdin may also be detected. The localization of immune deposits within the dermal– epidermal junction of the skin of epidermal junction of the skin of the patients is the ‘gold standard’ for the diagnosis.

SYSTEMIC LUPUS ERYTHEMATOSUS Systemic lupus erythematosus (SLE) is a systemic disease affecting multiple organ systems that is characterized by the presence of antibodies to nuclear antigens. Lupus is a Latin word for ‘wolf’. It is called so because of the way it eats away skin. Types of lupus: 1. 2. 3. 4.

SLE Discoid lupus erythematosus Drug-induced lupus erythematosus Lupus nephritis 597


5. 6.

Subacute cutaneous lupus erythematosus Neonatal lupus erythematosus.

Figure 4

Neonatal lupus erythematosus is a rare disease affecting babies born to women suffering from SLE. Subacute cutaneous form is characterized by non-scarring skin lesions on the areas of skin exposed to sunlight. Epidemiology Systemic lupus erythematosus is the most common connective tissue disease. The reported prevalence of SLE is 50.8 per 100,000 individuals above 17 years of age. The prevalence of SLE in individuals in the age group of 18–65 years is about 1:1,000 in white women and 1:250 in black women. In this age group, SLE is 10 times more frequent in females than in males. Among children and elderly, SLE is only twice as frequent in females than in males. Etiology and pathogenesis Genetic About 10% of the patients with SLE have a first degree relative with the disease. Multiple HLA associations have been reported, particularly for B8, DR2, DRW52, DQW1 and DQW2. The null gene for C4 occurs more often in patients with SLE in their families. Environmental A significant exposure to sunlight clearly precede the onset of the disease in about one-third of the patients.

Maculopapular rash on the face and chest of a patient suffering from SLE. Courtesy: Dr Ashok

2.

Medication Drugs that have been implicated in causing SLE are categorized into: ❍

High risk drugs (hydralazine, procainamide and isoniazid) ❍ Moderate risk to low risk drugs (quinidine, Dpenicillamine, carbamazepine, oral contraceptive pills). Pathogenesis The immune system is clearly abnormal in SLE. T cells do not control the activity of the B cells, which produce a large number of autoantibodies. Some of the autoantibodies (anti-DNA) participate directly in the renal disease forming immune complexes in the glomeruli. Other autoantibodies form complexes with their antigens to lead to vasculitis. At present, SLE is thought to be a disorder in which genetic defects are present but not yet delineated. These genetic defects lead to a defective homeostasis between B cells and T cells. When the individual is challenged by certain factors like ultraviolet light, infection or by an unknown stimulus, the B cells become hyperactive leading to a variety of autoantibodies. Clinical features 1.

598

General manifestations Fever (low grade or spiking), fatigue, weight loss and generalized malaise are general manifestations in patients suffering from SLE.

3.

4.

Cutaneous lesions Patients present with a typical erythematous rash over the malar region, which is popularly referred to as the butterfly rash. It is evident as an erythematous and slightly edematous lesion located on the cheeks, extending across the bridge of the nose (Figure 4). It is generally the first manifestation of the disease. It frequently occurs after exposure to sun. The rash heals well without scarring or pigmentation. Patients may also present with a pruritic maculopapular rash, which may resemble lesions of drug eruption. Joint manifestations About 95% of the patients show joint involvement. Arthritis with pain on movement, tenderness, or effusion is present in about 80% and arthralgia is present in about 15% of the patients with SLE. The proximal interphalangeal, knee, wrist and metacarpophalangeal joints are most often involved. Swan neck deformities occur in 15% of the individuals but unlike rheumatoid arthritis, no bony erosion is seen. Renal disease Renal involvement in SLE ranges from 29 to 53%. The WHO grading of type of renal lesions are a. Type I: normal b. Type II: mesangial hypercellularity and immune deposits confined to mesangium. These patients have mild proteinuria c. Type III (focal proliferative lupus nephritis): proteinuria, hematuria and occasionally nephrotic syndrome


d. Type IV (diffuse proliferative nephritis): significant proteinuria, hematuria, renal insufficiency, severe nephritic syndrome and hypertension may be present e. Type V (membraneous nephritis): significant proteinuria, hematuria and nephritic syndrome. 5. Cardiopulmonary manifestations The most common symptom is pleuritic chest pain, which is present in about 40% of the patients. Pleural effusions are rarely evident. The common cardiac manifestation is pericarditis which occurs in about 25% of the patients. 6. Nervous system manifestations Approximately 14% of the patients exhibit peripheral neuropathy and mixed sensory motor disturbances. Guillain–Barre syndrome may occasionally be present. Grand mal seizures are seen in about 15% of the patients in the early stages of the disease. Organic brain syndromes are characterized by impaired orientation, perception, memory and intellectual function. CSF studies revealed significant elevation of protein levels and WBC count in 32% of the cases. 7. Gastrointestinal manifestations Nausea, vomiting and anorexia are present in about 20% of the patients. Dysphagia may be present and is usually associated with Raynaud’s phenomenon. Hepatomegaly occurs in about 30% of the patients and splenomegaly is seen in 20% of the patients and is usually not associated with hemolytic anemia. 8. Ocular manifestations Approximately 15% of the patients exhibit conjunctivitis and episcleritis. Rarely occlusion of the central retinal artery may be seen. Blindness from retinal arteritis may ensue. 9. Hematologic abnormalities One or more hematologic abnormalities are present in nearly all patients of SLE. Most common is a mild to moderate normocytic normochromic anemia. Hemolytic anemia and reticulocytosis occur in only 10% of the patients. Leukopenia with WBC counts less than 4,000/l. Mild thrombocytopenia is present in 1/3rd of patients with SLE. Circulating anticoagulant in SLE produces a slight prolongation of the thromboplastin time or partial thromboplastin time. Bleeding and clotting times are normal. In contrast, antibodies directed against factors VII, IX and XII may prolong bleeding times and result in clinically significant state of anticoagulation. 10. Salivary gland manifestation Acute enlargement of one or both parotid glands occurs occasionally in patients with SLE. The swelling may be painful and usually returns to normal as the systemic disease is controlled. The enlargement may be associated with the presence of Sjögren’s syndrome. 11. Oral manifestations Oral manifestations of SLE were first described by Bazin in 1861. Monash in 1931

Figure 5

White plaque with dark reddish purple margins on the palate in a patient with SLE. Courtesy: Dr Ashok

examined 22 patients with SLE and reported that 50% had oral lesions. The most common sites affected by SLE are buccal mucosa, lips and palate. The typical intraoral lesions are multiple white plaques with dark, reddish purple margins (Figure 5). Hyperemia and edema are marked, increasing the tendency for bleeding and superficial ulceration. The prevalence of ulceration (most commonly reported oral manifestation of SLE) has been reported to be between 7 and 41%. Rhodes and Johnson in 1989 reported xerostomia, angular cheilitis, mucositis, glossitis, dental caries, periodontitis, dysphagia and glossodynia as the oral manifestations of SLE. Laboratory investigations 1.

2.

Presence of ANA: A wide spectrum of autoantibodies may be found in patients with SLE. ANA are usually detected for screening purposes by the indirect fluorescence antibody technique. ANA are positive in nearly all patients with SLE who have clinical evidence of active disease. But the diagnosis of SLE should never be made in a patient with a positive ANA and absence of multisystem disease. Polyclonal hypergammaglobulinemia is common in patients with SLE. Serum complement levels are generally decreased in active SLE, especially in patients suffering from active nephritis. 599


3.

4.

Rheumatoid factor: Approximately 18% of the patients exhibit rheumatoid factor in conjunction with nonerosive deforming arthritis. Lupus erythematosus (LE) cell phenomenon: A specific test for the disease was established with the discovery of the ‘LE cell’ inclusion phenomenon by Hargraves and associates in 1969. In this test, blood serum from a suspected person is added to the buffy coat of normal blood. If the patient is suffering from SLE, typical LE cells will develop. The LE cell phenomenon consists of a rosette of neutrophils surrounding pale nuclear mass apparently derived from a lymphocyte.

Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) is a rare condition which requires at least two of the following conditions to make the diagnosis: hyperparathyroidism, Addison’s disease and chronic mucocutaneous candidiasis. Porter et al (1995) and Perniola et al (1998) described developmental defects of teeth and oral candidiasis as the characteristic oral findings in these individuals.

LE cells are rarely found in discoid lupus erythematosus.

Clinical features

Management

1. 2.

The basis of treatment is the use of corticosteroids, given in a dose adequate to control the multisystem disease and to return the anti-DNA antibodies and complement levels to normal. Depending on the severity and nature of the disease the dose of corticosteroids can vary from 10 mg to 1 g intravenously per day. In patients with repeated exacerbations of the disease at moderately high doses of corticosteroids, azathioprine may be useful to allow the patient to be maintained on lower doses of corticosteroids. Antimalarial drugs are useful in patients with skin abnormalities, alopecia or mucosal ulcers. In the recent times, severe and unresponsive cases have been managed successfully with plasmapheresis or leukapheresis. Dental considerations 1.

2.

3.

4.

Platelet count estimation may be required prior to any oral surgical procedure, to evaluate the severity of thrombocytopenia. Bacterial endocarditis—Libman–Sacks vegetations may be found under mitral valve leaflets in SLE. These vegetations rarely affect function but can lead to bacterial endocarditis. Patients with SLE have to be considered for antibiotic prophylaxis before dental treatment that is likely to cause bacteremia. According to Roura et al (1991), drugs that have a photosensitizing potential like penicillin, sulfonamides and NSAIDs should be used judiciously as they tend to exacerbate SLE. SLE patients are susceptible to shock and infection as they are medicated with adrenal suppressing doses of corticosteroids or cytotoxic drugs.

Prognosis Literature review reveals a 5-year survival rate in almost 95% of the patients of SLE. However, these patients need to be constantly medicated with the lowest possible doses of corticosteroids. 600

AUTOIMMUNE POLYENDOCRINOPATHY– CANDIDIASIS–ECTODERMAL DYSTROPHY

3. 4.

Girls are more commonly affected. Hypoparathyroidism is the most common endocrinopathy that is seen. However, addisonian adrenocortical hypofunction, autoimmune thyroid disease, vitiligo, diabetes mellitus and other autoimmune disorders can also be associated with APECED. Oral manifestations include pseudomembranous candidiasis and recurrent angular stomatitis. Enamel hypoplasia may be seen secondary to hypoparathyroidism, usually affecting permanent dentition, reflecting the early postnatal onset of autoimmune hypoparathyroidism.

Management APECED management requires antifungal therapy and the management of endocrinopathy.

DIABETES MELLITUS TYPE I (IDDM) Diabetes mellitus is a clinical syndrome characterized by hyperglycemia due to absolute or relative deficiency of insulin. Among the various types of diabetes, insulin-dependent diabetes mellitus (IDDM) has an autoimmune basis. Edwards et al in 1995 proposed the following explanations as evidence to suggest autoimmune etiology for IDDM: 1. 2. 3. 4. 5.

HLA-linked genetic predisposition Association with other autoimmune disorders Circulating islet cell cytoplasmic and surface, insulin autoantibodies in new patients. Mononuclear cell infiltration of pancreatic islets resulting in selective destruction of insulin secreting cells. Recurrence of insulinitis and selective destruction of insulin-secreting cells in pancreatic grafts.

Dental considerations Median rhomboid glossitis is considered as a specific pathognomonic oral manifestation associated with diabetes.


However, various oral conditions are worsened in a diabetic individual such as gingivitis and periodontal diseases, oral candidiasis, delayed socket healing after extraction and burning tongue. Specific considerations pertaining to dental treatment 1.

2. 3.

Local anesthetics without epinephrine should be used because even minimal doses of epinephrine can elevate blood glucose concentration. Reduced blood supply in diabetics due to atherosclerosis may be accentuated further by vasoconstriction activity of epinephrine and can lead to dry socket. Complicated dental procedures are best delayed in uncontrolled diabetics. Post-surgical infections are common in uncontrolled diabetics. This can be managed with appropriate antibiotics.

seen. The characteristic claw-like deformity of fingers is seen due to flexural contractures and resorption of terminal phalanges (Figure 7). Some patients present with neuralgia or paresthesia. Dermal involvement can be divided into three distinct phases: 1. 2. 3.

Edematous phase (stiff, puffy fingers) Indurative phase (hard, tight, hidebound) Atrophic phase (softened skin, burned out).

Figure 6

However, all types of routine dental treatment may be performed safely in the dental setting in individuals whose blood glucose levels are under control.

SYSTEMIC SCLEROSIS Systemic sclerosis can be described as chronic, progressive dermatosis characterized by board-like hardening and immobility of the affected skin, with visceral involvement, especially of lungs, esophagus, kidneys and heart. It is characterized by alterations of the microvasculature, disturbances of the immune system and by massive deposition of collagen. Curzio in 1973, published the first detailed description of a scleroderma-like disease. A variant of systemic sclerosis is termed acrosclerosis, which is a combination of Raynaud’s phenomenon and scleroderma affecting the extremities. Epidemiology

Linear ribbon-like marking on the forehead resembling mark produced by blow of a saber in systemic sclerosis. Courtesy: Dr Ajit Auluck

Figure 7

The annual incidence of systemic sclerosis is approximately 6–12 patients per one million individuals. Individuals between the 3rd and 5th decades of life are mostly affected. Females are affected seven times more than males. Types of systemic sclerosis 1. Localized form a.

b.

Circumscribed morphea form (yellowish-white patches on the skin surface surrounded by a violaceous halo of varying size and shape). Linear ‘en coup de sabre’ form (linear ribbon-like markings that resemble marks produced by blow of a saber are seen) (Figure 6).

In the initial stages, indurated edema of skin followed by fixation of epidermis to the deeper subcutaneous tissues is

Claw-like deformity in systemic sclerosis. Courtesy: Dr Ajit Auluck

601


2. Diffuse form Diffuse form of systemic sclerosis is characterized by fibrosis of internal organs with loss of smooth muscle and loss of visceral function. More than 50% of the patients exhibit involvement of the gastrointestinal tract (mainly distal esophagus) resulting in dysphagia. Lung involvement results in dyspnea and hypoxia, due to interstitial inflammation and fibrosis. Involvement of the kidney and heart results in renal and cardiac failure respectively. Occasionally, soft tissue calcifications may also be seen.

Orofacial manifestations ❍ ❍ ❍ ❍ ❍ ❍ ❍

Figure 8

❍

Mask-like appearance of the face (due to loss of skin folds) (Figure 8). Alae of the nose will gradually atrophy to produce the characteristic ‘mouse-like facies’. Fibrosis of the buccal mucosa may be seen. Tongue and lips may turn rigid. Mucogingival periodontal problems (loss of attached gingiva, gingival recession) are seen. Mouth opening is significantly reduced, giving rise to a ‘purse string’ appearance to the mouth. Involvement of the minor salivary glands may mimic signs and symptoms of Sjögren’s syndrome. Some patients may complain of pain, paresthesia, or hyperesthesia along the course of the trigeminal nerve.

Radiographic features ❍

Mask-like facies in progressive systemic sclerosis. Courtesy: Dr Ajit Auluck

The most commonly seen radiographic finding in patients is the resorption of the terminal phalanges of the hand and the distal portions of the radius and ulna. ❍ Generalized widening of the periodontal ligament space (two to four times the normal width) is seen in 10–37% of the patients. In comparison to anterior teeth, widening of periodontal ligament space is more marked in the posterior teeth (Figure 9). ❍ Resorption of the mandible in patients suffering from scleroderma was first reported by Taveras in 1959. Literature review reveals that the incidence of mandibular resorption varies from 10 to 33%. The sites that are resorbed include the condyle, coronoid process, ascending ramus, posterior border of the ramus and the angle of the mandible. The sites of resorption predispose to pathological fractures, osteomyelitis, trigeminal

Figure 9

Generalized widening of periodontal ligament space in systemic sclerosis. Courtesy: Dr Ajit Auluck

602


neuropathy (associated with severe pain) and apertognathia. Diagnosis The diagnosis of systemic sclerosis is made by the presence of the characteristic clinical and radiographic features. However, some non-specific serological changes such as the presence of antinuclear antibodies and rheumatoid factor are seen. Syndromes associated with systemic sclerosis CREST syndrome was originally called Thibierge– Weissenbach syndrome in honor of two French physicians who described this condition in 1910. Winterbauer renamed this syndrome as CREST syndrome in 1964. CREST syndrome is a combination of calcinosis cutis, Raynaud’s phenomenon, esophageal hypomobility, sclerodactyly and telangiectasia. Dental considerations All forms of dental treatment can be safely carried out in these patients. However, since the mouth opening gradually reduces, mouth opening exercises, use of increased number of tongue blades between posterior teeth to stretch facial tissues and bilateral commissurotomy are done to manage these patients. These patients can be instructed to practice good oral hygiene practices as the gradual reduction in mouth opening will hinder maintenance of oral hygiene. Course and prognosis The prognosis is better when there are only dermal manifestations. Involvement of internal structures has an unfavorable prognosis. On an average the 5-year survival rate is about 70%.

it involves muscles that control facial expression, chewing and swallowing. In advanced stages, respiratory muscles are affected leading to acute respiratory failure. Epidemiology It affects approximately 2 out of every 100,000 people and can occur at any age. It is most common in women in the 2nd and 3rd decades of life. In men, the condition usually develops between 6th and 8th decades of life. Types of MG Generalized MG: Approximately 85% of the patients develop generalized form of this condition within 1 year of the onset of the disease. Patients report progressive weakness in the trunk, arms and legs. Ocular MG: Muscles that control eye movements are typically affected. Approximately 10–15% are affected by this condition. Congenital MG: Inherited condition caused by genetic defect, develops at birth or shortly after birth. Transient neonatal MG: It occurs in infants born to mothers who have MG. Around 10–20% of the neonates develop this condition. It occurs due to transfer of maternal antiAChR antibodies through the placenta to the newborn reacting with the AChR of the neonate. Etiology The exact cause of MG is still unknown. Females and individuals with certain HLA have a genetic predisposition to autoimmune diseases. It is proposed that there is a dysregulation of the immune system. Sensitization to a foreign antigen that has cross-reactivity with the nicotinic ACh receptor has been proposed as etiology for MG. Clinical features 1.

MYASTHENIA GRAVIS The term myasthenia gravis (MG) was coined by combining two Greek words for muscle and weakness to form the word myasthenia and adding the Latin word gravis, which means severe. The autoimmune etiology for MG was proposed for the first time in 1959–1960 by two independent workers, Simpson and Nastuck. Myasthenia gravis is an autoimmune disorder of the neuromuscular junction, in which autoantibodies are directed toward acetylcholine receptors (Ac in the motor end-plate units of skeletal muscle, resulting in a progressive fatigability of the skeletal muscle. In the initial stages, extraocular muscles are affected. As the disease progresses

2. 3.

4.

5. 6. 7. 8.

Patient’s face may appear expressionless due to the weak and slack facial muscles. Inability to hold the head upright. Mandibular movements are sluggish and slack. Patient may have to support his/her mandible with a finger. The patient’s mouth may remain open all the time. Patient is said to have a ‘snarling face’ when he/she try to smile. When the patient attempt to smile, the corners of the mouth are not drawn up and outward, and the levator muscles expose the canines. Gag reflex is often absent, and such patients are at risk for aspiration of oral secretions. Dysphagia is seen because of the weakness of the muscles associated with chewing and swallowing. Patient may complain of nasal regurgitation. Patient’s voice may acquire a nasal quality. 603


9.

In severe cases patient is unable to clear bronchial secretions which may predispose to pneumonia. 10. Ptosis is seen in almost all patients. Patients have difficulty in eye closure. Characteristically, pupils are unaffected in MG. Diagnostic tests Myasthenia gravis can be diagnosed with tests like edrophonium test, ice-pack test, test to assess eyelid twitch response, anti-AChR antibody test, anti-MuSK antibodies, electrophysiological tests (repetitive nerve stimulation test and single fiber electromyography), CT/MRI of chest (to screen for associated thymic tumors). Patients should also be evaluated for diseases associated with MG such as thyroid disease, diabetes mellitus, rheumatoid disease, pernicious anemia, systemic lupus erythematosus, sarcoidosis, Sjögren’s disease and polymyositis. Simple tests that can be performed in a dental setting Ice-pack test Patients having ptosis secondary to MG will improve when an icepack is applied to the eyelid. However, ptosis secondary to other conditions will not improve on application of icepack. Eyelid twitch response It is also referred to as Cogan’s lid twitch. Patient is instructed to gaze downward for

604

10–20 seconds. After 20 seconds the patient is advised to bring his/her gaze to the normal position. In patients suffering from MG, the upper eyelid elevates and may either slowly begin to droop or twitch several times before assuming a stable position. This phenomenon is brought about by rapid recovery and easy fatigability of muscles. However, this test can be positive in patients with brain stem or ocular disorders. Management of MG The current management of MG includes the use of anticholinesterase drugs for temporary improvement of neuromuscular transmission, removal of anti-AChR Abs by plasma exchange or specific immunoadsorption procedures, use of non-specific immunosuppressants or immunomodulators to curb the anti-AChR response, and thymectomy. MG when not treated with adequate dosage of medication can present with myasthenic crisis and when treated with excessive medication can exhibit cholinergic crisis. Myasthenic crisis may cause bronchospasm with wheezing, cyanosis and in extreme conditions respiratory failure can occur. Cholinergic crisis may be associated with miosis and SLUDGE syndrome, which is characterized by salivation, lacrimation, urinary incontinence, diarrhea, gastrointenstinal upset, hypermotility and emesis.

CHAPTER

Granulomatous Diseases Adel Kauzman, Iona Leong

21

➧ Tuberculosis

➧

Foreign Body Granulomas

➧

Leprosy (Hansen’s Disease)

➧

Wegener’s Granulomatosis

➧

Syphilis

➧

Sarcoidosis

➧

Deep Fungal Infections

➧

Orofacial Granulomatosis

Blastomycosis Histoplasmosis Aspergillosis Zygomycosis (Mucormycosis, Phycomycosis)

➧

Crohn’s Disease (Regional Ileitis, Regional Enteritis)

Granulomatous diseases are a heterogeneous group of disorders that are characterized by a specific pattern of chronic inflammation called granulomatous inflammation, in which granulomas are formed. Granulomas usually develop as a result of a cell-mediated hypersensitivity reaction to a non-degradable antigen. The clinical significance of a histological finding of granulomatous inflammation is that this type of inflammation is associated with a relatively limited number of conditions. A granuloma is a focal aggregate of inflammatory cells, composed predominantly of epithelioid macrophages, which may be surrounded by a rim of lymphocytes and/or plasma cells. Epithelioid macrophages resemble epithelial cells, having abundant pale pink cytoplasm, vesicular and oval nuclei and indistinct cell borders (Figure 1). Some activated macrophages may fuse to form multinucleated giant cells which may be located within the center or periphery of the granuloma (Figure 2). In Langhans type giant cells the nuclei are arranged in the periphery, often in the shape of a horseshoe. The nuclei of foreign body type giant cells are arranged haphazardly in the cytoplasm. Some granulomas may show central areas of necrosis. Caseous necrosis, in which the dead tissue is soft and dry and resembles cheese, is classically associated with tuberculosis. Long-standing granulomas may be surrounded by a rim of fibrous connective tissue and fibroblasts. Granulomas can be classified as immune or foreign body type. Foreign body type granulomas develop in response to inert endogenous or exogenous foreign material (Table 1).

Figure 1

Photomicrograph of a granulomatous inflammatory reaction showing multiple granulomas surrounded by lymphocytes. Each granuloma is composed predominantly of epithelioid macrophages and multinucleated giant cells. Epithelioid macrophages show abundant pale pink cytoplasm, vesicular and oval nuclei and indistinct cell borders. (Hematoxylin and eosin, original magnification 200)

Immune-mediated granulomatous inflammation represents a form of delayed type (cell-mediated) hypersensitivity reaction and may be secondary to specific types of bacterial, fungal and parasitic infections. Immune granulomas 605


TUBERCULOSIS

Figure 2

Photomicrograph showing a multinucleated giant cell in the center of a granuloma. The nuclei of the giant cell are arranged in the periphery of the cytoplasm. (Hematoxylin and eosin, original magnification 250)

Table 1

Granulomatous diseases that may affect the oral tissues

Infections Bacterial Tuberculosis Leprosy Syphilis Others

Foreign body

Diseases of unknown etiology

Silica Beryllium Talc Suture material Starch

Wegener’s granulomatosis Sarcoidosis Orofacial granulomatosis Crohn’s disease

Fungal Blastomycosis Histoplasmosis Aspergillosis Zygomycosis Others Parasitic Leishmaniasis Schistosomiasis

are mostly seen with mycobacterial and fungal infections because the infectious organisms typically have antigens which are poorly degraded by macrophages. Antigen exposure initiates a cell-mediated immune response, resulting in activated CD4 T lymphocytes of the Th1 type which secrete cytokines such as interleukin (IL)-2, IL-12, interferon (IFN)-, and tumor necrosis factor (TNF)-. The cytokines stimulate activation of macrophages to form granulomas. Some immune-mediated granulomatous diseases are of unknown etiology (Table 1). 606

Tuberculosis is a common worldwide infection caused by bacteria belonging to the Mycobacterium tuberculosis complex. Although tuberculosis usually affects the lungs, it may also involve other organs in up to one-third of cases. Initial infection, also known as primary infection, is followed by a long latency period characterized by absence of symptoms in most individuals. Latent infection progresses to active disease in a minority of individuals, due to reactivation or exogenous re-infection with a second strain of M. tuberculosis. Therefore infection must be distinguished from active disease. Active tuberculosis caused by drugsusceptible strains is curable if properly treated, but may be fatal within 5 years in more than half the cases if untreated. The M. tuberculosis complex includes M. tuberculosis, the most frequent and important agent of human disease. M. bovis is transmitted by unpasteurized milk and is the cause of a small percentage of cases in developing countries. M. tuberculosis is an aerobic, non-spore-forming, rod-shaped bacterium. The organism is classified as an acid-fast bacillus because the high mycolic acid and lipid content in the cell wall prevents decolorization by acid alcohol with acid-fast stains such as the commonly used Ziehl–Neelsen stain. Tuberculosis is a disease of poverty associated with overcrowding and undernutrition. Other risk factors for tuberculosis include human immunodeficiency virus (HIV) infection, diabetes, smoking, excessive alcohol consumption, end-stage renal failure, and therapy with tumor necrosis factor antagonists and corticosteroids. Based on World Health Organization (WHO) estimates, approximately two billion people or one-third of the world’s total population were infected with M. tuberculosis in 2010, with 1.4 million deaths caused by tuberculosis yearly. Tuberculosis occurs world-wide, but the majority of cases occur in low-income countries and in countries with emerging economies. The developing countries of Africa and Asia have the highest prevalence of tuberculosis, with the most cases occurring in India, China, South Africa, Indonesia and Pakistan. Tuberculosis is uncommon in North America and Europe, where it occurs predominantly in HIV-infected persons, immigrants from high-prevalence countries, disadvantaged and marginalized populations. Although intense efforts at disease control have resulted in stabilization or decreasing incidence of tuberculosis in most countries, there has been a rapid increase in Africa related to the spread of the HIV epidemic. Pathogenesis The disease is usually transmitted by the airborne spread of droplet nuclei produced by patients with infectious pulmonary tuberculosis. Droplets aerosolized by coughing,

Chapter 21 – Granulomatous Diseases

sneezing or speaking are inhaled. Thus transmission of infection is enhanced by crowded conditions in poorly ventilated rooms and prolonged, close contact with patients with active tuberculosis. Inhaled bacilli reaching the alveoli are ingested by non-specifically activated alveolar macrophages, which may contain the bacillary multiplication or be killed by the multiplying bacilli. Chemotactic factors released by lysed macrophages attract non-activated monocytes from the bloodstream to the site. These initial stages of infection are usually asymptomatic. Specific immunity develops about 2–4 weeks after infection. Large numbers of activated macrophages accumulate at the site of the primary lesion, forming granulomas or tubercles. Granuloma formation is mediated by cytokines released by alveolar macrophages, including TNF-. This delayed-type hypersensitivity reaction to bacillary antigens destroys macrophages and causes necrosis in the center of the tubercles. The necrotic material resembles soft cheese, hence the designation ‘caseous necrosis’. Its low oxygen tension and low pH inhibit growth of M. tuberculosis. Viable organisms may however remain dormant within the macrophages or in the necrotic material for years or even throughout the patient’s lifetime. Some tubercles in the lung parenchyma and hilar lymph nodes may heal by fibrosis and calcification, while others undergo further evolution.

Figure 3

Gross appearance of Ghon lesion in the lung of a patient with a history of healed primary pulmonary tuberculosis. It presents as a calcified spherical mass

Figure 4 Clinical features Tuberculosis is classified as pulmonary or extrapulmonary. Pulmonary tuberculosis can be primary or secondary. Primary pulmonary disease results from an initial infection with M. tuberculosis in previously unexposed individuals and is usually asymptomatic. The lesion is usually peripheral and localized to the middle and lower lung zones and is accompanied by hilar or paratracheal lymphadenopathy. In most cases, the lesion heals spontaneously and may later be evident as a small calcified nodule (Ghon lesion) (Figure 3). Approximately 5–10% of patients progress directly from initial infection to active disease, usually because of an existing state of immunosuppression. This is especially seen in children and in persons with impaired immunity, such as those with malnutrition or HIV infection. The initial lesion enlarges, cavitates, invades and destroys bronchial walls and blood vessels. Large numbers of bacilli spread into the airways and the environment through expectorated sputum. Patients may develop pleural effusion and progressive primary tuberculosis. Hematogeneous dissemination may result in fatal miliary tuberculosis (Figure 4) or tuberculous meningitis. Secondary pulmonary tuberculosis, also known as postprimary disease, is usually due to endogenous reactivation of latent infection. Triggers for reactivation include immunosuppression, especially AIDS, malnutrition and vitamin D deficiency. The disease usually occurs in the apical and posterior segments of the upper lung lobes, where the high

Gross appearance of miliary tuberculosis in the lung

oxygen tension favors mycobacterial growth. The extent of lung involvement varies greatly, from small infiltrates to extensive cavitatory disease. Massive involvement of the lungs, with coalescence of lesions, produces tuberculous pneumonia. The result may be death, spontaneous 607


Figure 5

Panoramic radiograph of a patient with a history of tuberculosis showing calcified cervical and submandibular lymph nodes

remission or chronic disease with a progressively debilitating course (‘consumption’). Individuals with chronic disease continue to discharge tubercle bacilli into the environment. Symptoms and signs are often non-specific and insidious early in the course of secondary pulmonary tuberculosis, consisting mainly of fever, night sweats, weight loss, anorexia, general malaise and weakness. Cough eventually develops in most individuals, often initially non-productive and subsequently accompanied by the production of purulent sputum. The sputum may be blood-streaked due to blood vessel involvement. Virtually any organ system may be affected by extrapulmonary tuberculosis, but the most commonly involved sites are the lymph nodes, pleura, genitourinary tract, bones and joints, meninges, peritoneum, pericardium, and the head and neck region. In the head and neck, tuberculosis can involve the larynx, middle ear, nasal cavity, nasopharynx, oral cavity, parotid gland, esophagus and spine. As a result of hematogeneous dissemination in HIV-infected individuals, extrapulmonary tuberculosis is seen more commonly nowadays than in the past. Lymph node tuberculosis (tuberculous lymphadenitis) is the most common form of extrapulmonary tuberculosis and is especially common in HIV-infected persons. It usually presents as painless swelling of the lymph nodes, most commonly at cervical and supraclavicular sites (scrofula). Lymph nodes are usually discrete in early disease but may develop caseous necrosis and form fistulas through the overlying skin draining caseous material. Involved nodes may radiographically appear calcified (Figure 5). Pulmonary tuberculosis is unusual in patients with scrofula. Oral manifestations The most common manifestation of tuberculosis in the oral cavity is a chronic painless ulcer. Less frequently tuberculous lesions present as nodular, granular or rarely firm 608

leukoplakic areas. Most oral lesions represent secondary infection from the initial pulmonary lesions, either from hematogeneous spread or from exposure to infected sputum. Secondary oral lesions usually occur on the tongue, palate and lip. Primary oral tuberculosis without pulmonary involvement is rare. It usually involves the gingiva, mucobuccal fold and areas of inflammation adjacent to teeth or in extraction sites. Primary oral lesions are frequently accompanied by enlarged regional lymph nodes. Tuberculous osteomyelitis has been reported in the jaws and appears as ill-defined areas of radiolucency. Histopathologic features Affected tissues show multiple granulomas called tubercles which consist of aggregates of epithelioid histiocytes, lymphocytes and Langhans multinucleated giant cells (Figure 1). The tubercles often show central caseous necrosis (Figure 6). Special stains such as Ziehl–Neelsen or other acid-fast stains are required to demonstrate the bacteria (Figure 7). Because of the relative scarcity of bacilli within tissue, organisms may not be successfully demonstrated in all cases, and a negative result therefore does not completely eliminate the possibility of tuberculosis. Granulomas may be absent or poorly formed in people with poor immune responses, especially those infected with HIV. Diagnosis and laboratory findings A presumptive diagnosis of active tuberculosis is commonly made on the finding of acid-fast bacilli on microscopic examination of a diagnostic specimen such as a tissue biopsy or a smear of expectorated sputum. Definitive diagnosis requires the isolation and identification of M. tuberculosis from a diagnostic specimen, usually sputum in a


Figure 6

Photomicrograph of a caseating granuloma from a tuberculous lesion. The center of the granulomas shows caseous necrosis. Multinucleated giant cells and lymphocytes are seen in the periphery of the granuloma. (Hematoxylin and eosin, original magnification 5)

Figure 7

Photomicrograph showing a positive Ziehl-Neelsen stain in a case of pulmonary tuberculosis. (Ziehl–Neelsen, original magnification 400)

patient with productive cough. Specimens are cultured on egg- or agar-based medium and incubated at 37C under 5% CO2. The organisms grow slowly in culture and 4–8 weeks may be required before growth is detected. Automated liquid culture systems are faster and show a greater yield than solid media-based systems. New automated molecular tests such as XpertMTB/RIF which is a nucleic acid amplification test allow rapid diagnosis not only of tuberculosis, but also of multidrug-resistant tuberculosis (MDR-TB).

Due to inconsistent results and high rates of falsenegative and false-positive results, serological tests for the diagnosis of active tuberculosis are not recommended. Screening for latent M. tuberculosis infection can be performed with skin testing with purified protein derivative (PPD). However, the test is of limited value in the diagnosis of active disease because of its low sensitivity and specificity. False-negative reactions are common in immunosuppressed patients and in those with overwhelming tuberculosis. Positive reactions are elicited from individuals who have been infected with M. tuberculosis but do not have active disease and from persons sensitized by non-tuberculous mycobacteria or Bacille Calmette–Guérin (BCG) vaccination. The gold standard for identifying M. tuberculosis infection is an interferon- release assay which measures interferon- titers released by T cells in response to stimulation with certain TB-speific antigens, such as ESAT-10 and CFP-10. Management protocols and prognosis Because of drug resistance, cure of tuberculosis requires prolonged concomitant administration of at least two agents to which the organism is susceptible. Four major drugs are considered as first-line treatment agents: isoniazid, rifampin (rifampicin), pyrazinamide and ethambutol. Second-line drugs include streptomycin, kanamycin, amikacin, capreomycin, ethionamide, cycloserine, para-aminosalicylic acid and fluoroquinolone antibiotics such as ofloxacin. Secondline agents are used in patients resistant to first-line therapy, because of their lower efficacy and higher toxicity. Infectious cases should be diagnosed rapidly and appropriately treated until cure. The development of drug-resistant tuberculosis is primarily the result of monotherapy or failure of the healthcare provider to prescribe at least two drugs to which the tubercle bacilli are susceptible. Resistance occurs also if the patient fails to take properly prescribed therapy. Multidrug-resistant tuberculosis (MDR-TB) is a form of tuberculosis that does not respond to the standard drug treatment, i.e. the two main first-line drugs: isoniazid and rifampicin. The term extensive (extreme) drug resistant tuberculosis (XDR-TB) has been used to describe a form of MDR-TB resistant to any fluoroquinolone and one of three injectable aminoglycosides (capreomycin, kanamycin and amikacin). Strategies for prevention and disease control include BCG vaccination and treatment of persons with latent tuberculosis infection who are at high risk of developing active disease, such as those infected with HIV, close contacts of persons with known or suspected active tuberculosis, persons with medical risk factors associated with reactivation of tuberculosis, medically underserved and low-income populations, alcoholics, injection drug users, persons with abnormal chest radiographs compatible with past tuberculosis, 609


and residents of long-term care facilities. BCG vaccine is recommended for routine use at birth in countries with high tuberculosis prevalence. However, general use of BCG may not be recommended in countries with low risk of transmission due to the wide variation in efficacy of the vaccines available.

LEPROSY (Hansen’s Disease) Leprosy is a chronic granulomatous disease affecting the skin and peripheral nerves caused by Mycobacterium leprae. Impairment of nerve function results in major disabilities which have physical, social and psychological consequences and are the basis of the stigmatization historically associated with the disease. M. leprae is an acidfast-staining, gram-positive, obligate intracellular bacillus with tropism for macrophages and Schwann cells. The organism grows preferentially in areas of lower temperature, which is why the skin seems to be a target site for infection. M. leprae does not grow in culture media. Animal reservoirs of M. leprae include the nine-banded armadillo (due to its low core body temperature), mice footpads and some non-human primates. According to the WHO, about 720,000 new cases of leprosy are reported each year, and about two million persons suffer from leprosy-related disabilities. The disease is endemic in several developing tropical countries, including India (which accounts for the majority of reported cases worldwide), Brazil, Myanmar, Madagascar and Mozambique. More than 80% of all new cases are reported in these geographic locations. Moreover, geographic and ethnic differences in disease distribution are noted within each of these countries. In contrast to other mycobacterial infections, leprosy does not seem to be more frequent in patients infected with HIV, and co-infection with HIV and M. leprae does not appear to alter the course of either disease. Pathogenesis The precise mechanism of transmission of leprosy is still unknown. Leprosy is not very contagious and has low infectivity. Leprosy is not spread by touching, and exposure to the microorganism rarely results in clinical disease. Transmission seems to require frequent and prolonged contact with an infected person and there is an eight-fold increased risk of disease development in household contacts. Disease transmission is thought to occur by inhalation of bacilli-laden aerosols from lesions in the respiratory tract. The inhaled microorganisms are disseminated by alveolar macrophages to different body organs. Growth occurs mainly in cooler body sites, such as the skin, mucosa and peripheral nerves. The incubation period between exposure to the M. leprae and disease development is very 610

long, and is thought to be between 3 and 5 years, with a range of a few months to 30 years. Interactions between host genetic factors and the microorganism determine the clinical pattern of the disease. Some genes control the overall susceptibility and resistance of the individual to the disease (innate resistance), while HLA-associated genes influence the ability and the pattern of the immune response mounted against the microorganism (through the function of T lymphocytes and antigen-presenting cells). Tuberculoid and lepromatous leprosy represent the two main clinical patterns of the disease situated at either end of a spectrum with borderline forms situated along this spectrum. Tuberculoid leprosy is seen in patients who are able to mount a vigorous immune response to the mycobacterium, and is characterized by low bacillary counts (paucibacillary leprosy), few skin lesions and involvement of a small number of nerve trunks. It shows a predominant Th1 cytokine response with high levels of IL-2, IL-12, IFN- and TNF-. Lepromatous leprosy is characterized by a limited cellular immune response, uncontrolled bacillary proliferation within host macrophages (multibacillary leprosy), diffuse skin lesions and extensive involvement of peripheral nerves. In this form, there is a defective Th1 or a dominant Th2 cytokine response. High levels of IL-4, IL-5 and IL-10 are detected in these lesions. Most patients, however, fall into a broad borderline category between these two ends of the spectrum, and are classified as borderline-tuberculoid, mid-borderline (or dimorphous) and borderline-lepromatous. These forms are clinically unstable, and affected patients can experience a shift of the disease toward any end of the spectrum. Clinical features Leprosy is twice as common in males as in females, especially after puberty. The age at diagnosis varies between 10 and 20 years. Leprosy can affect the skin, peripheral nerves, eyes and bone. Peripheral nerve lesions can cause numbness and weakness, which results in traumatic injuries to affected organs. Tuberculoid leprosy, which corresponds to the paucibacillary form of the disease, presents initially on the skin as hypopigmented, well-demarcated macules that enlarge slowly and develop elevated margins. The number of lesions is usually limited. Loss of dermal appendages (hair follicles and sweat glands) also is seen, especially in fully developed skin lesions. Nerve involvement occurs early in the course of the disease and sensory, motor and autonomic nerves are affected, with resulting hypoesthesia, muscle weakness and anhidrosis. Involved nerves are enlarged and can be visible clinically. Some patients can present with severe painful neuritis. Sensory loss in the hands and feet often leads to severe trauma and burns. When the facial nerve is affected, patients can experience lagophthalmos


(inability to close eyelids completely) and facial paralysis. When the ophthalmic branch of the trigeminal nerve is involved, anesthesia of the cornea and conjunctiva can increase the risk of corneal trauma and ulceration. These ocular lesions can result in blindness. Lepromatous leprosy, which corresponds to multibacillary form of leprosy, shows extensive, symmetric and bilateral skin lesions. The skin of the face is commonly affected, becoming thickened and corrugated. Earlobes become pendulous and the lateral portions of the eyebrows are lost. Involvement of the nose causes nasal stuffiness and nasal bleeds, while perforation of the nasal septum results in saddlenose deformity. Nerve involvement is less prominent in lepromatous leprosy. Leprosy reactions are acute inflammatory complications presenting as medical emergencies during the course of the disease. These can occur in untreated patients, but may often represent a complication of therapy. Oral manifestations Oral lesions are not common in patients affected by leprosy, nor are they considered pathognomonic of the disease. Their prevalence ranges from 0 to 60% of cases. This may decrease further with recent advances in therapy. Oral lesions seem to be more frequent in the lepromatous form of the disease and include papules, plaques, nodules, nonspecific erosions and ulcerations involving the tongue, buccal mucosa and palate. A triad of changes affecting the facial bones and termed facies leprosa was described through archaeological studies. It consists of atrophy of the anterior nasal spine, atrophy and recession of the maxillary alveolar process, and endonasal inflammatory changes. The alveolar destruction limited to the maxillary anterior region can result in loosening and loss of teeth in the area. Granulomatous inflammation of the nasal cavity can result in palatal perforation and oronasal communication. In lepromatous leprosy, M. leprae can infect the dental pulp and cause pulp necrosis. The microorganisms can accumulate within myelinated nerves in the pulp. Infected macrophages can be seen around capillaries. The resulting vascular damage may cause a reddish discoloration of the tooth. Histopathologic features Tuberculoid leprosy demonstrates well-developed noncaseating granulomas composed of histiocytes, lymphocytes and giant cells. Acid-fast bacilli are absent or difficult to find. Peripheral nerves become enclosed within and are destroyed by the granulomas. Tuberculosis, sarcoidosis and other granulomatous inflammatory reactions may show similar microscopic features and must be excluded by clinical and laboratory investigations.

In lepromatous leprosy, sheets of foamy macrophages called lepra cells are seen in the dermis. These cells contain very large numbers of acid-fast bacilli, best demonstrated with the Fite method. Well-formed granulomas are rare in lepromatous leprosy. Diagnosis and laboratory findings The diagnosis of leprosy is based on a positive history of prolonged contact with a known infected person, living in endemic areas of the disease, clinical presentation and laboratory findings. Important diagnostic signs include: (i) hypopigmented or reddish patches with definite loss of sensation, (ii) thickened peripheral nerves, and (iii) acidfast bacilli on skin smears or biopsy material. Skin smears obtained to detect the microorganism are highly specific, but not very sensitive, because bacilli may not be identified in tuberculoid leprosy. This test is not used routinely as a diagnostic aid because laboratory services are not readily available. Intradermal injection of heat-killed M. leprae (lepromin test) has no diagnostic utility in individual cases. A positive lepromin test reflects the ability of a person to develop a granulomatous response to the microorganism, but does not indicate infection with, or exposure to M. leprae. Major advances in the laboratory diagnosis of leprosy were made by the development of genetic probes and polymerase chain reaction (PCR) that can identify M. leprae DNA in clinical specimens. These molecular techniques are highly sensitive and specific, but are not currently used in clinical practice, in part due to the complexity of the procedures. The gold standard for the diagnosis of leprosy is a full thickness skin biopsy obtained from the advancing margin of an active lesion. Management protocols and prognosis The WHO recommends prolonged multidrug therapy for leprosy to overcome the problem of drug-resistant M. leprae. Paucibacillary leprosy is treated with dapsone and rifampin while multibacillary leprosy is treated with a regimen of dapsone, rifampin and clofazimine. The duration of treatment varies depending on the form of the disease. Other multidrug protocols with varying periods of treatment are currently being tested. Complications of leprosy include crippling of the hands and feet, facial deformities and blindness. Recovery from neurologic impairment is limited. Leprosy reactions, which can occur during treatment, require special and emergency care. No highly effective vaccine has yet been developed against leprosy, but there is evidence of a protective effect of BCG vaccine. The efficacy of this vaccine ranges between 20 and 80% in different trials. Other vaccines are being tested including BCG with heat-killed M. leprae. 611


SYPHILIS Syphilis, also known as lues, is a chronic sexually transmitted disease caused by Treponema pallidum. The disease has diverse clinical presentations and is characterized by periods of active disease and latency. The causative agent of syphilis, T. pallidum subspecies pallidum, hereafter referred to as T. pallidum, is a microaerophilic spirochaete which cannot be grown in vitro. The only known natural host for T. pallidum is the human. The genome has been fully sequenced and is small, rendering T. pallidum an obligate parasite with limited metabolic capabilities. Other pathogenic treponemes also can cause disease in humans, such as yaws and pinta. Syphilis occurs worldwide and usually is transmitted by sexual contact or from mother to infant. T. pallidum can be transmitted as a blood-borne infection, but this is infrequent. Syphilis is most common among the poor, those who lack access to healthcare and in those with many sexual partners. According to WHO estimates, approximately 12 million new cases of venereal syphilis occurred in 1999, most of them in developing countries. Congenital syphilis is a leading cause of perinatal and neonatal death in many of these countries. In North America and western Europe, syphilis is less common and disproportionately affects minority populations, men who have sex with men, and persons using cocaine and other drugs. The individuals at highest risk for syphilis also are at increased risk for HIV infection, and the two frequently coexist, as syphilis facilitates the transmission of HIV. Pathogenesis T. pallidum rapidly penetrates intact mucous membranes or microscopic abrasions in skin. It then enters the lymphatics and blood to produce systemic infection. Despite induction of a strong humoral and cell-mediated immune response, T. pallidum is able to survive in the untreated human host for decades and may continue to be transmitted or cause end-organ damage. T. pallidum can be transmitted from a syphilitic woman to her fetus across the placenta at any stage of pregnancy. The manifestations of congenital syphilis are thought to be due to the immune response of the host, rather than a direct toxic effect of the pathogen.

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with or without treatment. Because the ulcers are usually painless and can occur at sites where they are not visible or recognized, many individuals are not diagnosed at this stage. Hematogeneous dissemination of the pathogen in the primary stage results in the manifestations of secondary syphilis, approximately 6–8 weeks later. The most common manifestations of this stage are a maculopapular rash affecting the flank, shoulder, arm, chest, back, hands and soles of feet. A generalized non-tender lymphadenopathy also is present. Less common features of secondary syphilis are mucous patches, condyloma lata, alopecia, meningitis, myalgia, ocular complaints, hepatic, pulmonary and neurologic involvement. The secondary lesions resolve, with or without treatment, and the infection enters a ‘latent’ stage in which there are no clinical manifestations. Transmission of syphilis is by lesion contact and occurs through individuals with the primary or secondary stages of the disease. After many years, approximately one-third of individuals with latent syphilis progresses to tertiary syphilis, which is characterized by cardiovascular disease, neurosyphilis or gummas. Cardiovascular syphilis is the result of endarteritis obliterans of the vasa vasorum which provides the blood supply to large vessels, leading to aortitis, aortic regurgitation, aortic aneurysm or coronary ostial stenosis. Neurosyphilis may take the form of general paresis, insanity and tabes dorsalis. Nearly all direct mortality is due to cardiovascular or neurologic complications and is seen in a relatively small proportion of patients, years after infection. Gummas are foci of granulomatous inflammation which may occur in any tissue and present as nodular ulcerative lesions. The most commonly involved sites include skin and skeletal system, mouth and upper respiratory tract, larynx, liver and stomach. In pregnant women, syphilis may lead to stillbirth, spontaneous abortion or congenital infection of the neonate. Features of early congenital syphilis include rhinitis, mucocutaneous lesions, periostitis, hepatosplenomegaly, lymphadenopathy, anemia, jaundice, leukocytosis and thrombocytopenia. Later features of congenital syphilis are seen at least 24 months after birth and include the hutchinsonian triad of interstitial keratitis of the cornea, sensorineural hearing loss, and the dental anomalies described below.

Clinical features

Oral manifestations

Untreated syphilis is a chronic illness which is traditionally divided into primary, secondary and tertiary stages. In the primary stage a chancre appears at the site of inoculation about 21 days post-infection. The chancre begins as a painless papule that becomes ulcerated. Primary lesions most commonly occur on the genitalia and are frequently accompanied by regional lymphadenopathy. The primary lesion usually resolves spontaneously within 4–6 weeks,

Although the oral cavity is the most common extragenital site of infection, oral manifestations of syphilis are rare. Primary syphilis results from orogenital or oroanal contact with an active lesion and typically manifests as a solitary ulcer (chancre) with indurated margins on the lip, tongue or palate. The ulcer is usually deep, and is accompanied by cervical lymphadenopathy. The chancre usually heals spontaneously within 7–10 days.


In secondary syphilis, maculopapular and nodular mucosal lesions are common. Superficial mucosal erosions, called mucous patches, may be seen on the lips, oral mucosa, tongue, palate and pharynx. The mucous patches are typically painless, oval to crescentic erosions, surrounded by a red periphery. Snail track ulcers are serpiginous lesions that may arise de novo, or form by coalescence of a number of mucous patches. Condylomata lata are broad-based verrucous plaques which can be seen in secondary syphilis of the oral cavity. The oral manifestations of tertiary syphilis are mostly due to gumma formation. Gummas are caused by endarteritis obliterans and tend to involve the hard palate, tongue or lower alveolus. The gummas form swellings which may coalesce to form serpiginous lesions and eventually ulcerate, resulting in bone destruction, palatal perforation and oronasal fistula. Intraosseous gummas appear as ill-defined radiolucent lesions. Interstitial glossitis is rare and is the result of contracture of the tongue musculature after healing of a gumma. An association between interstitial glossitis and oral squamous cell carcinoma of the tongue has been suggested, but this may be due to the carcinogenic agents formerly used to treat syphilis (arsenicals and heavy metals) rather than the infectious agent. Tertiary syphilis can also give rise to both unilateral and bilateral trigeminal neuropathy and facial nerve palsy. Oral manifestations of congenital syphilis include Hutchinson teeth which are screwdriver-shaped incisors that may show notching of the incisal edge. ‘Mulberry’ molars have multiple poorly developed cusps. The facies of patients with congenital syphilis show frontal bossing, saddle nose, and poorly developed maxillae. Rhagades are linear scars at the angles of the mouth caused by secondary bacterial infection of a facial rash occurring in early congenital syphilis. Histopathologic features Primary and secondary syphilis are characterized by dense plasma cell infiltrates, especially in a perivascular distribution, and by capillary endothelial proliferation and obliteration of small blood vessels. However, the microscopic features are not specific for syphilis. Plasma cells are common in oral biopsies, especially those taken from the gingiva. The Warthin–Starry method is a silver impregnation technique which can be used to demonstrate T. pallidum, but the stain is not specific and may label other spirochaetes which inhabit the oral cavity. Gummas are composed of aggregates of epithelioid and giant cells, forming granulomas, usually with a prominent plasma cell infiltrate. T. pallidum is rarely demonstrated in gummas. Diagnosis The diagnosis of syphilis is usually based on clinical signs and symptoms and serologic tests. T. pallidum cannot be detected by culture. Dark-field microscopic examination of

exudate is of limited value in oral lesions because other commensal Treponema species found in the human mouth can be confused with T. pallidum. There are two types of serological tests for syphilis: treponemal and non-treponemal. Commonly used non-treponemal tests include the rapid plasma reagin (RPR) and venereal disease research laboratory (VDRL) tests. The non-treponemal tests measure IgG and IgM directed against the cardiolipin–lecithin–cholesterol antigen complex and are used for screening or for quantification of serum antibody. Treponemal tests are used for confirmation of reactive non-treponemal results and include fluorescent treponemal antibody-absorbed (FTAABS) test and T. pallidum particle agglutination assay (TPPA). The treponemal tests are qualitative tests and are not used in assessing treatment responses. Treatment Parenteral long-acting penicillin G is the drug of choice for all stages of syphilis. Resistance to penicillin has not been described. Other antibiotics effective against syphilis include the macrolides such as erythromycin and azithromycin, as well as tetracycline antibiotics, such as tetracycline and doxycycline. Unfortunately, with increased use of azithromycin for many infections, there has been an increased prevalence of macrolide-resistant T. pallidum. Vaccines are not available for this disease. Testing for HIV status in affected patients is also recommended.

DEEP FUNGAL INFECTIONS Fungal infections or mycoses usually are superficial and involve the skin, hair, nails and mucous membranes. In some cases, especially in immunocompromised patients, disseminated or deep fungal infections can cause extensive tissue destruction. In immunocompetent hosts, deep fungal infections can heal or remain latent for prolonged periods of time. Many fungal infections can initiate a granulomatous inflammatory response in the host as discussed below.

Blastomycosis Blastomycosis is caused by Blastomyces dermatitidis, a dimorphic fungus that grows in soil and decaying wood. The organism is endemic in some parts of the United States and Canada, but infections are also seen in Mexico, MiddleEast, Africa and India. Infection occurs through inhalation of the conidiae (asexual spores). In the lungs at body temperature, the conidiae are transformed into yeasts that multiply through budding. Yeasts represent the pathogenic forms of the organism. The infection usually is contained in the lungs and most patients are either asymptomatic or develop mild non-specific flu-like symptoms. In some patients, hematogeneous spread can occur. 613


Figure 8

Photomicrograph showing Blastomyces dermatitidis. The organism appears as round yeast with thick refringent cell wall. (Hematoxylin and eosin, original magnification 200)

Three clinical forms of blastomycosis are recognized: pulmonary blastomycosis, disseminated blastomycosis and cutaneous blastomycosis which is very rare. Pulmonary disease can be acute or chronic. Acute pulmonary blastomycosis presents clinically with productive cough, chest pain, dyspnea, fever and night sweats. Chronic pulmonary blastomycosis can be mistaken for tuberculosis, sarcoidosis, or even malignancy. Oral involvement is rare and can present as ulcers or exophytic mucosal lesions. The clinical differential diagnosis includes oral squamous cell carcinoma and biopsy usually is needed to exclude this possibility. The diagnosis of blastomycosis is based on the identification of B. dermatitidis in a tissue biopsy or a cytological smear of an infected body fluid. The organism appears as a round yeast cell which divides by broad-based budding. It has a thick, refringent cell wall (Figure 8). Biopsy from lesional tissue shows a mixed acute and granulomatous inflammation. Special stains such as periodic acid-Schiff (PAS) (Figure 9) and methenamine silver (Figure 10) can be used to identify the organism in tissue samples. Skin or mucous membrane lesions show marked pseudo-epitheliomatous hyperplasia. Diagnosis can be confirmed by culture as well, but this may take several weeks. Highly specific and sensitive DNA probes can be used to identify the organism, a few days after culture. Treatment is based on the severity of the disease. Patients with mild to moderate illness are treated with itraconazole. Those with severe disease, meningeal lesions and immunocompromised patients are managed with amphotericin B.

Histoplasmosis Histoplasmosis is caused by Histoplasma capsulatum, a dimorphic fungus found in soil contaminated with bird or 614

Figure 9

Periodic acid-Schiff (PAS) stain showing Blastomyces dermatitidis in the lung of a patient who died of disseminated blastomycosis. (Original magnification 400)

Figure 10

Methenamine silver stain of the same case shown in Figure 9. Note the broad-based budding of the yeast. (Original magnification 400)

bat droppings, and hence rich in nitrogen. The organism is endemic in some areas of the United States, especially in the Mississippi and Ohio River Valleys. It can also be seen in other parts of the world, including central America, Asia and some Mediterranean countries. Disease occurs through inhalation of the microconidia, the infectious form of the fungus. Macrophages, the main target of infection, can be destroyed by the intracellular multiplication of the pathogen.


The severity of the disease is proportional to the amount of inhaled spores and to the integrity of the immune response of the host. Therefore, immunocompromised patients, such as those with AIDS, organ transplant recipients, and those with hematological malignancies may develop disseminated histoplasmosis, with involvement of extrapulmonary sites. Acute pulmonary infection presents with fever, dyspnea, productive cough and anterior chest discomfort. Granuloma formation and coagulative necrosis can result in cavitation of lung tissues. Healing of the granulomatous lesions can cause fibrosis and concentric calcifications. A chronic progressive form of histoplasmosis exists as well and resembles tuberculosis clinically. The most common form of histoplasmosis, however, is an asymptomatic pulmonary infection or a mild respiratory illness. Oral involvement is seen mainly in disseminated disease in the form of ulcers, red or white lesions. Oral ulcers secondary to histoplasmosis may resemble squamous cell carcinoma or tuberculous ulcers. The diagnosis of histoplasmosis is based on culture, identification of the organism in tissue samples, and serologic tests. Growth of the organism in culture can take several weeks. More rapid identification can be achieved with specific DNA probes. Microscopic examination of lesional tissue can show granulomas and multinucleated giant cells or a diffuse, mixed inflammatory infiltrate dominated by macrophages. Special stains confirm the presence of small, uniform and oval budding yeast. Treatment is based on the severity of the disease. Mild-to-moderate forms of histoplasmosis are treated with itraconazole, while disseminated disease and immunocompromised patients require treatment with amphotericin B.

Aspergillosis Aspergillosis is a fungal infection caused by members of the Aspergillus species which are ubiquitous saprophytic molds growing on organic matter. Sporulation of the mold produces large numbers of conidia that can be inhaled by humans without adverse consequences in the majority of cases. In some patients, the inhaled organisms can cause allergic fungal sinusitis, allergic pulmonary aspergillosis or asthma. A mass of fungal hyphae, called aspergilloma, can form in the sinuses or the lungs of patients suffering from cavitary tuberculosis, bronchiectasis or lung abscesses. Immunocompromised patients, such as individuals with AIDS, bone marrow or organ transplant recipients, and patients with hematological malignancies, can develop invasive disease, where primary disease of the lungs is followed by widespread hematogeneous dissemination and multiple organ involvement. Aspergillus fumigatus and A. flavus are the most common species to cause human aspergillosis. A. fumigatus is

Figure 11

Aspergillosis of the maxillary sinus in an immunocompromised patient. Note the septate hyphae that branch at acute angles. (Hematoxylin and eosin, original magnification 400)

responsible for the majority of invasive infections in immunocompromised patients. Diagnosis of aspergillosis is based on the clinical signs and symptoms, individual patient risk, culture and histopathology. Microscopically, multiple septate hyphae, 3–4 m in diameter, with a tendency to branch at acute angles and with occasional fruiting bodies can be seen (Figure 11). Aspergillus has a tendency to invade blood vessels, which explains the presence of areas of hemorrhage and infarction in involved tissues. A non-caseating granulomatous inflammatory response with giant cells can be seen in immunocompetent patients. It can be intense enough to cause pressure necrosis of adjacent bone. Until recently, amphotericin B and itraconazole were the standard therapeutic regimen for patients with invasive aspergillosis. A recent trial showed that voriconazole is more effective in these cases and is associated with better survival and fewer side effects. Patients with allergic fungal sinusitis may require surgical debridement, systemic antifungal treatment and systemic or topical steroids. Aspergilloma requires surgical debridement.

Zygomycosis (Mucormycosis, Phycomycosis) Zygomycosis is a fungal infection caused by zygomycetes, especially those belonging to the order of Mucorales. The Rhizopus species and the Mucor species belonging to the Mucoraceae families of Mucorales are the most common species causing human zygomycosis. Rare human infections can be caused by the enthomophthorales order of zygomycetes. Mucorales fungi are ubiquitous and can grow on organic matter including bread, fruits, vegetables and soil. They produce abundant spores that can be spread in the environment 615


Figure 12

FOREIGN BODY GRANULOMAS A number of foreign materials of endogenous or exogenous origin, which cannot be phagocytosed by macrophages because of their size or composition, can induce a granulomatous inflammatory response in tissues. Examples include silica, beryllium, glass, talc, starch, suture material, and a large number of dental materials, such as pumice, gutta percha, endodontic sealers, and some impression materials. Some endogenous substances such as hair, keratin, amyloid and calcifications can also induce granulomatous inflammation in tissues. Macrophages accumulate in the site, become activated, and differentiate into epithelioid cells. Some of the macrophages fuse to form foreign body giant cells. Granulomas form and envelop the foreign material, which may be seen in the cytoplasm of some macrophages and giant cells.

Zygomycosis of the mandible in a patient undergoing chemotherapy. The photomicrograph shows multiple broad, thin-walled, aseptate hyphae that tend to branch irregularly or at right angles. (Hematoxylin and eosin, original magnification 400)

and inhaled by humans. Infection rarely occurs in immunocompetent patients. The most common underlying risk factors for zygomycosis are uncontrolled insulindependent diabetes mellitus (IDDM) with metabolic acidosis, immunosuppressive treatment, prolonged systemic corticosteroid use, solid-organ and hematopoietic stem cell transplantation, persistent neutropenia and ironchelating treatment. The most common human manifestation of this infection is rhinocerebral zygomycosis that affects the nose, maxillary sinus, midface with frequent extension into the brain. Sinonasal disease causes nasal obstruction, rhinorrhea, facial pain and facial swelling. Oral mucosal involvement presents with ulceration. Typically, the base of the ulcer is black and massive tissue destruction and necrosis can be seen in untreated patients. The diagnosis of zygomycosis relies on the identification of the broad, thin-walled, irregularly-branching and mostly aseptate hyphae in affected tissues. Branching occurs at right angles (Figure 12). The organism has high affinity for blood vessel invasion, which explains the massive tissue infarction and necrosis observed clinically and microscopically. Treatment of zygomycosis necessitates management of the underlying medical condition, use of effective antifungal treatment and surgical debridement. Amphotericin B is the treatment of choice. Posaconazole seems to provide encouraging results, especially in prophylaxis. Debridement is necessary because antifungal treatment cannot reach infected tissues, and correction of the surgical defects is needed once active disease is controlled. 616

Clinical features The clinical manifestations of foreign body reactions are usually non-specific and vary from a localized mass to superficial erosions and ulcerations. In the oral cavity, the gingiva seems to be the most common site of involvement and the condition has been termed granulomatous or foreign body gingivitis. Dental materials are the most common causative factors in these cases, but other substances including hair and nails have been reported. The condition presents clinically as a localized change in gingival color, ulceration or diffuse gingival erythema. Lesions start at the interdental papilla and extend laterally. An important diagnostic clue is that the condition does not regress with improvement of oral hygiene measures. Histopathologic features Biopsy material from the gingiva can show granulomas and foreign body giant cells in the absence of microorganisms. The foreign substance can be identified in hematoxylin and eosin stained sections (Figure 13) or by polarized light microscopy. Energy-dispersive radiographic microanalysis can help confirm the presence of foreign material in tissue sections and identify its nature. In the absence of identifiable foreign material, other causes of granulomatous inflammation have to be investigated. In some cases, the inflammatory response is lichenoid in appearance and the foreign body is too small to be identified microscopically. A diagnosis of lichen planus can therefore be rendered, but the lesions will not respond to conventional treatment of lichen planus. Management protocols and prognosis The treatment of foreign body reactions includes the elimination of the offending agent and excision of involved tissues. This results in adequate clinical response in the


Figure 13

The role of genetic factors is suggested based on disease association with distinct HLA alleles. Other genes involved in controlling the immune response can play a role in disease pathogenesis as well. Granulomatous vasculitis of the upper airways and lungs suggests that the disease may represent a cell-mediated reaction to an inhaled antigen of bacterial, viral or environmental origin. Chronic nasal carriage of S. aureus has been linked to the initiation and relapse of WG through a number of molecular mechanisms implicating B cells, T cells and neutrophils. Clinical features

Photomicrograph of a foreign body reaction following reconstructive surgery in the temporomandibular joint showing a large number of multinucleated giant cells engulfing a foreign material. Typical granulomatous inflammation was seen elsewhere in the specimen. (Hematoxylin and eosin, original magnification 100)

majority of cases. If a diagnosis of granulomatous gingivitis is made in the absence of an identifiable foreign material, the patient should be investigated for other causes of granulomatous inflammation.

WEGENER’S GRANULOMATOSIS Wegener’s granulomatosis (WG) is a systemic autoimmune disease that is invariably fatal if left untreated. The disease may occur in generalized and limited forms, and consists of the classical triad of (i) necrotizing granulomatous inflammation involving the upper respiratory tract, the lower respiratory tract, or both, (ii) necrotizing glomerulonephritis, and (iii) systemic vasculitis involving small to medium-sized vessels (capillaries, venules, arterioles, or arteries). WG is an uncommon disease, with an estimated prevalence of 3.0 per 100,000 persons in the United States. It is more common in whites than in blacks and affects both sexes equally. The mean age at onset is approximately 40 years, but the disease can occur at any age, with 15% of cases occurring in patients younger than 19 years. Etiology and pathogenesis The etiology of WG has not been fully elucidated. Genetic factors, exposure to environmental antigens such as silica and infection (in particular with Staphylococcus aureus) seem to play an important role in disease pathogenesis.

WG affects mainly the upper and lower respiratory tracts. In generalized WG, renal disease develops rapidly. Limited WG refers to disease restricted to the respiratory system without rapid renal involvement. In some cases, the disease is restricted to the skin and mucosa. This has been termed superficial WG. Pulmonary involvement is seen in more than 80% of patients who may present with cough, hemoptysis, dyspnea and chest discomfort. In asymptomatic patients, abnormal chest radiograph may be the only manifestation of the disease. Renal disease develops in the majority of patients (77%), and is the most common cause of morbidity and mortality. Early glomerulonephritis presents with proteinuria, hematuria and red blood cell casts in urine. Disease progression leads to renal failure, especially if no treatment is administered. Active disease is characterized in general by constitutional symptoms such as malaise, fever, night sweats and weight loss. Other organs can be involved by the granulomatous vasculitis, including peripheral and cranial nerves, heart, eyes and skin. Involvement of the head and neck region is very common in WG. The nasal cavity and paranasal sinuses are affected in 60–90% of the cases, with symptoms of nasal obstruction, sinusitis and headache, purulent nasal discharge, epistaxis, and mucosal ulceration. Nasal septal perforation can cause saddle nose deformity. The ears, the eyes, the larynx and the oral cavity can be affected as well. Eustachian tube blockage may result in persistent serous otitis media. Laryngeal disease can result in subglottic stenosis which can lead to upper airway obstruction requiring emergency tracheostomy. Salivary gland involvement is uncommon, but has been reported in WG. Oral manifestations Oral involvement is quite common in WG and it may be the first sign of the disease. Strawberry gingivitis, one of the characteristic signs of WG, is thought to be an early manifestation of the disease, occurring before renal involvement. Clinically, strawberry gingivitis appears as hyperplastic granular and friable gingival lesions with multiple surface petechiae. The buccal surface of the gingiva is more 617


frequently involved. The process originates in the interdental papillae and extends laterally to involve the rest of the gingiva. Periodontal bone loss has been described and can result in tooth mobility and extraction. Non-healing of extraction sockets is possible. Oral ulcers affecting any mucosal surface can be seen in WG, but are non-specific and seem to develop at an advanced stage of the disease, usually after renal involvement occurs. Necrosis and ulceration of the palate can be seen. Histopathologic features Wegener’s granulomatosis is characterized microscopically by granulomatous inflammation, geographic necrosis and vasculitis. The granulomas are ill-defined, surround areas of necrosis, and are not as compact and as defined as those seen in tuberculosis and sarcoidosis. In lung biopsies, areas of necrosis are surrounded by a shell of fibroblastic, inflammatory and giant cells, producing palisading granulomas. The inflammatory infiltrate can be dense, mixed, and non-specific and overshadow the underlying pathology. Special stains do not show microorganisms and foreign body cannot be identified by polarizing light microscopy. Affected vessels show a transmural inflammatory reaction, with focal or diffuse polymorphonuclear infiltrates causing vessel wall destruction and fibrin deposition within the walls and the lumen. The necrosis seen seems to be secondary to the vasculitis. Oral mucosal biopsies show an inflammatory infiltrate composed mainly of neutrophils and eosinophils that occasionally form microabcesses. Giant cells are common and ill-defined granulomas can be seen. Vasculitis is less prominent in mucosal biopsies from the head and neck region, including the mouth, mainly due to the small size of these biopsies and lack of larger vessels in mucosa. Strawberry gingivitis shows pseudoepitheliomatous hyperplasia and a prominent vascular component associated with red blood cell extravasation. Diagnosis and laboratory findings The diagnosis of WG is based on history, clinical presentation, laboratory test results and microscopic findings of necrotizing granulomatous vasculitis in a biopsy specimen. Laboratory tests show an elevated erythrocyte sedimentation rate (ESR), high C-reactive protein, leukocytosis and thrombocytosis. Renal involvement can result in urinary sediment, erythrocyturia, proteinuria and high serum creatinine levels. Chest radiographs and computerized tomography can confirm the presence of pulmonary infiltrates or nodules. Detection of c-ANCA by indirect immunofluorescence and confirmation of the specificity of ANCA against proteinase-3 (PR3-ANCA) by ELISA yields a specificity of 99% and a sensitivity of 73% in the diagnosis of WG. Identification of c-ANCA is an adjunctive test, as false positive results can be seen in some infectious and neoplastic 618

diseases. Furthermore, a negative c-ANCA titer does not exclude the diagnosis of WG. Changes in ANCA titers appear to reflect disease activity and rising titers can predict relapse in treated patients although this is not a consistent finding. Management protocols and prognosis Wegener’s granulomatosis is typically treated with longterm cyclophosphamide given in oral doses together with glucocorticoids which produces rapid and marked improvement in the majority of patients. Recently, it was shown that rituximab can play a role in the induction of remission. Less toxic drugs such as azathioprine, methotrexate and leflunomide can be used to maintain remissions. Approximately half of remissions are followed with one or more relapses, and many patients develop some degree of morbidity either from irreversible features of their disease or from the toxic side effects of treatment. Patients may suffer from varying degrees of renal insufficiency or impaired upper respiratory tract function. Cyclophosphamide-related toxicities include cystitis, bladder cancer, myelodysplasia and infertility. Diabetes mellitus, cataracts, infectious complications and osteoporosis are some of the glucocorticoidassociated side effects.

SARCOIDOSIS Sarcoidosis is a relatively common multisystem immunemediated disease primarily affecting the lungs and lymphatic systems. It is characterized by the presence of non-caseating granulomas in affected organs. The etiology of sarcoidosis is unknown, but familial, spatial (e.g. among people in the same household), seasonal and occupational clustering of the disease have been reported, suggesting multiple underlying factors, including genetic predisposition, infectious agents and environmental exposures. Possible microbial triggers include mycobacterial and propionibacterial organisms, with the mycobacterial catalase-peroxidase (mKatG) protein as a potential candidate antigen. Sarcoidosis likely develops from an exaggerated cellular immune response (acquired, inherited or both), to a limited class of persistent antigens or self-antigens. Space-occupying granulomas form from the accumulation of mononuclear inflammatory cells, mostly CD4 Th1 lymphocytes and mononuclear phagocytes in affected organs. Organ dysfunction and tissue injury result from physical distortion of the tissue by the granulomas. Sarcoidosis is found throughout the world, but is most prevalent in United States and Scandinavian populations. In the United States there is a three-fold to five-fold increased incidence in blacks compared to whites. Geographic, ethnic and genetic factors are linked to the specific clinical characteristics of patients with sarcoidosis. Blacks are more


likely to have severe musculoskeletal or constitutional symptoms on presentation, while whites appear to have higher rates of asymptomatic disease, disease limited to the chest and erythema nodosum.

Figure 14

Clinical features Sarcoidosis is more common in young and middle-aged adults, with approximately 75% of the cases in individuals younger than 40 years. Females appear to be slightly more susceptible than males. Sarcoidosis has a variable clinical presentation and course, and can affect many organs and tissues, but the lungs are most commonly affected. Unlike many lung diseases, sarcoidosis favors non-smokers. Other organ systems that may be affected by sarcoidosis include the heart, liver, spleen, bones, skin, eyes, lymph nodes, parotid glands, and uncommonly, the oral cavity. The majority of patients with sarcoidosis are asymptomatic, with the disease being discovered on routine chest radiographs. Symptomatic sarcoidosis may develop abruptly over a period of a few weeks. Less frequently sarcoidosis arises insidiously over months or years without significant symptoms. Symptomatic patients usually present with respiratory and skin manifestations or with constitutional and non-specific symptoms such as fever, night sweats, fatigue and malaise. Dry cough, dyspnea and chest pain are frequent respiratory complaints. Cutaneous manifestations occur in approximately 25% of patients and include erythema nodosum and lupus pernio. Erythema nodosum are scattered tender erythematous nodules occurring frequently on the lower legs, while lupus pernio represents chronic, violaceous lesions involving the face, limbs, back and buttocks. Ocular symptoms may be due to anterior uveitis or lacrimal gland involvement resulting in keratoconjunctivitis sicca. Two distinctive clinical syndromes are associated with acute sarcoidosis. Löfgren syndrome, a form of acute sarcoidosis usually found in white females, consists of erythema nodosum, bilateral hilar lymphadenopathy and arthralgia. Heerfordt syndrome (uveoparotid fever) is characterized by parotid enlargement, anterior uveitis, facial paralysis and fever. Oral manifestations Excluding salivary gland and lymph node involvement, oral manifestations of sarcoidosis are uncommon, and the disease is typically diagnosed before oral symptoms appear. Sarcoidosis may involve any oral mucosal site, most commonly buccal mucosa, followed by gingiva, lips, floor of mouth, tongue and palate. The lesions most commonly present as submucosal masses, which may vary in color from normal to brownish-red or violaceous or they may be hyperkeratotic. Sarcoidosis of the major and minor salivary glands may result in xerostomia. Sarcoidosis can cause bilateral enlargement of the major salivary glands which, in conjunction with xerostomia and keratoconjunctivitis

Photomicrograph of a granulomatous inflammatory lesion involving the lung of a patient with sarcoidosis. Well-formed non-caseating granulomas are noted and are surrounded by a rim of lymphocytes. (Hematoxylin and eosin, original magnification 200)

sicca, can mimic Sjögren’s syndrome. Intraosseous lesions are less common than soft tissue lesions, accounting for approximately one-fourth of all reported intraoral cases. Either jaw may be affected. Intraosseous lesions typically appear as non-expansile ill-defined radiolucent areas which may be accompanied by tooth mobility due to alveolar bone loss. Histopathologic features Lesions of sarcoidosis consist of tightly clustered aggregates of epithelioid histiocytes surrounded by a rim of lymphocytes (Figure 14). Multinucleated giant cells of the Langhans type or foreign body type are intermixed with the histiocytes. Necrosis is typically absent (Figure 15). The giant cells may contain laminated calcified structures called Schaumann bodies or stellate inclusions known as asteroid bodies. Special stains for fungal and bacterial organisms are negative. Polarizable, dissolvable and pigmented foreign materials are not detectable. Diagnosis and laboratory findings The diagnosis is based on clinical and radiographic findings, histopathologic evidence of non-caseating epithelioid granulomas, and exclusion of other known causes of granulomatous inflammation. Chest radiographs may show bilateral hilar lymphadenopathy, diffuse parenchymal infiltrates, or both, and 90% of patients have abnormal chest 619


Figure 15

The overall prognosis of sarcoidosis is good. Spontaneous resolution is common and in most patients symptoms resolve spontaneously within 2 years without treatment. Poor prognostic indicators include chronic disease, older age at onset, black race, lupus pernio, neurosarcoidosis, cardiac involvement and advanced pulmonary disease. Approximately 4–10% of patients die of progressive respiratory, central nervous system or cardiac involvement.

OROFACIAL GRANULOMATOSIS

Photomicrograph of sarcoidosis showing absence of necrosis. Scattered giant cells are noted within the granulomas. (Hematoxylin and eosin, original magnification 100)

radiographic findings sometime during the course of their disease. Lung function abnormalities typically found include decreased lung volumes and diffusing capacity. Elevated serum angiotensin-converting enzyme (ACE) levels support the diagnosis of sarcoidosis, but this test lacks sensitivity and specificity. Elevated serum calcium concentration and urinary calcium level may be found. The Kveim test, a skin test for sarcoidosis involving intradermal injection of human spleen extract of sarcoid tissue, is no longer used because of concerns of transmission of infectious diseases. Minor salivary gland biopsy may be helpful in suspected cases of sarcoidosis, with success rates between 19% and 58%. However, parotid biopsy provides a better diagnostic yield, with confirmation of sarcoidosis reported in 93% of patients following this procedure. Management protocols and prognosis The diagnosis of sarcoidosis usually is followed by a 3- to 12-month period of observation to define the general course of the disease. Immediate medical treatment is indicated for patients with neurological, cardiac, severe ocular, advanced pulmonary and disfiguring cutaneous disease, as well as persistent hypercalcemia. The standard treatment for sarcoidosis is systemic corticosteroids. Other immunosuppressive and immunomodulating drugs including tumor necrosis factor antagonists, have been used, but definitive evidence of their efficacy is lacking. Xerostomia secondary to sarcoidosis of the major salivary glands predisposes patients to caries, periodontal disease and candidiasis, necessitating preventative measures, salivary stimulants, topical fluoride and antifungal medications. Systemic corticosteroid therapy can result in adrenal suppression requiring special precautions before oral surgical interventions. 620

Orofacial granulomatosis (OFG) is a clinical and pathologic term introduced by Wiesenfeld in 1985 to describe a group of conditions affecting the oral and maxillofacial region, and characterized microscopically by noncaseating granulomatous inflammation. The spectrum of OFG includes cheilitis granulomatosa (CG) of Miescher, Melkersson–Rosenthal syndrome (MRS), Crohn’s disease, sarcoidosis and other granulomatous inflammatory conditions that could affect this region. Some cases of OFG can develop secondary to a chronic dental infection or to a contact hypersensitivity reaction while others appear to be idiopathic. A preliminary diagnosis of OFG should be followed by a thorough clinical and laboratory investigation to identify and treat any possible underlying local or systemic disease and thus idiopathic OFG is a diagnosis acquired by exclusion. The etiology of OFG is unknown and the disease is thought to represent an abnormal immune reaction. Infection, allergy and genetic predisposition have been suggested. Monoclonal lymphocytic expansion, which may be secondary to chronic antigenic stimulation, has been identified in OFG. Cytokine production by the monoclonal lymphocytic proliferation could stimulate granuloma formation. The spectrum of OFG encompasses cheilitis granulomatosa (CG) of Miescher and Melkersson–Rosenthal syndrome (MRS). Systemic conditions such as tuberculosis, Crohn’s disease, sarcoidosis and other granulomatous inflammatory conditions could present with granuloma formation in the oral and maxillofacial region. Clinical features The most consistent finding in OFG is a painless, persistent diffuse swelling involving one or both lips (macrochelia). The swelling can be unilateral or involve the whole lip (Figure 16). In the early phases of the disease, the swelling is usually soft, intermittent and recurrent. Later, the swelling becomes permanent and fibrotic. Generalized edema, erythema and non-specific erosions and ulcerations may be seen in the mouth. Gingival swelling can be seen in some cases. Some patients develop swelling elsewhere in the face, with or without lip involvement, making the diagnosis more difficult. Other reported manifestations of OFG include


Figure 16

Diffuse lip swelling in a patient with orofacial granulomatosis. Slight erythema was noted on the facial skin

fissures of the tongue, taste alterations, decreased salivary production and a cobblestone appearance of the buccal mucosa. When the swelling is limited to the lips, the term CG is used by some clinicians and when it is associated with a fissured tongue and a history of recurrent facial paralysis a diagnosis of MRS can be applied. It is better, however, to limit the use of these terms since they are considered as subsets of OFG rather than specific disease entities. It is also useful to use terms such as OFG in the context of Crohn’s disease or sarcoidosis, OFG secondary to contact hypersensitivity reaction, or idiopathic OFG to standardize terminology. Histopathologic features Orofacial granulomatosis is characterized by the presence of non-caseating epithelioid granulomas, usually with multinucleated giant cells (Figure 17). The granulomas may be concentrated around blood vessels, or they may be scattered in the connective tissue and lamina propria. Sometimes, minor salivary gland involvement can be seen. A perivascular lymphocytic infiltrate with marked dilation of lymphatic channels and marked edema of the superficial lamina propria is seen in some cases, and can be useful when typical granulomas are absent. Acid-fast bacilli and fungal organisms cannot be identified with special stains and foreign material is not seen with polarized light microscopy.

Figure 17

Photomicrograph of a buccal mucosal biopsy showing multiple non-caseating epithelioid granulomas with multinucleated giant cells. An intense lymphoplasmocytic infiltrate is associated with the granulomas. (Hematoxylin and eosin, original magnification 100)

exclusion of possible causes of granulomatous inflammation should be followed by a systematic work-up, including clinical, laboratory and radiographic investigations, to rule out underlying local or systemic disease. All oral foci of infection should be identified and treated. Elimination diet and patch testing against potential allergens such as food additives, cosmetics, fragrances and dental hygiene products should be performed if contact hypersensitivity reaction is suspected. Chest radiographs and serum levels of angiotensin-converting enzyme can be obtained to screen for evidence of sarcoidosis. Complete blood count, ESR, and serum levels of folic acid, vitamin B12, and iron are useful in patients with unusual gastrointestinal manifestations. These patients also should undergo specialized gastrointestinal examination to assess for Crohn’s disease. If this investigation is negative, it can be repeated later, especially if clinically indicated and in younger patients with OFG as these patients are more likely to have concomitant intestinal disease. Tuberculin test and chest radiographs should be performed even if acid-fast stains were negative on histology to exclude tuberculosis. Management protocols and prognosis

Diagnosis and laboratory findings Special stains, such as the PAS stain, Grocott methenamine silver stain, Ziehl–Neelsen and Gram stain applied to the lesions of OFG do not show fungal or specific bacterial organisms. Foreign body is not demonstrable within the lesions with polarized light microscopy. The microscopic

Intralesional corticosteroid injection is the treatment of choice in OFG. The response to intralesional treatment is usually fast, but relapses are common, and therefore repeated injections are needed. Systemic corticosteroids are effective, but their long-term use is limited by the recurrent and chronic nature of the disease and by their 621


serious side effects. Other therapeutic measures have been used with variable success, including hydroxychloroquine, methotrexate, clofazimine, metronidazole, minocycline alone or in combination with oral prednisone, thalidomide, dapsone and danazol. One study showed that the impact of dietary manipulation in patients suffering from OFG can be significant, especially in the presence of oral mucosal inflammation. Other investigators reported improvement of oral manifestations upon removal of amalgam restorations, but this has not been reproduced in controlled studies. Surgical intervention (cheiloplasty) is performed when the response to medical treatment is weak and in severely disfiguring cases. It is not a first-line therapy because of the high risk of recurrence. The treatment of OFG is difficult and often disappointing due to the chronic nature of the disease and the high risk of recurrence. Identifying the underlying causative factor is not feasible in many cases, which increases the risk of recurrence. Spontaneous remissions have been reported but do not seem to be very common.

CROHN’S DISEASE (Regional Ileitis, Regional Enteritis) Etiology and pathogenesis Crohn’s disease is a chronic, relapsing, immunologically mediated inflammatory bowel disorder. Its etiology and pathogenesis have not been clearly defined. Crohn’s disease is thought to be due to an inappropriate acquired T-cell immune response to certain commensal enteric bacteria developing in genetically susceptible hosts. Environmental factors seem to play a role in disease pathogenesis as well. T cells implicated in Crohn’s disease are primarily activated CD4 Th1 lymphocytes which secrete cytokines such as IL-12, IFN- and TNF. Although Crohn’s patients show loss of tolerance to enteric commensal bacteria, no specific infectious etiology has been identified. The role of environmental triggers such as smoking, use of antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs), stress and infection is not well understood, but these factors appear to play a role in precipitating the onset or the reactivation of disease. Evidence for hereditary factors in the pathogenesis of Crohn’s disease includes a concordance rate of approximately 50% in monozygotic twins and an increased risk of the disease in relatives of patients with Crohn’s disease. Genes associated with innate immunity, such as NOD2 (nucleotide-binding oligomerization domain 2) and ATG16L1 (autophagy-related, 16-like) genes, have been implicated in Crohn’s disease. NOD2 is an intracellular protein that senses bacterial products and activates components of the innate immune system. Other genetic loci linked to Crohn’s disease include several genes involved in 622

endoplasmic reticulum and metabolic stress, regulation of adaptive immunity and inflammation. The role of genetics in disease development is actively investigated and susceptibility genes such as NOD2/CARD15, IL23R, ATG16L1 and others have been identified. Of these, the NOD2/CARD15 gene (caspase recruitment domain family member 15) is the most replicated and understood. It plays a role in regulating innate immune responses, bacterial killing, immune responses to endogenous microbial antigens and epithelial function. NOD2 (nucleotide-binding oligomerization domain containing 2) is an intracellular protein that senses bacterial products and activates components of the innate immune system. Clinical features Crohn’s disease is more prevalent in western countries than in developing countries and is more prevalent in northern regions compared to southern regions. Urban areas have a higher prevalence of Crohn’s disease than rural areas. The disease frequency is highest in Ashkenazi Jews. Higher economic status and active smoking increase the risk for Crohn’s disease. The peak age of onset is between 15 and 30 years, and a second peak occurs between the ages of 60 and 80. The male-to-female ratio is 1:1 to 1.8:1. Crohn’s disease can affect any part of the gastrointestinal tract from the mouth to the anus, with the terminal ileum being involved in the majority of patients. Symptoms commonly include long-standing diarrhea, abdominal pain, weight loss, and some patients may experience non-specific symptoms such as malaise, anorexia or fever. Transmural inflammation (inflammation affecting all layers) of the gut may result in fissures, abscesses, fistulas, thickening of the bowel wall and limited distensibility. Aphthous-like superficial ulcerations can be seen. These can fuse longitudinally and transversely around normal tissue to produce a ‘cobblestone’ appearance of the bowel mucosa. Extraintestinal manifestations are relatively common and include dermatologic conditions such as erythema nodosum, pyoderma gangrenosum, pyodermatitis vegetans, and Sweet syndrome, a neutrophilic dermatosis. Rheumatologic manifestations include asymmetric polyarticular migratory polyarthritis most often affecting the large joints of the upper and lower extremities, and ankylosing spondylitis. Ocular complications include conjunctivitis, anterior uveitis/iritis and episcleritis. Oral manifestations Oral lesions of Crohn’s disease can vary and be relatively non-specific. These do not necessarily reflect intestinal disease activity. Oral involvement can occur at any time during the course of the disease and may precede gastrointestinal manifestations in as many as 30% of the cases. Findings include diffuse or nodular swelling of the oral and perioral tissues, a cobblestone appearance of the oral


Figure 18

A linear ulcer in the upper left vestibule of a young patient with Crohn’s disease

Figure 20

Clinical appearance of pyostomatitis vegetans, presenting diffuse erosive and erythematous lesions involving the labial mucosa, the gingiva and the vestibule

Figure 19 Figure 21

Diffuse hyperplastic gingivitis in the same patient shown in Figure 18. Biopsy confirmed the presence of non-caseating granulomas

mucosa and deep linear ulcers involving the buccal vestibule (Figure 18). Aphthous ulcers can be seen, but their significance in Crohn’s disease is uncertain, as they occur as frequently in the general population and in the same age group affected by Crohn’s disease. Other reported oral manifestations include fibroepithelial hyperplasia, granulomatous gingivitis (Figure 19), angular cheilitis, persistent submandibular and superficial cervical lymphadenopathy, and metallic dysguesia. Less than 1% of patients with Crohn’s disease may develop diffuse stomatitis, with some cases caused by Staphylococcus aureus, and others being non-specific. A rare condition called pyostomatitis vegetans may be associated with Crohn’s disease. Pyostomatitis vegetans is usually seen on the buccal, labial mucosa, soft palate, ventral tongue and facial gingiva

Photomicrograph of a gingival biopsy from the patient shown in Figure 19 demonstrating multiple non-caseating granulomas with a large number of multinucleated giant cells. (Hematoxylin and eosin, original magnification 100)

and is characterized by the development of multiple yellowish, serpiginous pustules on erythematous oral mucosa (Figure 20). The pustules often rupture, leading to erosions and fissuring. Histopathologic features In the bowel, Crohn’s disease is characterized by transmural non-necrotizing granulomatous inflammation. Oral lesions show non-necrotizing granulomas in the submucosa similar to those seen in OFG (Figure 21). The severity of the granulomatous inflammation may vary tremendously from 623


patient to patient and from various sites in the same patient. Therefore, a negative biopsy at one site and time may not necessarily rule out a diagnosis of Crohn’s disease. Special stains should be performed to rule out the possibility of deep fungal or mycobacterial infection. Diagnosis A single gold standard for the diagnosis of Crohn’s disease is not available. The diagnosis is confirmed by clinical evaluation and a combination of endoscopic, histopathologic, radiographic and biochemical investigations. Serological tests for anti-Saccharomyces cerevisiae antibodies/perinuclear ANCA (ASCA/ANCA) have a high specificity for the diagnosis of Crohn’s disease if the pattern is positive (ASCA/ ANCA). High serum levels of C-reactive protein are useful for assessing a patient’s risk of relapse and may correlate with disease activity. Management and prognosis Current therapeutic options include anti-inflammatory and immunosuppressive medications, such as sulfasalazine, 5-ASA agents, prednisone, budesonide, azathioprine and 6-mercaptopurine. Anti-TNF therapies such as infliximab, adalimumab and certolizumab are effective against Crohn’s disease as they block TNF, a key inflammatory cytokine and mediator of intestinal inflammation. Antibiotics, especially metronidazole and ciprofloxacin, are used for their anti-inflammatory and anti-infectious properties. Surgery is required for most patients and is related to the duration of disease and site of involvement. Oral Crohn’s disease

624

shows a variable and unpredictable response to topical and systemic glucocorticoid therapy. Topical treatment may yield remission in almost 50% of patients and should be used as first-line therapy in patients with asymptomatic intestinal disease, while intra-lesional corticosteroids and systemic treatment should be considered when topical treatment fails to control symptoms. Crohn’s patients have an increased risk of colorectal cancer, non-Hodgkin’s lymphoma, squamous cell carcinoma of the skin and small bowel cancer. The management of Crohn’s disease is based on controlling acute flares followed by maintenance of clinical remissions. This is achieved by the use of corticosteroids as first-line therapy followed by immunosuppressive drugs such as azathioprine, 6-mercaptopurine and methotrexate for maintenance. Sulfasalazine and 5-ASA can be used to maintain remissions or for the treatment of mildly active disease, but their role is questioned and considered to be modest. Budesonide, a locally active steroid with limited systemic activity, can be used as single agent or in combination therapy to induce remissions in mild and localized ileocaecal disease. Its role in maintenance is questioned. TNF antagonists such as infliximab and adalimumab seem to be extremely effective against Crohn’s disease as they induce and maintain mucosal healing and reduce surgery and hospitalization rates. However, in current treatment protocols, they are reserved for patients resistant to steroids and immunosuppressors as well as for those with severe fistulizing disease. This concept is challenged and use of TNF antagonists is tested for the treatment of early Crohn’s disease and for the maintenance of remissions.

CHAPTER

Sexually Transmitted Diseases Praveen BN, Nagaraj A, Ravikiran Ongole

22

➧ Fellatio Syndrome

➧

Condyloma Acuminatum

➧

Traumatic Lesions of Lingual Frenum

➧

Oropharyngeal Gonorrhea

➧

Syphilis or Lues

➧

Oropharyngeal Chlamydial Infection

➧

Human Immunodeficiency Virus Infection

➧

Oropharyngeal Trichomonal Infection

➧

Intraoral Molluscum Contagiosum

Sexually transmitted diseases (STDs) or sexually transmitted infections (STIs) or venereal diseases are infections that can be transferred from one person to another through sexual contact. Sexually transmitted diseases have been a part of human existence from ages. However, in the last couple of decades with changing sexual practices among heterosexual and homosexual individuals, the incidence of STDs have exponentially increased. Moreover, with the emergence of various multidrug resistant strains of pathogens, newer spectra of diseases such as acquired immunodeficiency syndrome (AIDS) and the evidence of venereal spread of various pathogens, the need to prevent, recognize these diseases and manage them effectively is important. According to the statistics of the Centers for Disease Control and Prevention (CDC), approximately 19 million STD cases are reported annually in the United States. Among these 19 million cases about 50% of these are seen in people in the age group of 15–24 years. It is believed that there are more than 25 diseases that are transmitted through sexual activity. The most common STDs are HIV, chlamydia, gonorrhea, syphilis, genital herpes, human papillomavirus, hepatitis B, trichomoniasis and bacterial vaginosis. As most of these venereal diseases have characteristic oral findings, the oral physician needs to keep abreast of the latest updates about the whole range of clinical manifestations of these diseases. This chapter will deal with common STDs associated with oral manifestations.

FELLATIO SYNDROME It is described as submucosal hemorrhage secondary to repetitive negative pressure and/or blunt trauma associated with fellatio (Terezhalmy et al, 2000). These oral lesions are typically found in sexually active adults. However, presence of such lesions in children may be associated with sexual abuse. Clinical features The submucosal hemorrhages are characteristically seen at the junction of the soft and hard palate without involvement of the uvula, pharyngeal wall or other oropharyngeal structures. These lesions may appear bilaterally as solitary lesions, occasionally connected hemorrhagic bridge. They may also appear as a well-defined band of ecchymosis stretching across the soft palate. These non-ulcerated hemorrhagic areas are painless and do not blanch on palpation. Diagnosis and differential diagnosis A good personal history will help in the diagnosis. However, other conditions that may mimic such lesions are frequent use of drinking straws, habit of sucking on candies (produces negative pressure), petechiae secondary to forceful sneezing, vomiting or coughing, upper respiratory tract infections, blood dyscrasias, infectious mononucleosis, nasopharyngeal tumors and anticoagulant or antithrombotic medications. 625


Management Patient should be made aware of the nature and cause of the lesion. Hemorrhagic diathesis should be considered when the lesions do not subside in about 10 days time following cessation of the habit.

TRAUMATIC LESIONS OF LINGUAL FRENUM Lesions on the lingual frenum are usually seen in individuals who practice cunnilingus (tongue projected into the vaginal area). During such tongue thrusting, the ventral surface of the tongue and particularly the lingual frenum rubs against the incisal edges of the mandibular anterior teeth. Clinical features Patient may complain of pain and soreness in relation to the ventral surface of the tongue. On clinical examination, the ventral surface of the tongue and the lingual frenum may exhibit an ulcerative lesion usually covered by a fibrinous exudate. The ulcer is typically bounded by an erythematous halo. In chronic cases irritation fibroma may be evident on the lingual frenum. Management In most patients the ulcer will resolve in about a week’s time. Topical anesthetic agent can be prescribed for symptomatic relief. Irritation fibroma will have to be surgically excised.

SYPHILIS OR LUES Syphilis is a chronic venereal infection caused by fragile spirochete Treponema pallidum. The term ‘syphilis’ was coined by the Italian physician and poet Girolamo Fracastoro (1530). Other names which have been used in literature are French disease, Italian disease, Christian disease, British disease, lues venerea and Cupid’s disease. In the 16th century syphilis was recognized as ‘Great Pox’ in Europe. Diseases caused by other species of Treponema include Yaws (caused by T. pertenue), Pinta (caused by T. carateum) and bejel (endemic syphilis, caused by T. endemicum). The major source of transmission of syphilis is by sexual contact (acquired). The other modes of transmission include transplacental spread (congenital/neonatal) or accidental inoculation of the causative organism (non-sexual modes of transmission). T. pallidum is a delicate fastidious spirochete whose only natural hosts are humans. It is of 10–15 ␮m in length and 0.2 ␮m in thickness, tapering ends and possesses 10–15 spirals. It has a graceful ‘to and fro’ and angulating 626

movement under dark-field microscopy in a wet preparation. Organisms can be demonstrated in tissue/tissue fluids by silver staining and immunofluorescence. Pathogenic T. pallidum (Nicholas strain) has not yet been able to culture but organisms can be maintained in rabbit’s testicular tissue with retaining its pathogenicity. In refrigerated blood the organisms die within 5 days and can be easily killed with soap and water. Pathogenesis The organisms gain entry through mucous membrane or abraded skin during sexual contact. It is estimated that only about 50% of people who come in contact develop syphilis. It is believed to be due to the presence of local factors and ‘immobilins’ in the blood which immobilize T. pallidum. Incubation period varies from 9 to 90 days. Natural immunity to syphilis does not occur in humans and vascular changes appear to be more significant, characterized by endarteritis and periarteritis. Fibroblastic proliferation leads to fibrosis and scar formation. Clinical features Primary syphilis Primary syphilis is typically acquired via direct sexual contact with the infectious lesions of a person with syphilis. Approximately 10–90 days after the initial exposure (average 21 days), a skin lesion appears at the point of contact, which is usually the penis, vagina or rectum, but can occur anywhere on the body. It is estimated that only about 2% of the primary lesions are evident on extragenital sites such as the rectum, fingers, lips, tongue, palate, tonsils, nipple and chin. Lee et al (2006) reported a case of syphilitic chancre presenting as a solitary nodule of the nipple. Primary lesions on the fingers usually result from contact with genital lesions during sexual foreplay or as an occupational exposure in physicians and nurses as a result of direct contact with infectious ulcers in their patients. Little (2005) suggested that syphilis can be spread by direct contact with mucosal lesions of primary and secondary syphilis or blood and saliva from infected patients. This lesion, called a chancre, is a firm, painless ulceration localized at the point of initial exposure to the spirochete. The chancre begins as a papule that subsequently ulcerates. The chancre may persist for 3–8 weeks and usually heals spontaneously. Localized lymphadenopathy may be evident. The oral primary syphilitic lesion (chancre) like elsewhere in the body, is generally seen after about 3 weeks after the exposure at the site of inoculation of the virus. Initially a papule is formed which subsequently ruptures to form a painless ulcer. The ulcer is generally punched out and may be indurated. Regional lymphadenopathy is usually a characteristic feature. The chancre resolves in about 4 weeks leaving a scar.

Chapter 22 – Sexually Transmitted Diseases

Secondary syphilis Though it is often believed that the secondary lesion of syphilis appears about 2 months after the primary lesion has healed, an estimated 30% of the individuals may present a chancre along with the secondary lesion. The secondary lesions of syphilis affect the skin, liver, kidneys, genitalia, oral mucosa, eyes, ears and bones. Skin rashes may be seen which may have varied presentations such as papules, macules and pustules. These lesions are typically copper colored and sometimes referred to as ‘raw-ham’ colored lesions. The palms and soles are commonly affected. These lesions are generally not pruritic. It is estimated that about 5–10% of the patients present with patchy or ‘moth-eaten appearance’ alopecia. Systemic signs and symptoms associated with secondary syphilis include malaise, prostration, cachexia, low-grade fever (seldom exceeding 100⬚F), headache, asymptomatic meningitis, cranial nerve palsies (nerves II to VIII), painless lymphadenopathy, vague bone pain, jaundice, syphilitic hepatitis, proteinuria, nephrotic syndrome, rapidly progressive glomerulonephritis, renal failure and ulcers affecting the antral and pyloric areas of the stomach. Ophthalmic signs and symptoms include episcleritis, scleritis, interstitial keratitis, posterior uveitis, papillary abnormalities and optic nerve involvement. Patients can also complain of bilateral tinnitus and deafness. Genital mucosa reveals the presence of macules, papules, ulcers or condylomata. These lesions usually resolve in about 3 weeks. It is estimated that about 30% of the patients with secondary syphilis present with oral mucosal involvement. Secondary syphilis in the oral mucosa can exhibit two characteristic features: mucous patches and maculopapular lesions. Occasionally nodular lesions may be seen. A severe generalized form of secondary syphilis is referred to as ulceronodular disease (lues maligna). This form of syphilis is characterized by fever, headache and myalgia, followed by a papulopustular eruption that rapidly transforms into necrotic, sharply demarcated ulcers with hemorrhagic brown crusts on the face and scalp. The incidence of lues maligna in AIDS patients is high. Intraorally crateriform or shallow ulcers are seen on the gingivae, palate or buccal mucosa, with multiple erosions on the hard and soft palates, tongue and lower lip. Mucous patches Mucous patches are evident as oval or crescent-shaped erosions or shallow ulcers of about 1 cm diameter, covered by a grayish-white pseudomembrane surrounded by an erythematous halo. These may be seen bilaterally on the mobile surfaces of the mouth. However, the gingiva, hard palate, tonsils and pharynx may be involved. At the commissures, the mucous patches may appear as split papules, while on the distal

and lateral aspects of the tongue, they tend to ulcerate or manifest as irregular fissures. The mucous patches may coalesce to give rise to, or arise de novo as serpiginous lesions, which are popularly referred to as snail track ulcers. Maculopapular lesions The macular lesions are seen on the hard palate as flat-toslightly raised, firm, erythematous lesions. The papular lesions are seen as erythematous, raised, firm round nodules with a gray center that may ulcerate. The papules may be evident at the commissures and condyloma lata (papillary outgrowths) on the buccal mucosa. Nodular disease Occasionally lesions of secondary syphilis present as nodules. These lesions may mimic keratoacanthoma or squamous cell carcinoma when they occur on the vermillion border of the lip. These nodular lesions are usually seen on the face, mucous membranes, palms of the hands and soles of the feet. Latent syphilis Latent syphilis is defined as having serologic proof of infection without signs or symptoms of disease. Latent syphilis is further classified as early or late. Early latent syphilis is defined as having syphilis for 2 years or less from the time of initial infection without signs or symptoms of disease. Late latent syphilis is infection for more than 2 years but without clinical evidence of disease. Early latent syphilis is considered more infectious than the late latent syphilis. Tertiary syphilis The evidence of the tertiary stage of syphilis may occur anywhere from a year of the primary infection to about 10 years. The pathognomonic feature of this phase is the presence of gummas. These soft masses of inflammation (granulomas) can occur anywhere in the body. Other clinical manifestations of tertiary stage of syphilis include neuro- and cardiovascular syphilis. Neurologic complications include generalized paresis of the insane or general paresis (chronic dementia along with progressive personality changes and memory loss). Other neurologic manifestations are hyperactive reflexes and Argyll Robertson pupil (small and irregular pupils constrict in response to focusing the eyes, but not to light) and tabes dorsalis (locomotor ataxia). Cardiovascular complications include syphilitic aortitis, aortic aneurysm and aortic regurgitation. Syphilitic aortitis can cause de Musset’s sign (bobbing of the head). Trophic lesions such as Charcot’s joints and distal extremity neuropathic perforating ulcers are seen in some patients. Oral manifestations Gumma formation, syphilitic leukoplakia and neurosyphilis are the oral manifestations seen in the tertiary stage of syphilis. 627


The initial gummatous lesion is evident as a painless swelling that commonly occurs on the hard palate and tongue. However, occasional reports of the gumma occurring on the lower alveolus, parotid gland and soft palate have been described. These swellings subsequently ulcerate. Gumma on the palate may cause palatal perforation and formation of an oronasal fistula formation. Radiographically, gumma involving bone show ill-defined destruction of bone mimicking malignant lesions. These gummatous lesions heal by scarring over a period of time. Gumma involving tongue is referred to as interstitial glossitis. The tongue appears irregular, enlarged and lobulated. Occasionally, papillary atrophy may be appreciated on the dorsal surface of the tongue resulting in a condition termed luetic glossitis. Syphilitic leukoplakia Syphilitic leukoplakia appears as a homogeneous white patch on the dorsum of the tongue. Some studies have shown that the prevalence of syphilis in patients with squamous cell carcinoma of the tongue was about 60%.

Neurosyphilis Tertiary syphilis can cause unilateral and bilateral trigeminal neuropathy and facial nerve palsy. It is also believed that syphilitic osteomyelitis may give rise to trigeminal neuropathy.

Congenital Syphilis Congenital syphilis or prenatal syphilis is caused when T. pallidum is transmitted to the offspring by an infected mother. T. pallidum crosses the placenta only after the 16th week of intrauterine life. Untreated mothers can drastically affect the status of the offspring. Most of the pregnancies result in spontaneous abortion, stillbirth, premature delivery or perinatal death. Prematurity and low-birth weight have also been reported. Kassowitz’s law is an empirical observation used in context of syphilis. It states that greater the duration between infection of mother and pregnancy, better is the outcome for the infant. Better outcome includes lesser chances of stillbirth and of developing congenital syphilis. The rate of vertical transmission in untreated women is 70–100% for primary syphilis, 40% for early latent syphilis and 10% for late latent disease. These statistics show very clearly that the longer the interval between infection and pregnancy, the better is the prognosis for the newborn. Based on the time of presentation of the signs and symptoms, the clinical manifestations can be categorized as early manifestations (occurring in the first 2 years of life) and late manifestations occur after 2 years of age. 628

Early manifestations The earliest clinical finding is persistent rhinitis. Other associated findings include hepatomegaly, splenomegaly, glomerulonephritis and nephrotic syndrome. Palms and soles of these neonates show erythematous maculopapular rashes or vesiculobullous lesions. Generalized lymphadenopathy is evident. Bone lesions such as osteochondritis and osteomyelitis. Late manifestations Hutchinson’s triad (interstitial keratitis, peg-shaped upper incisors, and eighth cranial nerve deafness), saber shins, irregular thickening of the sternoclavicular portion of the clavicle (Higoumenakis sign), flaring scapulas, mental retardation and hydrocephalus are the late manifestations of syphilis. Bilateral hydrarthrosis (Clutton’s joints) and neurosyphilis are other common late manifestations of syphilis. Orofacial manifestations in congenital syphilis Localized periostitis of the frontal and parietal bones is manifested as frontal bossae of parrot. Appearance of the ‘Olympian row’ is seen when the supraorbital region is involved. Inflammation of the nasal mucosa may destroy the underlying bone and cartilage, perforate the nasal septum and manifests as saddle nose. A short maxilla along with the saddle nose may present as concave or shallow-dish appearance of the middle third of the face. A relative mandibular prognathism results in a ‘bulldog jaw’. Other oral changes include high palatal arch. The dental anomalies of congenital syphilis only arise in teeth in which calcification occurs during the first year of life, namely, the permanent incisors and first molars. Hutchinson’s teeth are short, barrel-shaped or peg-shaped widely spaced central incisors. Other findings include notching of incisal edges. The incisors have a screwdrivershaped morphology (convergence of the lateral margins toward the incisal edge). Mulberry molars, hypocalcification of enamel and presence of rhagades extending from the angle of the mouth are other prominent features. Occasionally, atrophic glossitis and facial neuropathies may be seen. Diagnosis Along with the typical history and clinical picture of syphilis, serological tests are necessary for an accurate diagnosis. Dark-field microscopy has been used extensively for the diagnosis of primary syphilis. However, it cannot differentiate T. pallidum from the other treponemal species. Serological tests can be used effectively to diagnose secondary, latent and tertiary syphilis. The serologic tests include non-treponemal tests (Venereal Disease Research Laboratory [VDRL] test and the Rapid Plasma Reagin [RPR]


test) and treponemal tests (serum fluorescent treponemal antibody absorption test [FTA-ABS] and microhemagglutination test for T. pallidum [MHA-TP]).

5.

Management

6.

Parenteral penicillin G is the drug of choice for the treatment of all stages of syphilis. Patients allergic to penicillin can be treated with doxycycline, tetracycline or erythromycin.

HUMAN IMMUNODEFICIENCY VIRUS INFECTION In 1981, homosexual men with symptoms of a disease that now are considered typical of the AIDS were first described in Los Angeles and New York by the CDC. In 1983, researchers in the United States and France described the virus that causes AIDS, now known as the human immunodeficiency virus (HIV) and belonging to the group of viruses called retroviruses. It is estimated that about 33.2 million people are affected by AIDS worldwide. Modes of transmission HIV is transmitted through direct contact of a mucous membrane or the bloodstream with a body fluid containing HIV, such as blood, semen, vaginal fluid, preseminal fluid and breast milk. The transmission of HIV can result from vaginal, anal or oral sex, infected needles, blood transfusion, maternal-fetal transmission during pregnancy, birth and breast feeding. Sexual mode of transmission It is estimated that the transmission through sexual contact accounts for 75–85% of all HIV infections. Sexual transmission occurs with the contact between sexual secretions of one person with the rectal, genital or oral mucous membranes of another. Some facts about sexual mode of transmission 1. 2.

3. 4.

Unprotected receptive sexual acts are riskier than unprotected insertive sexual acts. Anal sex is the most efficient means of sexual HIV transmission compared to vaginal intercourse or oral sex (the rectal mucous membranes seem to have more receptors to bind HIV and the tissue is more easily traumatized). HIV can be transmitted through both insertive and receptive oral sex. The risk of HIV transmission from exposure to saliva is considerably smaller than the risk from exposure to semen.

7.

Other STIs increase the risk of HIV transmission and infection, because they cause the disruption of the normal epithelial barrier by genital ulceration and/or microulceration. HIV transmission through oral exposure to semen or vaginal fluids have been documented. Fellatio (mouth to penis contact) and cunnilingus (mouth to vulva contact) cannot be considered to be totally safe practices. Transmission appears to be highest during the early and late stages of HIV when the viral load is at its peak.

HIV and AIDS are described in detail in Chapter 4 on Bacterial, Viral and Fungal Infections.

INTRAORAL MOLLUSCUM CONTAGIOSUM Molluscum contagiosum is a DNA poxvirus that generally affects the skin or mucous membranes. Juliusburg (1905) discovered the viral nature of this condition. Molluscum contagiosum has also been known as epithelioma contagiosum and dimple wart. Molluscum contagiosum is primarily caused by MCV-1 and MCV-2 (molluscum contagiosum virus subtypes 1 and 2). The virus is transmitted by direct contact and autoinoculation. Upon entering the host cell the virus replicates in the cytoplasm of epithelial cells producing cytoplasmic inclusions and cause enlargement of the infected cells. Molluscum contagiosum is more common in patients who are on steroid therapy or in those who have atopic dermatitis, immunodeficiency or lymphoproliferative disorders. Clinical features The infection affects both adults and children. In children, the transmission is via non-sexual skin contact whereas in young adults it occurs as an STD. In children, the lesions are generally seen on the face, trunk, extremities (especially in the axillae), and sometimes on the mucous membranes of the lips, tongue and buccal mucosa. In adults, involvement of the pubic, genital and perineal areas is common. The typical lesion is an umbilicated or waxy papule associated with itching and pain. Some patients develop eczema around the papule. The papules are flesh-colored and occasionally yellowish-white in color. These papules can occur as solitary lesions and sometimes several in number. These are generally about 2–5 mm in diameter. Large sized lesions (⬎5 mm) and a greater number of lesions (⬎30 in number) are usually seen in AIDS patients. Oral manifestations Oral lesions are rarely encountered in molluscum contagiosum. These lesions mimic the skin lesions. 629


The common sites of involvement include the lips, buccal mucosa, hard palate, retromolar area and tongue. Fornatora et al (2001) described a rare case of molluscum contagiosum occurring on the gingiva. Histologic features Hematoxylin and eosin-stained biopsy sections reveal thickening (almost six times more than normal) and downgrowth of epithelium. Presence of intracytoplasmic inclusion bodies (molluscum bodies or Henderson–Patterson bodies) is typical of molluscum contagiosum. Alternatively, smears taken from scrapings of the lesion show inclusion bodies when stained with Papanicolaou, Wright, Giemsa or Gram stain. An advanced technique to identify the antigen of MCV by fluorescent antibody technique may be employed. Management Most of the lesions are self-limiting and usually resolve in about 9–12 months. The goal of the treatment is to limit the transmission and autoinoculation. Topical application of cantharidin, podophyllin or tretinoin cream may be beneficial. Cryotherapy with liquid nitrogen is a popular management strategy. Surgical excision of the lesion is also an accepted treatment modality. Antiviral medications such as ritonavir, zidovudine have been used to manage the molluscum contagiosum in immunocompromised individuals.

CONDYLOMA ACUMINATUM Condyloma acuminatum commonly termed genital or venereal wart occurs commonly on external genitalia; however, oral lesions can occur either through orogenital sex or by auto-inoculation of genital lesions. Condyloma acuminatum is caused by human papilloma virus types 6, 11 and 16. Condylomata acuminata are now thought to be one of the four most common STDs. Clinical features Typical lesions are evident as solitary or multiple papular eruptions. These eruptions are usually flesh colored and appear pearly, filiform, fungating, cauliflower or plaque like. The most commonly affected areas are the penis, vulva, vagina, cervix, perineum and perianal area. Rarely, mucosal lesions in the oropharynx, larynx and trachea have been reported. Oral manifestations The typical oral lesions of condyloma acuminatum are minute, multiple pink colored nodules which tend to coalesce 630

to form bulbous/papillomatous lesions. These papillomatous lesions can affect any part of the oral cavity. The common sites of involvement are the dorsal surface of the tongue, palate, alveolar ridge, buccal mucosa and gingiva. The nodules proliferate and coalesce to form soft, red or dirty gray, sessile or pedunculated papillary growths. Lesions develop rapidly to form discrete single or extensive clusters of granular or cauliflower-like neoplasms. Diagnosis Diagnosed indirectly by cytology, biopsy or the appearance of white areas after the application of acetic acid (acetowhitening). The affected area is wrapped with a gauze piece soaked with 5% acetic acid for 5 minutes. A magnifying lens (10⫻) or a colposcope can be used to visualize the warts which appear as minute white colored papules. A more definitive diagnosis can be made by detecting the viral nucleic acid or capsid protein. Management Podophyllin (cytotoxic agent) is the drug of choice. Alternatively, topical trichloroacetic acid and 5-fluorouracil can be used. Surgical modalities include the use of cryotherapy and carbon dioxide laser ablation.

OROPHARYNGEAL GONORRHEA Gonorrhea is a caused by Neisseria gonorrheae. The disease is characterized by purulent inflammation of mucous membrane surfaces. Clinical features The bacterial infection spreads through sexual contact. Gonococcal infections are 1.5 times more common in men than in women. It is usually seen in sexually active adolescents and young adults. Like most STDs, the presence of gonorrhea in a child can be considered as an indicator for sexual abuse of the child. Men may present with urethral discomfort, dysuria and purulent discharge. Other notable feature is epididymitis. Women may complain of thin, purulent and mildly odorous discharge from the vagina. Another important complication of gonorrhea in women is pelvic inflammatory disease (PID). PID indicates that the offending organism has ascended to involve the endometrium, fallopian tubes, ovaries and peritoneum. PID is characterized by midline mild or severe pain and cramps. Right upper quadrant pain from perihepatitis (Fitz– Hugh–Curtis syndrome) may occur following the spread of organisms upward along peritoneal planes. Occasionally rectal discharge, bloody stools and pruritus may be evident.


Many of the patients may suffer from dysphagia secondary to pharyngitis. An extensive form of gonorrhea, disseminated gonorrheal infection (DGI) is seen in some patients. The disseminated form is characterized by joint or tendon pain (gonococcal arthritis), skin rash, gonococcal meningitis and gonococcal endocarditis.

Oral manifestations

Oral manifestations

Diagnosis

In the initial stages of the infection, patients may complain of burning sensation, drying of the mouth and foul breath. This phase may be followed by the evidence of painful ulcers usually seen on the lips, gingival, tongue, palate (hard and soft) and the tonsillar regions. The ulcers are typically punched out in the interdental gingiva. The tongue may exhibit papillary atrophy. The ulcers are usually covered by grayish-white or yellowishwhite pseudomembrane. Pharyngitis is a characteristic feature. Regional lymphadenopathy may be evident. In some patients, the TMJ may be affected (gonococcal arthritis of TMJ).

Cultures are usually difficult to obtain and expensive. However, direct immunofluorescent antibody and enzyme immunoassay can be used. Alternatively, PCR can be used.

Diagnosis The evidence of gram-negative diplococci in a Gram stained smear of exudates from the gonococcal lesions is suggestive of N. gonorrheae infection.

Patients may present with pharyngitis. The oral mucosa appears intensely erythematous. However, painless mucositis is the characteristic feature. Lips, buccal mucosa, floor of mouth, tongue, tonsillar regions and uvula are the common sites affected. Occasionally, cervical lymphadenopathy may be present.

Management The drugs of choice are doxycycline or azithromycin with ofloxacin.

OROPHARYNGEAL TRICHOMONAL INFECTION Trichomonas vaginalis is the causative agent of trichomoniasis. It is a parasitic protozoan with humans as the only natural host. It infects the squamous epithelium of the genital tract. Incubation time is generally between 4 and 28 days. It is believed that T. vaginalis infections are a marker for high risk sexual behavior as they are generally associated with other STDs, especially gonorrhea.

Management Oropharyngeal gonorrhea is best managed with intramuscular injection of ceftriaxone. Other drugs that have been used effectively include cefixime and ciprofloxacin.

OROPHARYNGEAL CHLAMYDIAL INFECTION Chlamydial infection is caused by Chlamydia trachomatis, an obligate intracellular bacterium that infects the urethra, epididymis, uterus and cervix. The bacterium is usually spread through sexual activity. However, it can also spread vertically to cause pneumonia and conjunctivitis in neonates. Chlamydial infection is usually seen in the 2nd and 3rd decades of life. Clinical features Women may present with dysuria, vaginal bleeding, vaginal discharge and lower abdominal pain. Men may exhibit dysuria, rectal and/or urethral discharge and proctitis.

Clinical features Women complain of foul smelling, frothy vaginal discharge. However, the pathognomonic sign is the presence of ‘strawberry cervix’ or ‘colpitis macularis’ on colposcopy. Patients may also complain of lower abdominal pain and dysuria. However, some patients may remain asymptomatic. Male patients may remain asymptomatic or present with urethritis. Oral manifestations The characteristic feature is strawberry-like inflammation of the oral mucosa secondary to vasodilation. The mucosal surface may show presence of exudate. Diagnosis The gold standard for diagnosing trichomonads is by culture. The Diamond’s medium is the ideal medium for this procedure. Few simple diagnostic tests that may be used are the immediate examination of a wet slide and whiff test. The easiest method to visualize motile trichomonads is by placing a small amount of vaginal discharge on a 631


microscope slide and mixing with a few drops of saline solution within 20 minutes of obtaining the sample. The slide is then examined under a microscope at low or medium power. The presence of flagellated, pyriform protozoa indicates a positive result. Alternatively, several drops of 10% potassium hydroxide are mixed with a sample of vaginal discharge. Presence

632

of a strong fishy odor is indicative of a positive result. This test is referred to as the whiff test or amine odor test. Management Metronidazole and tinidazole are the drugs of choice. The recommended dose is 2 g orally in a single dose.

CHAPTER

Nutritional and Metabolic Disorders Shubha Sairam, Praveen BN

➧ Nutritional Requirements of Indians ➧

Carbohydrates

➧

Proteins

➧

Lipids

➧

Vitamins Vitamin A Vitamin D Vitamin K Vitamin C Vitamin B Complex

Nutriology as per Dorland’s Medical Dictionary is the science of nutrition. It is the science of how the body utilizes food to meet requirements for development, growth, repair, and maintenance. Nutrients are biochemical substances that can be supplied only in adequate amounts from an outside source, usually from food. The relationship between nutrition and oral health is multifaceted. Nutrition has both local and systemic impacts on the oral cavity. While diet and eating patterns have a local effect on the teeth, saliva and soft tissues, the systemic impact of nutrition also has considerable implications and it too merits assessment as a component of comprehensive care. The systemic effect is the impact of the nutrients consumed as they assume their biological functions in relation to the development and maintenance of the extra- and intraoral structures and secretions. The oral cavity is often one of the first sites where nutrient deficiencies can be clinically noted. Clinical manifestations of nutrient deficiencies can have a significant impact on the function of the oral cavity. Functional properties of the oral cavity include taste, salivation, mastication and swallowing food. Any alterations in the structure and function of the oral cavity may compromise intake and contribute to the development of a nutrient-deficiency state. When the associated oral structures are affected, these alterations may be compounded

➧

23

Metabolic Disorders Lysosomal Storage Diseases Lipoid Proteinosis Hand–Schuller–Christian Disease or Multifocal Eosinophilic Granuloma Letterer–Siwe Disease

➧

Lipid Reticuloendothelioses Gaucher Disease Niemann–Pick Disease

even further, leading to subsequent inadequate dietary intake and compromised nutritional status. There are six classes of nutrients: water, carbohydrates, proteins, fats, minerals and vitamins. Nutrients work together and interact in complex metabolic reactions. Proteins, carbohydrates and fats provide energy for body needs. However, the body cannot use this energy without adequate amounts of vitamins and minerals.

NUTRITIONAL REQUIREMENTS OF INDIANS Energy requirement is defined as the amount that will balance the energy expenditure of the individual (as determined by body size and composition and level of physical activity) consistent with long-term good health. This intake will allow for the maintenance of economically necessary and socially desirable physical activity. In children and pregnant/lactating women, the energy requirement will include energy needed for deposition of tissue and secretion of milk at the rate consistent with good health. All estimates of requirement are based on habitual intakes though these are expressed as daily intake. Recommended dietary allowance (RDA) is the amount of selected nutrients considered adequate to meet the known 633


nutrient needs of healthy people. The Canadian equivalent is the recommended nutrient intakes (RNIs). The energy needs of men and women for different activity levels computed on the basis of recommendations made by a Joint Expert Consultation of the World Health Organization (WHO)/Food and Agricultural Organization (FAO)/United Nations University (UNU) in 1985 and by an Expert Committee constituted in 1988 by the Indian Council of Medical Research (ICMR) are as shown in Tables 1 and 2. The ICMR's RDA is higher than those recommended by the WHO/FAO/UNU. For computing RDA, the ICMR has taken body weight of ‘reference man’ as 60 kg and that of ‘woman’ as 50 kg. Average weight of Indian men is 52 kg and women 44 kg. For children and adolescents, weight for age from National Center for Health Statistics (NCHS), USA/well-to-do Indian children have been utilized by ICMR for deriving the RDA so that energy intake enables optimum growth. However, as in adults, majority of children and adolescents weigh substantially less and hence their energy requirement is lower.

CARBOHYDRATES Carbohydrates have been the major sources of energy since the dawn of history and furnish up to 90% of energy needs. Carbohydrates provide about 4 kcal/g. The average adult stores about 300 g of carbohydrate in the liver and muscle tissue as glycogen.

❍

Mainly provides fuel for the body, especially the central nervous system. ❍ Adequate consumption has a protein sparing function, i.e. proteins consumed are used for anabolic function rather than as an energy source. ❍ In the absence of carbohydrates, fat metabolism is incomplete and leads to formation of ketone bodies. ❍ Carbohydrates are required for the formation of structural components such as cartilage, nervous tissue and bone.

Sex

Sources Grains (wheat, corn, rice, oats, rye, barley, buckwheat and millet) provide complex carbohydrates and starches. Vegetables, especially root and seed varieties (potatoes, sweet potatoes, beet and peas) contain considerable amounts of starch. Milk is a good source of lactose. Dietary fiber can be obtained from whole grain breads and cereals and legumes. Dental considerations For decades, dietary carbohydrates have one of the major constituents incriminated in the causation of caries. The occurrence of caries depends upon the frequency of consumption, chemical constitution, route of administration, and physical properties of carbohydrates. Sugar substitutes have been claimed to be non-cariogenic due to their inability to act as substrates for the enzyme glucosyltransferase. Xylitol is one such commonly used sugar substitute. It has been found to be non-cariogenic. Some studies also show that chewing xylitol gum has Recommended dietary allowance of infants and children

Age of infant

Energy (kcal)

Weight (kg)

3–6 months*

700

7

6–9 months*

810

8.5

9–12 months*

950

9.5

6 months†

583

5.4

6–12 months†

844

8.6

Source: *WHOIFAO/UNO (1985); †ICMR (1988).

ICMR's recommended dietary allowance for energy Ref. body weight (kg)

Actual body weight (kg)

Man

60.0

Woman

50.0

Energy RDA Activity category

For ref. body weight

For actual body weight

Percentage difference

52.0

Sedentary Moderate Heavy

2,425 2,875 3,800

2,115 2,492 3,293

13 13 13

44.0

Sedentary Moderate Heavy

1,875 2,225 2,925

1,740 1,958 2,594

12 12 11

Source: Dr BS Narasinga Rao-Gopalan Oration (2001).

634

Carbohydrates are required for the formation of nonessential amino acids. ❍ Non-starch polysaccharides constitute dietary fibers that are required to prevent constipation, reduce blood cholesterol and give satiety. ❍ It is recommended that 55–60% of total energy intake should be obtained from carbohydrates.

Table 2

Functions

Table 1

❍

Chapter 23 – Nutritional and Metabolic Disorders

cariostatic properties. Other sugar substitutes, sorbitol, aspartame, sucralose have been found to have a negligible effect on the development of caries.

PROTEINS Second to water, proteins are the most abundant substances in the body. The structural units of proteins are amino acids. Of the 20 amino acids present in nature, nine are considered essential, i.e. these are to be supplied by the diet. Functions ❍ ❍ ❍ ❍ ❍ ❍

Generation of new body tissues Repair of body tissues Production of enzymes, hormones, immunoglobulins Regulation of fluid balance Transport of insoluble fats Provide energy—4 kcal/g.

Sources Meat and milk food groups provide most of the dietary proteins. Soy is also a good source of proteins.

Dental considerations During tooth development, mild-to-moderate protein deficiency results in smaller molars, chemical alterations of the exposed enamel surface, significantly delayed eruption and retardation of mandibular development. Smaller salivary glands develop resulting in decreased salivary flow. This saliva has a different protein, amylase and aminopeptidase activity, thereby compromising its immune function. Delayed eruption and decreased salivary flow lead to increased incidence of dental caries. Epithelium, connective tissue and bone may be poorly developed. Insufficient intake of protein results in negative nitrogen balance, decreased levels of secretory IgA. This leads to a lowered resistance to infections, reduced ability to withstand the stresses of injury or surgery, and prolonged recovery time. PEM may be a major reason for the occurrence of necrotizing ulcerative gingivitis (NUG) and noma.

LIPIDS Lipids provide more energy per gram than either carbohydrates or proteins and are an essential component of tooth enamel and dentin. Chemistry and sources

Deficiency Protein energy malnutrition This term covers the spectrum of clinical conditions seen in undernutrition. The two clinical forms of protein energy malnutrition (PEM) include kwashiorkor and marasmus. Kwashiorkor occurs when a child is fed on a diet with very low protein content relative to energy. This results in a high level of plasma insulin and low levels of plasma cortisol. This hormonal pattern leads to an uptake of amino acids in muscle, diverting these from liver, leading to decreased albumin synthesis and therefore edema. Thus a child with kwashiorkor shows apathy, lethargy and severe anorexia. There is generalized edema, muscle wasting in shoulders and upper arms. The child may have a ‘moon face’. Potbelly due to weakness of abdominal muscles occurs. Skin changes in the form of thickening, cracking and areas of denudation occur. Hair changes color and becomes sparse. Marasmus occurs when there is inadequate food intake resulting in energy deficiency. This leads to low insulin and high plasma cortisol levels. This results in amino acids being released from muscles making them available for protein synthesis. A child with marasmus presents with no subcutaneous fat and wasted muscles. The body weight is severely reduced. There is no edema, and skin and hair changes are mild or absent. Studies have shown that the incidence of PEM among Indian children could be as high as 51.6–70%.

The structural units of lipids are fatty acids. Saturated fatty acids contain only single bonds. Examples include palmitic and stearic acids found in animal fat, butter, coconut oil, chocolate, etc. Monounsaturated fatty acids contain only one double bond. The most abundant of these is oleic acid found in olive, peanut oil and animal products. Polyunsaturated fatty acids (PUFAs) contain two or more double bonds. Three PUFAs that are considered to be essential fatty acids include linoleic, linolenic and arachidonic acids. These are found in safflower, soybean, fish and corn oils, nuts and seeds. Deficient consumption of fats leads to loss of weight. Deficiency of linoleic acid leads to growth retardation, skin lesions, and reproductive failure. Over consumption of fats leads to excessive fat stores and obesity. Other conditions related to fat consumption include diabetes mellitus, hyperlipidemia, fatty infiltration of liver, and certain types of cancer. Dental considerations Epidemiological and laboratory studies indicate that fats have a cariostatic effect. Dietary fats probably have local rather than systemic influence. Hypotheses for anticariogenicity include: 1.

Some fatty acids, such as oleic acid act as growth factors for lactobacilli, others, such as lauric acids inhibit the growth of streptococci. 635


2.

Long-chain fatty acids may decrease the dissolution of hydroxyapatite by acids. Oral food retention decreases with increased fat intake. Fats may lubricate the tooth and prevent acid penetration into enamel. Fats may produce a film on food particles and prevent partial digestion of food particles in the mouth. Dietary fat delays gastric emptying, enhancing fluoride absorption and increasing tissue fluoride concentration.

Characteristics of fat-soluble vitamins: These are soluble in fats or fat solvents. Chemically, these are organic substances and do not contain nitrogen. These are absorbed in the intestines in the presence of bile. These are fairly stable to heat, as in cooking. Larger amounts of these vitamins can be stored in the body and for long periods of time. Thus, symptoms of deficiencies appear late. Increased intake may lead to toxicity.

The growth and differentiation of epithelial cells throughout the body is especially affected by vitamin A deficiency. In addition, goblet cell numbers are reduced in epithelial tissues and as a consequence, mucous secretions (with their antimicrobial components) diminish. Cells lining protective tissue surfaces fail to regenerate and differentiate, hence they flatten and accumulate keratin. Both factors—the decline in mucous secretions and loss of cellular integrity—reduce the body’s ability to resist invasion from potentially pathogenic organisms. Pathogens can also compromise the immune system by directly interfering with the production of some types of protective secretions and cells. Classical symptoms of xerosis (drying or nonwettability) and desquamation of dead surface cells as seen in ocular tissue (i.e. xerophthalmia) are the external evidence of the changes also occurring to various degrees in internal epithelial tissues. Current understanding of the mechanism of vitamin A action within cells outside the visual cycle is that cellular functions are mediated through specific nuclear receptors. Binding with specific isomers of retinoic acid (i.e. all-transand 9-cis-retinoic acid) activates these receptors. Activated receptors bind to DNA response elements located upstream of specific genes to regulate the level of expression of those genes. These retinoid-activated genes regulate the synthesis of a large number of proteins vital to maintaining normal physiologic functions. There may, however, be other mechanisms of action that is as yet undiscovered.

Vitamin A

Dietary sources

Vitamin A (retinol) is an essential nutrient needed in small amounts by humans for the normal functioning of the visual system; growth and development; and maintenance of epithelial cellular integrity, immune function, and reproduction. These dietary needs for vitamin A are normally provided as preformed retinol (mainly as retinyl ester) and provitamin A carotenoids or -carotene.

Preformed retinal is found in milk, cheese, butter, eggs, meat, cod liver oil and liver. -Carotene is also present in yellow, orange and green leafy vegetables (spinach, turnip greens, broccoli). To express the vitamin A activity of carotenoids in diets on a common basis, a Joint FAO/WHO Expert Group in 1967 introduced the concept of the retinol equivalent (RE) and established the following relationships among food sources of vitamin A: 1 g retinol 1 RE 1 g -carotene 0.167 g RE 1 g other provitamin A carotenoids 0.084 g RE.

3. 4. 5. 6.

VITAMINS Vitamins are catalysts for all metabolic reactions using proteins, fat and carbohydrates for energy, growth and cell maintenance. Vitamins are vital to life, but are required in minute amounts. Vitamins are classified as fat soluble—vitamins A, D, E, K and water soluble—vitamins B, C.

Functions Vitamin A functions at two levels in the body: the first is in the visual cycle in the retina of the eye; and the second is in all body tissues where it systemically maintains the growth and soundness of cells. In the visual system, carrier bound retinol is transported to the retina. Rhodopsin, the visual pigment critical to dim-light vision, is formed in rod cells after conversion of all-trans-retinol to retinaldehyde, isomerization to the 11-cis-form, and binding to opsin. Alteration of rhodopsin through a cascade of photochemical reactions results in the ability to see objects in dim light. The speed at which rhodopsin is regenerated is related to the availability of retinol. A deficient intake of vitamin A thus leads to night blindness. 636

Older literature describes the International Unit of vitamin A. This may be converted to RE as depicted in Table 3: 1 IU retinol 0.3 g retinol 1 IU -carotene 0.6 g -carotene 1 IU retinol 3 IU -carotene. Deficiency Vitamin A deficiency leads to xerophthalmia and night blindness due to degeneration of epithelial cells. Xeroderma can also occur. Mild deficiency may be related to a depressed immune response.


Table 3

Estimated mean requirement and safe level of intake for vitamin A

Group

Mean requirement (mg RE/day)

Infants and children 0–6 months 7–12 months 1–3 years 4–6 years 7–9 years

Recommended safe intake (mg RE/day)

180 190 200 200 250

375 400 400 450 500

330–400

600

270 300

500 600

300 300

600 600

Pregnant women

370

800

Lactating women

450

850

Adolescents 10–18 years Adults Females 19–65 years 65 years Males 19–65 years 65 years

Source: Vitamin and mineral requirements in human nutrition, WHO.

Dental considerations Vitamin A is necessary for growth of both soft tissue and bone. It is required for resorption of old bone and synthesis of new bone, formation of ameloblasts, odontoblasts, and maintenance of the integrity of epithelial tissues. Severe deficiency of vitamin A may result in enamel hypoplasia and defective dentin formation in developing teeth. Odontoblasts lose the ability to arrange themselves in normal parallel linear formation leading to altered dentin deposition. This further leads to degeneration and atrophy of ameloblasts. This results in enamel hypoplasia characterized by defects in enamel matrix and incomplete calcification. Clinical applications Carotenoids possess antioxidant properties and are very efficient in scavenging singlet oxygen and peroxyl radicals. These free radicals are known to damage the structure and function of cell membranes. Thus a diet rich in antioxidants is associated with a lower risk of cancer and heart disease. Stich and colleagues gave large quantities of -carotene and sometimes vitamin A to chewers of betel quids in Kerala, India, and to Canadian Inuits with pre-malignant lesions of the oral tract and witnessed reductions in leukoplakia and micronuclei from the buccal mucosa. However, the amount of supplements used in these studies have been large and hence, not advisable other than increasing consumption of fruits and vegetables.

Retinoids have been used in oral precancer, cancer and immunologically mediated diseases such as lichen planus. Retinoids have a potent growth inhibiting effect on cancer in vivo and in vitro. They can induce apoptosis and regulate the function of the immune system. On this basis, retinoids have been used as chemopreventive agents in oral squamous cell carcinoma (SCC). However, clinical trials of retinoids have not yielded significant results. Retinoids have been used in the treatment of oral leukoplakia, and has been shown to cause temporary remission, but also causes toxicity. Retinoids have been used as an adjunctive treatment in the management of oral lichen planus. Retinoids eliminate reticular and plaque-like lesions but these recur following withdrawal of therapy. Toxicity Because vitamin A is fat soluble and can be stored, primarily in the liver, routine consumption of large amounts of vitamin A over a period of time can result in toxic symptoms, including liver damage, bone abnormalities and joint pain, alopecia, headaches, vomiting, and skin desquamation. Other clinical symptoms include diplopia, alopecia, dryness of mucous membranes, reddened gingiva, thinning of epithelium, cracking and bleeding lips, and increased activity of osteoclasts. Overconsumption of -carotene leads to hypercarotenemia and yellow pigmentation of skin.

Vitamin D Functions Vitamin D is required to maintain normal blood levels of calcium and phosphate, which are in turn needed for the normal mineralization of bone, muscle contraction, nerve conduction and general cellular function in all cells of the body. Vitamin D achieves this after its conversion to the active form 1,25-dihydroxy vitamin D (1,25-(OH)2D), or calcitriol. This active form regulates the transcription of a number of vitamin D-dependent genes that code for calcium-transporting proteins and bone matrix proteins. Vitamin D also modulates the transcription of cell cycle proteins, which decrease cell proliferation and increase cell differentiation of a number of specialized cells of the body (e.g. osteoclastic precursors, enterocytes, keratinocytes). This property may explain the actions of vitamin D in bone resorption, intestinal calcium transport and skin. Sources The most physiologically relevant and efficient way of acquiring vitamin D is to synthesize it endogenously in the skin from 7-dehydrocholesterol by sunlight (UV) exposure. In most situations, approximately 30 minutes of skin exposure (without sunscreen) of the arms and face to sunlight can provide all the daily vitamin D needs of the body (Table 4). 637


Table 4

Recommended nutrient intakes (RNIs) for vitamin D

Group

RNI (mg/day)

Dental considerations


5 5 5 5 5

Adolescents 10–18 years

5

Adults 19–50 years 51–65 years 65 years

5 10 15

Pregnant women

5

Lactating women

5

Units: For vitamin D, 1 IU 25 ng, 40 IU 1 mg, 200 IU 5 mg, 400 IU 10 mg, 600 IU 15 mg, 800 IU 20 mg. Source: Vitamin and mineral requirements in human nutrition, WHO.

Skin synthesis of vitamin D may be influenced by: ❍ ❍ ❍

❍

❍

Latitude and season—both influence the amount of UV light reaching the skin The aging process—thinning of the skin reduces the efficiency of this synthetic process Skin pigmentation—the presence of darker pigments in the skin interferes with the synthetic process because UV light cannot reach the appropriate layer of the skin Clothing—virtually complete covering of the skin for a medical, social, cultural or religious reasons leaves insufficient skin exposed to sunlight Sunscreen use—widespread and liberal use of sunscreen, though reducing skin damage by the sun, deleteriously affects synthesis of vitamin D.

It is recommended that individuals not synthesizing vitamin D should correct their vitamin D status by consuming the amounts of vitamin D appropriate for their age group. Other food sources include cod liver oil, catfish, salmon, turnip greens, tuna, milk, egg yolk and butter. Deficiency Rickets is a clinical syndrome that occurs when there is a deficiency of vitamin D in the growing skeleton. Infants with rickets exhibit delayed development and muscle hypotonia, craniotabes (small non-calcified areas in skull bones), bossing of frontal and parietal bones, swelling of the rib costochondral junctions (rickety rosary). Severe rickets may be associated with hypocalcemic tetany, giving rise to laryngeal stridor when the vocal cords are affected. Vitamin D deficiency in the adults is termed osteomalacia. Osteomalacia is characterized by bone pain, pathologic 638

fractures. Muscle weakness and a waddling gait may be present.

Patients with rickets also have involvement of alveolar bone resulting in its weakening. Patients with severe vitamin D deficiency develops enamel hypoplasia. This is characterized by pitting of surface enamel. These surfaces are prone to adherence of plaque. However, studies of susceptibility to caries among these teeth reveal conflicting results.

Vitamin K Vitamin K is an essential fat-soluble micronutrient. Thus far, the only unequivocal role of vitamin K in health is in the maintenance of normal coagulation. The vitamin K-dependent coagulation proteins are synthesized in the liver and comprise factors II, VII, IX and X, which have a hemostatic role (i.e. they are procoagulants that arrest and prevent bleeding), and proteins C and S, which have an anticoagulant role (i.e. they inhibit the clotting process). Despite this duality of function, the overriding effect of nutritional vitamin K deficiency is a bleeding tendency caused by the relative inactivity of the procoagulant proteins. Chemistry and function Vitamin K is the family name for a series of fat-soluble compounds which have a common 2-methyl-1,4-naphthoquinone nucleus but differ in the structures of a side chain at the 3-position. These are synthesized by plants and bacteria. In plants, the only important molecular form is phylloquinone (vitamin K1). Bacteria synthesize a family of compounds called menaquinones (vitamin K2). The biological role of vitamin K is to act as a cofactor for a specific carboxylation reaction that transforms selective glutamate (Glu) residues to -carboxyglutamate (Gla) residues. The reaction is catalyzed by a microsomal enzyme, -glutamyl, or vitamin K-dependent carboxylase. Dietary sources Phylloquinone is distributed ubiquitously throughout the diet, and the range of concentrations in different food categories are very wide. In general, the relative values in vegetables confirm the known association of phylloquinone with photosynthetic tissues, with the highest values being found in green leafy vegetables. The next best sources are certain vegetable oils (e.g. soybean, rapeseed and olive); other vegetable oils, such as peanut, corn, sunflower and safflower. Menaquinones seem to have a more restricted distribution in the diet than does phylloquinone. Menaquinone-rich foods are those with a bacterial fermentation stage. Intestinal microflora synthesize large amounts of menaquinones, which are potentially available as a source


of vitamin K. Most of these menaquinones are present in the distal colon. It is noteworthy that menaquinones with very long chains are known to be synthesized by members of the anaerobic genus Bacteroides. It is commonly held that animals and humans obtain a significant fraction of their vitamin K requirement from direct absorption of menaquinones produced by microfloral synthesis, but conclusive experimental evidence documenting the site and extent of absorption is lacking. The most promising site of absorption is the terminal ileum, where there are some menaquinone-producing bacteria as well as bile salts. However, the balance of evidence suggests that the bioavailability of bacterial menaquinones is poor because they are for the most part tightly bound to the bacterial cytoplasmic membrane and also because the largest pool is present in the colon, which lacks bile salts for their solubilization (Table 5). Deficiency Primary deficiency of vitamin K is uncommon, but may occur due to impaired fat absorption in celiac disease, sprue, ulcerative colitis and jaundice. The gut remains sterile for the first few days after birth and hence newborns may suffer from vitamin K deficiency. Deficiency also occurs secondarily following antibiotic therapy.

Table 5

Recommended nutrient intakes (RNIs) for vitamin K

Group

RNIa (mg/day)


5b 10 15 20 25

Adolescents Females, 10–18 years Males, 10–18 years

35–55 35–55

Adults Females 19–65 years 65 years Males 19–65 years 65 years

55 55 65 65

Pregnant women

55

Lactating women

55

a

The RNI for each group is based on a daily intake of approximately 1 mg/kg

body weight of phylloquinone. bThis intake cannot be met by infants who are exclusively breast-fed. To prevent bleeding due to vitamin K deficiency, it is recommended that all breast-fed infants should receive vitamin K supplementation at birth according to nationally approved guidelines. Source: Vitamin and mineral requirements in human nutrition, WHO.

Dental considerations Oral manifestations of vitamin K deficiency include gingival bleeding, petechiae and ecchymoses. Bleeding on brushing occurs when prothrombin levels fall below 35% and spontaneously when the levels fall below 20%. Characteristics of water-soluble vitamins: These are water-soluble organic substances. The B vitamins also contain nitrogen. These vitamins are readily absorbed in the jejunum. The body stores very small quantities of each of these vitamins and hence, daily intake is important.

Vitamin C Vitamin C (chemical names: ascorbic acid and ascorbate) is a six-carbon lactone which is synthesized from glucose by many animals. Vitamin C is synthesized in the liver in some mammals and in the kidney in birds and reptiles. However, several species including humans are unable to synthesize vitamin C. When there is insufficient vitamin C in the diet, humans suffer from the potentially lethal deficiency disease scurvy. Functions Vitamin C is an electron donor (reducing agent or antioxidant), and probably all of its biochemical and molecular roles can be accounted for by this function. Dietary sources Ascorbate is found in many fruits and vegetables. Citrus fruits and juices are particularly rich sources of vitamin C but other fruits including cantaloupe and honeydew melons, cherries, kiwi fruits, mangoes, papaya, strawberries, tangelo, tomatoes and water melon also contain variable amounts of vitamin C. Vegetables such as cabbage, broccoli, Brussels sprouts, bean sprouts, cauliflower, mustard, greens, red and green peppers, peas and potatoes are also important sources of vitamin C (Table 6). Deficiency Deficiency of vitamin C leads to scurvy, which can manifest in as little as 20 days. From the 15th century, scurvy was dreaded by seamen and explorers forced to subsist for months on diets of dried beef and biscuits. Scurvy was described by the Crusaders during the sieges of numerous European cities, and was also a result of the famine in 19th century Ireland. Three important manifestations of scurvy, namely, gingival changes, pain in the extremities, and hemorrhagic manifestations precede edema, ulcerations, and ultimately death. Skeletal and vascular lesions related to scurvy probably arise from a failure of osteoid formation. In infantile scurvy, the changes are mainly at the sites of most active bone growth; characteristic signs are a pseudoparalysis 639


Table 6 Recommended nutrient intakes (RNIs) for vitamin C

Vitamin B Complex

Group

Vitamin B1—Thiamine

RNI (mg/day)


25 30 30 30 35

Adolescents 10–18 years

40

Adults 19–65 years 65 years

45 45

Pregnant women

55

Lactating women

70

Sources


of the limbs caused by extreme pain on movement and caused by hemorrhages under the periosteum, as well as swelling and hemorrhages of the gums surrounding erupting teeth. In adults, one of the early principal adverse effects of the collagen-related pathology may be impaired wound healing. Vitamin C deficiency can be detected from early signs of clinical deficiency, such as the follicular hyperkeratosis, petechial hemorrhages, swollen or bleeding gums and joint pain, or from the very low concentrations of ascorbate in plasma, blood or leukocytes. Dental considerations One of the earliest manifestations of scurvy is gingivitis leading to periodontitis and resulting in tooth mobility and loss of teeth. However, vitamin C deficiency per se does not lead to gingivitis. Gingivitis is caused by bacterial plaque. Vitamin C deficiency may aggravate the gingival response to plaque and worsen the edema, enlargement and bleeding. Acute vitamin C deficiency results in edema and hemorrhage in periodontal ligament, osteoporosis of alveolar bone, tooth mobility and degeneration of collagen fibers. Vitamin C deficiency accentuates the destructive effect of gingival inflammation on the underlying periodontal ligament and bone. Vitamin C influences the metabolism of collagen in the periodontium, affecting the ability of the tissue to regenerate and repair itself. Scurvy also leads to changes in teeth in the form of hypoplastic teeth. Vitamin C deficiency leads to the atrophy of ameloblasts and odontoblasts leading to a disruption in their orderly polar arrangement. Thus, dentin formed resembles osteodentin, with a lack of parallel arrangement of dentinal tubules. Severe deficiency of vitamin C leads to hypercalcification of predentin. 640

It functions as a coenzyme, thiamine pyrophosphate (TPP) in the metabolism of carbohydrates and branched-chain amino acids. It is required for the normal functioning of the brain, nerves, muscles and the heart. Carbohydrate metabolism is impossible without thiamine.

Whole grains, nuts, legumes, pork are good sources of thiamine. Deficiency Intake of polished rice, alcoholism and ingestion of raw fish lead to the deficiency of thiamine. Mild deficiency of thiamine leads to depression, anorexia, fatigue and inability to concentrate. Hence, this vitamin has also been called as ‘morale vitamin’. Severe deficiency leads to beriberi. Beriberi occurs in two forms: wet and dry. Dry beriberi is characterized by impairment of sensory and motor function and muscle wasting. Wet beriberi presents with edema, cardiac enlargement and tachycardia. Wernicke–Korsakoff syndrome occurs in the deficiency of thiamine and is characterized by nystagmus, ataxia and mental confusion in alcoholics. Dental considerations Tongue changes in the form of an enlarged, flabby, red and edematous appearance with enlargement of fungiform papillae have been associated with thiamine deficiency. The gingiva becomes inflamed and presents with an ‘old rose’ color (Table 7). Vitamin B2—Riboflavin Riboflavin is a flavoprotein and is part of the oxidation chain in the mitochondria, acting as a coenzyme in oxidationreduction reactions. It is required for the metabolism of carbohydrate, proteins and fat. It is also required for the maintenance of mucous membranes (Table 8). Sources Milk and milk products, grains, meat, poultry and fish. Deficiency Riboflavin (vitamin B2 ) deficiency results in the condition of hypo- or ariboflavinosis. As riboflavin deficiency almost invariably occurs in combination with a deficiency of other B complex vitamins, some of the symptoms (e.g. glossitis and dermatitis) may result from other complicating deficiencies.


Table 7 Recommended nutrient intakes (RNIs) for thiamine Group

RNI (mg/day)

Dental considerations


0.2 0.3 0.5 0.6 0.9


1.1 1.2

Adults Females, 19 years Males, 19 years

1.1 1.2

Pregnant women

1.4

Lactating women

1.5


Table 8

resection of the small bowel, and decreased gastrointestinal passage time.

Recommended nutrient intakes (RNIs) for riboflavin, by group

Group

RNI (mg/day)


0.3 0.4 0.5 0.6 0.9


1.0 1.3

Adults Females, 19 years Males, 19 years

1.1 1.3

Pregnant women

1.4

Lactating women

1.6


The major cause of hyporiboflavinosis is inadequate dietary intake as a result of limited food supply, which is sometimes exacerbated by poor food storage or processing. Children in developing countries will commonly demonstrate clinical signs of riboflavin deficiency during periods of the year when gastrointestinal infections are prevalent. Decreased assimilation of riboflavin also results from abnormal digestion, such as that which occurs with lactose intolerance. This condition is highest in African and Asian populations and can lead to a decreased intake of milk, as well as an abnormal absorption of the vitamin. Absorption of riboflavin is also affected in some other conditions, for example, tropical sprue, celiac disease, malignancy and

Oral symptoms are a prominent feature of riboflavin deficiency. These are characterized by angular cheilitis and glossitis. In the initial stages, there is a reddish appearance of the tip and lateral margins of the tongue. The tongue appears to be coarsely granular due to atrophy of filiform papillae and swelling of fungiform papillae. Severe cases lead to atrophy of all papillae causing the tongue to appear smooth and glazed. Riboflavin deficiency also leads to increased vascularization causing the tongue to appear magenta in color. Angular cheilitis initially presents as pallor of the lips at the angles of the mouth. This is followed a few days later by reddening of lips due to the desquamation of the epithelium and fissuring at the angles of the mouth. There may be only one or multiple fissures. These fissures develop a yellow crust, which can be removed without bleeding. If the deficiency is not treated, the fissures become deep and may bleed and become painful. Secondary infection with oral and/or skin microorganisms may occur. The incidence of the orolingual and dermal lesions in India is high about 5–10%, particularly in pregnant women and in school-going children. Angular stomatitis, however, may be associated with iron deficiency anemia. Angular cheilitis, however, is often associated with fungal infections, lip-sucking and dehydration. Patients with riboflavin deficiency also reveal a scaly, greasy dermatitis of the alae of nose and nasolabial folds. Corneal vascularization, superficial and interstitial keratitis have also been reported in ariboflavinosis. Impairment of psychomotor performance tests in riboflavin deficiency has been reported to occur since physical work increases riboflavin requirement. Riboflavin deficiency has also been implicated in the etiology of cataract.

METABOLIC DISORDERS Lysosomal Storage Diseases Lysosomes are subcellular organelles containing specific hydrolases that allow targeted processing or degradation of proteins, nucleic acids, carbohydrates and lipids. There are more than 40 different types of lysosomal storage diseases. Metabolic diseases can be categorized as: 1. 2. 3.

Disorders of protein metabolism Disorders of carbohydrate metabolism Disorders of lipid metabolism 641


Disorders of Protein Metabolism Amyloidosis It is a rare disease characterized by the deposition of an insoluble extracellular fibrillar protein in various tissues of the body. This protein called amyloid is not a single entity, but has three major and several minor biochemical forms. The major biochemical forms include AL (amyloid light chain), derived from plasma cells; AA (amyloid-associated) protein synthesized by liver; and A amyloid found in the cerebral lesion of Alzheimer's disease. The characteristic physical nature of amyloid is its crossed -pleated sheet conformation as demonstrated by X-ray crystallography and infrared spectroscopy. Classification Amyloidosis can be primary systemic, secondary systemic, localized, myeloma-associated or hereditary-familial. These categories constitute 56%, 8%, 9%, 26% and 1% of cases respectively. The primary systemic form affects mainly mesenchymal tissues such as the heart, tongue, and gastrointestinal tract and is characterized by the deposition of AL amyloid. The secondary form is however associated with destructive chronic inflammatory diseases such as tuberculosis, leprosy, rheumatoid arthritis, ankylosing spondylitis and osteomyelitis and is characterized by the deposition of AA amyloid. This form affects primarily the kidneys, adrenals, liver and spleen. About 12% of myeloma patients develop amyloidosis. Various heredofamilial types have been reported including familial Mediterranean fever and transthyretin-related amyloidosis (ATTR) type. Clinical features Generally, peak age incidence is in the fifties, with a male-to-female ratio of 2:1 and no racial bias. Clinical manifestation depends on the organ or site of involvement and the severity of involvement. Its manifestations range from asymptomatic deposition to serious clinical impairment to even death. Initial symptoms include fatigue, weakness and weight loss. Later, the disease may manifest as renal disease, hepatomegaly, splenomegaly or cardiac abnormalities. Oral considerations Oral manifestations of systemic amyloidosis have been well documented. The tongue is the most frequently reported location of intraoral amyloid deposition. Macroglossia commonly develops, and difficulty with speaking and chewing may ensue. Dental indentations of the lateral borders of the tongue may be evident owing to pressure against the teeth. Other sites in the oral cavity that may have amyloid deposition include the buccal mucosa, palate, gingiva and floor of the mouth. A rare instance of amyloid deposition of amyloid in the parotid gland has been reported. In the absence of clinical symptoms, oral tissues have been advocated for biopsy to detect amyloid deposition. Oral biopsy sites that have demonstrated presence of amyloid are numerous, including the gingiva, parotid gland, minor salivary glands of the lower lip and buccal mucosa. 642

Investigations A diagnosis of amyloidosis is first made on the basis of clinical suspicion; a tissue biopsy is used to establish a definitive diagnosis. Biopsy followed by Congo red staining is considered the gold standard for diagnosis. Amyloid shows an apple-green birefringence when viewed with polarized light microscopy. Biopsy is generally from the organ suspected to be involved. Gingival biopsy may be taken in generalized amyloidosis. After the sample has yielded a positive result, the type of amyloidosis must be determined. Immunofixation electrophoresis of serum or urine will enable the detection of monoclonal immunoglobulins or light chains in 90% of patients with AL amyloidosis. In patients whose light chains are not detected, a bone marrow biopsy can be used to detect the clonal dominance of plasma cells by immunohistochemical staining techniques. If no evidence of plasma cell dyscrasias is noted, other types of amyloidosis should be considered, such as the hereditaryfamilial type. Patients suspected of having AA amyloidosis should undergo immunohistochemical staining of their serum for the detection of the AA protein. Treatment The treatment of amyloidosis is directed both toward the affected organ and the specific type of the disease. Nephrotic involvement may necessitate the need for diuretics and dialysis, and cardiac involvement may dictate the need for diuretics as well. Colchicine, intermittent oral melphalan, prednisone, vincristine and adriamycin, in combination with dexamethasone have met with considerable success. Treatment with high-dose intravenous melphalan with autologous blood stem cell support results in complete remission of the plasma cell dyscrasia. Renal transplantation is extremely successful in providing dramatic symptom relief for patients with dialysis-related amyloidosis. The definitive therapy for ATTR amyloidosis is liver transplantation. Prognosis The prognosis for patients with generalized amyloidosis is poor if left untreated. The disease is rapidly fatal within 1–3 years of diagnosis. Diagnosis is mostly made at postmortem; the 5-year survival rate has been put at 20%. Prognosis of secondary amyloidosis depends on the control of the underlying condition. Patients with myelomaassociated amyloidosis have a poorer prognosis. Porphyria The term ‘porphyria' is derived from the Greek word porphuros, meaning ‘purple pigment’, after the purple-red urine that some patients produce during an acute attack. Porphyrias are a group of inherited or acquired disorders of certain enzymes in the heme biosynthetic pathway (also called porphyrin pathway). Porphyrias can be categorized into acute porphyria and cutaneous porphyria. Acute porphyrias are further subdivided into acute intermittent porphyria, hereditary coproporphyria, variegate porphyria and ALA dehydratase-deficient porphyria.


Cutaneous porphyria is divided into congenital erythropoietic porphyria (Gunther’s disease), porphyria cutanea tarda and erythropoietic protoporphyria. Clinical features Acute intermittent porphyria It is an autosomal dominant disorder caused by the deficiency of uroporphyrinogen I synthetase. Acute attacks in this disease are triggered by alcohol consumption, tobacco use, stress and hormonal changes such as in luteal phase of menstrual cycle and pregnancy. Men and women are equally affected. The symptoms of the disorder are frequently manifested after puberty. In acute episodes the urine turns purple-red following exposure to sunlight. Acute attacks are characterized by nausea, vomiting, malaise, myalgia and chest pain. Some individuals may present with depression, confusion, hallucinations and seizures. Severe forms of the condition may result in respiratory paralysis. Downey (1992) reported a patient who complained of severe abdominal pain, seizures, diarrhea, drooling of saliva associated with a metallic taste immediately after placing a fixed partial denture containing pallidum (76%), copper (10%) and gold (2%). The symptoms subsided on removing the denture. This patient was diagnosed as suffering from acute intermittent porphyria. Acute intermittent porphyria can be diagnosed by the qualitative assessment of urine for porphobilinogen. Hereditary corpoporphyria It is the rarest form of acute porphyria characterized by the deficiency of enzyme corpooxidase. It is an autosomal dominant condition which is usually more common in women. The trigger factors are the same as that of the acute intermittent porphyria. However, acute attacks are less common and less severe. The clinical symptoms are the same as that of the acute intermittent type. These patients may exhibit cutaneous photosensitivity. Elevated levels of coproporphyrins in stool analysis is diagnostic of hereditary corpoporphyria. Variegate porphyria The term ‘variegate' is used to describe the variety of clinical manifestations that this form of porphyria exhibits. It can manifest as an acute form, cutaneous form, both or occasionally appear clinically latent. Protocoproporphyria hereditaria or South African porphyria (widely prevalent in the white population of South Africa) are other names by which variegate porphyria is known. Vareigate porphyria is diagnosed based on the marked increase in the levels of protoporphyrin in stool. ALA dehydratase-deficient porphyria It is an acute form of porphyria whose pattern of inheritance is still not known. The clinical presentation mimics that of acute intermittent porphyria.

Congenital erythropoietic porphyria Congenital erythropoietic porphyria or Gunther’s disease is a rare autosomal recessive disorder that usually presents with marked skin photosensitivity, hypertrichosis, blistering, scarring, milia formation and dyspigmentation of the photo-exposed areas. The enzyme URO-3-synthetase is deficient. It typically begins in infants or young children. Sun-exposed regions of the body such as the hands, neck and face may exhibit vesicular or bullous lesions. These vesicles subsequently rupture and heal with scar formation. Owing to its physical affinity to calcium phosphate, porphyrin binds to teeth, nails and bones. Both the deciduous and permanent dentition appear red or brown in color (erythrodontia). Porphyria cutanea tarda It is an autosomal dominant disorder and the most common of all the porphyrias. It is caused by the deficiency of URO-decarboxylase. Alcohol consumption, hepatitis C and medications such as iron supplements and hormonal replacements can predispose to porphyria cutanea tarda. Cutaneous photosensitivity is the most striking feature. Exposure to sun leads to the formation of vesicles and bullae which subsequently heal forming crusts. These individuals may exhibit hyperpigmentation and hirsutism. Erythropoietic protoporphyria It is an autosomal dominant disorder caused by the deficiency of ferrochelatase. The striking feature of this type of porphyria is the development of cutaneous manifestations of pain, redness, itching and burning sensation within a few minutes of sun exposure. Thickening of the skin and nail deformities are seen in chronic cases. Unlike other forms of porphyria hyperpigmentation and hirsutisms are rare. Orofacial manifestations and dental considerations Individuals suffering from cutaneous porphyria may present with long eyelashes, bushy eyebrows and facial hair (facial hirsutism). Oral mucosa is very vulnerable even to the mildest trauma due to the accumulation of porphyrin precursors. Intraoral erosions and bullae may be seen. Patients suffering from congenital erythropoietic porphyria (CEP) may exhibit pallor of the oral mucosa. Occasionally, the alveolar mucosa may appear bluish purple owing to the discolored underlying alveolar bone. Deciduous dentition of CEP patients may appear deep red-brown in color. Permanent teeth may not be severely discolored. The cervical regions of teeth are more intensely discolored compared to the occlusal region. These discolored teeth tend to fluoresce with Wood’s light (near UV light of 365 nm wavelength). It is believed that the concentration of porphyrin is higher in the dentin compared to the enamel. 643


Fayle and Pollard (1994) reported that the enamel showed marked thinning in a 4-year-old child suffering from CEP. They believed that the thinning of enamel can increase the caries risk in these individuals. Use of carbohydrate in the management of acute porphyria can cause extensive periodontal disease and high caries incidence. Oral B carotene which is used to improve tolerance to light in CEP and erythropoietic protoporphyria patients can induce carotenemia, leading to yellowish-orange discoloration of the oral mucosa and tongue. As heavy metals can provoke an acute episode of porphyria, dental amalgam has been recommended to be avoided in these patients. Light in the operation theatre have known to cause burns in some patients. Hence, the light on the dental chair should be considered a potential hazard to these patients. It is advisable to use filters that remove light in the wavelength of 400–550 nm. Various medications that can be used and those that have to be avoided are listed in Table 9.

Disorders of Carbohydrate Metabolism Mucopolysaccharidoses (MPS) These are normal components of the cornea, cartilage, bone, connective tissue ground substance and the reticuloendothelial system. MPS are characterized by the storage of mucopolysaccharides in various tissues. Theses are caused by the deficiency of the enzymes required for their degradation. The overall prevalence of MPS is about 1 in 25,000. The variants of MPS have been classified as types I through VII. Of these, Table 9 Drug recommendations in patients suffering from porphyria

644

Safe drugs (commonly used)

Contraindicated drugs (commonly used)

Acetaminophen

Alcohol

Acetyl salicylic acid

Clindamycin

Acyclovir

Diclofenac

Amoxicillin

Erythromycin

Amphotericin B

Lidocaine

Bupivacaine

Mepivacaine

Codeine

Miconazole

Dexamethasone

Prilocaine

Gentamicin

Pyrazolones

Ibuprofen

Carbamazepine

Iron

Phenytoin sodium

Nitrous oxide

Dapsone

Penicillins

Sulfonamides

Streptomycin

Oral contraceptives (some)

MPS I or Hurler syndrome is the most common. All of them are inherited as autosomal recessive traits except MPS type II—Hunter syndrome, which is inherited as an X-linked trait. Mucopolysaccharidosis I (MPS I) It is caused by deficient or absent activity of the lysosomal hydrolase-Liduronidase. This enzyme is responsible for the degradation of heparan sulfate and dermatan sulfate, and a deficiency in the enzyme leads to accumulation of these substances in various tissues. MPS I includes three subtypes: ❍

MPS I-H (Hurler syndrome): The most severe form in which the onset is in infancy. ❍ MPS I-H/S: The intermediate form, characterized by mental retardation and other features of Hurler syndrome. ❍ MPS I-S (Scheie syndrome): The least severe form having its onset in adulthood and presenting no features of mental retardation. Hurler syndrome (Gargoylism) The worldwide incidence of MPS I-H has been reported to be 1:100,000. The chromosomal abnormality in this syndrome has been mapped to 4p16.3. Clinical features The disease becomes apparent in the first 2 years of life, progressing in childhood. Death usually occurs before the 2nd decade of life, unless affected patients are treated by bone marrow transplantation. Patients are characterized by dwarfism, mental retardation, skeletal malformations, hernias, cardiac disease and systemic hypertension, hepatosplenomegaly and flexion contractures. The facial features are characteristic, with patients having a large head, prominent forehead, a broad saddle nose, hypertelorism, puffy eyelids and an open mouth. The oral and dental findings of MPS I-H include hyperplastic gingiva, macroglossia, high-arched palate, short mandibular rami with abnormal condyles, spaced hypoplastic peg-shaped teeth with retarded eruption; and localized dentigerous cyst-like radiolucencies. Gingival hyperplasia has been reported in some patients. Guven et al reported that MPS I-H—affected dentin was characterized by extremely narrow dentinal tubules, whose direction followed an irregular wave-like pattern. The enamel–dentin junction had microgaps, and the enamel displayed irregular arrangement of prisms. There was a decrease in the protein content of enamel and dentin. The mucopolysaccharides accumulate in fibroblasts, giving them an appearance of ‘clear’ or ‘gargoyle’ cells, and hence the term ‘gargoylism’. Elevated levels of mucopolysaccharides are found in urine. Mucopolysaccharidosis II (Hunter syndrome) The biochemical cause of Hunter syndrome is a deficiency in the activity iduronate-2-sulfatase and is characterized by the deposition of dermatan sulfate and heparan sulfate in tissues.


It has an estimated prevalence of 1 in 170,000 male live births. Its prevalence among Ashkenazi and Oriental Jews is reported to be approximately twice that reported in other populations. Hunter syndrome is an X-linked, recessive inherited disease that affects males nearly exclusively. The gene responsible for the syndrome is located at Xq28. Clinical features In its severe form, clinical features appear between 2 and 4 years of age in the form of severe mental impairment. Death usually occurs in the 1st or 2nd decade of life, following obstructive airway disease and/or cardiac failure. The disease may have a slightly later onset, with minimal neurologic dysfunction. These patients have normal intelligence and survive into adulthood. Clinical features include coarsening of facial features, broad noses with flared nostrils, prominent supraorbital ridges, large jaws, and thick lips, enlarged protruding tongue. Mobility is restricted because of joint stiffness and contractures. The skeletal findings of Hunter syndrome are collectively known as dysostosis multiplex. Corneal clouding is not a feature of Hunter syndrome. There may be progressive hearing loss, sleep apnea, hepatosplenomegaly, valvular heart disease, progressive airway obstruction, and distinctive skin lesions, described as ivory-white papules that are 2–10 mm in diameter, often coalescing to form ridges. Diagnosis is established by measurement of urine mucopolysaccharide levels and enzyme activity. Mucopolysaccharidosis III (Sanfilippo syndrome) It is characterized by the deposition of heparan sulfate in tissues. Based on the deficient enzyme, this syndrome is classified into four subtypes A, B, C and D. The incidence of the combined MPS III subtypes has been estimated at 1 in 24,000 births to 1 in 66,000 with MPS III A being the most common subtype. MPS III A is characterized by the deficiency of heparan-N-sulfatase, MPS III B by N-acetyl-glucosaminidase, MPS III C by acetyl-CoA-glucosaminide N-acetyltransferase deficiency, and MPS III D by the deficiency of N-acetylglucosamine-6-6-sulfate sulfatase. Clinical features Symptoms begin in late infancy with various patterns of neurodegeneration resulting in severe mental retardation characterized by rapid loss of social skills with aggressive behavior and hyperactivity, and disturbed sleep patterns. In profoundly affected patients, delayed speech development is often noticed at 2 years of age. Hirsutism, coarse facies and diarrhea are found. Mild hepatosplenomegaly and mild skeletal disturbances may be found. Diagnosis depends on enzymatic analysis and heparan sulfaturia. Mucopolysaccharidosis IV (Morquio syndrome) This syndrome is characterized by the deposition of keratan sulfate and chondroitin-6-sulfate in tissues. It is subclassified into Morquio type A, characterized by the deficiency of N-acetyl galactosamine; and Morquio type B, caused by the deficiency of -galactosidase.

Clinical features The syndrome is characterized by severe skeletal changes including hypoplasia of odontoid process, short neck, pectus craniatum, kyphoscoliosis and dwarfism. Other findings include laxity of joints, neurosensory deafness and corneal clouding. Mental retardation is absent. Characteristic dental findings are found in MPS IV A, but not in MPS IV B. These have been described as mineralization disturbances of enamel leading to the appearance of dull grayish to yellowish crowns, small teeth, severe attrition, and pointed cusps. The enamel, however, had a normal radiodensity. Damage to TMJ has been reported in the form of irregularity of cortical bone of the head of condyle, possibly aggravated by severe attrition of teeth. Diagnosis of the disease is by the estimation of keratan sulfate levels in urine and plasma. Mucopolysaccharidosis V: absent Mucopolysaccharidosis VI (Maroteaux–Lamy syndrome). It occurs due to a deficiency of arylsulfatase B (N-acetylgalactosamine-4sulfatase), which results in the accumulation of dermatan sulfate within lysosomes. An incidence of 1:100,000 to 1:1300,000 has been reported. Clinical features Patients suffering from Maroteaux– Lamy syndrome have similar somatic features resembling those of the other mucopolysaccharidoses, but distinguished by the presence of normal intelligence, prominent metachromatic inclusions in leukocytes and a deficient activity of arylsulfatase B. Characteristic features of this disease include growth retardation, hernias, a large deformed head, typical facies, a short neck and spinal abnormalities. Hepatosplenomegaly results from mucopolysaccharide deposits in several organs. Severely affected MPS VI patients are usually diagnosed in infancy or early childhood and the condition usually results in death in the 2nd decade of life. Death is usually a result of either respiratory tract infection or cardiac disease, which are caused by the deposition of mucopolysaccharides. The craniofacial features in this syndrome are similar to Hurler syndrome. The head is large, with a prominent forehead, often marked supraorbital ridges and temporal bulge. Rhinitis with rhinorhea is common and corneal opacity is also observed. At rest, the mouth is open and the enlarged tongue tends to protrude. The teeth have been reported as being short or stubby, misshapen, malformed, peg-shaped, poorly formed, abnormal, poorly calcified, and hypoplastic. Usually there is an anterior open bite relationship in association with macroglossia. Localized radiolucent areas resembling dentigerous cyst-like follicles are also reported in Maroteaux–Lamy syndrome. The margins of the radiolucencies are usually smooth and clearly defined. These radiolucencies are caused by accumulation of mucopolysaccharides in the tissues. Mucopolysaccharidosis VII (Sly syndrome) It is caused by a deficiency in the enzyme -glucuronidase. This 645


results in the accumulation of heparan sulfate and dermatan sulfate in tissues. Clinical features The syndrome is highly variable, with clinical presentation ranging from severe lethal hydrops fetalis to mild forms with survival into adulthood. Sewell et al suggested that MPS VII comprises three main clinical groups: an early severe lethal form, an intermediate form with slight organomegaly and moderate skeletal anomalies and a very mild form in which patients present later and show longer survival. Most patients show hepatosplenomegaly, and skeletal anomalies such as disproportionate dwarfism, sternal protrusion, kyphosis, scoliosis, and a broad-based gait. Craniofacial dysmorphism characterized by epicanthus, anti-mongoloid eyelids, short nose with anteversion of the nostrils, macroglossia, and coarse facies may be seen. A variable degree of mental impairment and delayed speech is present. Management of mucopolysaccharidoses Methods of replacing the enzyme missing in MPS have included bone marrow transplantation, human amnion membrane implantation, fibroblast transplantation, serum or plasma infusion, white blood cell infusions, gene therapy, intraperitoneal implantation of myoblasts overexpressing I2S and enzyme replacement therapy. Future prospects include gene therapy, newborn screening and prenatal screening.

Lipoid Proteinosis Lipoid proteinosis also known as hyalinosis cutis et mucosae or Urbach–Wiethe disease. It is transmitted as an autosomal recessive disorder. Lipoid proteinsosis is characterized by generalized thickening and scarring of the skin, mucosae and occasionally some viscera secondary to diffuse deposition of a hyaline-like substance. Recent studies have shown that lipoid proteinosis is caused by the mutations in a glycoprotein (extracellular matrix protein 1) that is expressed in various tissues. The mutation was mapped to a locus on chromosome 1q21. Clinical features Deposits in the vocal cords may manifest as inability of babies to cry at birth and hoarseness of voice from early infancy or childhood. The skin characteristically shows whitish, moniliform papules on the eyelids (blepharosis moniliformis, eyelid beading), and yellowish or waxy papules or nodules on the lips, knuckles, hands, knees, elbows, axillae and the perineal regions. Occasionally, the face may exhibit vesiculobullous eruptions which later form scars. Patchy alopecia has also been reported. Other features include dyspnea, dysphagia, corneal opacities and glaucoma. Calcifications of intracerebral parasellar or hippocampal gyri may be associated with epilepsy, 646

mental retardation and neuropsychiatric illnesses. Intestinal bleeding has been reported following hyaline deposits in the small bowel. Oral manifestations The oral mucosa appears thickened and nodular. The sites of involvement are the labial, buccal and palatal mucosa, posterior tongue, uvula, tonsillar region and lingual frenulum. The typical oral lesions are seen as yellowish-white papules or plaques. Involvement of the lingual frenum causes difficulty in tongue protrusion. Macroglossia and ‘wood-hard’ tongue are other characteristic features. Lips may be enlarged, nodular and may exhibit fissuring. Occasionally, patients may report dry mouth secondary to infiltration and obstruction of the parotid duct by the hyaline material. Gingival hyperplasia has also been reported. Oezarmagan et al (1993) in their report of lipoid proteinosis in two sisters, describe the findings of overretention of deciduous teeth and oligodontia. Radiographic features Bean-shaped radiopacities in the temporal lobe or hippocampus on skull radiographs are typical findings in lipoid proteinosis. Histopathologic features On histopathologic evaluation the hyaline deposits exhibit positivity for periodic acid-Schiff (PAS) and Congo red. However, the material is diastase resistant. Ultrastructural features include concentric rings of excess basement membrane surrounding blood vessels, and irregular reduplication of lamina densa at dermoepidermal junction resulting in onion-skin appearance. Dyer et al (2006) studied the lesional epidermis, cultured monolayer keratinocytes and raft keratinocyte cultures from blistering lesions of a child with lipoid proteinosis. Their ultrastructural studies showed the dissociation of relatively intact desmosomes from keratinocytes, with desmosomes which were ‘free-floating’ in the intercellular spaces or attached by thin strands to the cell membrane. They suggest that these ‘free-floating’ desmosomes could be a result of an inherent defect in keratinocyte adhesion. Management Lipoid proteinosis to date has no definitive treatment. However, Wong and Lin (1988) successfully used oral dimethyl sulfoxide in a 41-year-old man. They initially used a dose of 40 mg/kg/day, which was subsequently increased progressively to 60 mg/kg/day. In their follow-up after 3 years of treatment, the patient’s skin lesions, hoarseness of voice and abnormal esophageal function improved to a great


extent. The only side effect they encountered was the garlic-like smell on the patient’s breath. Intralesional heparin and ketretinate have also been used with limited success. Other treatment options used include CO2 laser surgery of vocal cords and beaded eyelid papules, and dermabrasion of skin for aesthetic and functional reasons. In severe forms of the condition, resulting in respiratory embarrassment, tracheostomy is performed.

Disorders of Lipid Metabolism Non-lipid reticuloendothelioses It involves diseases such as unifocal eosinophilic granuloma, multifocal eosinophilic granuloma (Hand–Schuller–Christian disease) and Letterer– Siwe disease. These diseases are collectively referred to as histiocytosis X disease. Histiocytosis X is the term used to describe a group of conditions affecting the reticuloendothelial system. Lichtenstein in 1953 coined the term histiocytosis X. It is a non-neoplastic lesion of unknown etiology characterized by an intense proliferation of histiocytes along with a number of eosinophilic leukocytes, neutrophilic leukocytes, lymphocytes, plasma cells and multinucleate giant cells. However, this term has now been changed to Langerhans cell histiocytosis (LCH) by Risdall et al (1983), as these diseases are known to involve Langerhans cell precursors. Eosinophilic granuloma is considered to be the chronic localized form of LCH which also includes Hand–Schuller– Christian disease (the chronic disseminated form) and Letterer–Siwe disease (the acute disseminated form). Radiographic features of histiocytosis X Dagenais et al (1992) described the characteristic radiographic features of histiocytosis X. They reported that seven characteristics, either alone or in combination, are useful in the identification of histiocytosis X. These include the appearance of solitary ‘intraosseous’ lesions, the multiplicity of ‘alveolar bone’ lesions, the ‘scooped-out’ effect in the alveolar process, the well-defined periphery, sclerosis in the alveolar bone lesions, periosteal new bone formation and slight root resorption. Eosinophilic granuloma It affects men twice as more than women. It is usually seen in young adults. The condition may have varied presentations. Some patients may complain of pain whereas in some others it may be incidentally evident on routine radiographic evaluation. It is believed that oral involvement is usually associated with pain, swelling, mucosal ulcerations and gingival inflammation. Ardekian et al (1999) in their study found that 44% of patients complained of pain and about 48% also complained of swelling in the affected area. The bones that are commonly affected are the skull bones, mandible, ribs, femur, humerus and pelvis. However, the bones of the

hand and feet are usually spared. Mandibular posterior region is usually the site to be affected. Radiographic features Alveolar bone may show irregular radiolucent lesions. Larger lesions may cause destruction of the cortical plate resulting in pathological fracture. However, lesions within the mandible appear as well-defined radiolucent areas mimicking cysts. These varied radiographic appearances of eosinophilic granuloma can be mistaken for odontogenic cyst, osteomyelitis or a malignancy. Management The currently accepted methods of managing eosinophilic granuloma include surgical curettage, low dose radiation (not more than 10 Gy) and chemotherapy used alone or in combination.

Hand–Schuller–Christian Disease or Multifocal Eosinophilic Granuloma The condition was named after Henry Asbury Christian, Alfred Hand Jr and Artur Schüller. It is a chronic form of eosinophilic granuloma characterized by disseminated form of skeletal and extraskeletal (soft tissue) lesions. Clinical features Facial asymmetry secondary to involvement of the facial bones is a characteristic feature. Patients may complain of pain, swelling and progressive facial asymmetry. Ribs, vertebrae, femur and pelvis are other bones that are commonly affected. It is believed that about 25% of the patients present with the classical triad of signs and symptoms that include punched-out radiolucent areas in the skull on a radiograph, exophthalmos and dwarfism, infantilism or polyuria. Oral manifestations The oral manifestations in these patients may mimic manifestations of advanced periodontitis such as halitosis, gingival inflammation with purulent discharge, spontaneous exfoliation of teeth and extensive loss of alveolar bone. Other symptoms include loss of taste sensation and oral mucosal ulceration or soreness. Radiographs may reveal displacement of teeth, and sometimes teeth ‘floating in air’ appearance may be appreciated. Bone scan may help in identifying multifocal disease. The bone destruction may be round, oval or irregular, occasionally with a periosteal reaction Diagnosis Radiographic features, histopathologic features and laboratory investigations are sufficient to diagnose this condition. 647


Histologically the lesion progresses through the phase of proliferative histiocytic phase, vascular granulmatous phase, diffuse xanthomatous phase (abundance of foam cells), and finally the fibrous or healing phase. Laboratory studies reveal normal serum cholesterol level and an elevated tissue cholesterol level. Management Surgical curettage or excision is the ideal mode of treatment. Lesions that are not amenable to surgery can be irradiated or drugs such as vinblastine or cyclophosphamide can be used. However, almost 50% of the patients exhibit spontaneous remission over a period of time.

LIPID RETICULOENDOTHELIOSES Gaucher Disease Gaucher disease is a rare autosomal recessive disorder characterized by defective function of the catabolic enzyme -glucocerebrosidase, leading to an accumulation of its substrate, glucocerebroside, in the mononuclear phagocyte system, lymph nodes, bone marrow; Kupffer cells in the liver; osteoclasts in bone; microglia in the central nervous system; alveolar macrophages in the lungs; and histiocytes in the gastrointestinal tracts, genitourinary tracts, and the peritoneum. Cells with this deposition are termed Gaucher cells. Classification

Letterer–Siwe Disease It is named after Erich Letterer and Sture August Siwe. Unlike the other forms of Langerhans cell histiocytosis, Letterer–Siwe disease is an acute disease and almost always seen in infants. It usually runs a short course and ends fatally. Clinical features In Letterer–Siwe disease, recurrent pyoderma-like lesions with crusting and scaling, vesicopustular and purpuric eruption occurs in crops over the face, scalp and trunk, resembling seborrheic dermatitis. Oral manifestations In most of the cases, oral manifestations may not be appreciated owing to the rapid course of the disease. However, mucosal ulceration associated with hemorrhage, gingival inflammation, extensive loss of the maxilla and mandible and spontaneous exfoliation of teeth may be seen. Diagnosis Tzanck smear of the vesicopustules shows pale histiocytes which can be used as a rapid screening test. Skin biopsy shows a proliferative reaction with extensive upper dermal infiltration and epidermal invasion with histiocytes, some of which are atypical, along with erythrocytes. Typically foam cells and fibrosis are appreciated histologically.

There are three clinical variants caused by distinct allelic mutations. Type I, also called as chronic non-neuronopathic form, accounts for 99% of cases of Gaucher disease and has an incidence of 1:100,000 in general population. It is most common among Ashkenazi Jews and is compatible with long life. Type II is termed acute neuronopathic form and is highly lethal. Type III, termed chronic/subacute neuronopathic form has a course intermediate between types I and II. Clinical features Type I is characterized by the absence of neurologic symptoms. Patients may present with hepatosplenomegaly, leukopenia and thrombocytopenia due to marrow replacement and cortical erosion. Extensive skeletal disease and pathologic fractures may be seen. Neurologic symptoms (in types II and III) include convulsions, dementia, ocular muscle apraxia, mental retardation and myoclonus. Oral manifestations Oral mucosa has a yellow pigmentation and presents petechiae. Jaw involvement is often asymptomatic and may be detected on routine dental radiographs. Generalized osteopenia, loss of trabecular structure, effacement of lamina dura, displacement of mandibular canal, pseudocystic radiolucent lesions and apical root resorption of teeth adjacent to lesions have all been reported. Involvement of maxillary sinus has been reported in a few cases. Delayed eruption has been reported in more than 50% of cases. Diagnosis

Management and prognosis The prognosis of this condition is very poor. It is believed that the presence of purpura is a lethal sign. Chemotherapy is usually the only mode of treatment. 648

Bone marrow aspiration or biopsy of liver and spleen reveal the presence of Gaucher cells, which appear as large cells having abundant granular, or fibrillary blue-gray cytoplasm with a wrinkled tissue paper-like appearance


with abundant lightly PAS–positive fibrillary material in the cytoplasm. The level of glucocerebrosidase in leukocytes or cultured fibroblasts is also helpful in diagnosis. Prognosis and treatment The infantile form (type II) of Gaucher disease may lead to early death. Most affected children die before the age of 5 years. Type I of Gaucher disease requires close medical follow-up with periodic assessment. With the availability of recombinant enzyme, most patients with the adultchronic form can look forward to normal or near-normal life expectancy. Enzyme replacement therapy with a recombinant glucocerebrosidase known as imiglucerase (Cerezyme) given intravenously is the mainstay of treatment for Gaucher disease. Hepatosplenomegaly, anemia and thrombocytopenia usually improve within 6 months. Unfortunately, it is not effective on neurologic symptoms, because it does not cross the blood–brain barrier. Future treatments may include gene therapy and intervention with chemical chaperones.

Niemann–Pick Disease It is characterized by the deficiency of the enzyme, sphingomyelinase, and accumulation of sphingomyelin in tissues. Classification It can be classified into two categories based on biochemical and molecular criteria. The first category includes types A and B, the second, type C. Clinical features The organs most commonly involved are spleen, liver, bone marrow, lymph nodes and lungs. The entire central nervous system also becomes involved. The patient presents with massive visceromegaly and severe neurologic deterioration. Diagnosis is achieved by the estimation of sphigomyelinase activity in leukocytes or cultured fibroblasts. Prognosis is poor and affected infants die before the age of 3 years. Antenatal diagnosis is possible.

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Forensic Dentistry

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Clinical and Radiological Perspective

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CHAPTER

Clinical and Radiological Perspective Ashith B Acharya

➧ Introduction, History and Relevance ➧

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Incinerated Teeth Postmortem Pink Teeth Tongue Hemorrhage

Social Profiling

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Identifying the Edentulous Denture Marking Systems Palatal Rugae in Identification

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Craniofacial Identification Cranial Suture Pattern Frontal Sinus Configuration Skull-Photograph Superimposition Challenges in Superimposition Three-Dimensional Digital Superimposition

INTRODUCTION, HISTORY AND RELEVANCE Forensic odontology is the branch of dentistry which deals with the law. The last half-century has seen forensic dentistry make tremendous progress globally, both in terms of research as well as application in routine casework. Forensic odontology primarily involves identification. Right through history, the human dentition has been used several times in identifying individuals. Harvey (1973) has traced one of the earliest recorded incidences of dental identification to 66 AD, when the severed head of the wife of Roman emperor Nero was identified by a rival from her

Bite Mark Procedures How Does a Bite Mark Look? Type of Injury Site of Injury Differential Diagnosis of Human Bite Marks Bite Mark Investigation Collecting Bite Mark Evidence Demographics of the Case Visual Examination and Documentation Photographs Saliva Swab Obtaining Dental Evidence from a Suspect Analyzing and Comparing Bite Mark Evidence Conclusions of Bite Mark Analysis

Postmortem Alterations to Teeth and Oral Tissues

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Age Estimation Methods Clinical Methods of Age Assessment Radiographic Methods for Age Assessment Estimating Age in Children and Adolescents Third Molars in Age Estimation A Combined Clinical and Radiographic Method Estimating Age in Adults

Challenges in Postmortem Examination Rigor Mortis Incineration Jaw Resection Tooth Colored Restorations

Facial Approximation Clay Modeling Computer-assisted Approximation

Dental Identification What is Identification? Importance of Teeth in Postmortem Identification Principle of Dental Identification Dental Identification Procedure

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24

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Lip Print Investigation

black anterior tooth. In 1193 AD the Maharaja of Kannauj, Jai Chandra Rathor, was recognized by his false teeth following death in a battle. The English duke Charles of Burgundy, who also died in a battle in 1477 AD, was identified from his dental features courtesy, the court physician who recognized two recently extracted teeth (Furness, 1972). Paul Revere is credited as being the first dentist to identify a person from dental features (Luntz, 1970). He identified a friend—who died in the American Revolution in 1775—from a silver and ivory bridge prepared by him. Subsequently, intermittent cases of forensic dental identification in 19th century Europe and America have 653

Section VIII – Forensic Dentistry

been reported (Pedersen, 1965). However, Gustafson (1962) believed that the role of forensic odontology in human identification came to prominence toward the end of the 19th century after two major fires in Europe: the first occurred in 1881 when the ‘Ring Theatre’ in Vienna was destroyed during a performance with 449 casualties; and the second— the Charity Bazaar fire in Paris in 1897—resulted in 127 deaths. In both tragedies, dental features were used for identification. According to Harvey (1973), one of the dentists who assisted the identifications in Paris was a Cuban named Oscar Amoedo. In 1898, he authored one of the first books on forensic odontology, L’art Dentaire en Medicine Legale, and is considered a pioneer of modern forensic dentistry. It is noteworthy that Yasutami Kojimahara of Japan had published a similar work titled Dental Jurisprudence a few years earlier in 1894 (Suzuki, 1996). The routine use of dental evidence in human identification gained impetus during the 1950s and 1960s, and forensic dentistry gained organized status in 1972 with the formation of the International Organization for Forensic OdontoStomatology (IOFOS). With the evolution of criminal investigation in the industrialized world, scientific methods of detecting both the victim and culprit in a crime concurrently developed. Fingerprinting was one such method—the dermal ridges on our fingers are so unique even twins do not share an identical pattern. The human dentition is considered to be as unique to an individual as fingerprints are. The adult dentition normally consists of 32 teeth of which some may be missing, decayed or treated. Effects of various environmental factors such as fluorosis may also manifest in the teeth. Hence, it is extremely rare to have two identical dentitions, and this concept makes use of identifying the deceased. Moreover, teeth are one of the most durable parts of the body and can withstand physical, chemical and biological insults. As a result, teeth can be used to build the profile of skeletal remains. For example, race and sex differences in tooth morphology are known to occur; age estimation using tooth eruption, calcification and histological methods is frequently applied. Dental age estimation gained prominence following a case in Britain in 1935, where the age of two badly mutilated bodies was estimated from the calcification of third molars (Taylor, 1963). This contributed to the eventual identification of the bodies using photographic superimposition. In an age when heightened social, emotional and legal importance is placed on identifying the dead, dental identification methods has great relevance. Apart from identification, forensic odontology is applied in the investigation of crimes where traces of the teeth, such as bite marks, are observed. The ability to match a bite mark to the uncommon arrangement of the dental arch can prove important in investigating sex crimes and violent fights. It is interesting to note that as early as the 6th century AD, the Indian sage Vatsy a¯ yana had recognized the prevalence of bites during love-making. Consequently, he devoted an 654

entire chapter to ‘love bites’, with its detailed classification, in the treatise Kama Sutra. The unique arrangement of the dental arch was recognized in medieval Britain during the reign of William I (1027–1087 AD), green wax seals with the impression of the king’s teeth were implanted on state documents to avoid falsification and indicate the authenticity of the seal. The use of bite marks as evidence in court can be traced back to 1692 in the United States. Harvey (1973) cites a 1906 case where a burglar was convicted in Britain because his dental models fit the marks left in cheese found at the crime scene which was probably the first successful conviction based on bite mark evidence in Europe. Subsequently there have been numerous cases that made use of bite marks but, with varying degrees of success. Therefore, bite marks remained a contentious area of forensic sciences. However, over the latter half of the 20th century, bite mark procedures have greatly advanced and it is now routinely used in court proceedings of Europe, America and Asia Pacific. Its objective application as evidence in crime can have far reaching implications for the society in general and criminology in particular. The potential of teeth as legal evidence has rendered forensic dentists as an integral part of the forensic team of experts. Interest in the subject is not only confined to specialist forensic dentists but also oral physicians and radiologists, oral pathologists, pedodontists, prosthodontists and forensic medical professionals. This chapter attempts to address relevant clinical and radiological aspects of forensic odontology and it is intended to further stimulate the reader’s inquisition in this fascinating area.

DENTAL IDENTIFICATION What is Identification? Identity refers to the characteristics by which a person may be recognized (Acharya and Taylor, 2003) and identification is the establishment of a person’s individuality. Accurate identification of the dead is required both for legal and humanitarian reasons (Brown, 1984). It enables the settlement of insurance and property, permits remarriage of the surviving spouse and facilitate last rites of the body in accordance with appropriate religious customs. Haglund and Morton (1994) believe that a majority of individual identifications in forensic settings are nonproblematic since most individuals die in the company of family and friends. These deaths may occur at home or in a hospital, allowing visual identification. However, in cases where the body is burned, traumatized or decomposed, visual identification can prove unreliable. Hence, Sopher (1972) believes that visual recognition and use of personal effects are the least dependable methods of identification in such circumstances. Therefore, the safest option is for

Chapter 24 – Clinical and Radiological Perspective

the forensic expert to analyze physical features present in the body.

Importance of Teeth in Postmortem Identification Every individual has a variety of physical features that include built, height, epidermal ridges and dental characteristics. Most of these, however, are prone to change over an individual’s lifetime. Epidermal ridges (which produce fingerprints) are exceptions but, like other soft tissues, are susceptible to postmortem decomposition. Teeth are considered as the hard tissue analog to fingerprints and gain importance in identification as the time period since death increases. Although teeth are susceptible to disease during life, they are the most durable part of the body after death. Apart from teeth being relatively resistant to postmortem change, practically all materials used by the dentist are also resistant to postmortem destruction. Therefore, the use of dental evidence is considered essential for establishing identity in traumatized, decomposed and incinerated remains.

Principle of Dental Identification The underlying principle of dental identification is that combinations of dental characteristics are never the same in any two individuals. Several authors believe that the human dentition is unique (Johanson and Lindenstam, 1961; Keiser-Nielsen, 1977; Fellingham et al, 1984; Phillips and Scheepers, 1990). Human beings normally have 32 permanent teeth which vary in morphology and arrangement. Although teeth are relatively resistant to environmental factors and postmortem proteolysis, during life they are susceptible to disease such as caries. As a result, teeth may have undergone treatment in the form of fillings, crowns, etc. Those teeth that cannot be restored may have been extracted and, thus, missing from the oral cavity. According to Keiser-Nielsen (1977), the number of combinations 16 missing teeth can produce is approximately 60 crore. Sixteen filled teeth produce a similar combination. Four missing and four filled teeth combined can produce about 70 crore combinations. Every tooth has five surfaces and taking the 160 tooth surfaces individually would produce astronomical variations. In addition to the features visible on oral examination, radiographs reveal distinct shape and outline of various restorations of the crown and root and anatomic features of the teeth and bone (Sopher, 1972). Hence, the permutations resulting from observing the teeth clinically and radiographically would be phenomenal. It has been calculated that there are 1.8 1019 possible combinations of 32 teeth being intact, decayed, missing or filled (Fellingham et al, 1984). Therefore, dental identity can be considered as the sum total of all characteristics of teeth and associated structures which, while not individually unique, equal a unique totality (Acharya and Taylor, 2003).

Dental Identification Procedure Having ascertained the value of teeth in identification and the principle for the same, one can proceed with the procedure. Dental identification may be required in establishing the identity of a single person, a small group of individuals or in large fatalities such as accidental or natural disasters. The method for the different scenarios is essentially the same and is addressed together in the following columns although, considering the magnitude of the latter, the approach may vary. The identification procedure includes a number of steps, namely: 1. 2. 3. 4. 5.

On-site evidence recovery Postmortem dental examination and radiography Obtaining dental records Comparing post- and antemortem data Preparing the identification report and conclusion

On-site evidence recovery To begin with, it is essential to collect all dental evidence from the dead body (Haglund and Morton, 1994). This may require the dentist’s presence at the site where the dead body is recovered (Brown, 1984). Dental evidence present at the site where the body was found may be overlooked and not recovered—decomposition and skeletonization often leads to loosening of teeth and the anterior teeth, which have conical roots, may get dislodged. Oliveira and associates (2000) and Ðuric and coworkers (2004) have reported that incisors, especially maxillary, are most prone to getting lost postmortem. Incinerated bodies have fragile bones and teeth, which can easily be mishandled by an untrained individual; trauma may result in scattering of dental evidence around a large area. Acharya and Taylor (2003) have found that the inability to recover complete and intact postmortem dental data can undermine successful identification. Therefore, to maximize success, one must try to recover all dental evidence that may be present at the site. Hence, care must be taken to document and photograph the scene at which the body is recovered; a forensic odontologist should be present to ensure proper search and recovery of all material of dental significance needed for identification. Postmortem dental examination and radiography The postmortem dental examination is usually conducted in a mortuary. Case numbers allotted to the body should be verified and entered in the modified Interpol postmortem dental odontograph, also referred to as the ‘pink form’ (Figure 1) before the commencement of examination. A visual appraisal of the body may enable preliminary assessment of the ethnicity, gender and approximate age of the victim. The body bag used to transport the deceased should be thoroughly searched for dislodged teeth or dental appliances. Postmortem dental examination is similar to routine examination of the oral cavity. All oral and dental features, 655


Figure 1

Modified Interpol postmortem form

including intact and missing teeth, caries and other pathology, restorations, attrited and rotated teeth should be carefully charted on the postmortem form. This will be the basis for later comparison and verification. Brown (1984) suggests that postmortem examination should be undertaken by dentists working in pairs—one examining and the other recording. The roles are then reversed and the procedure repeated ‘as an added check’. Any dental evidence missing should be reported to the forensic pathologist or accompanying law enforcement personnel. Subsequent dental evidence recovered must be labeled properly. 656

The dental examination must be complemented with postmortem dental radiography as this will reveal what cannot be observed clinically. Radiographic films may be stabilized in the mouth using readily available materials such as gauze or cotton rolls. Whenever possible, postmortem radiographs should be taken to replicate the type and angle of the antemortem radiographs (Goldstein et al, 1998). According to these authors, if the difference in horizontal angulation between the ante- and postmortem radiographs is more than 10, comparison will not facilitate identification. However, changes in the vertical angulation or the focal point-film distance do not affect the outcome of comparison. Pretty and


Sweet (2001) have suggested that ante- and postmortem radiographs could be marked using a rubber-dam punch to differentiate the two—‘one hole for antemortem films and two holes for postmortem films’. The exposure time may need to be increased or decreased respectively in bloated bodies recovered following drowning and in skeletal remains.

Therefore, the authors examined whether radiographs with no restorations could be used in postmortem identification. Their results indicated that dental anatomy observable on the radiographs, especially ‘root morphology and alignment’, facilitated correct identification in more than 85% of cases.

Obtaining dental records

Identification report and conclusion

Dental records contain information on treatment and dental status of a person during life. These antemortem records can be obtained from the local dentist, specialist or hospital records. Whenever possible, the original records should be examined. Records include hand-written dental charts, radiographs, study casts and photographs. An individual may have visited more than one dentist for therapy and multiple dental records may exist. Relevant information from the dental records should be transcribed onto the modified Interpol antemortem odontograph (the ‘yellow form’) (Figure 2). Contribution of dental records in successful identification depends on the availability of original records, their completeness and quality (Acharya and Taylor, 2003). By maintaining good dental records, dentists reflect their awareness and responsibility to forensic identification (note: quality dental records are also important as a counter to malpractice lawsuits). It is also important that these records are relatively recent—records made for a 6-year-old child may not be useful 20 years later in adulthood.

Subject to the availability of adequate postmortem data and quality antemortem records, Haglund and Morton (1994) have stated that ‘the comparison and eventual dental identification are straightforward and routine’. These authors believe that the quality and quantity of information required for establishing positive dental identification has not been established. In fingerprinting, differences in the ante- and postmortem data rule out a positive match. This concept, however, does not apply to dental identification as long as the inconsistencies are explainable. For example, the postmortem data may reveal a restoration on a tooth but the dental records indicate that the same tooth is intact. This difference, however, can be explained since the restoration may have been placed on a date after the last available dental record. On the other hand, if the postmortem data shows an intact tooth but the same tooth is indicated as being restored in the dental record, this would probably suggest a mismatch. Having compared the ante- and postmortem data, one should address whether the similarities are significant and the differences can be explained. Based on this, a range of conclusions can be reached which have been modified below from McKenna (1986), Silverstein (1995) and Acharya and Taylor (2003).

Comparing the dental data The comparison of known antemortem data with the obtained postmortem data is called comparative identification. Sholl and Moody (2001) have stated that ‘the basic principle of any method of identification is to determine that individual characteristics observed postmortem are congruent with those known to have been present in life’. Once the postmortem findings and antemortem records are available, the data can be compared. Comparison should be qualitative rather than quantitative in nature; it must also be systematic and methodical. Features compared include dental restorations, pathology, crown, root and pulp anatomy, associated bony structures, artifacts and dental anomalies. An individual with multiple dental treatment and uncommon dental features has a better probability of being identified than someone with no extraordinary dental characteristics. Radiographic morphology in dental identification Presence of restorations are an important component of comparative dental identification. Sholl and Moody (2001) have suggested that the incidence of restorative work among younger age groups in Europe and North America appears to be declining, probably a long-term benefit of fluoridation and improved oral hygiene. Hence, there may be the necessity to rely on other features of the dentition.

Positive identification This indicates that the ante- and postmortem data match each other with no unexplainable differences. The identity is proven ‘beyond reasonable doubt’ and should include radiographic support. Probable identification The ante- and postmortem data have a high level of concordance but a lack of quality information precludes positive identification. Explainable differences may exist between the two sets of data and radiographic support is, usually, not available. Possible identification The ante- and postmortem data are in agreement but the available information is insufficient both in terms of quantity and quality. The available information neither permits a definitive identification nor enables the identity to be excluded. Insufficient evidence The available ante- and/or postmortem information are insufficient to form the basis for a conclusion. Excludes identity The ante- and postmortem data are clearly inconsistent; the data contain unexplainable differences that comprehensively indicate a mismatch. 657


Figure 2

Modified Interpol antemortem form

It is necessary for the forensic odontologist to be absolutely certain for an identification to be ‘positive’. One also needs to remember that any attempt at establishing identity is addressed to the legal authorities. Hence, the report and conclusion should be as definitive and clear as possible. Digital radiography in dental identification Traditional methods of radiography involve the use of film. The advent of digital radiography over the past decade, which replaces the radiographic film with an image capturing sensor, 658

presents certain advantages to forensic investigation. Since the images can be viewed immediately after exposure, the operator has the choice to either accept or reject the image depending on its quality. Further, postmortem images may be retaken to replicate the antemortem radiographic position and angulation. This could be particularly relevant in postmortem settings where access to radiographic processing may be unavailable or the ability to retake the radiographs of the decedent at a future date is unlikely.


Hanaoka and colleagues (2001) have successfully used the technology in postmortem dental identification and predicted its routine application in the future. They have stated that receiving, sending and storing digital radiographs through computer networks is effortless. According to Hubar and Carr (1999) and Du Chesne and associates (1999), the radiographic image may be enlarged, rotated and its brightness and contrast modified. Several images may be viewed together which allow convenient comparison of ante- and postmortem images. ‘Subtle features difficult to visualize on conventional radiographs such as trabecular bone patterns are seen with greater detail digitally and may further help to corroborate identification of a decedent’ (Hubar and Carr, 1999). However, manipulations which distort the structures visible on the radiograph by changing their angular relationship are not admissible by the courts of law (Du Chesne et al, 1999). Hence, these authors have stated that it must not be the objective of postmortem radiology to manipulate the images ‘to such an extent that optimal or even misleading results are presented’. While it is reasonable to expect forensic experts to avoid such alterations on postmortem radiographs, one cannot be so sure about antemortem digital images. Therefore, the conclusions based on comparison of post- and antemortem digital radiographs may be brought into question by the courts of law, which will probably give greater weight to documentary evidence such as conventional radiographic films than electronic data files.

CHALLENGES IN POSTMORTEM EXAMINATION Examining dental remains may be challenging in cases of rigor, incineration and other circumstances. Described below are some techniques to overcome difficulties, as well as precautions to be taken while using them.

Rigor Mortis Limited opening of the mouth due to severe postmortem rigor will affect dental examination since access to the oral cavity is limited and viewing the dentition is impaired. In such cases, where the muscles are extremely rigid, the mouth will have to be forced open. The use of trismus screws (made from acrylic) for obtaining initial opening in the anterior dentition followed by Fergusson or Heister mouth gags to increase jaw separation at the posterior region has proven useful in the author’s experience. However, one must be careful not to fracture the teeth. Nakayama and coworkers (2001) have advocated an intraoral approach for myotomy of the temporalis muscle. They contend that mouth opening demands relaxation of the temporalis and, hence, its myotomy will facilitate easy

dental examination. Their method prescribes an intraoral incision to expose the coronoid process followed by the insertion of a curved Cooper type scissors through the incision to dissect temporalis fibers that are inserted to the top of the coronoid process (Figure 3A, B). The deep fibers, which may also insert to the mandibular notch, are drawn forward with a channel retractor for dissection (Figure 3C, D). The myotomy is carried out on both the left and right sides.

Incineration Due to the fragility of dental tissues consequent to fire, it is essential to maintain their integrity during examination of charred human remains. According to Delattre (2000), ‘charred dental remains are by nature rather delicate’ and can crumble if not handled cautiously. The color of the teeth, apparently, gives an indication of its relative fragility— blackened teeth are less fragile than those that are ashen gray (the appearance of incinerated teeth is described later in this chapter). The lips and cheek may contract in prolonged or intense fire and withdraw exposing the anterior teeth. As a result, these teeth are the most exposed to fire and the enamel and dentin on their anterior surface can simply crack off when touched. To prevent the loss of tooth structure, Mincer and associates (1990) have listed a variety of materials that can stabilize incinerated teeth. They endorse clear acrylic spray paint and cyanoacrylate glue as the best agents since these are readily available, economical, portable, permeate the teeth well and set fast. However, in their study, not all specialists surveyed considered reinforcing incinerated teeth essential. Many felt problems could be circumvented by very careful handling of the teeth or photographing the teeth prior to handling. Intraoral radiography without jaw opening can be accomplished by removing the tongue through the floor of the mouth and inserting the films through the opening. This has been referred to as the ‘tunneling technique’ by Griffiths and Bellamy (1993), who have also suggested the use of material such as bubble plastic or a sheet of foam to protect the fragile skeletal and dental remains during transportation.

Jaw Resection Depending on the circumstances of death and condition of the body, the forensic dentist can decide to cut open the soft tissue of the cheek to reach the teeth, or remove the jaws entirely. Resected jaws are easier to examine and radiograph. However, such ‘invasive’ procedures can pose obstacles, especially when the body needs to be viewed by relatives. Furthermore ethical and legal hurdles may be faced. Therefore, one must consider jaw resection as a last option and obtain prior permission from the forensic pathologist. 659


Figure 3 A

B

C

D

(A, B) Intraoral approach for myotomy: when the temporalis is attached to the top of the coronoid process, myotomy is accomplished with scissors only; (C, D) in case the temporalis is attached both to the coronoid and mandibular notch, a channel retractor is inserted to draw forward the deep end of the muscle to facilitate dissection. (Reprinted from Nakayama Y, Aoki Y, Niitsu H, et al (2001), ‘Forced oral opening for cadavers with rigor mortis: two approaches for the myotomy on the temporal muscles’, Forensic Science International, Vol. 118, pp. 37–42, with permission from Elsevier)

Tooth Colored Restorations

Incinerated Teeth

Tooth colored restorations such as composites and glass ionomers may be missed during examination. These can be disclosed using dyes such as mercurochrome or tinted benzalkonium chloride, which are applied on the teeth with cotton swabs. However, using dyes may leave the oral cavity stained and messy (Clark and Meeks, 1989). Therefore, Carson and colleagues (1997) have suggested the use of commercially available alternative light sources. They discovered that tooth colored restorations are best revealed at wavelengths of 415–530 nm. This range of wavelength also revealed restorations when the teeth were burnt, although standard UV light (350 nm) may have more practical value in fire-damaged bodies.

The identification and recovery of burnt teeth subsequent to accidents, arson or terrorist activities—where human remains may only be recovered in parts—can assist in establishing the origin of the remains and help reconstruct the scene.

POSTMORTEM ALTERATIONS TO THE TEETH AND ORAL TISSUES While teeth are known for their relative postmortem stability, their appearance may be altered, and this can provide clues about the circumstances of death. 660

Crown Muller and associates (1998) have undertaken one of the few detailed works on changes that teeth undergo when exposed to high temperatures. They observed that enamel shows crazing (fine surface cracks) at 150C but retained its normal color although at 200C, enamel loses its gloss. Further increase in temperature causes more crazing— initially over the neck, then more coronally—followed by a few frank cracks. Initial separation of enamel from dentin occurs at 400C and the enamel shell separates totally at 450C. At 500C, Harsányi (1975) has observed deep longitudinal furrows on the crown which almost divide it into several pieces. At this temperature, the pulp chamber and root canal are preserved and not narrowed. Above 500C, the crown undergoes


fragmentation and consistently becomes smaller with further rise in temperature. The narrowed cavities of the pulp chamber and root canal are recognizable even at 1,100C. The coronal dentin is exposed at 450C (following total separation of the enamel shell). Cracks appear at 600C with disintegration from 800C onward. While enamel is converted to powder, dentin is not. This has been attributed to hypermineralized pretubular zone of the dentin. Myers and colleagues (1999) believe that the mineral content of dentin, located within its organic matrix composed of type I collagen, helps stabilize the collagen against thermal denaturation and shrinkage. The color changes in the crown and root at different temperatures has been demonstrated by Muller and associates (1998) (Table 1). However, these authors have cautioned that in real-life scenarios, it may be much more difficult to observe the color changes since teeth found at the site of fire need to be carefully cleaned. They added that ‘the presence of a superficial metallic layer,

resulting from the dry distillation of organic matter, can lead to observational errors’. Root The root shows a light yellow color at 150C and exhibits a calcinated appearance at 300–400C when exposed directly without protection of the alveolar bone. Further rise in temperature displays crazing of the coronal one-third of the root. This progresses to the apical part at a temperature beyond 800C and the root begins to fragment at 900C.

Root

Off-white to light yellow

200

Crown

Dull, light brown surface

300

Crown

Light brown to grayish with dark brown spots

Root

Black

Crown

Dark brown/gray

Root

Shiny black

Crown

Enamel is dark brown or gray; dentin is gray

Root

Gray/brown

Effects of temperature on restorative materials Like teeth, restorative materials used in treatment are equally resistant to the effects of high temperature. According to Rossouw and associates (1999), composites, compomers and glass ionomers can withstand 250–500C for a short time but, beyond 5 minutes their compressive strength is reduced to almost zero. Hence, they need to be handled very carefully. Compomers (14.3%) and glass ionomers (18.6%) have higher volume shrinkage when compared to composites (6–10%). This means that the former restorative materials may get dislodged, especially from the buccal and lingual preparations. Most tooth colored restorative materials turn grayish-black at the aforementioned temperatures. Their change in color means that it is difficult to spot them visually. However, the radiodensity is not altered and, therefore, they can be viewed on radiographs. Metallic restorative materials melt and distort at different temperatures: gold alloys melt at 915–1,090C; silver amalgam’s range depends on the mercury content (some amalgams may resist up to 870C). Porcelain denture teeth have been cited as resisting temperatures as high as 900C (Taylor et al, 2002); however, acrylic denture material depolymerizes to monomer at 450C.

Crown

Dark gray enamel and blue-tinted gray dentin

Postmortem Pink Teeth

Root

Blue-tinted gray with white spots

Crown

Dark gray enamel and blue-tinted white dentin; the cusp tips are blue

Root

Blue-tinted white or white only

Crown

Dark gray enamel with white spots; white dentin

Root

White with gray spots

Crown

White dentin

Root

White with dark gray or black spots at CEJ

Crown

White dentin

Root

White with pink tinge at apex

Crown

Chalky white

Root

Chalky white

Crown

Chalky white

Root

Chalky white

Table 1 Color changes in burned teeth Temperature (C) 150

400 500

600

700

800

900 1,000 1,100 1,150

Appearance Crown

Normal color and shiny appearance

Source: Modified from Muller and associates (1998).

Pink colored teeth are encountered on occasions during postmortem dental examinations. This intrinsic pigmentation is believed to be associated with victims of sudden death (Padayachee, 1988). Van Wyk (1989) cites a number of studies which suggest that the phenomenon requires increased blood supply to the pulp. This may be the result of raised venous pressure caused by an event such as strangulation (Whittaker et al, 1976) although van Wyk (1988) could not correlate the cause of death or the time since death to the presence of pink teeth. Padayachee (1988) has stated that pink teeth show ‘conspicuous bleeding in the dental pulp and the resultant pigmentation is thought to be due to an increased pressure in the pulpal circulation’. The phenomenon of postmortem pink teeth is believed to be analogous to postmortem lividity produced by the flow of blood into a dependent part of the body after death (Whittaker et al, 1976; van Wyk, 1987). According to van Wyk (1988), the blood vessels in the 661


pulp become distended due to pooling of blood. The red cells undergo hemolysis followed by autolysis of the blood vessel walls and release of pigment in solution which diffuses into the dentinal tubules. The degree of dentinal staining varies and van Wyk (1988) concludes that teeth appear pink clinically only when the dentin is stained extensively. The pigment responsible for the pink discoloration is undegraded hemoglobin (van Wyk, 1989).

Tongue Hemorrhage Hemorrhage of the tongue can be observed associated with strangulation deaths. Bockholdt and Maxeiner (2002) consider tongue hemorrhage to be the result of either cranial congestion, compression by the dental arches or the hyoid bone pressing onto the base of the tongue following neck compression. These authors have reported tongue hemorrhage in 71% of homicidal strangulations, 19% of which were the result of biting caused by compression of the tongue between the teeth. However, tongue injury was observed in only 5% of suicidal strangulations. A protruded tongue, compressed between the jaws, is observed in a significant number of suicidal hangings although the number of grossly visible tongue bites with hemorrhages is small; a similar small number of internal hemorrhages ‘restricted to the tip or anterior part of the tongue (development during a protrusion of the tongue in the course of the hanging agony)’ are evident. However, extensive internal hemorrhages in suicidal strangulations should be treated with some degree of caution—Bockholdt and Maxeiner (2002) have cited reports of internal tongue hemorrhage in victims who were first strangulated and then hung by the killer (‘simulated suicide’), i.e. extensive internal tongue hemorrhage could indicate a presumed sucide as being a homicide. But they may also be the result of highly atypical suicidal strangulation.

SOCIAL PROFILING According to van Wyk (1976), information about habits and occupational antecedents can be obtained from the dentition. This can provide valuable information on the person’s social background and prove useful in identification. Based on personal observation and epidemiological studies, van Wyk (1976) categorized such features as: (i) lesions of the teeth only, (ii) lesions of the teeth and soft tissues, and (iii) lesions of the soft tissues only. This section, however, will emphasize on the lesions of the teeth, since they are more likely to survive postmortem vagaries than soft tissues. According to Gustafson (1966), grooving of the upper anterior teeth may be encountered in cobblers, carpenters and electricians. Such a groove commonly results from the habit of opening hairpins with an upper central incisor— the constant abrasion of the metal pin against the tooth edge eventually leaves a shallow groove. Among pipe 662

smokers, a typical elliptical type of attrition of the anterior teeth corresponding to the pipe stem is visible. In musicians also, specific form of attrition on the anterior teeth caused by a musical instrument’s mouthpiece can be seen. Padayachee (1988) has highlighted certain forms of occupational staining, e.g. extrinsic staining in industrial workers has been attributed to exposure to metals and their salts. He also cited black/gray pigmentation of teeth in anemics taking liquid iron supplements. Sociocultural practices such as betel nut chewing prevalent in India also result in characteristic brown deposits on the teeth (Padayachee, 1988). On the other hand, van Wyk (1976) draws attention to an unusual sociocultural custom among a particular group of people from South Africa—the deliberate extraction of the maxillary incisors, especially in females, to facilitate oral sex. Probably more unusual is a purported case of selfextraction of the teeth among drug abusers reported by Pretty and Hall (2004). These authors have suggested that ‘dentists should consider self-injury as an explanation for intra- and peri-oral injuries of unknown origin’. They add that the presence of extraction sockets due to self-mutilation could be a finding in mentally imbalanced individuals or among those with an altered state of mind resulting from drug abuse. Bécart and coworkers (1997) have reported that heroin users have a greater incidence of decayed teeth, especially atypical carious lesions on the labial/buccal surfaces. These lesions may appear larger, darker and less painful than usual cervical caries, convincing some authors to consider them as a pathognomonic sign of drug addicts (Lowenthal, 1967; Colon, 1972). Pretty and Sweet (2001) cited a number of studies that also indicate the presence of dental erosions in drug abusers and alcoholics. Cattaneo and coworkers (2003) have detected morphine and codeine in the teeth of skeletal remains found 2 years after death. They believes that such findings suggest—but do not prove—a drug related death. This not only throws light on the social antecedents of the unidentified individual but also gives clues to the circumstances surrounding the death (e.g. drug overdose).

IDENTIFYING THE EDENTULOUS Borrman and coworkers (1999) have cited studies that project an increase in the percentage of elderly around the world in the coming decades. While the percentage of edentulousness among this group may decrease, the number of edentate individuals may actually remain the same or even increase. From a forensic odontology point of view, problems arise when attempting to identify edentulous cases. The absence of a ‘dental combination’ may render conventional comparative identification of little use. In fact, it is believed that most problems in postmortem identification are encountered in complete denture cases (Gustafson, 1966). The denture, however,


can be a crucial piece of evidence in identifying the edentulous as they remain intact or only slightly damaged following traumatic accidents. Dentures may have been fabricated to replicate an individual’s dentition. For example, Taylor and coworkers (2002) were able to positively identify an individual based on, among other evidences, distinct features of a maxillary denture which contained a midline diastema and gold inlays on two of the teeth (Figure 4). In addition, the type, size and shape of teeth used in the denture can be used for identification. This, however, warrants detailed dental records. Therefore, use of denture-marking systems may be more practical; comparison of palatal rugae may also hold some use. Figure 4

Characteristic features in a maxillary denture. (Reprinted from Taylor PTG, Wilson ME, Lyons TJ (2002), ‘Forensic odontology lessons: multishooting incident at Port Arthur, Tasmania‘, Forensic Science International, Vol. 130, pp. 174–82, with permission from Elsevier)

Denture Marking Systems A widely recommended technique for identifying the edentulous is to mark dentures with the individual’s name and/or a personal number. Markers such as printed onion skin paper and adhesive labels, electronically inscribed clear laminated tape, photochemically etched ‘microchips’ (Figure 5) or typewriter-punched stainless steel bands ‘can be placed either in the tissue surface during trial packing or in the polished surface after processing’ (Borrman et al, 1999). The materials and the mode of imprint should be strong enough and preferably resistant to high temperatures expected in a fire. Moreover the marker should not compromise the denture strength. However, these forms of markings—where identity can be revealed easily and publicly—may raise privacy issues. Hence, Rötzscher and associates (1999) have suggested ‘writing’ and ‘reading’ personal data on a microchip by means of a handheld electronic scanner. This personal information pertaining to the individual cannot be directly viewed but may be accessed using specific computer hardware and software. Issues of privacy notwithstanding, marking a denture enables a simple mean to identification when other methods are unavailable. However, Borrman and coworkers (1997) highlighted that the ‘denture per se does not prove identity since it is not a fixed appliance but it is a significant link in a chain of evidence of personal identity’.

Palatal Rugae in Identification Since denture marking is still an uncommon practice, alternatives for identifying the edentulous need to be explored. The use of palatal rugae pattern could prove useful for this purpose. The rugae on the maxilla or maxillary

Figure 5 A

B

Denture marking ‘microchip’ with inscription (A) and the ‘microchip’ incorporated in a maxillary denture (B). (Reprinted from Rajan M, Julian R (2002), ‘A new method of marking dentures using microchips’, Journal of Forensic Odonto-Stomatology, Vol. 20, No. 1, pp. 1–5, with permission from authors)

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denture of the deceased can be compared to previous dentures recovered from the decedent’s home, or plaster models that may be available with the dentist or laboratory technician. Palatal rugae are well protected by the orofacial tissues in fires and traumatic accidents. In a recent pilot study, Muthu, Subramanian and colleagues (2005) have found that rugae were unaltered in 93% of victims of third-degree burns; they also discovered that the rugae withstood decomposition and were recognizable in more than 80% of the cases. Furthermore, rugae patterns are unique to an individual and can be used in identification— Limson and Julian’s study (2004), which obtained highpercentage accuracy in identifying individuals in a simulated ante- and postmortem comparison of the palatal rugae, bears reasonable testimony to this premise. These authors employed a software—RUG FP-ID Match—for the comparison. First, rugae outlines on the casts were demarcated using a graphite pencil and photographed. The image was transferred to a computer where the medial and lateral ends of the rugae were marked manually (Figure 6). Based on the principle commonly employed in fingerprint analysis, the software compared the marked points between ante- and postmortem cast images to ascertain a match.

CRANIOFACIAL IDENTIFICATION In cases where comparative dental identification is not possible due to reasons such as unavailability of dental Figure 6

records or unidentified skeletal remains, craniofacial methods of identification may be applied. The utility of these methods is variable and may result in establishing the identity of the deceased or providing broad clues.

Cranial Suture Pattern The cranial sutures are seam-like joints of bone exclusive to the skull. As the cranial bones grow and meet, the margins become highly complex and irregular. In a study of ectocranial suture patterns on 320 skulls, Sekharan (1985) observed that their configuration differed in every individual (Figure 7), including twins. He categorized the suture patterns into serrated (saw-like junctions), denticulate (characterized by small tooth-like projections), squamous, limbous and plane types. For example, the sagittal, lambdoid and coronal sutures on the cranial vault can be divided into a number of subdivisions and within these subdivisions one may appreciate serrations and denticulations. Therefore, the patterns produced by cranial sutures are highly variable and individualistic and may be used in identification. To accomplish this, however, antemortem radiographs of the lateral and anteroposterior view (preferably Townes’ view) should be available. Sekharan (1985) observed that the suture patterns, which are visible in the majority of such radiographs, can be compared with sutures on forensic skull specimens in situ. Alternatively, he suggests taking postmortem radiographs and comparing the suture pattern on these to those on the antemortem radiograph. However, the cranial vault reaches adult dimensions at about 7 years of age. Therefore, one needs to be cautious while comparing postmortem radiographs of an adult to those taken during childhood. Recently, Rogers and Allard (2004) have pointed to the success of viewing sutures on computerized tomography (CT) scans and recommend this technology over conventional radiography.

Frontal Sinus Configuration

Characteristic points are plotted manually on the rugae pattern image. (Reprinted from Limson KS, Julian R (2004), ‘Computerized recording of the palatal rugae pattern and an evaluation of its application in forensic identification‘, Journal of Forensic Odonto-Stomatology, Vol. 22, No. 1, pp. 1–4, with permission from authors)

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The frontal sinuses are irregular shaped, pneumatic cavities located along the inferior aspect of the frontal bone, deep to the superciliary arches (Harris et al, 1987). Although absent or insignificant at birth, it increases in size and complexity with age and attains maximum size by about 20 years (Schuller, 1943). In fact, Schuller (1943) is attributed having stated that the radiographic appearance of these sinuses show individual variation. In a pilot study, Harris and associates (1987) have also observed that ‘no two frontal sinuses were alike’ in terms of height, width and number of edge loculations, but Schuller (1943) has warned that certain diseases and disorders may alter the size and shape of the sinuses. For example, acromegaly renders the sinuses extremely large while sinusitis can also cause some changes. Moreover, the sinus walls become thinner in old age and look larger (Nambiar et al, 1999), although these changes are minor (Kullman et al, 1990).


Figure 7 A

B

C

D

Cranial suture pattern of different skulls. (Reprinted from Sekharan PC (1985), ‘Identification of skulls from its suture pattern‘, Forensic Science International, Vol. 27, No. 3, pp. 205–14, with permission from Elsevier)

The radiograph which best reveals frontal sinuses is the anteroposterior view (especially occipitomental view), a record which may be available on occasion. Depending on the condition of the postmortem remains, radiographs from ‘several views with different angulations and densities’ may need to be taken for proper comparison with antemortem radiographs (Nambiar et al, 1999). Schuller (1943) attempted to describe frontal sinus configuration and defined seven characteristics: 1. 2. 3. 4. 5. 6. 7.

Septum and its deviation Upper border (scallop, arcades) Partial septum Ethmoidal and supraorbital extensions Height from planum Total breadth Position of sinus midline.

Yoshino and coworkers (1987) have provided a simpler classification of the frontal sinuses based on the size,

shape, symmetry and septa. However, these categories may hold little practical value since investigators resort to simple visual comparison of radiographs placed side-byside or superimposed. Harris and associates (1987) have suggested tracing the sinus outlines visible on radiographs onto orthodontic tracing paper for comparison although, Kullman and coworkers (1990) obtained near 100% accuracy in a study that compared simulated ante- and postmortem radiographs per se. The latter also state that successful comparison is not influenced by the experience of the observer. The frontal sinuses have been used to establish identity in numerous cases and it has seen an increase in its use and acceptance among forensic anthropologists and radiologists (Christensen, 2004). However, successful identification using frontal sinuses is contingent to standard methods of comparison including uniform angulation and orientation of radiographs taken ante- and postmortem and substantial empirical evidence pertaining to their uniqueness. 665


Skull-Photograph Superimposition Superimposing the facial photograph (of the suspected deceased) and skull was first successfully put to use in a criminal case by Glaister and Brash (1937). They superimposed antemortem photographic negatives of the heads of two homicide victims to the respective postmortem skull radiographs and obtained positive identification. Since the anterior dentition may be visible on many personal photographs, the use of tooth size, shape, angulations may be of particular relevance in superimposition. However, adjustments need to be made to orient the ante- and postmortem images. It is advisable to use superimposition as a corroborative tool, rather than the sole method, for identification. Actually, it may have more value in exclusion rather than identification per se. Nevertheless, it gains prominence in the Indian context since research and case work have been reported on a regular basis. The infrequent availability of quality dental records has probably encouraged its use in forensic identification. It includes photographic superimposition, video superimposition and newer digital techniques.

❍

Camera-object distance: Differences in the focal lengths of camera lens can alter the contour of high-curvature areas on the face ❍ Scaling factors: Appropriate magnification of the photograph may be essential to obtain equivalence in size vis-à-vis skull specimen. Figure 8

Photographic superimposition The conventional superimposition method, photographic superimposition utilizes antemortem photographs, radiographs or portraits (Nickerson et al, 1991) for comparison with the skull specimen at hand. The skull is photographed and its tracing laid over that of the antemortem photograph. The superimposed images are carefully studied to determine how closely the skull and face fit each other. The general size and shape of the skull and bony landmarks such as the orbits, nasal cavity, dentition, etc. are used to indicate the proximity of the fit. The facial soft tissue thickness should also be considered during superimposition. Recently, Bilge and coworkers (2003) have reported a case where identification was established by superimposing a photograph of an unidentified skull with the antemortem photograph (Figure 8) using commercially available software such as Adobe Photoshop. They state that ‘the photo-to-photo superimposition technique is quite a supportive system for positive identification, especially when the questioned person displays uncommon features, and good quality photographs are achieved’. As an aid to enhance the success of photographic superimposition, Jayaprakash and colleagues (2001) have suggested that the skull surface details be studied carefully and correlated to that of the face photograph before drawing a conclusion. The similarity between the dry skulls and photographs with respect to, for example, the frontal eminence or nasal bone morphology (Figures 9 and 10) can be correlated adding due weight to the superimposition. Nevertheless, a number of practical problems may undermine the outcome of photographic superimposition: ❍

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Angular positioning: The skull and the facial image should have reasonably equal horizontal and vertical angulations

Superimposition of the putative deceased’s photograph and skull. (Reprinted from Bilge Y, Kedici PS, Alakoç YD, et al (2003), ‘The identification of a dismembered human body: a multidisciplinary approach‘. Forensic Science International, Vol. 137, No. 2–3, pp. 141–6, with permission from Elsevier)

Figure 9 A

B

(A) Broad and raised nasal ridge and nasomaxillary notches in a male skull and (B) the nasal morphology in the corresponding face photograph. (Reprinted from Jayaprakash PT, Srinivasan GJ, Amravaneswaran MG (2001), ‘Cranio-facial morphoanalysis: a new method for enhancing reliability while identifying skulls by photo superimposition‘, Forensic Science International, Vol. 117, pp. 121–43, with permission from Elsevier)


Figure 10 A

B

image and anatomical landmarks such as the glabella, nasion, ectocanthion and maxillary dentition compared to determine the fit of the images. The authors claim ‘gains in terms of image restoration and enhancement and nearoptimal superimposition’ as potential advantages of this technique.

Challenges in Superimposition

(A) Narrow, prominent and wavy nasal ridge, conspicuous nasomaxillary notches and asymmetric bulge in the lateral aspects of the nasal ridge in a male skull and (B) the nasal morphology in the corresponding face photograph. (Reprinted from Jayaprakash PT, Srinivasan GJ, Amravaneswaran MG (2001), ‘Cranio-facial morphoanalysis: a new method for enhancing reliability while identifying skulls by photo superimposition‘, Forensic Science International, Vol. 117, pp. 121–43, with permission from Elsevier)

One of the challenges to proper superimposition is to obtain life-sized enlargement of the photograph to the corresponding skull. The presence of an object of known size on the photograph is helpful in reaching this end. However, in its absence, a number of reference points have been suggested. Sekharan (1971) has recommended measuring the distance between various anatomical landmarks (gonion, nasion, menton, etc.) independently on the skull and photograph. Their ratio are calculated and compared between the skull and photograph for concordance. However, the use of teeth to achieve life-sized enlargement may be more reliable. Teeth are the only craniofacial components visible clinically during life and may be evident on antemortem photographs where the subject is smiling. Hence, dental features on the photograph, such as the outlines of teeth or intercanine width, can be compared to the same on the skull to obtain a 1:1 magnification (McKenna et al, 1984).

Video superimposition The advent of videography led to improvements in conventional still photography superimposition. Video superimposition usually makes use of two video cameras, one focussing on the skull and another on the antemortem photograph. The resulting images are ‘mixed into one composite image’ (Nickerson et al, 1991) using image mixing devices. The advantage of video superimposition over photographic superimposition is that the skull can be placed on a flexible mounting device and its angular position and distance from the camera adjusted according to the position of face on the photograph. In addition, image mixers enable added advantage of fade-in and fade-out, and vertical and horizontal ‘sweep’ mechanisms. This allows different images to be progressively superimposed upon each other.

FACIAL APPROXIMATION

Three-Dimensional Digital Superimposition

According to Phillips and coworkers (1996), facial approximation is a combination of art and science in which a 3D representation of the facial features is produced using the skull as foundation. These authors have described the following steps to manually approximate a face: first, one needs to make an assessment of the ethnicity, sex and age using the skull bones and teeth. This information can add value to, and assist in, the approximation. The mandible is articulated with the skull and jaws and the soft tissue profile is drawn around the underlying bone using average facial tissue thickness; the nasal profile can be constructed

The use of three-dimensional (3D) superimposition imaging techniques has been suggested by Nickerson and coworkers (1991). The antemortem photograph is digitized to produce a two-dimensional (2D) image whereas the skull is laser-scanned to produce a 3D image. The 2D digitized facial image is mapped onto a polygon—a process known as texture mapping. The texture-mapped image can be manipulated as easily as the 3D skull model. This texture-mapped image is then projected onto the 3D skull

When virtually no information is available on the identity of skeletal remains, an attempt at ‘reconstructing’ the face from the skull may be considered. Since such a reconstruction usually results in an approximate reproduction of the target face, the term ‘facial approximation’ is believed to be more appropriate. Facial approximation is used as a technique of last resort for identifying individuals in forensic cases. It can involve 2D sketches using the artist’s perception or, as described in the next section, 3D methods which use clay modeling techniques and computer-generated images.

Clay Modeling

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at this stage using a cephalograph. The skull cavities (orbits, nasal fossa, etc.) are blocked with modeling wax and an impression of the entire skull is made using rubber-base impression material. The cast is poured in plaster and reference points marked on it; shallow holes are then drilled at these points. Thin dowel sticks are placed in the holes to indicate the thickness of facial tissues at these points. The muscles of facial expression and mastication are reproduced on the plaster cast using modeling clay. Once the basic face is sculpted, finishing touches such as wrinkles, hair pattern, eyes, etc. are added. The authors claim that artistic creativity developed during the method may result in a more life-like reproduction of the face. However, the method has a variable success rate, is subjective and, at best, merely replicates ‘certain facial features which may be characteristic’ (Phillips et al, 1996).

Computer-assisted Approximation Vanezis and associates (2000) have developed a computerassisted 3D facial approximation technique. To begin with, the defects and natural orifices of the skull are covered with cotton and the skull placed on a turn-table. The table is rotated 360 and scanned under a low-intensity laser beam. This results in the production of 200–250 skull profiles which are fed to a computer system to enable viewing of a 3D skull image (viewing is achieved by means of a ‘Facial Reconstruction’ software). The same software is then used to mark landmarks on the skull image at which the facial depth has been previously determined (Figure 11). From a database of facial templates, a face is chosen which has average features and matches the skull anthropologically; landmarks corresponding in location to those of the skull are placed on the face (Figure 12). The facial template is then carefully placed on the skull image so that

the landmarks of the face lie on top of those of the skull; soft tissue thickness is selected to give the face a thin, medium or fat appearance. The computer is now ready to fit the face over the skull which is achieved using a 3D transformation termed ‘warp’, resulting in an approximated face (Figure 13). A limitation of this method is that it relies on the operator’s ability to select the ‘average’ facial template—a procedure that may be inaccurate and prone to bias. To overcome this, Claes and associates (2006) have recently developed a facial template that is based on the features of 118 individuals. This would be a more realistic average, although the database could be further expanded. Certain advantages of the computerbased approximation over clay modeling include: ❍

A plaster cast of the skull need not be prepared. Therefore, it circumvents potential damage to the skull arising from impression making (Vanezis et al, 2000). ❍ Faster, easier and more efficient generation of approximations (Vandermeulen et al, 2006). ❍ Superimposition of the skull and approximated face allows the operator to assess soft tissue to skull alignment and check for any obvious errors (Vanezis et al, 2000). ❍ Multiple approximations, that can take into account differences in facial appearance due to subject-specific attributes such as race, gender, age and body mass index, is possible (Claes et al, 2006; Vandermeulen et al, 2006). Facial approximation is by no means a definitive form of identification, rather a means to it. It can be difficult to obtain facial models which reflect the exact likeness of a missing person. However, an image approximated may be published or broadcast in the media to revive the public’s memory about a victim and obtain further leads. As Vanezis and associates (2000) point out, the purpose of

Figure 11 A

B

C

Views of digitized image of the skull with landmarks in position. (Reprinted from Vanezis P, Vanezis M, McCombe G, et al (2000), ‘Facial reconstruction using 3D computer graphics‘, Forensic Science International, Vol. 108, pp. 81–95, with permission from Elsevier)

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Figure 12 A

B

C

Anthropologically matching facial template with landmarks in position. (Reprinted from Vanezis P, Vanezis M, McCombe G, et al (2000), ‘Facial reconstruction using 3D computer graphics‘, Forensic Science International, Vol. 108, pp. 81–95, with permission from Elsevier)

Figure 13 A

B

C

The facial template has been ‘warped’ on the skull-image to produce an approximated face. (Reprinted from Vanezis P, Vanezis M, McCombe G, et al (2000), ‘Facial reconstruction using 3D computer graphics‘, Forensic Science International, Vol. 108, pp. 81–95, with permission from Elsevier)

facial approximation is ‘to trigger the recognition process to see whether a name can be put to a face. Once this is achieved, one can proceed to a more definitive identification using comparative antemortem data’.

histologic age has been presented elsewhere (Acharya and Sivapathasundharam, 2006). In this chapter, a few clinical and radiographic methods for dental age estimation are described.

Clinical Methods of Age Assessment

AGE ESTIMATION METHODS . Krogman and Is¸can (1986) considered age, sex, population affinity and stature to be the four essential parameters in identification of the deceased when no clue is available. The dentition can reveal the first three of these parameters. An overview of estimating sex, ethnicity and

Estimating age by observing the teeth clinically is a convenient and economical method. In clinical set-ups, the age of children is routinely estimated by examining the type of tooth that has emerged into the oral cavity although, this method falls short of scientific credibility. A more objective ‘clinical count’ of the number of erupted teeth has also been developed for assessing age in young 669


individuals (Foti et al, 2003), which is described later. In adults, however, where all the teeth have emerged other parameters, such as dental attrition, may be utilized. Dental attrition According to Solheim (1988), dental attrition has been used to assess age in archeological and forensic contexts. An advantage of using attrition in age estimation is that it is one of the few regressive changes of the teeth that can be clinically examined. However, the degree of attrition in modern humans may have reduced as a result of diet that comprises processed food. Moreover, attrition can be aggravated in certain pathological conditions such as bruxism. Solheim (1988) assessed attrition in different types of teeth by measuring the surface area, length of the crown and certain other criteria, and observed a weak correlation with age. He further developed multiple regression formulas which showed that attrition may best be applied for age assessment using the premolars. However, the author adds that age estimates from attrition should be based on examination of several teeth or the entire dentition.

Table 2

Tooth-calcification stages and their coded symbols

Stage

Coded symbol

Initial cusp formation

Ci

Coalescence of cusps

Cco

Cusp outline complete

Coc

Crown 1/2 complete

Cr½

Crown 3/4 complete

Cr¾

Crown complete

Crc

Initial root formation

Ri

Initial cleft formation

Cli

Root length 1/4 complete

R¼


R½


R¾

Root length complete

Rc

Apex 1/2 closed

A½

Apex completely closed

Ac

Source: Modified from Moorrees et al (1963).

Demirjian’s method

Radiographic Methods for Age Assessment Gleiser and Hunt (1955) first stated that ‘the calcification of a tooth may be a more meaningful indication of somatic maturation than is its clinical emergence’. Calcification is a continuous process which can be assessed from radiographs. This relies on stages of tooth formation ranging from the actual formation of crypt to the fully mature tooth. There is a continuous change in the shape and size of the teeth with each tooth following the same sequence. The radiographic appearance of the teeth may be used for age estimation even after tooth development is complete, e.g. deposition of secondary dentin can be viewed indirectly in terms of the size of the pulp chamber.

Estimating Age in Children and Adolescents Moorrees’ method Moorrees and colleagues (1963) categorized permanent tooth calcification into 14 stages (Table 2). The developing tooth is compared to a chart and an appropriate development stage assigned. The selected stage is compared to chronological age-conversion charts. The charts are composed of segments, one for a specific tooth, in which the chronology of its development is recorded graphically by horizontal bars for each stage. On the horizontal bar, the mean age of attainment of that stage and the range (1 and 2 SD) are indicated. A scale is provided at the top and bottom of the chart for indicating chronological age. The assessment of tooth formation is recorded by ticking the appropriate stage for a particular tooth. 670

Demirjian and coworkers (1973, 1976) developed a method of age estimation which, over the years, has become the most widely used technique to assess age from the dentition of children and adolescents. The method utilized seven permanent mandibular teeth on the left side (incisor to second molar) and did not make use of the third molar. Consequently, it was not applicable to individuals older than 16 years (since the second molar is fully developed by this age). A recent modification of the method (Chaillet and Demirjian, 2004) incorporated the third molars allowing its application to just over 18 years of age. In addition, the development of each tooth was divided into 10 stages, instead of the original eight. These stages were numbered ‘0’ (no visible tooth calcification) to ‘9’ (complete closure of the root apex). Each of the eight teeth on the radiograph is compared to a chart that contains a diagrammatic representation of the 10 stages and assigned an appropriate developmental stage (any one of 0–9). Next, corresponding to the developmental stage, a ‘maturity score’ is allotted to each tooth. The maturity score assigned for the eight teeth are added and a ‘total maturity score’ obtained. The total maturity score (S) is substituted in regression formulas and the chronological age derived. Owing to differences in dental development in males and females, different formulas for age estimation were developed. In females the formula used is: Age (0.0000615 S3) – (0.0106 S2)(0.6997 S) – 9.3178 In males, the formula used is: Age (0.000055 S3) – (0.0095 S2)(0.6479 S) – 8.4583


The estimated age should accommodate an age range of 2.65 years for females and 2.28 years for males. While the method is convenient to use and applied extensively, it has a few limitations:

Demirjian’s 8-teeth method was recently tested on an Indian sample (n 100) by Rimal and Sumanth (2006) who revealed that the method underestimated age by 1.14 0.34 years. This reinforces long-held observations that the accuracy of the method varies from one population to another, possibly due to regional variations in tooth development. Demirjian’s method was developed on children of French ancestry and will need local modifications on large samples if it is to be reasonably reliable in the population to be tested.

respects and not an ideal development marker however, in the absence of other biological indicators of age in the lateteens and early adulthood, they are used to estimate age (Mincer et al, 1993). Arany and associates (2004) have adapted Demirjian’s developmental stages exclusively to the third molar and assessed if its calcification can be used to estimate ages with legal implications (e.g. 14, 16 and 18 years). They calculated a ~97% probability that an individual is at least 14 year old if the root length crown height (Demirjian’s ‘Stage 7’); ~93% probability of 16-years if the root development is complete but apex patent (Demirjian’s ‘Stage 8’); and ~98% probability of 18-years if the root apex is closed (Demirjian’s ‘Stage 9’). The latter has important implications in India and other countries since 18 years is the age of majority, and the consequent change in legal outlook toward a person’s rights and actions. Interestingly, third molar develops faster in males, which is in contrast to the earlier development of all other teeth in females. One must remember that the probabilities described above are based on a study on the Japanese and can vary in different populations.

Open apices method

A Combined Clinical and Radiographic Method

❍

If a tooth is missing, the method may not be used (unless the tooth is present on the right side). ❍ The 10 developmental stages may not describe the entire gamut of stages of tooth development. ❍ Choosing a tooth developmental stage may have inherent subjectivity.

A recent age estimation method suggests measuring the open apices of developing permanent teeth (Cameriere et al, 2006). This method also examined seven mandibular teeth on the left side, probably to test its effectiveness in age assessment vis-à-vis Demirjian’s original method (1973, 1976). For assessing age, orthopantomographs are digitized using a flat-bed scanner and the images measured with the aid of the software Adobe Photoshop. Since measurements of the open apexes may be influenced by factors such as radiographic magnification and angulation errors, the ratio of each tooth apex in terms of the respective tooth length was obtained. A multiple linear regression equation was developed from these ratio which estimated age, on the average, to within 0.04 years of the actual age. The highprecision level in age estimation has been verified by Rimal and Sumanth (2006) in an Indian sample where, chronological age was marginally underestimated (0.32 years). Accuracy of the method notwithstanding, the relative effort involved in measuring the apices and tooth length may preclude its widespread use, and it is unlikely to replace the acceptance enjoyed by Demirjian’s method in the near future.

Third Molars in Age Estimation With the completion of development of all teeth by about 16 years, the third molars remain the only tooth that continues to develop. Consequently, radiographic evaluation of third molars is one of the two parameters for age estimation in adolescents and young adults (Arany et al, 2004), the other being morphological examination of skeletal features. The third molar is the most variable tooth in many

To facilitate clinical age assessment, Foti and coworkers (2003) have suggested a method which utilizes the number of erupted teeth. In addition, they also give provision for using tooth calcification visible on radiographs. Using multiple regression analysis, they presented formulas for age estimation for different clinical and forensic scenarios. For example, when the teeth are visible clinically as well as radiographs are available for observing the calcifying tooth germs, the following formula is recommended: Age 16.088 (0.226 number of erupted permanent upper 1st molars) (1.564 number of erupted permanent upper 2nd molars) (0.832 number of erupted upper 3rd molars) (0.912 number of erupted lower 3rd molars) (1.699 number of tooth germs on radiographs excluding 3rd molar germs). There may be instances when partial skeletal remains, e.g. only the mandible, are recovered and one may need to estimate the age based solely on clinically visible teeth. The formula for estimating age from a mandible in such a scenario is: Age 9.726 (0.571 number of erupted deciduous lower incisors) (0.378 number of erupted permanent lower canines) (0.579 number of erupted lower premolars) (1.056 number of erupted permanent lower 2nd molars) (2.236 number of erupted lower 3rd molars). Using this method, the authors claim reasonable accuracy in age estimation comparable to those obtained with Demirjian’s method. While the technique is promising, 671


it is as yet untested and needs to be validated on diverse populations. The accuracy of dental aging is not uniform from birth to maturity. Age estimation in younger ages tends to be more accurate since more teeth are calcifying and the intervals between morphologic stages are shorter and more precise; in older children, ‘the biological variation increases considerably’ (Hägg and Matsson, 1985). These authors have reported an age range of 12 months in younger children while the same increases to 20 months in older children. Moreover, the diversity in the rate of dental development among children and adolescents of different populations undermines accuracy of the preceding age estimation methods. Development of population-based dental development standards could render the age estimates more acceptable.

Figure 14 T P

A

R

B

C

Estimating Age in Adults In adults, the teeth are completely developed and one cannot rely on tooth emergence or stages of calcification for assessing the age. Traditionally, histological methods have been used for estimating age in this group, most notable of these being Gustafson’s pioneering work (1950) and its subsequent modification by Johanson (1971). A major disadvantage of these methods, however, is the necessity to extract and section the teeth. While this may be practical in dead individuals, it is neither possible nor ethical among living adults. Kvaal’s radiographic method A method developed by Kvaal and associates (1995) sidesteps the necessity for extracted teeth in adult age estimation. Their method used the tooth, root and pulp size measurement of six teeth (maxillary central and lateral incisor and second premolar; mandibular lateral incisor, canine and first premolar) observed on periapical radiographs. The measurements included several length and width ratio (Figure 14) such as pulp/root length (P), pulp/ tooth length (R), tooth/root length (T), pulp/root width at CEJ (A), pulp/root width at mid-root level (C), pulp/root width at mid-point between levels A and C (B), mean value of all ratio excluding T (M), mean value of width ratio B and C (W), mean value of length ratio P and R (L). These ratio were used to compensate for magnification and angulation errors of teeth on the radiograph. When six teeth (right or left side) from both jaws are available, the following regression formula can be used: Age 129.8 316.4 (M) 66.8 (W – L). The length measurements may be recorded using a calliper however, the widths need to be measured using a stereomicroscope—an equipment that may not be available routinely in Indian dental set-ups. Hence, applying this method on digitized radiographs and measuring the teeth on a computer monitor with accompanying software tools may be more convenient. Kolltveit and colleagues (1998) first tested 672

Diagram showing measurements made on the radiograph of each tooth. The ratio of these lengths and widths were used in age assessment. (Reprinted from Kvaal SI, Kolltveit KM, Thompsen IO, et al (1995), ‘Age estimation of adults from dental radiographs‘, Forensic Science International, Vol. 74, pp. 175–85, with permission from Elsevier)

the efficacy of the method on digitized radiographs and obtained lower correlation with age. However, more recently, Bosmans and coworkers (2005) have obtained accurate age estimates on digital orthopantomographs. Further testing on conventional and digital radiographs in different population groups will reinforce the validity of this method.

BITE MARK PROCEDURES Dental identification makes use of the randomness of intact, diseased, restored and missing teeth. Bite mark investigation, on the other hand, uses the configuration of teeth to establish the identity of a biter. The size, shape, angulation and pattern of the biting edges of the anterior teeth in the upper and lower dental arches can be arranged in 1.36 1026 different ways (Rawson et al, 1984). But the dynamics involved during production of bite marks—such as movement of the biter’s jaw, movement of the victim and flexibility of the bitten tissue—renders the appearance of the mark highly variable (Figure 15) and the presumed uniqueness of the dentition may not be depicted on the mark (Pretty, 2006a). Therefore, investigating bite marks, perhaps, provides the greatest challenge to forensic odontologists (Brown, 1985). Bite marks have been described as marks made by the teeth either alone or in combination with other mouth parts (MacDonald, 1974). Bite marks may be caused by humans


Figure 15 A

B

Two distinct bite marks (A, B) on the back of a victim made by the same dentition. In both photographs, mandibular arch mark is further from the scale. (Reprinted from Sheasby DR, MacDonald DG (2001), ‘A forensic classification of distortion in human bitemarks‘, Forensic Science International, Vol. 122, pp. 75–8, with permission from Elsevier)

or animals; these may be on tissue, edible items or objects. Biting is considered to be a primitive type of assault and results when teeth are employed as a weapon of attack, dominance or self-defense. As a result, bite marks are usually associated with sex crimes and violent fights. Hence, matching a bite mark to a suspect’s dentition may enable law enforcers to implicate the suspect in the crime.

How Does a Bite Mark Look? Features of a bite mark The human bite mark may be identified by its gross, class and individual features (Sweet, 1995): Gross features Grossly, a bite mark usually appears as a circular or elliptical mark with a central ecchymosed area. The circular/elliptical mark is caused by the dental arches while the central area of ecchymosis is apparently due to sucking action or negative pressure created by the mouth. Class features The marks produced by different types of teeth are usually distinct allowing one to differentiate the tooth class. For example, incisors produce rectangular, canines triangular and premolars spherical-shaped patterns. Individual features Class features may, in turn, have characteristics such as rotations, fractures, etc. Such features are known as individual features and render the bite mark distinct.

Type of Injury A bite mark may appear as an indentation, contusion, abrasion, laceration or avulsion. Initially, compression of the skin

surface as a result of tooth pressure during a bite causes indentations. Indentations, while ideal for collecting as evidence and subsequent analysis, seldom persist for long durations unless the victim is deceased. Owing to the elastic nature of skin, indentations soon disappear and the skin regains its original contour. This is followed by a brief period of edema over the bitten area, which usually obscures the bite mark completely. Once the edema subsides, subcutaneous bleeding becomes apparent. These are referred to as contusions or bruises and are the most common presentation of bite marks. These appear as reddish/purplish discoloration on the skin surface, a result of blood escaping into the subcutaneous tissue from ruptured vessels. With increased intensity of the bite, there may be abrasions and lacerations of the skin. The most extreme form of bite mark injury is avulsion, where part of the tissue is bitten off. However, the forensic significance of a bite mark does not necessarily increase with the severity of the injury. Pretty (2006b) has proposed a ‘bite mark severity and significance scale’ to assist forensic dentists in determining how valuable a bite mark is as forensic evidence. The proposed index has two parts—a textbased index (Figure 16) and a pictorial guide (Figure 17). As illustrated in these figures, well-defined bruising and lacerations are usually best suited for forensic investigation.

Site of Injury Bite marks may be found on any part of the body (Pretty and Sweet, 2000). However, females are bitten most often on the breast followed by the arms, legs and thighs while males are bitten on the arm, hands/fingers and the back. Interestingly, many of the male ‘victims’ received bites during the course of a crime committed by them, i.e. they were bitten by their victims, probably in self-defense. 673


Figure 16 1. Very mild bruising, no individual tooth marks present, diffuse arches visible, may be caused by something other than teeth—low forensic significance

Increasing severity

2. Obvious bruising with individual, discrete areas associated with teeth, skin remains intact—moderate forensic significance 3. Very obvious bruising with small lacerations associated with teeth on the most severe aspects of the injury, likely to be assessed as definite bite mark—high significance 4. Numerous areas of laceration, with some bruising, some areas of the wound may be incised. Unlikely to be confused with any other injury mechanism—a high forensic significance

High forensic significance

5. Partial avulsion of tissue, some lacerations present indicating teeth as the probable cause of the injury—moderate forensic significance 6. Complete avulsion of tissue, possibly some scalloping of the injury margins suggested that teeth may have been responsible for the injury may not be an obvious bite injury—low forensic significance

The bite mark severity and significance scale. (Reprinted from Pretty IA (2006), ‘The barriers to achieving an evidence base for bitemark analysis’, Forensic Science International, Vol. 159S, pp. S110–20, with permission from Elsevier)

Differential Diagnosis of Human Bite Marks Grey (1989) has reported a case where defibrillator paddles used in resuscitation caused artifacts that resembled bite marks. He urges caution while investigating what may appear as a bite mark to the casual eye—‘things are not always what they seem to be; care must always be taken not to misinterpret findings’. Other bite mark-mimicking injuries may be caused by: ❍ ❍ ❍ ❍

Hair curling iron The ends of a pipe Jewellery Shoe heel.

These, however, are usually differentiated from true bite marks by the absence of class characteristics.

Bite Mark Investigation Any attempt at bite mark investigation should begin with the following questions (Drinnan and Melton, 1985; Sweet, 1995): ❍ ❍ ❍ 674

Is the injury a bite mark? If a bite, was it caused by human teeth? Was it caused by an adult or a child?

❍

Does the age of the bite mark correspond to the time and type of crime? ❍ Are there unique, individual characteristics in the bite mark? ❍ Can these characteristics be compared to the teeth of the suspect? Once these questions have been answered satisfactorily, one may proceed with the next step—collecting bite mark evidence.

Collecting Bite Mark Evidence When a suspected case of bite mark is presented, immediately report it to the law enforcement agency and collect necessary evidence. However, the primary concern is patient care—at no time should collection of bite mark evidence interfere with timely patient treatment. This is especially important since Pretty and associates (1999) have reported that human bites have a great potential for infection (including HIV, hepatitis B and syphilis), particularly when the bite injury presents as an abrasion or laceration. Drawing from the experience and suggestions of accredited forensic dentists, the American Board of Forensic Odontology (1995) has suggested the following protocol for bite mark evidence collection.


Figure 17 A

B

C

D

E

F

Visual index of the bite mark severity and significance scale. (Reprinted from Pretty IA (2006), ‘The barriers to achieving an evidence base for bitemark analysis‘, Forensic Science International, Vol. 159S, pp. S110–20, with permission from Elsevier)

Demographics of the Case

Visual Examination and Documentation

Vital information pertaining to the case should be noted first, e.g. name, age and sex of the victim; case number, date of examination and name of the examiner(s).

Visually examine the bite mark and document the following: ❍ ❍

Location, shape, color and size Type of injury 675


❍ ❍

Contour, texture and elasticity of the bite site Differences between upper and lower arches, and between individual teeth

Note: If the victim is dead, examine the bite mark prior to autopsy (Brown, 1985).

Photographs High-quality photographs provide a permanent record of the bite mark appearance. No time should be lost in obtaining photographs as the injury rapidly changes appearance due to healing in living victims or postmortem change in the deceased. Color and black-and-white photographs may be taken using off-angle light source. Orientation and close-up photographs (Figure 18) should be taken: orientation photographs depict the location of the bite mark on the body; close-up photographs of the bite mark should be made with a rigid reference scale—a ruler, such as the ABFO No. 2 scale, should be placed on the same plane as the bite mark. The entire scale and bite mark must be visible on the photograph. A second closeup photograph depicting the bite mark without the scale can be made to indicate that no portion of the mark has been concealed by the scale. The camera should be positioned directly over the injury site with the long axis of the lens perpendicular to the surface of the bitten skin—this decreases perspective distortion of the image due to offangle camera position (Sweet and Pretty, 2001). If the bite is on a curved surface and the upper and lower arch marks are widely spaced, separate photographs of each mark

should be taken. In case of a living victim, photographs can be repeated every 24 hours for 3–4 days to record progressive changes in the pattern of bruising (Brown, 1985).

Saliva Swab It is reasonable to assume that a bite cannot be inflicted without leaving saliva behind. Saliva deposited in the bitten area may be a source of cellular DNA, enabling a direct link to the suspect. Care should be taken not to wash the bite area before saliva swabbing. According to Clift and Lamont (1974), the amount of saliva deposited in a bite mark is about 0.3 ml, distributed over an area of 20 cm2. However, by the time of evidence collection, the bite area may have dried up. Therefore, a cotton swab moistened with distilled or clean tap-water should be used for swabbing. This rehydrates the dry cells in the bite area. The swab is held vertical along its long axis making circular motion with moderate pressure over the bitten surface. A second swab, which is dry, is used to collect the moisture left on the skin by the first swab and cells that remain. This constitutes the ‘double swab technique’ recommended by Sweet and associates (1997) and is supposed to yield higher amounts of salivary DNA. Both swabs are then air-dried at room temperature for about 30 minutes. Following this, the swabs should be placed in paper envelopes to facilitate continued air circulation around the swab tips (Sweet and Pretty, 2001). These are labeled and stored under refrigeration. The latter prevents degradation of salivary DNA and bacterial growth in case of delay in lab processing. A third control swab may be taken from an anatomically similar

Figure 18 A

B

(A) Anatomical location of bite mark on victim’s left shoulder; (B) close-up photograph of the bite mark. (Note: The use of flexible scales is not recommended for bite mark evidence collection and ABFO No. 2 scale (Figure 17) is preferred). (Reprinted from Pretty IA (2006), ‘The barriers to achieving an evidence base for bitemark analysis’, Forensic Science International, Vol. 159S, pp. S110–20, with permission from Elsevier)

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location outside the bite area and bagged separately. Clark (1992) has suggested that if the bite has occurred through clothing, the clothes must also be swabbed. The use of high-intensity alternative light source (such as UV light) to locate stains from body fluids enable saliva traces to be recovered even in the absence of visible bite marks. There are some disadvantages to salivary DNA analysis, including the need for extensive laboratory equipment and expertize, high cost and possible degradation of DNA. Nevertheless, ‘there is an increasing uptake of such technology’ among forensic dentists (Pretty, 2006a). Note: Saliva swabs may also be collected according to the recommendations of the testing laboratory. Some important steps in managing bite mark cases: ❍

Notify concerned legal authorities and consult a forensic odontologist. ❍ Record history and perform a detailed physical examination. ❍ Obtain adequate records of the bite marks including: – Documentation – Photographs – Saliva swab.

Obtaining Dental Evidence from a Suspect The bite mark evidence collected should be complemented with dental evidence from the suspect who has purportedly caused the bite. Evidence must be obtained in the presence of law enforcers, using a signed and witnessed informed consent or a warrant; infection control and asepsis must be adhered to. Begin by obtaining history of any dental treatment subsequent to, or in proximity of, the date of bite mark; follow it up with a detailed extra- and intraoral clinical examination. Other evidence recovered should include:

testimony that proves that the evidence has not been altered or tampered with in any way since it was obtained. This is necessary both to assure its admissibility in courts of law and its probative value in preceding investigations.

Analyzing and Comparing Bite Mark Evidence Ideally, bite mark analysis should begin with a qualitative and quantitative analysis in situ. This should be followed by the analysis of life-sized or enlarged photographs. A separate qualitative and quantitative analysis of the models and occlusal registrations of the suspect’s dentition can be performed at this stage. Rather than relying on the number of teeth depicted in the mark, analyze uncommon characteristics such as presence or absence of a particular tooth, mesiodistal dimension of the teeth and dental arch, rotation, fracture and diastema. Following this, one may proceed with the comparison. According to Sweet (1995), the protocol for bite mark comparison is made up of two broad categories: (i) metric analysis, and (ii) pattern association. Metric analysis The measurement of specific features of the bite mark and suspect’s dentition is known as ‘metric analysis’. Measurements may be made on life-sized photographs of the bite mark and include: ❍ ❍ ❍ ❍ ❍

Overall size of the mark Intercanine distance The length and width of the tooth Spacing between tooth marks Rotation from normal arch form.

❍

A similar procedure is employed on the suspect’s dental casts. The measurements thus obtained from the mark and the cast are compared to one another. Simple instruments like callipers may be used for the measurements. Recently, computer-based measurements using software such as Adobe Photoshop have also been used (Johansen and Bowers, 2000). Metric analysis, however, must be applied in conjunction with ‘pattern association’.

All evidence obtained must be labeled and stored appropriately—the case number, date, time, place, as well as any witnesses involved must be recorded at every step of evidence collection to maintain the chain of custody. In practical terms, a chain of custody is the documentation and

Pattern association Matching the configuration of the bite injury to the arrangement of teeth on the suspect’s dental cast is called ‘pattern association’. This can be done by hand-tracing the incisal and occlusal edges of the suspect’s teeth on transparent acetate sheets and superimposing these ‘overlays’ on life-sized bite mark photographs. Sweet and coworkers (1998) developed a computer-based technique to produce overlays, which was found to be the most accurate tracing method (Sweet and Bowers, 1998). Johansen and Bowers (2000) have elaborated on this technique to develop a digital method for bite mark comparison and newer methods have since been reported (Thali et al, 2003) (Figure 19). The trend today appears to be moving toward the use of computer-based methods (Pretty, 2006a); nevertheless, standardization of the comparison

Photographs of the suspect’s teeth in occlusion and in open bite ❍ Maxillary and mandibular impressions made with rubber-base impression material or irreversible hydrocolloid and models poured in dental stone. It is useful to pour at least one additional cast of the suspect as backup ❍ Bite registration on a sheet of wax may be obtained in the absence of impressions ❍ If saliva has been recovered from the bite mark, swab should be obtained from the suspect for DNA comparison.

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Figure 19

However, in a recent review of bite mark analysis, Pretty (2006a) has warned against considering such a system of conclusion as an absolute interpretation of bite mark evidence. He believes that existing research data on physical bite mark comparison is not infallible and has stressed that ‘to prevent miscarriages of justice it is essential that odontologists are highly trained, undergo proficiency testing and aim to collect biological evidence whenever possible’. Further, he adds that while presenting conclusions to the courts of law one must avoid overstating the level of certainty and acknowledge the subjectivity of the analysis.

LIP PRINT INVESTIGATION

A bite mark is compared to digitized casts of the suspect using 3D/CAD program. (Reprinted from Thali MJ, Braun M, Markwalder TH, et al (2003), ‘Bitemark documentation and analysis: the forensic 3D/CAD supported photogrammetry approach‘, Forensic Science International, Vol. 135, No. 2, pp. 115–21, with permission from Elsevier)

process is yet to be achieved and conclusion of the analysis is usually based on the expert’s level of personal experience and judgment (Rothwell, 1995).

Conclusions of Bite Mark Analysis Levine (1982) has suggested three likely outcomes or conclusions to bite mark comparison, which has been modified as follows: Positive identification There is reasonable dental certainty to indicate that the bite mark has been produced by the suspect’s dentition—this implies that there are characteristic matches between the bite mark dimensions/pattern and that of the suspect’s teeth. Possible identification The bite mark and the suspect’s dentition are consistent— although the suspect’s teeth could have made the bite mark, there are no characteristic matches to be absolutely certain. Excludes identification The bite mark and the suspect’s dentition are not consistent—features on the bite mark indicate that the suspect’s teeth have definitely not caused them. *These grooves may traverse the lips completely or partially. 678

Lip print—the study of which is called cheiloscopy—can be important in crime investigation (Caldas et al, 2007). According to Ehara and Marumo (1998), lipstick smears are frequently encountered in forensic investigations as an important form of transfer evidence. These researchers have stated that ‘lipstick smears on the suspects’ clothing can indirectly prove a link between the suspect and a female victim, and smears left on cigarette butts, glasses or cups can prove a link between a suspect and a crime scene’. Snyder (1950) is believed to have first pointed out that the lines and fissures on the lips have individual variations, much like fingerprints. Renaud (1972) examined lip prints on 4,000 individuals and found them to be singular. The uniqueness of lip grooves has also been confirmed by Tsuchihashi (1974), who studied more than 1,300 lip prints. These researchers and a few others studied lip prints using similar classification, a composite of which is: 1. 2. 3. 4. 5. 6.

Vertical grooves* Branched grooves* Bifurcated grooves* Intersected grooves Reticular grooves Other grooves (comma, ellipse, triangle, horizontal, etc.)

Both Renaud (1972) and Tsuchihashi (1974) recorded the lip pattern of an individual quadrant-wise, i.e. the lips were divided into four quadrants, much like the dentition— a horizontal line dividing the upper and lower lip and a vertical line along the sagittal plane dividing the lips into right and left sides. Grooves in each quadrant of the lip were recorded according to the above classification. Suzuki and Tsuchihashi (1975) applied the classification in two criminal cases, both of which enabled the exclusion of the suspects—in effect proving the innocence of the


Figure 20 A

B

(A) Invisible lip print prior to and (B) after developing with lysochrome powder. (Reprinted from Navarro E, Castelló A, López JL, et al (2006), ‘Criminalisitic, effectiveness of lysochromes on the developing of invisible lipstick-contaminated lipmarks on human skin—a preliminary study‘, Forensic Science International, Vol. 158, pp. 9–13, with permission from Elsevier)

suspected perpetrators, which is of equal importance as proving the identity of criminals. These two cases investigated lip prints caused by the use of lipsticks that leave behind a visible mark. More recently, however, the cosmetics industry has developed lipsticks that do no leave a visible trace on contact with a surface (Seguí et al, 2000). Such colorless lip prints, too, can be visualized using developing reagents such as metallic powders (Seguí et al, 2000) or lysochromes (Navarro et al, 2006) (Figure 20). However, developing lip prints on colored or multicolored surfaces using these reagents may not prove useful due to contrast problems (e.g. Sudan Black—a lysochrome powder of the same color—may not be useful in developing lip prints on a black ceramic cup). Therefore, some authors have advocated the use of fluorescent reagents such as Nile Red (Castelló et al, 2005). This reagent can either be used in powder form or in solution (0.1 mg Nile Red dissolved in 100 ml ethanol). The reagent powder or solution is applied to the area of interest (with a brush or piece of cloth, respectively) and visualized under UV or blue light. The shape, outline and grooves of the lips were discernible and the authors believe that it has value in identification.

However, further studies on whether the lip prints developed can be accurately compared to those of a suspect are warranted. According to Tsuchihashi (1974), lip grooves are on the zone of transition of the lips which, being extremely mobile, are affected by the pressure applied by the lips and their direction. Consequently, there is the possibility that lip prints of one individual may be mistaken for another’s. However, the classification provided and quadrant-based recording of the lip grooves will probably render a successful comparison. The suggested method for comparison is to examine lip prints closest to the mid-line and then work laterally (Tsuchihashi, 1974). Whether lip print evidence is admissible in court and can stand the rigors of legal scrutiny is a matter of debate. According to Ball (2002), there is very little science and research to support a methodology for collecting and comparing lip print evidence which has gained acceptance within the forensic community. Further research to verify the uniqueness of lip prints, develop protocols for lip print investigation and establish its accuracy in comparative analysis is essential, without which it ‘would fail to meet any scientific standards of reliability’ (Ball, 2002).

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SECTION

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Basics of Radiology

25 Basics of Radiation Physics 26 Radiation Biology

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CHAPTER

Basics of Radiation Physics Ravikiran Ongole

➧ Pioneers in Dental Radiology ➧

➧

PIONEERS IN DENTAL RADIOLOGY Wilhelm Conrad Röentgen (1845–1923) Wilhelm Röentgen, the physicist from Germany is considered the father of diagnostic radiology. Röentgen discovered X-rays in 1895. Personal life and early years Wilhelm was born to a German father Friedrich Conrad Röentgen and Dutch mother Charlotte Constanze on March 27th, 1845 in the small town of Lennep in Rhineland. When Röentgen was 16 years old he enrolled in Utrecht Technical School, Netherlands. In 1868, he obtained a diploma in mechanical engineering from the Polytechnic School in Zurich. Under the tutelage of AEE Kundt, Wilhelm studied the properties of gases and obtained a doctoral degree in 1869. After obtaining his PhD, he worked as Kundt’s assistant at the University of Würzburg and later elevated to the post of an associate professor in theoretical physics. Wilhelm married Anna Ludwig in 1872. She was the daughter of an inn-keeper and 6 years elder to him. His wife died in 1919, following a prolonged illness and Wilhelm died due to intestinal cancer at the age of 73 years on February 10th, 1923. They were buried in Giessen. Recognition and awards The University of Würzburg appointed Röentgen as professor of physics in 1888. Just 6 years later in 1894, he was chosen as the Rector of the same university. After serving

Intraoral X-ray Units Components of an Intraoral X-ray Machine Filters and Collimators

Fundamentals of Radiation Physics Radiation Particulate Radiation Electromagnetic Radiation Ionizing and Non-ionizing Radiation Production of X-rays Properties of X-rays

25

➧

Interaction of X-rays with Matter Scattering Absorption

the University of Würzburg for 6 years as Rector, he took over as Director of a new physical institute in the University of Munich. For his outstanding work, Röentgen was awarded an honorary MD degree by the University of Würzburg. He was awarded the Rumford Gold Medal from the Royal Society (1896) and a gold medal from the Franklin Institute of Philadelphia. He was honored with the first Nobel Prize in Physics in 1901. The International Union of Pure and Applied Chemistry (IUPAC) in honor of Röentgen, named element number 111 as roentgenium (Rg) in 2004. Publications on X-rays 1.

2. 3.

‘On a New Kind of Rays, A Preliminary Communication’. Journal of Würzburg Physical-Medical Society, December 28, 1985. ‘On a New Kind of Rays, Continued’. Journal of Würzburg Physical-Medical Society, March 9, 1896. ‘Further Observations on a New Kind of Rays’. Journal of Prussian Academy of Science, March 10, 1897.

William Herbert Rollins (1852–1929) William Herbert Rollins was an American scientist and dentist. He was a pioneer in radiation protection and is known as the father of radiation protection. It is believed that he had published over 200 scientific articles regarding the hazards of radiation. Rollins, although a practicing dentist, also had a medical degree from Harvard Medical School. He called X-rays ‘X-light’ and documented them 685

Section IX – Basics of Radiology

extensively in 1904. He is called the ‘Forgotten Man’ of dentistry. William Rollins proposed the use of filters to remove the low energy X-rays from the primary beam and introduced collimation. He recommended a long targetfilm distance to improve image quality. He pioneered the sandwiching of the X-ray film between two intensifying screens to increase the film speed. Dr Rollins advocated the need to determine a safe and harmless dose of radiation. In 1901, he advocated the use of leaded glasses for radiation personnel and a lead shield to cover all areas on the patient’s body that were not being imaged. Rollins also felt the need to construct a lead hood that would cover the X-ray tube head.

Howard Riley Raper (1887–1978) In 1909, Dr Howard Raper, was the first to introduce radiology as a subject in the dental school. He also had three other ‘firsts’ to his credit—first Professor of Radiology, first academician to teach dental radiology and published the first textbook dealing with oral radiology titled Elementary and Dental Radiography, in 1913. In 1917, he proposed the first model of angle meter used with a chart of vertical angles for various teeth to avoid distortion. In 1925, in co-operation with Eastman Kodak Company, Dr Raper developed the bitewing technique for the detection of interproximal caries.

used to help him to mix materials and take the X-rays. In 1986, Edmund Kells and Brown Ayres devised a technique for radiographing the teeth and jaws. Dr Kells, in Dental Cosmos, mentioned the importance of keeping the film and object at right angles to the source using a film holder. In 1903, he introduced processing tanks and time-temperature processing. In 1909, Kells cut, wrapped and used rolltype photographic film.

Friedrich Otto Walkhoff (1860–1934) Friedrich Otto Walkhoff was a Berlin dentist, a pioneer of dental X-ray diagnostics and a dedicated fighter for civil interests of dentists. It was barely 14 days after the announcement of the discovery of roentgen rays that Walkhoff wrapped a photographic glass plate in a routinely used rubber dam material and held it with his teeth. He then laid still on the floor for an X-ray exposure that lasted a full 25 minutes. This was considered the first dental radiograph. A year later, he managed to take extraoral radiographs with an exposure time of 30 minutes.

Gordon Fitzgerald (1907–1981) In the 1940s, Dr Fitzgerald designed the long cone for the dental X-ray machine. He published four papers on long cone technique in the Journal of American Dental Association between 1947 and 1950.

Weston A Price (1870–1948) Weston Andrew Valleau Price was a dentist known primarily for his theories on the relationship between nutrition, dental health, and physical health. Dr Price, in 1897, a founding member of the American Roentgen Ray Society, designed and patented lead-lined gloves for protection against X-ray burns, but placed his innovation in the public domain instead of commanding fees from users. In 1900, Price designed a celluloid-based dental film. In 1904, he proposed two techniques for film positioning in the oral cavity, namely, the paralleling technique and the bisecting angle technique.

Frank Van Woert (1856–1927) Dr Frank Van Woert is credited for his work on the use of films, film holders and processing of films. He was the first to use films as image receptors which were developed by Kodak. He also engineered a metallic holder which could be used to hold films. His other inventions include the daylight film processing tank, an improved angle meter for bisecting angle technique and an automated exposure timer switch.

Franklin W McCormack Edmund C Kells (1856–1928) Edmund Kells was born in New Orleans, Louisiana, to a dentist Charles E Kells. He became a dentist, researcher, and inventor. His experiments caused the loss of most of his left arm. In 1899, he set up the first X-ray laboratory (The New Orleans X-Ray Laboratory) for radiographs and fluoroscopic examinations. He demonstrated the radiograph of chest and hip, a bullet in the head and the measurement of a root canal. He hired the first acknowledged dental assistant—Malvina Cuera, before which, his wife

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Franklin McCormack, an American medical X-ray technician, employed paralleling technique principles in intraoral radiography. He wrapped the film with a black paper and used a flat metal plate to make the film packet rigid. He was also known for using bite blocks and hemostat as film holders to stabilize the film in the mouth. Readers are encouraged to visit the website of the roentgen museum for more information on the chronology of events in origin of radiology (http://www.roentgenmuseum.de).

Chapter 25 – Basics of Radiation Physics

Particulate Radiation

Films and Processing of Films 1896:

The exposure time varied between 5 and 15 minutes and the processing time varied between 30 and 60 minutes 1913: Hand-wrapped, moisture-proof, dental packet containing two films 1919: First machine-wrapped dental X-ray film packet called Regular film (Kodak) with emulsion on only one side 1920: Film hangers were introduced Early 1920s: Cellulose nitrate as base, emitted poisonous gases on burning 1924: Radia-tized film (Kodak) with double side emulsion 1924: Non-flammable cellulose triacetate film base 1940: Ultra speed (improved Radia-tized film) doubled the film speed of the 1924 film Early 1960s: Polyester film base 1980s: Ektaspeed film introduced by Kodak

FUNDAMENTALS OF RADIATION PHYSICS Radiation Radiation is the transmission of energy through space and matter. There are two basic forms of radiation, namely, particulate radiation and electromagnetic radiation.

Particulate radiation consists of a stream of atomic or subatomic particles that transmit kinetic energy by means of their small masses moving at very high velocities. They may carry a positive charge (alpha particles), negative charge (beta particles) or no charge (neutrons). Examples of particulate radiation are alpha rays, beta rays and cathode rays.

Electromagnetic Radiation There are two concepts to understand electromagnetic radiation, namely, classical theory and modern quantum theory. According to the classical theory, the flow of energy at the universal speed of light through free space or through a material medium is in the form of the electric and magnetic fields that make up electromagnetic waves such as radio waves, visible light, and gamma rays. In such a wave, time-varying electric and magnetic fields are mutually linked with each other at right angles and perpendicular to the direction of motion (Figure 1). In terms of the modern quantum theory, electromagnetic radiation is the flow of photons (also called light quanta) through space. Photons are packets of energy (h␯) that always move with the universal speed of light. The symbol h is Planck’s constant, while the value of ␯ is the same as that of the frequency of the electromagnetic wave of classical theory. The spectrum of frequencies of electromagnetic radiation extends from very low values over the range of radio waves, television waves, and microwaves to visible light and beyond to the substantially higher values of ultraviolet light, X-rays, and gamma rays.

Figure 1 Propagation vector

Electric field

Magnetic field

Electromagnetic spectrum

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Production of X-rays

Figure 2 1 10, 000

Measured in angstrom units

1 1000 1 100 1 10 1

X-ray radiography

10 100

Ultraviolet ray Sun lamp

1000 10,000 100,000 1,000,000

Measured in meters

X-ray therapy

1 1000 1 100 1 10 1

Light ray photography Infrared ray toaster Microwave oven

Radar

10 100 1000 10,000

Television

100,000 1,000,000

Radio

10,000,000 100,000,000

Various energy levels of the electromagnetic spectrum

Ionizing and Non-ionizing Radiation Radiation has a wide range of energies that form the electromagnetic spectrum (Figure 2). The spectrum has two major divisions: 1. 2.

Non-ionizing radiation Ionizing radiation.

Radiation that has enough energy to move around atoms in a molecule or cause them to vibrate, but not enough to remove electrons, is referred to as ‘non-ionizing radiation’. Examples of this kind of radiation include radio waves, infrared, ultraviolet, visible radiation and microwaves. Radiation that falls within the ‘ionizing radiation’ range has enough energy to remove tightly bound electrons from atoms, thus creating ions. 688

X-ray photons are produced within the X-ray tube by accelerating electrons with a high voltage and allowing them to collide with a metal target. This collision results in the production of X-rays by two basic mechanisms: Bremsstrahlung radiation and characteristic radiation. Bremsstrahlung radiation is the major source of X-ray photons from the X-ray tube. Characteristic radiation contributes only to a small amount of X-ray photons that are produced from the X-ray tube. Bremsstrahlung radiation It is also referred to as braking radiation or deceleration radiation (Figure 3). Bremsstrahlung is derived from the German words bremsen meaning ‘to brake’ and strahlung meaning ‘radiation’. The sudden ‘braking’ of high speed electrons at the target produces bremsstrahlung radiation. When high speed electrons are directed toward the tungsten target, they interact with the nuclei of the atoms in the tungsten target in two ways, namely, direct hit and near miss/wide miss. Direct hit interaction In this interaction the high speed electrons collide head on with the nuclei of the atoms in the tungsten target. However, very few electrons display such direct collisions. When such a collision takes place, the total kinetic energy of the high speed electron is converted into a single X-ray photon whose energy is numerically equal to the energy of the high speed electron. Near miss/wide miss interaction Majority of the interactions of the high speed electrons with the nuclei of the atoms of the tungsten target are near/wide misses. Because of the attractive force of the nucleus, the high speed negatively charged electrons are drawn toward the nucleus (however, does not collide head on), resulting in the deflection of the electron from its original path. This results in the electron losing some of its kinetic energy, which is given out in the form of an X-ray photon. The closer the high speed electron is drawn toward the nucleus greater will be the stopping/braking effect and resultant energy of the photon. Characteristic radiation (Figure 4A, B) Apart from the direct hit and near/wide misses many of the high speed electrons interact with the electrons in the outer orbit around the nucleus. This interaction causes removal of the electron from its shell, thereby ionizing the atom. The vacant site in the inner shell produced by the displaced electron is quickly filled up by another electron from an outer shell. When the displaced electron is replaced, a photon is emitted with the energy equivalent to the difference in the two orbital binding energies.


Figure 3 X-ray photon

Near miss

Direct hit

X-ray photon High speed electron Target Bremsstrahlung radiation

Bremsstrahlung radiation. Courtesy: Dr Jaideep Shekhar

Figure 4 A

B

Characteristic radiation. (A) Interaction with inner shell electron. (B) interaction with outer shell electron. Courtesy: Dr Jaideep Shekhar

Properties of X-rays 1. 2.

X-rays are forms of electromagnetic radiation. They have short wavelength and hence exhibit great penetrating power. 3. They travel at the speed of light (3 ⫻ 108 meters/second or 186,000 miles/second). 4. They affect (produce images) photographic plates and X-ray films. 5. They travel in straight lines in the form of waves. 6. X-rays are made up of small packets of energy called photons or quanta. 7. They can ionize gases. 8. They cannot be focused using a lens. 9. They cannot be reflected, refracted or deflected by magnetic or electric field. 10. They can penetrate opaque objects. 11. They follow the inverse square law.

12. 13. 14. 15. 16. 17.

18.

(Inverse square law: For a given beam, the intensity is inversely proportional to the square of the distance from the source). They are invisible to eye and cannot be heard or smelt. They exhibit properties of interference, diffraction and refraction similar to visible light. They produce an electric field at right angles to their path of propagation. They produce a magnetic field at right angles to the electric field and path of propagation. They do not require any medium for propagation. X-rays can penetrate liquids, solids and gases. The degree of penetration depends on quality, intensity and wavelength of X-ray beam. They are absorbed by matter, the absorption depends on the anatomic structure of the matter and the wavelength of the X-ray beam. 689


Figure 5

Figure 6

Wall mounted intraoral radiographic unit

19. X-rays interact with materials they penetrate and cause ionization. 20. When X-rays fall upon certain materials, visible light will be emitted called fluorescence. 21. X-rays have the property of attenuation, absorption and scattering. 22. They exhibit heating effect. 23. They can stimulate or destroy living tissues. 24. They have a germicidal or bactericidal effect.

Mobile intraoral radiographic unit mounted on a stand with casters

Figure 7

Other biological effects of X-rays are discussed in Chapter 26 on Radiation Biology.

INTRAORAL X-RAY UNITS Various types of dental X-ray (intraoral radiography) units are available to suit the needs of the maxillofacial radiology department. Majority of the intraoral X-ray units are meant for wall mounting (Figure 5) or simply fixed to the floor. However, mobile versions are also widely used. These mobile units comprise of a standard intraoral X-ray unit mounted on a stand with casters (Figure 6). These are referred to as ‘stand-type’ units. These units can be freely moved between multiple operatories. A few dental clinics prefer the a ceiling mounted version of the X-ray unit. The ideal location of the X-ray unit (Figure 7) is on the wall right behind the patient’s head (12 o’clock wall). Alternatively, mounting the lateral wall is also acceptable as this allows the X-ray unit to be shared between two treatment rooms via a lead-lined pass through cabinet. Over the last few years, portable handheld X-ray units have gained popularity. These are battery operated (usually rechargeable Ni–Cd), weighing 5–9 pounds (Figure 8). Since these handheld devices can be taken from room to 690

Photograph depicting the X-ray unit mounted on the wall behind the patient’s head

room, it eliminates the need for multiple X-ray units, and these can be used effectively in remote rural areas. Studies have shown that these systems help in reducing the number of repeat radiographs by 50% and are also twice as fast in taking radiographs compared to the conventional dental X-ray units. Another recent development in the dental X-ray systems is the use of direct current (DC) for X-ray generation. Until relatively recently, many of the dental X-ray generators applied alternating current (AC) to the tube when generating X-rays. Constant potential generators produce a relatively constant stream of radiation and a greater percentage of higher energy ‘useful’ radiation. With an AC generator, voltage across the tube goes from zero up to the maximum kilovolt peak (kVp), then


back to zero. This produces X-ray photons of varying energies. The lowest energy photons are filtered out, but the average photon energy produced by an AC tube for a given kVp is still lower than the average photon energy produced by a constant potential tube at that same kV. Lower energy photons are more readily absorbed by the patient, so the more homogeneous beam of higher energy photons produced by constant potential units may slightly reduce patient exposure. When using conventional film, the lower average photon energy of an alternating current unit will produce films of higher contrast than a constant potential unit (for a given kVp). However, constant potential units typically operate at 60 or 65 kV compared to the 70 kVp of an alternating unit which brings the contrast levels closer to each other. While most X-ray units operate at a single, fixed kVp, some models have a facility to vary the kVp settings. In summary, AC and DC units are both capable of producing diagnostic images whether using conventional film or digital radiography. Constant potential units (DC) produce Figure 8

lower contrast conventional films compared to AC units at any given kVp, but these units typically operate at a slightly lower kV than AC units, which decreases this difference. Constant potential units may reduce patient exposure slightly and may produce more consistent exposures at the very short exposure times associated with digital radiography.

Components of an Intraoral X-ray Machine The intraoral X-ray machine is made up of the following parts: 1. 2. 3.

X-ray tube head (Figure 9A, B) Control panel Swivel arms for maneuverability.

X-ray tube head It is made up of an evacuated (vacuumed) borosilicate glass envelope, which encloses the anode and cathode, power supply circuit, protective lead housing and insulating (coolant) oil between the glass envelope and the outer protective housing (Figure 10). Glass envelope (Figure 11) It is made of borosilicate glass that is evacuated. The glass tube is evacuated in order to: ❍

Prevent collision of the electrons with gas molecules, which might reduce their speed. ❍ Prevent oxidation ‘burn out’ of the tungsten filament. Anode (Figure 12) The anode is positively charged. It comprises of a tungsten target that is embedded in a copper stem. Tungsten Tungsten is chosen as an ideal target material because of the following reasons: Portable handheld X-ray unit

❍

It has a high atomic number (74)—very efficient for production of X-rays.

Figure 9 A

B

(A) X-ray tube head with a long cone. (B) X-ray tube with a short cone

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Figure 10

1

4 5

3

6

2

8

10

11 12

7 9

13

14

15 1. Swivel arms 2. Yoke 3. External housing 4. Step down transformer 5. Step up transformer 6. Borosilicate glass housing 7. Cathode 8. Molybdenum focusing cup 9. Tungsten filament

17 16

10. Electron beam 11. Anode 12. Copper stem 13. Tungsten target 14. Aluminum filter 15. Collimator 16. Primary X-ray beam 17. Position indicating device

X-ray tube—schematic diagram. Courtesy: Dr Jaideep Shekhar

Figure 11

❍

Low vapor pressure—it helps in maintaining the vacuum in the tube at high temperatures during the operation of the machine.

The tungsten target is angulated at about 20⬚ to the central ray of the X-ray beam. Copper stem The tungsten target is embedded in a copper stem. In order to compensate for the poor thermal conductivity of tungsten, the target is embedded in a copper stem, which is a good conductor of heat. It carries away the heat from the tungsten target thereby preventing tungsten from melting at high operating temperatures. Cathode The cathode is negatively charged. It comprises of a filament and focusing cup. Borosilicate glass tube housing the anode and cathode

❍

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High melting point (3360⬚C)—it is a known fact that almost 99% of the kinetic energy of electrons is converted to heat, therefore making it necessary for the target to withstand high temperatures.

Filament The filament is made up of tungsten. The tungsten filament is in the shape of a coil, which is about 1 cm in length, and the coil of wire used is about 2 mm in diameter. The coil is mounted on supporting rods that carry the power supply to the filament. To produce X-rays, the filament is heated to incandescence using current from a low voltage source. The tungsten filament in turn gives out electrons at a rate that is proportional to the temperature of the filament.


Figure 12

Figure 13

Anode and cathode of the X-ray tube head

Focusing cup The filament lies in the focusing cup. The focusing cup is made up of molybdenum. It is a negatively charged concave reflector, which electrostatically focuses the electrons into a narrow beam that is directed toward the focal spot. Power supply circuit The power supply circuit of the X-ray tube head mainly consists of a step down transformer, high voltage transformer and electrical insulating oil surrounding the transformers. The transformers are encased in an electrically grounded metal housing. Other parts of the power supply circuit are a filament current (mA) control switch and a kilovolts peak (kVp) selector dial. Step down transformer It helps to reduce the voltage of the incoming alternating current to about 10 volts. This is controlled by the mA switch. The step down transformer provides a low voltage current to heat the filament of the X-ray tube. High voltage transformer It helps in generating a high potential difference between the anode and cathode, thereby accelerating the electrons from the cathode toward the anode to generate X-rays. Electrical insulating oil This oil acts as a coolant as well as an electrical insulator. The insulating oil aids in dissipation of heat produced by the X-ray tube. Control panel (Figure 13) Most of the intraoral machines available have the facility to adjust the tube voltage and tube current. However, most of the machines operate at fixed parameters. X-ray machines used for taking intraoral radiographs are calibrated at about 60–65 kVp and 8 mA. The exposure time is usually one parameter that the dentist can control. The exposure time in most machines can be adjusted from 0.1 to 3 seconds.

Control panel of an intraoral radiographic unit

Working mechanism of the X-ray machine To ensure a sufficient rate of electron emission, the tungsten filament should be pre-heated to an optimum operating temperature. The timer circuit initially sends a current through the filament for about half a second to heat the filament and bring it to an optimum operating temperature. Once the filament is heated to an optimum temperature, the timer applies power to the high voltage circuit. However, it is not practical to keep the filament preheated continuously as it shortens the lifespan of the tungsten filament. Accordingly, it is not advisable to leave the X-ray machine switched on all through the working hours. Dissipation of heat from the X-ray machine It is understood that 99% of the electrons emitted, contribute to the heat generated within the X-ray machine and only 1% contribute to X-ray production. Various methods are employed to dissipate heat from the X-ray machine: 1.

2. 3.

4. 5.

The X-ray machine should be operated in an air conditioned environment with the temperature about 18—20⬚C. Presence of an insulating oil or coolant between the X-ray tube and the outer protective housing. Embedding the tungsten target in a copper stem. Copper being a good conductor of heat carries away the heat from the target. Angulating the target to about 20⬚ helps in minimizing the heat generated at the focal spot. Using a rotating anode minimizes the heat generated during the production of X-rays. A rotating anode provides a large surface area at the focal spot thereby aiding in the dissipation of heat. 693


Figure 14

components of the X-ray tube such as the borosilicate glass envelope, insulating oil and the sealant that prevent the leakage of the insulating oil, by way of design prevent low energy X-ray photons to leave the X-ray tube housing. This inherent filtration is equivalent to 0.5–2 mm of aluminum. 2. Added filtration Aluminum disks of various thicknesses as per the requirement are placed at the exit portal. 3. Total filtration It is the sum of both the inherent filtration and added filtration. The amount of filtration required is based on the tube voltage of the machine that is used. The quantity of filtration required is expressed as ‘half value layer’.

Photograph showing the aluminum filter at the far end of the PID

Filters and Collimators X-rays produced in the X-ray tube exit the glass envelope through the exit port. Before the X-rays reach the object to be imaged they pass through the filter and then the X-ray beam is collimated and directed at the area of interest using the position indicating device (PID). Filters X-ray photons produced in the X-ray tube consists of photons of various energy levels. It is a known fact that photons of the maximum energy contribute to the production of the latent image on an image receptor system film and photons of low energy contribute to exposure of the patient. Studies have shown that the surface exposure levels reduce to about 20% when the X-ray beam is filtered. Photons of low energy levels have a low penetrating power and hence do not aid in the formation of an image of diagnostic quality. It becomes necessary to prevent photons of low energy and low penetrating power from reaching the patient. This is achieved by using a filter at the exit port of an X-ray tube (Figure 14). Design: The filter is made up an aluminum disc. It selectively allows the passage of high-energy X-ray photons and prevents the low energy X-ray photons from leaving the X-ray tube. The aluminum disk is about 0.1 mm in thickness. Types of filtration 1. Inherent 2. Added 3. Total. 1. Inherent filtration As the name suggests it is the filtration offered by the design of the X-ray tube. Various 694

Half value layer It is the thickness of aluminum required to reduce by half the number of X-ray photons passing through it. For a machine operating between 30–70 kVp, total filtration should be about 1.5 mm and a machine operating at 90 kVp the total filtration required is about 2.5 mm of aluminum. Along with aluminum filters, rare earth materials like erbium, yttrium and samarium have been used as filters. These filters used in conjunction with aluminum filters further reduce the patient exposure. However, the exposure time has to be increased by almost 50% and the contrast, resolution and sharpness of the resultant image is reduced. Collimators Collimator is a metallic barrier with a central aperture, which is used to contain the size of the X-ray beam to the required site of exposure. The collimator is generally made up of a thick plate of lead (radiopaque substance). It is desirable that the collimated beam should be contained within a circle having a diameter of 7 cm or 2¾ inches. Functions of the collimator 1. Reduces patient exposure by containing the size of the X-ray beam to the site that has to be exposed. 2. Prevents scattered radiation from reaching the film, that add to film fog and thereby degrading the diagnostic quality of the radiographic image. Types of collimators be classified as: 1. 2. 3.

Based on the shape collimators can

Rectangular collimators Diaphragm collimators (Figure 15) Tubular collimators.

A rectangular collimator (Figure 16) reduces the skin surface exposure by almost 60% compared to that of a diaphragm collimator.


Figure 15

Figure 17

Coherent scatter Compton scatter Photoelectric absorption

Interaction of X-rays with matter

Photograph of a diaphragm collimator with the central aperture

Figure 18

Figure 16

Coherent scatter. Courtesy: Dr Jaideep Shekhar

Scattering Coherent scatter

Rectangular collimator

INTERACTION OF X-RAYS WITH MATTER The X-ray beams that exit out of the X-ray tube interact with matter that they encounter. Such encounters result in absorption of scattering of X-ray photons. It is believed that almost 9% of the X-ray photons pass through matter without any interaction.

Coherent scattering is also referred to as classic scattering. It accounts for only about 8% of the total interactions of X-rays with matter, therefore has a very small role in producing film fog. When a low energy X-ray photon passes near an atom’s outer electron, it may not be absorbed but scattered without loss of energy. The incident photon interacts with the electron by causing it to vibrate momentarily at the same frequency as the incoming photon. Following this interaction, the incident photon ceases to exist (Figure 18). The vibration causes the electron to radiate energy in the form of another X-ray photon with the same frequency and energy as in incident photon. This secondary photon is emitted at an angle to the path of the incident X-ray photon. Compton scatter

Types of Interaction (Figure 17) Scattering Coherent scatter Compton scatter

❍ ❍

Absorption Photoelectric effect.

❍

Compton scatter accounts for about 62% of the interactions of X-rays with matter. It occurs when a X-ray photon interacts with an outer electron. The incident photon collides with the electron, which receives kinetic energy and recoils from the point of impact. The incident photon is deflected by its interaction and scattered from the site of collision (Figure 19). 695


Figure 19

Compton scatter. Courtesy: Dr Jaideep Shekhar

Energy of the scattered photon equals energy of the incident photon minus the kinetic energy gained by the recoil electron plus its binding energy. Compton effect results in loss of the electron, thus ionization of absorbing atom. The scattered photons travel in any direction. On reaching the film, they cause film fog.

Absorption Photoelectric effect Photoelectric effect accounts for about 30% of all the interactions of X-rays with matter. It is characterized

696

Figure 20

Photoelectric absorption. Courtesy: Dr Jaideep Shekhar

by the absorption of X-rays by matter. It occurs when incident photon collides with a bound electron in an atom. During this interaction, the photon ceases to exist (Figure 20). The electron is ejected from its shell and becomes a recoil electron (photoelectron). The kinetic energy of recoil electron is equal to the energy of photon minus that required to overcome the electron binding energy. Photoelectric effect results in electron deficiency, which is instantly filled by an electron from outer orbit with the release of characteristic radiation, which is absorbed within the object.

CHAPTER

26

Radiation Biology Shubhasini AR, Bhanushree R, Praveen BN

➧ Effects on Living Systems ➧

Molecular and Cellular Radiobiology

➧

Deterministic and Stochastic Effects

➧

Patient Exposure and Dose Reducing Dental Exposure Conducting the Examination Protecting Personnel X-ray Equipment Installation and Related Factors Shielding Radiation in the CT Suite

Deterministic Effects on Tissues and Organs Effects of Total Body Radiation Effects of Radiation on Oral Tissues

Radiation Safety and Protection ➧

➧

Sources of Radiation Natural Radiation Man-made Radiation

X-rays were discovered in 1895, and since then, these rays were applied in several fields such as physics, chemistry and biology. In the beginning, people using these rays were not aware of the biological effect of X-rays. X-ray tubes were calibrated based on the erythema produced on skin when the operator placed his hand in front of the X-ray beam. There were numerous episodes of injury to operators and patients. The first biological effects of X-rays were reported in 1896 and included skin burns, epilation and eye irritation. In 1906, two French radiobiologists, Bergonie and Tribondeau described a law which states that ‘the radiosensitivity of a cell is directly proportional to its reproductive activity and inversely proportional to its degree of differentiation’. X-rays interact with atoms and molecules in the body within pico to femto second (10⫺13 to 10⫺15 s) of exposure. This reaction may occur directly on biological molecules or indirectly through the action on water molecules. This results in the formation of free radicals. Free radicals are fragments of molecules which have unpaired electrons, and hence high reactivity. They react with surrounding molecules and become stable by cross-linking or dissociation. Thus, there is an alteration of cellular molecules which further results in biological effects.

Dose and Risk in Radiography

Radiation Detection and Measurement Personnel Dosimetry Wearing the Dosimeter

➧

Film Exposure and Processing

EFFECTS ON LIVING SYSTEMS Living tissues may be affected by radiation in two ways— directly by the action on cellular molecules and indirectly by the action on water. While direct effects account for one-third of damages, indirect effects account for the remaining two-thirds. Direct effect X-rays interact with biological molecules causing excitation and ionization. This results in the breakage of chemical bonds in these molecules and results in the formation of free radicals. These reactions may be represented as follows: X-ray photon ⫹ RH → R* ⫹ H⫹ ⫹ e⫺, where RH represents a biological molecule such as a carbohydrate and R* is a free radical formed after the loss of an electron e⫺. Both R* and H⫹ immediately react with other biological molecules either by dissociation: R* → X ⫹ Y* or cross-linking: R* ⫹ S* → RS

697


The altered molecules differ structurally and functionally from the original molecules resulting in a biological change in the irradiated tissues. Indirect effect Water is the most abundant molecule in living tissues and hence X-rays passing through the body readily encounter water molecules. A series of complex chemical reactions then occur in water and finally result in the formation of highly reactive molecules. This is termed radiolysis of water. In the first step, X-ray photons displace an electron resulting in the formation of positively charged water molecule. X-ray photon ⫹ H2O → H2O⫹ ⫹ e⫺ This positively charged water molecule reacts with another water molecule, thus: H2O⫹ ⫹ H2O → H3O⫹ ⫹ OH* The free electron produced in the first reaction combines with a water molecule: e⫺ ⫹ H2O → H2O⫺ → OH⫺ ⫹ H* The electron may also be dissolved in the solution to form aqueous electron, e⫺aq. e⫺ → e⫺aq X-ray photons may act directly on water molecules to produce electronically excited water molecules, which in turn breakdown to hydroxyl and hydrogen radicals: X-ray photon ⫹ H2O → H2O* → OH* ⫹ H* The end result of the radiolysis of water is the production of OH*, H*, and e⫺aq. All these are highly reactive radicals and react readily with cellular molecules such as DNA and lipids. RH ⫹ OH* → R* ⫹ H2O RH ⫹ H* → R* ⫹ H2 The hydrogen free radical combines with dissolved oxygen to form hydroperoxyl free radicals: H* ⫹ O2 → HO2* These hydroperoxyl free radicals form hydrogen peroxide: HO2* ⫹ H* → H2O2 HO2* ⫹ HO2* → H2O2 ⫹ O2 These hydroperoxyl free radicals and hydrogen peroxide react with biological molecules, alter them and cause cell destruction.

MOLECULAR AND CELLULAR RADIOBIOLOGY Exposure of proteins to radiation leads to changes in their secondary and tertiary structures although the primary 698

structure remains unaffected. Exposure of enzymes, however, has a cascading effect, since altered enzymes may not perform their physiological actions, resulting in intracellular molecular alterations. These changes occur at radiation doses much higher than that which causes cell death. The nucleus is more often affected due to radiation, but changes can occur in mitochondria on exposure to higher doses of radiation. Mitochondria become swollen with disorganization of internal cisternae.

Radiation Effects in DNA Radiation causes a wide range of lesions in DNA such as: ❍ ❍ ❍ ❍ ❍

Single strand breaks Double strand breaks Base damage Protein–DNA crosslinks Protein–protein crosslinks involving nuclear proteins such as histones and non-histone proteins.

Most base damages, protein–DNA crosslinks and protein– protein crosslinks are usually minor damages which can be repaired and probably play a minor role in carcinogenesis. Single strand breaks are characterized by damage to a single strand of the helix of DNA and are repaired easily using the intact strand as a template. However, double strand breaks, characterized by damage to both strands at the same site or in close proximity, are more difficult to repair. Thus, they frequently result in cell death. Fortunately, these are less common in occurrence. An exposure of 1–2 Gy to a cell produces approximately more than 1,000 base damages, about 1,000 single strand breaks and only about 40 double strand breaks. Cell cycle effects Dividing cells participate in cell division which, although a continuous process, can be described in the following phases: ❍

First Gap (G1) phase or phase characterized by division of synthesis of organelles ❍ Synthetic (S) phase characterized by division of DNA ❍ Second Gap (G2) phase characterized by preparation for mitosis ❍ Mitotic (M) phase in which the actual cell division occurs. Cells not undergoing division remain in G0 phase. Typical cell division times are 10–40 hours with the G1 phase taking about 30%, S phase 50%, G2 phase 15% and M phase 5% of the cell cycle time. There are checkpoints at the G1/S and G2/M boundaries that monitor the accuracy of cell division. Radiosensitivity differs throughout the cell cycle with late S phase being most radioresistant, G2/M being most radiosensitive and G1 phase taking an intermediate position. In G2/M phase, chromatin is tightly compacted and a poor repair capacity. This explains the high radiosensitivity

Chapter 26 – Radiation Biology

of this period. DNA synthesis is almost complete by late S phase. Damage by X-rays at this phase can be repaired, and thus the cell is radioresistant at this phase. DNA has an open structure in G1 phase having a better repair capacity; this makes G1 phase radioresistant. Bystander effect Cells close to irradiated cells but not themselves exposed to radiation may also exhibit DNA damage and reduced survival. This phenomenon is termed bystander effect. This may occur due to the damaging signals communicated by irradiated cells through gap junctions, or through damaging molecules released into the surrounding medium.

DETERMINISTIC AND STOCHASTIC EFFECTS Radiation exposure can lead to many harmful health effects. Such effects were classified by International Commission on Radiological Protection (ICRP) in 1990 into deterministic and stochastic effects. Deterministic effects Deterministic effects also called ‘tissue reactions’, refer to those effects in which the severity of response is proportional to the dose. These effects, usually cell killing, occur in all people when the dose is large enough. Deterministic effects have a dose threshold below which the response is not seen. Examples of deterministic effects include oral changes after radiation therapy. Stochastic effects Stochastic effects also called ‘cancer/ heritable effects’, refer to those effects for which the probability of the occurrence of a change, rather than its severity, is dose dependent. Stochastic effects are all-or-none, i.e. a person either has or does not have the condition. For example, radiation-induced cancer is a stochastic effect because greater exposure of a person or population to radiation increases the probability of cancer but not its severity. Stochastic effects are believed not to have dose thresholds. ICRP introduced another term ‘detriment’ to measure the harmful health effects of low-dose radiation to individuals and their offsprings. The detriment in a population is defined as the mathematical expectation of the induction of cancer and hereditary damage caused by an exposure to radiation. Detriment is a complex concept combining the probability, severity and time of expression of radiation harm.

Deterministic Effects on Tissues and Organs Cellular and tissue response Based on the law of Bergonie and Tribondeau, cells may be classified into five groups based on their radiosensitivity. 1. Vegetative intermitotic cells Early precursor cells of blood cells and spermatogenic cells, and basal cells of oral

mucous membrane are all cells which divide regularly and do not undergo differentiation. These cells are extremely radiosensitive. 2. Differentiating intermitotic cells Intermediate precursors of blood cells, spermatocytes and oocytes, dividing cells in inner enamel epithelium are cells that divide less frequently and undergo some differentiation. These cells are less radiosensitive than the first group. 3. Multipotential cells Connective tissue cells such as fibroblasts, vascular endothelial cells, and mesenchymal cells are cells that divide when there is a need for more cells. These cells have an intermediate radiosensitivity. 4. Reverting post mitotic cells Cells such as acinar and ductal cells of salivary glands, and parenchymal cells of liver, kidney and thyroid are cells which are differentiated and specialized in their function. These are divided infrequently and hence are usually radioresistant. 5. Fixed post mitotic cells Cells such as neurons, striated muscle cells, epithelial cells close to the surface and erythrocytes are cells which are highly differentiated and are incapable of division. These cells are most resistant to radiation. Effects of radiation on tissues The effects of radiation treatment on normal tissues have been divided into the following: ❍

Early (or acute) response—when clinical symptoms are seen within a few weeks of radiation treatment. This response occurs in more radiosensitive tissues. ❍ Late response—when clinical symptoms take many months or years to develop. It occurs in organs where parenchymal cells divide rarely.

Effects of Total Body Radiation Acute radiation syndrome It refers to the various effects on the health of an individual exposed to high doses of radiation. These effects present within 24 hours of irradiation and may last for months. These have been classified into gastrointestinal, hematopoietic and neural/vascular presentations. Prodromal symptoms of total body radiation include nausea, vomiting, fever, headache, fatigue and a brief skin erythema. These changes occur on exposure to minimum dose of 1.5 Gy. Hematopoietic syndrome It occurs after exposure to 2–7 Gy of radiation. It occurs due to the exposure to active hematopoietic areas such as sternum and pelvis. This results in destruction of the blood cell precursors, which in turn leads to lower levels of peripheral blood cells. Circulating blood cells themselves are not affected by radiation. 699


Granulocytes which have a short lifespan, are not replaced by maturation of precursor cells. This predisposes to infections. As thrombocytes disappear in peripheral blood, bleeding ensues. As erythrocytes, which have a long lifespan, disappear, anemia occurs. Gastrointestinal syndrome It occurs after an exposure of about 7–15 Gy. Exposure of the stomach and intestines to radiation results in injury to the rapidly dividing basal epithelial cells. This results in ulceration of the mucosa, resulting in loss of plasma and electrolytes, bleeding, and diarrhea. The normal microbial flora invades the mucosa resulting in septicemia. The combined effects of gastrointestinal and hematopoietic syndromes result in death within 2 weeks. Neurovascular syndrome It occurs after exposure to more than 50 Gy of radiation. It is uniformly fatal and death occurs in 1 or 2 days. It occurs due to extensive injury to the central nervous system and the vascular system. There may be dizziness, headache, incoordination, convulsions, and stupor. Radiation effects in the developing embryo and fetus Cells and tissues in embryos and fetuses are more radiosensitive than adult cells. In the early fetus, radiation exposure has an all-or-none effect, i.e. there is either spontaneous abortion or normal development. The most sensitive period for the occurrence of developmental anomalies is between 18 and 45 days of gestation. The period of brain development, from 8 to 15 weeks post conception is also a very sensitive period. Radiation exposure during this period may result in microcephaly and mental retardation. Exposure after this period may result in general growth retardation and an increased risk for childhood cancer. However, all these changes occur after exposure to radiation levels of about 1 Gy, whereas full mouth dental radiography using a lead apron results in an exposure of just 0.25 ␮Gy. Radiation-induced heritable diseases Radiation exposure to germ cells may result in chromosomal alterations which are heritable. The major genetic effect of radiation is due to microdeletions, which refer to the deletion of multiple, functionally unrelated but contiguous genes. These effects do not cause death of the individual but result in several malformations such as mental and physical retardation and various malformations. These diseases are rare. It has been estimated that the risk of these multi-organ congenital disorders after exposure to 1 Gy is approximately 0.1%. Mechanism of radiation-induced cancer Exposure to ionizing radiation is an established cancer risk factor. Cancer risk has been described based on the linear 700

non-threshold hypothesis, according to which, at low doses and dose rates, total radiation-related cancer risk is proportional to dose. The mechanism of carcinogenesis is thought to be due to gene mutations. These may not be repaired and the unrepaired genes may be transmitted to daughter cells, which may lead to the development of cancer. It has been suggested that radiation acts as both an initiator and a promoter of carcinogenesis.

Effects of Radiation on Oral Tissues One of the modalities used in the treatment of cancer is radiotherapy. Irradiation of a high dose given to patients suffering from cancer in the orofacial region invariably exposes the oral tissues. The source of radiation is usually gamma rays from external source, while brachytherapy with inserted radon or iodine-125 implants may occasionally be used. The dose of radiation is about 50 Gy, given in divided doses of 2 Gy/day. This results in several effects which are described below. Mucositis The basal layer of the oral mucosa consists of dividing cells which are susceptible to radiation damage. Death of these cells results in mucositis. Mucositis begins 12–17 days after initiation of radiotherapy. Based on severity, mucositis has been classified into four grades: Grade 1 Begins at the end of first week of radiotherapy. Characterized by the presence of white areas in the oral mucosa due to hyperkeratosis. This stage is usually asymptomatic. Grade 2 Occurs around the end of second week of radiotherapy. Small areas of ulceration are noted. Patient can take a soft diet. Grade 3 Severe mucositis characterized by large ulcers covered by pseudomembrane. Patient has pain and difficulty in eating and can tolerate only liquid diet. Grade 4 Even more severe mucositis characterized large areas of ulceration covering almost the entire oral mucosa. Patient can consume only liquids, or may need nasogastric intubation. Mucositis continues up to the completion of radiotherapy. After this, the mucosa heals and healing is complete by 2 months. Later, the mucosa tends to become atrophic. Xerostomia Salivary glands are frequently in the path of radiation and are exposed during radiotherapy. The parenchyma of these glands is radiosensitive, which finally results in a fibrosis of the gland. This results in a progressive decrease


in salivary secretion, termed xerostomia. This decrease is dose dependent and secretion reaches zero at about 60 Gy. Patients complain of dry mouth and difficulty in swallowing. As lubricating properties of saliva are lost and its pH decreases, demineralization of enamel begins. Teeth Mature teeth are not affected by radiation, however, radiation doses as low as 400 cGy may retard the development of incompletely formed teeth. Irradiation to developing teeth may result in short roots, incomplete calcification, dilaceration, and delayed or arrested eruption. Radiation caries It is a form of rampant caries that occurs in individuals exposed to curative radiation. Radiation causes a change in saliva by decreasing its secretion, lowering its pH, and reducing its buffering capacity. This reduces the cleansing action of saliva on teeth and results in accumulation of debris, demineralization, and finally, rampant caries. Three types of radiation caries have been described: Type 1: The most common type. It is characterized by caries occurring around the teeth in the cervical region. As caries deepens, there is amputation of the crown. Type 2: It is characterized by the initiation of caries on all crown surfaces, eroding away the entire coronal structure. Type 3: The least common type. It is characterized by color changes in dentin resulting in a diffuse blackening or dark brown discoloration of the crown.

radiation and have adequate knowledge regarding the methods to minimize unnecessary exposure to radiation. This section will attempt to highlight various measures to protect the patient, radiation personnel and public from the long-term hazards of diagnostic radiology.

Historical Events in Radiation Safety and Protection ❍

❍

❍

❍

Osteoradionecrosis It refers to the secondary infection of irradiated bone. Radiation exposure to bone affects the vascularity of bone, destroys osteoblasts and some osteoclasts. The normal vascular bone marrow is converted to fatty and fibrous marrow. Thus, the marrow tissue becomes hypoxic, hypovascular and hypocellular. If secondary infection is then superimposed on irradiated bone, the bone readily undergoes necrosis. Infection may occur from sequelae of caries, periodontitis, denturesore or a tooth extraction. Osteonecrosis is more common in mandible than the maxilla, presumably because of the rich vascular supply of maxilla, and also since the mandible is irradiated more frequently. Thus, before the initiation of radiotherapy, the dental status of a patient should be assessed. Any pre-existing disease such as caries, periodontal disease, third molar pathology, defective restoration, etc. should be treated.

RADIATION SAFETY AND PROTECTION It is imperative that dental professionals as well as the public are aware of the potential hazards of the ionizing

❍

❍

X-ray induced case of severe dermatitis was published in July 1896. The first dose limit of 10 rad per day (or 3,000 rad per year) was recommended in 1902 based on fogging observed on a photographic plate. The destructive effect of X-rays on living tissues, such as skin, blood forming-organs and reproductive organs was first evident by the animals studies performed in 1903. In 1928, the first formal radiation unit—the roentgen, was adopted. In 1953 and 1954, the bone marrow dose limit of 300 millirem (mrem) per week and skin dose limit of 600 mrem per week was adopted by ICRP and NCRP (National Council on Radiation Protection and Measurements), respectively. An annual occupational dose limit of 5 rem per year was recommended by ICRP in 1957. A lifetime occupational dose limit of 235 rem for individuals in the age group between 18 to 65 years and an annual dose limit of 500 mrem per year to public was recommended by NCRP in 1958. The three parts of dose control—justification, optimization and limitation was put forth by ICRP, in 1961 (Table 3). The ALARA (As Low As Reasonably Achievable) guidelines for radiologic protection for radiation personnel, the maximum annual radiation dose limit of 5 rem per year was recommended. In 1980, ICRP limited the radiation exposure to 10 rem over any 5-year period and 5 rem in any 1 year. The public limiting dose as 100 mrem per year averaged over any 5-year period.

SOURCES OF RADIATION (Table 1, Figure 1) Radiation is the transmission of energy through space and matter. It is natural and part of our lives. The radioactive materials present naturally in the earth’s crust can be encountered in the building construction materials, food substances and the air we breathe. Muscles, bones, and tissues of our own bodies contain naturally occurring radioactive elements. It is estimated that about four-fifths of the average annual radiation dose worldwide is the contribution from natural radiation. 701


Table 1

Average effective dose of ionizing radiation from different sources

Source

Dose (␮Sv)

Natural Cosmic

0.4

Terrestrial External Radon Other

0.5 1.2 0.3 2.4

Total Man-made Medical (estimated) Diagnostic X-ray Nuclear medicine

2 0.5 0.08

Other consumer products Other Professional Fallout Nuclear fuel cycle Dental radiology

0.01 0.01 0.01 0.01 2.5

Total

Cosmic sources It is estimated that cosmic radiation accounts for about 8% of the annual total body exposure. In different parts of the world the cosmic radiation varies in dosage due to difference in altitude (radiation doubles for every 6,000 feet) and magnetic field. The sources of cosmic radiation are protons, electrons, X-rays and gamma rays. Terrestrial sources Terrestrial sources originate from both external and internal sources; external sources being soil and internal sources, including radon and other nuclides that are inhaled or ingested. Radon contributes 1.2 mSv to natural radiation and the average whole body radiation from it is 228 mrem per year. Potassium-40 and carbon-14 are two of the main enlisted internal sources of radiation. The entrapment of radioactive materials by the body’s own tissues through the soil, water and air constitute about 11% of our total annual exposure.

Man-made Radiation

Figure 1 Nuclear medicine 4%

Consumer products 3%

Other 1%

Cosmic rays 8% Terrestrial 8% Internal sources 11%

Sources of radiation exposure radon 54% Medical X-rays 11%

Sources of radiation exposure

Natural Radiation The natural background radiations are from three sources— cosmic radiation, terrestrial radiation and internal radiation. The annual effective dose of radiation from cosmic and terrestrial sources is about 2.4 millisieverts (mSv) worldwide. The average whole body radiation to an individual from background radiation is estimated to be around 620 mrem. 702

Exposure to man-made radiation increases depending on its usage; place of residence, lifestyle, pattern of house construction, kind of traveling and smoking also affects radiation exposure. People residing in the coastal regions are more protected than airline crew due to the thick cover of earth’s atmosphere. Medical and dental diagnosis and treatment Medical and dental X-rays account for an average of about 11% of our total annual exposure. But dental X-ray examinations account for less than 1% of the average annual exposure from man-made exposures. Annually worldwide, over one billion medical examinations and 300 million dental examinations are performed which include radiation therapy, nuclear medicine and diagnostic medical exposure. The average dose received from all medical exposures is 300 mrem which represents six-fold increase in average medical exposures over the past 25 years. Half of the average background medical exposure (147 mrem) is from computed tomography (CT) examinations, a relatively new technology that has significantly improved diagnostic imaging. For a professional medical or dental radiologist, technologist or assistant, the occupational dose limit is 5,000 mrem per year. For the non-medical or dental public, the dose limit is 100 mrem per year. Although the risk involved in dental radiography is very less, it becomes imperative for the practitioner to avoid even the smallest unnecessary dose of radiation in working area. For this, developing basic concepts on radiation units and measurements and applying the same for safety and protection measurement is indispensable (Table 2).


Table 2

Radiation unit conversion factors Radiation units of measurements

Unit of measure

Conversion equivalent

1 curie

3.7 ⫻ 1010 disintegrations/second

1 becquerel

1 disintegration/second

1 millicurie (mCi)

37 megabecquerel (MBq)

1 rad

0.01 gray (Gy)

1 rem

0.01 sievert (Sv)

1 roentgen (R)

0.000258 coulomb/kilogram (C/kg)

1 megabecquerel (MBq)

0.027 millicurie (mCi)

1 gray (Gy)

100 rad 1 joule/kilogram

1 sievert (Sv)

100 rem 1 Gy ⫻ Wr

1 coulomb/kilogram (C/kg)

3,880 roentgen

For diagnostic and therapeutic purposes of a patient, NO LIMIT has been set for the exposure. Consumer and industrial products Consumer products account for 3% of annual exposure (0.10 mSv). To name a few—smoke detectors, color television, domestic water supply, tobacco products, combustible fuel, dental porcelain, pocket watches are all included in this group. Other man-made sources Workers in mining, milling, nuclear plants including weapons are occupationally exposed to radiation. Among these sources strontium-90 and iodine-131 are important. Strontium-90, a beta emitter gets easily assimilated in bones and teeth of children and young adults due to its chemical similarity to calcium. Iodine-131, a gamma emitter gets accumulated in the thyroid gland. Nuclear power contributes 0.01 mSv annual exposure.

DOSE AND RISK IN RADIOGRAPHY The goal of health physics is prevention of deterministic effects and reduction of stochastic effects by minimizing the exposure of radiation workers and patients during radiographic examinations. This is usually performed by the government agency, regulatory bodies, advisory bodies or registered bodies by setting up regulations. This limits the individuals who are occupationally exposed, patients and general population, from unnecessarily being exposed to radiation. This section deals with radiation dose, risk and limitations in medical and dental radiography.

Dose limits The regulatory bodies at the international and national levels, namely, ICRP, its counterpart the NCRP in the United States, and the Atomic Energy Regulatory Board (AERB) in India have laid down recommendations for radiation safety and protection to humans without limiting their beneficial application. In spite of low dosage in dental radiography, radiation should be minimized wherever practicable. The efficacy of radiology department lies in wise choice of investigative procedures which aims at reduced radiation exposure and diagnostic accuracy.

Patient Exposure and Dose Risk estimates Man-made as well as naturally occurring radiation can result in birth defects. Six out of one hundred live-births can present birth defects from natural radiation. This fact may be explained with the concept that the fetus which has a rapid rate of development and a yet to be formed immune mechanism is vulnerable to hazardous chemicals and infections. The severity of the complication exhibited by the fetus depends on the radiation dose as well as the stage of growth (particularly, specific organ defects) at the time of exposure. Severe birth defects including mental and physical growth retardation can occur if a pregnant lady is exposed to a radiation dose higher than 100 rem. The ignorance period of radiation exposure to birth defect will be between 8–12 weeks of gestation period, the time matching with the non-conformity with pregnancy. Small head size can result if the radiation received in the womb is greater than 10 rad. If a dose of 25 rad is received after 8 weeks of gestation period, mental retardation along with a small head size is seen. For public The whole body’s maximum permissible dose is 100 mrem (1 mSv) in a year or the average dose for 5-year period should not exceed 100 mrem (1 mSv). For occupational exposure The whole body’s maximum permissible dose is 2 rem (20 mSv) and over 5 years should not exceed 100 mSv. The effective dose should not exceed 30 mSv in any single year.

Reducing Dental Exposure ICRP is a non-governmental, independent organization, a registered charity, created in 1928 by International Congress of Radiology, the primary body in protection against the unwise usage of ionizing radiation in different fraternity including medicine, dentistry, industry, nuclear enterprise and also from naturally occurring radiation sources. 703


The reports and recommendations of ICRP are published four times a year in the journal Annals of ICRP. The key principles of ICRP are:

(American Dental Association) and FDA (Food and Drug Administration) for dental radiographic examination which include the following:

1. Principle of justification This means the situation dependent alteration of radiation exposure should be beneficial for the receiver.

1.

2. Principle of optimization of protection This means to follow ALARA principle for individual or mass radiation protection. 3. Principle of application of dose limit This implies for usage of radiation in different field area, the ICRP dose limit recommendation should be followed with exception in medical fraternity and unexpected or urgent attention situations. Patient selection criteria Clinical examination is a must irrespective of the kind of receptor and the imaging operating technique. Radiographic exposure in an asymptomatic patient is non-evidence supportive. But in a symptomatic patient, the images should be limited to diagnosis and treatment plan in addition to adherence to published patient selection criteria by ADA

Dose limits Application

Dose limits Occupational

Effective dose

Annual equivalent dose Lens of the eye Skin Hands and feet

20 mSv per year, 1 mSv in a year averaged over a period of 5 consecutive years 150 mSv 500 mSv 500 mSv

15 mSv 50 mSv

Effective doses from conventional dental imaging techniques in Sv Examination

Effective dose (␮Sv) ⬍1.5

Panoramic radiograph

2.7–24.3

Rem

Sievert

Cephalometric radiograph

⬍6

Whole body

5

0.05

Maxillomandibular MSCT

280–1,410

Individual organ or tissue other than the lens of the eye

50

0.5

Lens of the eye

15

0.15

Skin

50

0.5

Typical doses from common diagnostic radiology procedures

Extremity

50

0.5

Examination

Estimated loss of life expectancy from health risks

MSCT: multislice CT.

Skull radiograph PA chest radiograph

Health risk

704

Public

Intraoral radiograph

Annual allowable occupational dose Part of the body

Consideration to be given to patient’s susceptibility to dental caries and periodontal disease, growth and development stage and other unambiguous status.

Estimate of reduced life expectancy (average)

Cigarette smoking—20 per day

6 years

Overweight (15%)

2 years

Alcohol ingestion

1 year

All kinds of accidents

1 year

Motor vehicle accidents

207 days

Home accidents

74 days

Drowning

24 days

Natural hazards (earthquake, lightning, flood, etc.)

7 days

Medical radiation

6 days

Occupational exposure 0.3 rem/yr from age 18 to 65 1 rem/yr from age 18 to 65

15 days 51 days

Effective dose (mSv)

Equivalent period of natural background radiation

0.18

2.6 weeks

0.029

3.4 days

8

Computed tomography: head

2

1 year

Computed tomography: chest

88

4 years

Barium meal

8

5

2.5 years

PA: posteroanterior.

Dose guidance levels for computed tomography for a typical adult patient Guidance levels of dose for diagnostic radiography for a typical adult patient Examination Head

Multiple scan average dose (mGy) 50

Lumbar spine

35

Abdomen

25


Effects resulting from acute whole body external exposure of radiation to men 0–25 r

25–100 r

100–200 r

200–300 r

300–600 r

600 or more

No detectable clinical effects

Slight transient change in lymphocytes and neutrophils

Nausea and fatigue with possible vomiting above 125 r

Nausea and vomiting on first day

Nausea, vomiting and diarrhea in first few hours

Nausea, vomiting and diarrhea in first few hours

Latent period up to 2 weeks or perhaps longer

Latent period with no definite symptoms, perhaps as long as 1 week

Short latent period with no definite symptoms in cases during first week

Delayed effects may occur

Disabling sickness not common, exposed individuals should be able to proceed with usual duties

Reduction in lymphocytes and neutrophils with delayed recovery

Following latent period symptoms are mild: loss of appetite, malaise, sore throat, pallor, petechiae, diarrhea, moderate emaciation

Epilation, loss of appetite, general malaise and fever, during second week followed by hemorrhage, purpura, petechiae, inflammation of mouth and throat, diarrhea and emaciation in the third week

Diarrhea, hemorrhage, purpura, inflammation of mouth and throat, fever toward the end of first week

Delayed effects possible, but serious effects on average individual very improbable

Delayed effect may shorten life expectancy in the order of 1%

Recovery in likely about three months, unless complicated by poor previous health, superimposed injuries or infections

Some death in 2–6 weeks, possible eventual death to 50% of the exposed individuals for about 450 r

Rapid emanciation and death as early as the second week with possible eventual death of up to 100% of exposed individuals

r: Rads.

NCRP and ICRP radiation protection recommendations Recommended annual limits for human exposure to ionizing radiation Recommendation

NCRP

ICRP

Relative to stochastic effects

50 mSv annual effective dose limit and (10 mSv) (age [yr]) cumulative effective dose limit

50 mSv annual effective dose limit and 100 mSv in 5 years cumulative effective dose limit

Relative to deterministic effects

150 mSv annual equivalent dose limit to lens of eye and 500 mSv annual equivalent dose limit to skin and extremities

150 mSv equivalent dose limit to lens of eye and 500 mSv annual equivalent dose limit to skin and extremities

Occupational dose limits

Non-occupational (public) dose limits Relative to stochastic effects

5 mSv annual effective dose limit for infrequent exposure and 1 mSv annual effective dose limit for continuous exposure

1 mSv annual effective dose limit and if higher, not to exceed annual average of 1 mSv over 5 years

Relative to deterministic effects

50 mSv annual equivalent dose limit to lens of eye, skin and extremities

15 mSv annual equivalent dose limit to lens of eye and 50 mSv annual equivalent dose limit to lens of eye, skin and extremities

Embryo/fetus

0.5 mSv equivalent dose limit per month after pregnancy is known

2 mSv equivalent dose limit after the pregnancy has been declared

Negligible individual dose

0.01 mSv annual effective dose

None established

2. 3. 4.

Radiographs based on sound professional judgment on clinical diagnosis and treatment plan. To avoid routine dental radiographs for all patients at preset intervals. Prescription of dental radiograph may be based on clinical suspicion of oral disease secondary to medical or dental history.

5.

6.

For a referred patient, the clinician’s first option should be to obtain all the previous medical and dental records including radiographs from previous health care providers which help in comparing as well as future investigations and treatment protocols. For female patients under gestation period, it is best to adhere to FDA selection criteria guidelines. In these 705


7.

patients, to prevent the transmission of diseases from mother to fetus through dental diseases and to diagnose and manage the same, dental radiographs become obligatory. Patients under treatment for head and neck malignancy, no special consideration is necessary as the risk of developing oral diseases is of high rate rather than the diagnostic usage of X-ray exposure for review patients.

Conducting the Examination As the patient selection for radiographic examination is justified, the choice and operation of the equipment, the radiographic technique, processing and interpretation of the image, will also have an impact on patient radiation exposure. Conducting examination should be under protection beneficiary for both patient and the operator. Choice of the equipment A boon to the modern dental health care is to have qualitative diagnostic radiographs which are preliminarily as a result of good X-ray equipment with certain basic requirement. 1. Control panel requirements a. Warning signals incorporation: (i) during unauthorized usage, (ii) during X-ray emission b. X-ray machine status indicators: should alert (i) when energized to produce X-rays, (ii) when a single control panel is controlling multiple X-ray tubes, each X-ray tube should have a separate indicator during ready for usage and one usage at a time by interlock option. 2. Irradiation switch: Must be an intentional pressure operator. If cable mounted or wall mounted, the exposure timer should be placed about 10–12 feet away from the X-ray tube. 3. Exposure parameters indicators: Indicators like electrical meters are advisable for adjustable X-ray tube voltage, X-ray tube current and timer. For non-adjustable indicators—permanent markers or labels can be sufficient. 4. X-ray tube voltage: To operate the X-ray tube, the minimum tube voltage should not be below 50 kilovolt peak (kVp). The actual kVp should not deviate 7% the selected value from the manufacturer. 5. X-ray tube current: The actual value should not depart 5% by the manufacturer specification. 6. Timer: It should be a. An automated electronic timer b. An automated or manual preset loader with zero or OFF position starter set c. Automated termination after each exposure d. The maximum pre-settable irradiation time should be within 5 seconds, or the time required to deliver 50 milliampere-seconds, whichever is shorter. 706

7. Filtration: Radiation absorbing filters, aluminum, the degree of attenuation should not be less than the halfvalue layer of the X-ray beam. 8. X-ray tube mechanical stability: Within the tube housing, the X-ray tube should be aligned and precisely fixed by mechanical means without vibration, drift or movement. 9. X-ray tube protection: By enclosing within shielded housing. The housing should be leakage proof and should not exceed 0.87 mGy (100 mR) in 1 hour. The tube leakage is measured at a distance of 1 m in any direction from focal spot. 10. Position indicating device (PID): It must be open ended. Pointed cone or close ended applicators should not be used. It limits the minimum focal spot to skin distance above 18 cm. 11. Beam limiting devices: These are collimators at the end of applicators, round or rectangular size with the size of 7 cm or 38.5 cm2 for round and rectangular collimators, respectively. Panoramic X-ray equipment 1. 2.

3.

4.

Position-indicating device: should not be less than 15 cm. Collimators: should be of scanning slit dimension or 2% of the focal spot to image receptor distance, whichever is less. Cassette carrier: should be irradiation proof and interlocked. Irradiation is possible only with film cassette in the cassette carrier. Timer: The maximum presettable irradiation time must be within 25 seconds, or the time required to deliver 250 milliampere-seconds, whichever is shorter.

Cephalometric X-ray equipment Collimator The central beam of X-rays should be fully blocked by the film cassette at the focal spot to film distance. The round collimator should provide the central X-ray beam size within 30 cm in diameter or with the rectangular collimator, 800 cm2 area, at a distance of 1.5 m or maximum focal spot to film distance, whichever is less. Film receptors The film speed standard was pioneered by the American National Standards Institute and the International Organization for Standardization. A, B, C, D, E and F film speeds are available in dental radiography with A-speed being slowest and F-speed being the fastest (Figure 2). The exposure to the patient will be reduced by 50% without forfeiting the diagnostic quality by the faster films. So the films lesser than E-speed are not desirable to be used in dental radiography.


Figure 2

Typical doses from dental radiographic examinations Acceptable X-ray exposure ranges speed groups D, E and F film

600

Examination

Effective dose (mSv)

Equivalent period of natural background radiation

2 X bitewings, 70 kV, 200 mm FSD2, rectangular collimation, E-speed film

0.0023

8.8 hours

2 X bitewings, 70 kV, 200 mm FSD2, round collimation, E-speed film

0.0043

17.5 hours

2 X bitewings, 50–60 kV, 100 mm FSD2, round collimation, E-speed film

0.0083.7

1.5 days

2 X bitewings, 50–60 kV, 100 mm FSD2, round collimation, D-speed film

0.0163.5

3 days

Dental panoramic, rare earth intensifying screens

0.0074

1.3 days

Dental panoramic, calcium tungstate intensifying screens

0.0144

2.6 days

550 500 450

mA of 10–3 Gy

400 D

350 300

E

250 200 F 150 100 50 0 50

60

70 80 Kilovoltage

90

100

Relationship between surface exposures delivered to a patient by exposure of group D, E, F intraoral films and diagnostic density at various kilovoltages

Intensifying screens used in extraoral films reduce the patient exposure to radiation. This accounts to 55% reduction with rare earth intensifying screen compared to its contemporary calcium tungstate intensifying screens. The phosphor crystals in the intensifying screen fluoresce when exposed to radiation and in turn that light exposes the film aiding in reduced exposure. Film storage For film storage, dry and cool area is preferable. The limitation for radiation perception before use should not exceed 1.75 Gy (0.2 mR). Shielding of film storage is time dependent and 1.5 mm of lead shielding is sufficient for all kinds of workload facility.

Digital Radiography Numerical formatting with networked computer system in obtaining high quality image constitutes digital radiography. This adopted software technology in imageology has the additional advantage of reduced exposure to both patient and operator, speedy recovery of the image, digital storage of the image with its electronic transmission, discontinuation of chemical processing and its associated hazardous wastage, elimination of lead foil, saving darkroom equipment and adjustable diagnostic quality of the image.

Intensifying Screen The rare earth phosphors in modern intensifying screens emit green light on interaction with X-rays. The rare earth intensifying screens decrease patient exposure up to 55% in panoramic and cephalometric radiography. A further reduction in patient exposure during extraoral radiography may be achieved with the use of T-grain film. Introduced as T-Mat by the Eastman Kodak Company in 1983, this film contains silver halide grains that are tabular or flat in shape. With its flat surface and greater cross-section oriented toward the X-ray source, it can gather more light from intensifying screens. T-grain film used with rare earth screens is twice as fast as calcium tungstate screen-film combinations and thrice as fast as conventional rare earth screen-film combinations with retained image quality. The T-grain technology was incorporated into intraoral film by Kodak to achieve the faster speeds of E and F films. Extraoral films exposed by intensifying screens achieve a level of image resolution that is about half of the direct exposure intraoral film. One reason for image degradation in extraoral imaging systems is crossover; which refers to the loss of image sharpness and resolution resulting from light emitted by one screen passing through the X-ray film to expose the emulsion on the opposite side of the double emulsion film. The Ultra-Vision (DuPont) and Ektavision (Kodak) screen film systems were designed to minimize crossover by using phosphors that emit ultraviolet light, which is less able to pass through the film base to expose the opposite emulsion. 707


Results have shown that images produced by these systems have higher resolution than corresponding rare earth screen-film systems. This allows for the use of a screen one speed class higher and a 50% reduction in patient exposure. Unlike digital intraoral imaging, there is no significant dose reduction to be gained by replacing extraoral screenfilm systems with digital imaging. Image resolution with digital systems appears to approach that obtained with rare earth regular-speed screens matches with T-Mat film.

Source to skin distance Distance is one of the important parameter in reducing the exposure to an individual. Source to skin distance is one of the parameters in reducing the exposure to an individual. The inverse square law, ␣ I/d2 is pertinent, which states that exposure and distance are inversely proportional. If the distance is doubled, the exposure is reduced by fourfold. ‘I’ stands for intensity of radiation and ‘d’ stands for distance. Source to image receptor distance (SID)

Grids Grids are the devices used in extraoral radiography to improve the image quality by reducing the scattered radiation. Though the grids require slightly higher exposure, the advantage of obtaining high quality radiographs, transcend the minor risk of increased radiation dose to the patient. This in turn reduces the repeated chance of exposure.

Figure 3 16" distance

The appropriate SID is another distance related parameter in reducing the patient exposure and also repeated exposure. Concentration of photons in patients has direct relation with SID. Longer the SID, lesser is the exposure due to less divergent beam (Figure 3). Shorter the SID, greater is the exposure secondary to concentration of photons. Variation in SID results in compromised film density. So, it is advisable to stick to recommended standardization. The primary beam should be within 2% of the SID. Collimation

8" distance

Source to image distance

Image Film

Collimator reduces the radiation exposure by limiting the primary and scattered beam of radiation which sequentially helps in recuperating the image quality. The central X-ray beam should be within the minimum coverage area. The Federal Regulation (US) has recommended the restricted diameter of collimator beam to 2.75 inches at the patient’s face. To reduce the radiographic exposure in intraoral radiographs, an inbuilt rectangular collimator in radiographic machine can be a complimentary (Figure 4). This will reduce the radiation dose up to five-fold in comparison with the circular ones.

Figure 4

Round and rectangular collimators

708


Figure 5

Skin entrance exposure Patient examination view

Skin entrance exposure

Dental bitewing (3 inch diameter area)

300 mrem—film 90 mrem—digital radiography 140 mrem—computed radiography

Chest X-ray (14 ⫻ 17 inch area)

20 mrem

Abdominal film (14 ⫻ 17 inch area)

300 mrem

Lumbar spine (14 ⫻ 17 inch area)

350 mrem

Extremity X-ray (8 ⫻ 10 inch area)

30 mrem

Skull X-ray (8 ⫻ 10 inch area)

100 mrem

Breast (mammogram) (glandular tissue dose)

175 mrad

Long position indicating device

filter and for above 70 kVp, 2.5 mm aluminum filter are the recommendations.

Figure 6

Lead aprons and collars Tube head

Cylinder tip

Cylinder

Lead diaphragm Aluminum filter

Aluminum filter

Position Indicating Device A long position indicating device (PID) with open ended and metallic lining reduces the radiation exposure by restricting the primary beam and reducing the tissue volume exposed to radiation (Figure 5). Filtration The aim of filtration is to reduce the patient exposure by absorbing low energy photons from beam of X-rays which do not have any role in the diagnostic image (Figure 6). Absorption of low energy photons increases the mean energy of the primary beam in addition to its penetrating power. There is 20% reduction in exposure with an inbuilt X-ray machine of 3 mm of aluminum filters. So half-value layer is designated for specific amount of filtration in dental X-ray machines operating at a choice of kilovoltages. For X-ray machines operating at 50–70 kVp, 1.5 mm aluminum

Lead aprons and thyroid collars are the patient protecting equipments used against scattered radiation. The recommended lead shielding outfit for radiation workers is of 0.5 mm thickness. These protecting equipments are strongly recommended for children and pregnant women as they are susceptible to radiation effects but not to all adult patients if recommended guidelines are followed stringently. As part of maintenance and long shelf life, the leaded shields should always be hung and not folded to prevent crack formation. Film and sensor holders The clear-cut alignment of the collimated beam with the teeth or jaws can be achieved through the film holder or the digital sensor holders. In addition, PID also helps in proper alignment and prevention of cone cut images. This will prevent the repeated unnecessary unacceptable images. Among intraoral periapical radiographic techniques, paralleling technique will reduce the exposure to more than half the bisecting angle technique which is mainly based on the alignment of the film holder with the PID. For safety infection control, disposable holders or sterilizable ones are recommended. To reduce the radiation exposure to the clinician, he/she should not hold the holders during exposure. Under extraordinary situation, the patient attender should be under moderation to hold the film after being prepared with appropriate shielding. Kilovoltage Kilovoltage is the energizing exposure factor that controls the X-ray beam. This operating potential affects the radiation 709


dose and the backscatter radiation. Though the operating potential of dental X-ray machine ranges between 50 and 100 kVp, the operating potential between 60 and 80 kVp is the most useful for diagnostic purposes. For less than 60 kVp machine, an internal installation of aluminum filter makes the mean beam energy to 60 kVp. As the kVp increases, there will be an increase in the effective energy of the X-ray beam and image contrast will decrease. This helps in visualization of smaller difference in density within the object, better resolution and reduction in the effective dose, for example, in periodontal diseases. As the kVp decreases, there will be decrease in the effective energy of the X-ray beam and image contrast will increase and there will be higher entrance skin dose, for example, in visualization of caries and soft tissue calcification. The introduction of constant-potential (fully rectified), high-frequency or direct current (DC) dental X-ray units have made possible the production of diagnostic quality radiographs with lower kilovoltage and at reduced levels of radiation.

always beneficial to humans. Therefore, we should respect radiation rather being afraid of it. In spite of less radiation exposure to dental professionals compared to other fraternity, it is indispensable to minimize occupational exposure to ionizing radiation. For a health care worker, the maximum permissible annual dose limit is 50 mSv and maximum permissible lifetime dose is 10 mSv multiplied by person’s the age in years. For operating personnel, it is recommended to use protection barrier. For this reason, the operator protection measures including education, the implementation of a radiation protection program, annual and lifetime limits of exposure to ionizing radiation, recommendations for personnel dosimeters and the use of barrier shielding should be incorporated.

X-ray Equipment Installation and Related Factors 1.

Milliampere-seconds Exposure time is the most vital factor in influencing diagnostic quality. Both overexposed and underexposed radiographs result in repeated exposures, thereby leading to needless additional patient exposure. Milliampere-second (mAs) is the combination of milli amperage and exposure time affecting the quantity of X-rays produced and sequentially the image density. Patient exposure is directly related to mAs. Typically a radiograph of correct density will demonstrate very faint soft tissue outlines. Enamel and dentin will have an optical density of about 1.0. Optimal image density can be obtained by using values listed, after considering the age and physical stature of the patient. For example, 3.5 mAs is suggested for an average adult when F-speed film and an operating kilovoltage of 70 are used. This value may be arrived at by using milliamperage of 10 and an exposure time of 0.35 second. If the kilovoltage is increased to reduce image contrast, the mAs must be decreased or the radiograph will be overexposed. Phototiming technique uses a phototimer to measure the quantity of radiation reaching the film and automatically terminates the exposure when enough radiation has reached the film to provide the required density. A form of this technology is currently available with some panoramic machine.

Protecting Personnel Radiation and humans are inseparable. Minimal usage in daily activities, diagnostic and therapeutic modalities is 710

2.

3.

The concluding X-ray equipment installation plan, either a new or amendment of the existing one has to be reviewed by an appropriate government agency. The plan and supplementary papers should clearly state the following: (i) the design and dimension of the X-ray equipment operating room; (ii) the materials used for construction, barrier, shielding should be mentioned; (iii) the position of doors, windows and louvers; (iv) status of adjacent or surrounding area, above and below the room facility; (v) concise narration of the X-ray unit, manufacturer details and working parameter; (vi) information on location and orientation of dental chair, ray equipment, patient and film supporting devices. The X-ray equipment installation should be in a safe environment, providing safety for both patient and operator by directing the primary radiation always toward the shielded barrier or an unoccupied area. The setting of switching off the X-ray equipment should always be located outside the room, behind an adequate barrier with sufficient distance from the primary source.

X-ray equipment room design 1.

2.

3.

4.

First of all, the X-ray equipment installed room should be designed such that the operator is not exposed to the primary radiation beam. For designing the shielding of the X-ray equipment room, including the floor, wall, ceiling and door, the location and dimension of the room, equipment parameters including workload, tube voltage, etc., should all be taken into consideration. Lead is the choice of material for room shielding. This should be uninterrupted and with supportive barrier to prevent drooping. The CT room dimension should be above 25 m2.


Figure 7

Figure 8

Protection of the operator

Lead gloves

Protection of the operator 1.

2.

The operator should stand at least 3 meters or 6 feet or at an angle of 90–135 degrees from the X-ray tube or the central X-ray beam. To view the radiographic procedures by the operator without protective barrier, leaded glass window or shielded barrier view is an alternative option (Figure 7).

Figure 9

Radiation protection inspection 1.

2.

It should be on a customary basis to have an updated and validated standard of working condition according to parliamentary requirements. Implementation and maintenance of Quality Assurance Program.

Shielding Radiation shielding is a mass of radiation absorbing material placed around the radiation source to reduce the radiation to a safe level for humans. Different types of shielding in diagnostic radiology are: 1. 2. 3. 4. 5.

Operating personnel shielding Patient shielding X-ray equipment room shielding X-ray tube shielding Patient waiting room shielding.

Lead apron and thyroid collar

minimum 0.5 mm of lead equivalence protection device is necessary.

Personnel shielding Appropriate personnel shielding can be achieved by having (i) a lead protective barrier of 1.5 mm between operator and X-ray tube; (ii) lead apron and gloves of 0.25 mm thickness (Figures 8 and 9); (iii) lead gonadal shield of 0.5 mm thickness. For any specialized radiological investigation,

Patient shielding The susceptible organs, namely, thyroid, breasts and gonads should be shielded in children and young adults with 0.25 mm of lead thickness for lead apron, collar and gloves and gonadal shield of 0.5 mm of lead thickness. 711


X-ray equipment room shielding

Patient waiting area

A few of the mandatory decisive factors about X-ray equipment room are:

1.

1.

2. 3. 4.

5.

The equipped room location should always be away from maternity and pediatric wards and with the minimum dimension of 18 m2. The wall opposing the central beam must be of minimum 35 cm thick brick. The wall opposing the scattered beam must be of minimum 23 cm thick brick. For protection of adjacent area, the door and windows of the X-ray equipped room should be at least 23 cm thick brick or 1.7 mm of lead equivalent. For ventilation or natural lightening, an unshielded opening of 2 m above height from the finished level outside the X-ray equipped room is permissible.

Shielding of X-ray control room It is a secondary protective measure from ionizing radiation. Based on the operating potential, the control room can be situated either within the X-ray equipped room or outside. If the operating potential is up to 125 kVp, the controlling panel can be situated within X-ray equipped room with a minimum distance of 3 m between fixed X-ray equipment and the control panel. If the operating potential is above 125 kVp, then the control panel should be installed outside the X-ray equipped room with appropriate shielding for the room along with accommodation of direct vision and oral communication. The location of the control booth should be in such a way that the primary beam should scatter twice before entering the room. In addition to this, the control booth wall and window shielding should be of 1.5 mm lead thickness.

2.

3.

The patients’ waiting area should be outside the X-ray room. A suitable alert signal in the form of red light should be placed at a noticeable place outside the X-ray room and should be kept in ON position during working to warn the people. A warning placard should be attached at the eyecatching place.

RADIATION DETECTION AND MEASUREMENT The principle behind detecting the radiation is the physical and chemical effects produced by the radiation. The following are the principal methods used to detect radiation: 1. 2. 3. 4.

Ionization Photographic effect Luminescence Scintillation.

Ionization The process of converting an atom or molecule into an ion by adding or removing charged particles such as electrons or ions is termed as ionization. Principle

Ionization in air by radiation.

Radiation detection device The ionization chamber (Figure 10). Functioning mode It consists of an electrode positioned in the middle of a cylinder that contains gas. When X-rays enter the chamber, they ionize the gas to form negative

X-ray tube shielding (source shielding) The rationale of X-ray tube shielding is to protect the patient and operating personnel from leakage radiation. This can be achieved by placing thin sheets of lead lining over tube housing, which helps in reducing the scattered radiation. The limitation of radiation leakage exposure rate is 0.1 R h⫺1 at 1 m. The recommended maximum allowable leakage radiation from tube housing should be less than 1 mGy h⫺1/100 cm2.

Radiation in the CT Suite In the CT suit, in order to reduce the scattered radiation from 0.3 Gy/day to 1 mGy/year, an additional lead thickness of 2.5 mm or 162 mm of concrete to shield the front and rear reference point is recommended. 712

Figure 10

Radiation source −

−

−

−

+

+

+

+ A

Ionization chamber

−

Ionization chamber

+

−


ions (electrons) and positive ions (positrons). The electrons are collected by the positively charged rod, while the positive ions are attracted to the negatively charged wall of the cylinder. The resulting small current from the chamber is subsequently amplified and measured. The strength of the current is proportional to the radiation intensity.

Figure 11

Photographic effect Principle The ability of radiation to blacken the photographic film. Application

Detection of radiation exposure in films.

Luminescence Principle The property of certain materials that emit light when stimulated by a physiological process, a chemical or electrical action, or by heat. Functioning mode When radiation strikes luminescence materials, the electrons are raised to higher orbital levels. When they fall back to their original orbital level, light is emitted. The amount of light emitted is proportional to the radiation intensity. Example: Lithium fluoride will emit light when stimulated by heat. Radiation measuring device on luminescence property is thermoluminescence dosimetry (TLD), a method used to measure exposure to patients and personnel. Scintillation

Personnel dosimeter

Radiation measurement By time-integrated dose, i.e. the dose summed over a period of time, usually about 3 months. The dose is consequently stated as an estimate of the effective dose equivalent to the whole body in mSv for the reporting period. Dosimeters used for personnel monitoring have dose measurement limit of 0.1–0.2 mSv (10–20 mrem). Pocket dosimeter It is a personnel radiation monitoring device.

Principle and working mode The property of certain crystals such as sodium iodide and cesium iodide to absorb radiation and convert it to light. The direction of this light to a photomultiplier tube, converts the light into an electrical pulse. The size of the pulse is proportional to the light intensity, which is in turn is proportional to the energy of the radiation.

Working mode It consists of an ionization chamber with an eyepiece and a transparent scale, as well as a hollow charging rod and a fixed and a movable fiber. When the X-rays enter the dosimeter, ionization causes the fibers to lose their charges and, as a result, the movable fiber moves closer to the fixed fiber. The movable fiber provides an estimate of gamma or X-ray dose rate. The pocket dosimeter can measure radiation up to 50 ␮C/kg (200 mR).

Personnel Dosimetry

Film badge monitoring

Radiation dosimeter is the instrument used to measure radiation.

The film badge consists of small X-ray films sandwiched between several filters, which help to detect radiation. Film badges are inexpensive, simple mode of functioning. They are useful for detecting radiation at or above 0.1 mSv (10 mrem). Drawbacks of film badge are:

Personnel dosimeter It is used for the monitoring of individuals who are exposed to radiation during the course of their work (Figure 11). Personnel dosimetry policies are must for all occupationally exposed individuals. It is mandatory to wear personnel dosimeter if the annual dose is greater than 1 mSv. The values obtained from the dosimeter are honorable only when the dosimeters are properly worn and irradiated only during occupational exposure and are returned on time. Appreciation of a few personnel dosimeters are the pocket dosimeter, the film badge or the thermoluminescent dosimeter.

1. 2.

3.

4.

They are insensitive to radiation below 0.1 mSv. They cannot be worn longer than 4 weeks duration at a stretch due to fogging as an outcome of high temperature and light. The colossal task of chemically processing a large number of small films and subsequently comparing each to some standard test films. The film badge cannot measure exposures less than 2.6 ␮C/kg (10 mR). 713


These two positions will indicate:

Figure 12

1. 2.

Estimation of the whole body exposure at the trunk level badge. Estimation of exposures to internal organs like thyroid at the collar level badge.

During fluoroscopy

Thermoluminescent dosimetry (TLD)

The protective apron should always be worn during fluoroscopy. Preferably two dosimeters should be worn by radiation personnel. One at the collar level outside the lead apron indicates an accurate estimate of the radiation dose to the unprotected regions of head and neck; and the other at the trunk level underneath the lead apron illustrates an accurate estimate of the radiation to the protected organs. If only one dosimeter is worn it must be worn at the collar outside the lead apron, because, the neck receives 10–20 times more radiation than the trunk which is protected by lead.

Principle of thermoluminescence It is the property of certain materials to emit light when they are stimulated by heat (Figure 12).

FILM EXPOSURE AND PROCESSING

TLD badge

In India, film badges have been recently replaced by TLD badges.

Reserves of TLD Lithium fluoride (LiF), lithium borate (Li2B4O7), calcium fluoride (CaF2), and calcium sulfate (CaSO4). Working mode When an LiF crystal is exposed to radiation, a few electrons become trapped in higher energy levels. For these electrons to return to their normal energy levels, the LiF crystal must be heated. As the electrons return to their stable state, light is emitted because of the energy difference between two orbital levels. The amount of light emitted is measured (by a photomultiplier tube) and it is proportional to the radiation dose. Advantages of TLD are: 1. 2. 3. 4.

It can measure exposures to individuals as low as 1.3 ␮C/kg (5 mR). It can withstand a certain degree of heat, humidity, and pressure. Its crystals are reusable. Instantaneous readings are possible if the department has a TLD analyzer. Disadvantage of a TLD: It is not cost effective.

Wearing the Dosimeter During radiography Site of personnel wearing dosimeter during radiography are at two regions: 1. 2.

714

On the trunk of the body at the level of the waist, on the anterior side of the individual. On the upper chest region at the level of the collar area on the anterior surface of the individual.

Exposure parameters and film processing events can affect the quality of the radiographic image. The milliamperesecond is an important parameter set by the operator for optimal quality of radiograph. Acquainting the skill of film processing is another important dexterous parameter as the overexposed and underdeveloping of a film, lead to excessive patient exposure and can produce images of poor diagnostic quality. The methods to reduce radiation exposure, result in radiation protection. These are stated as follows: 1. 2.

Stick on to proper exposure factors. Maintain proper record of films.

The processing recommendations include: 1. 2. 3. 4.

Adequate ventilation for darkrooms. Proper handling of the processing solutions. Judicious use of safe light. Following waste disposal regulations in relation to processing solution and lead foil.

Darkroom For manual processing of films, well-equipped darkroom under recommended guidelines is obligatory to get good quality radiographs. This will indirectly reduce the exposure to the patient. 1. 2. 3.

The darkroom must be light-taut. The darkroom should integrate a lockable, double doors with blackened warren entrance. A warning light should be located outside the darkroom at the entrance and it should be in ON position indicating work in progress.


Recordings in operational check log book Frequency

Operational check

Daily

Check the quality of a film with reference radiograph

Monthly

Check and analyze problems with the film, developing process, the X-ray unit or the user

Six monthly

Check the light leaks in processing box Check the condition of personnel protective equipment Check the X-ray film storage and its shelf life Check that the oldest X-ray film is used first Check the expiry date of the film specified by the manufacturer Check that exposure factors for specific examinations are readily available Check the RSO details are displayed in a prominent location adjacent to the X-ray equipment and are correct Check the processor maintenance procedures are displayed in a prominent location contiguous to the film processor Check the instructions for mixing chemicals and processing films are available Check time and temperature with timer and thermometer, respectively for manual processing Check the warning signs of X-ray equipment being displayed and control panel are in good condition

4. 5.

6.

Safelight bulbs of 15 W intensity must be placed 4 feet above the work area within the darkroom. Safelight filters: Red GBX-2 filters should be placed at proper distances and must be checked regularly as they may deteriorate with time or may crack. The darkroom must be equipped with proper stainless steel processing tanks with water bath and lids, including an accurate thermometer and timing device.

The processing chemistry should be evaluated daily, and each type of film should be evaluated monthly or when a new box or batch of films is opened. Lead aprons and thyroid collars should be inspected visually for damage on a monthly basis and should be examined fluoroscopically on an annual basis. Lead aprons and collars in poor condition should be disposed off using a recycler licensed to handle lead wastes.

Quality assurance

Continuing education

Quality assurance etiquette is essential for all the user needs. This includes X-ray machine, imaging receptor, film processing, darkroom, and lead aprons and thyroid collars which can be implemented in each dental health care setting. All quality assurance procedures including date, procedure, results and corrective action, should be logged for documentation purposes. A thorough survey during installation period and re-survey in every 4 years should be done by a qualified expert of state agencies. The film processor should be evaluated every month in addition to initial installation.

Radiation protection is a fundamental component of the working infrastructure of any radiology department. Every update about the radiation safety issues, recent models and upgradations of equipment, materials and techniques should be adopted by every practitioners to improve the quality of the radiographic practices. Before undertaking any radiological examination, it is important that the physician, radiologist and technologist all understand the potential risks of radiation and also its advantages or benefits to the patients in dentistry, medicine and everyday life.

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SECTION

X

Radiographic Methodology

27 Radiographic Films and Accessories 28 Radiographic Techniques

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CHAPTER

Radiographic Films and Accessories

27

Ravikiran Ongole, Praveen BN

➧ Intraoral Films

Constituents of an Intraoral Film Packet Composition of Intraoral Film Dimensions of Intraoral Films

Radiographic films and accessories such as cassettes, film holders and grids are essential in every day dental practice. Use of appropriate accessories will help in improving diagnostic quality of the films, enhance patient care and aid in improving work efficiency. This chapter will describe the constituents of an intraoral film, cassettes and intensifying screens, grids and film holders.

INTRAORAL FILMS These films are used for periapical, bitewing and occlusal radiography. These are also referred to as direct action films (primary sensitive to X-rays) and non-screen films (not used in combination with intensifying screens).

Constituents of an Intraoral Film Packet

➧

Extraoral Films Cassettes Intensifying Screens Grids

The outer jacket (on the tube side/white surface) is incorporated with a raised dot, which relates with a similar area on the dental film inside the packet. This dot aids in orientation of the film during the exposure (always places such that the dot lies closer to the incisal or occlusal aspect of the teeth). Once the film is processed the orientation of the raised dot is used to identify the left and right sides of the patient. Lead foil Once the outer jacket is opened a thin sheet of lead foil is seen. This lead foil has parallel indentations or markings along the surface in one corner of the foil. If the film is exposed placing the wrong side toward the tube head, these markings are seen on the resultant radiograph. If the wrong side of the film is exposed, though the radiograph will reveal an image, the image will appear light. The markings on the film will help to identify the cause for

Figure 1

An intraoral film packet consists of an outer protective jacket, lead foil, black-colored paper wrapper and the film (Figure 1). Film

Outer protective jacket The outer protective jacket is essentially made of light proof and moisture proof soft vinyl. A recent development is the use of phthalate free film packets which are otherwise considered potentially harmful to health. The outer jacket is dual colored. The tube side of the film packet is white colored and the opposite side is twin colored. The cover is sealed to prevent contamination of the film from moisture, exposure to light and ingress of oral fluids when placed in the mouth. The packet on the non-tube side has a flap which is pulled open in the darkroom to remove the exposed film for processing.

Black-colored paper wrapper Lead foil

Outer protective plastic jacket

Contents of the intraoral film packet

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Section X – Radiographic Methodology

the underexposed or light radiograph. These markings (diamond markings) are seen on the resultant radiograph. Lead foil is incorporated into the film packet to:

silver halide grains and trace amount of sulfur compounds and gold so as to enhance the sensitivity of the silver halide grains to X-rays.

❍

1.

Minimize the amount of X-rays from passing through the film and interact with the tissues beyond the film and reflect back leading to multiple exposures, thereby minimizing the quality of the final image. ❍ Minimize exposure of the patient’s tissues, which are in line with the X-ray beam but beyond the imaging area.

Black paper wrapper Once the lead foil is folded back, the black paper wrapper is seen in which the film is placed. The paper wrapper protects the film from extraneous visible light and protects the emulsion of the dental film during handling and storage. It also helps in absorbing any moisture created within the film packet as a result of humid storing conditions. The film has a raised dot on one side and the other side has a small concave depressed area. The film holder used for processing is clipped onto the film conforming to the depressed shallow concave area. This allows a one-point contact between the clip and the film. The advantage of this one-point contact is that processing solutions freely flow into the shallow depression on the film, thereby exposing every single area of the film. Holding the film in any other area will obscure the diagnostic details on the film.

Composition of Intraoral Film Intraoral films are made up of two principal components, namely, emulsion and the base (Figure 2). Emulsion The emulsion is sensitive to X-rays and visible light. The emulsion is composed of a vehicle matrix which holds the

2.

Silver halide grains: Silver bromide makes up most of the silver halide grains that are incorporated in the emulsion. However, silver iodide is added in small quantities as they have crystals of larger diameter which help in increasing the sensitivity of the film. Vehicle matrix: The vehicle matrix helps in the even distribution and dispersion of the silver halide grains. It is made up of gelatinous or non-gelatinous substances.

Base The base of the intraoral film is made up of polyester polyethylene terephthalate and is about 0.22 mm in thickness. It is believed that a blue tinted base will improve the viewing characteristics of the radiograph. Requirement of an ideal base: 1. 2. 3. 4.

It should support the emulsion. It should have enough flexibility to enable easy handling of the film. It should be uniformly translucent and should not hamper the diagnostic quality of the film. It should be able to withstand the effects of the chemicals in the processing solutions.

An adhesive is usually applied in between the emulsion and base to improve the adhesion between the two. An additional layer of the gelatinous substance is added to the film emulsion, which is referred to as an overcoat. It protects the film from scratching or contamination of the film during handling or contact with the processing tanks and it also protects the film from the pressure of rollers of an automatic processor.

Figure 2 Overcoat

B A S E

Emulsion consisting of silver halide grains

Composition of the intraoral film. Courtesy: Dr Jaideep Shekhar

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Chapter 27 – Radiographic Films and Accessories

Dimensions of Intraoral Films Intraoral periapical radiographs (IOPAR) Intraoral periapical radiographs are available in three sizes (Figure 3). Size 0—(22 ⫻ 35 mm) used for child patients Size 1—(24 ⫻ 40 mm) these narrow films are used for imaging adult anterior teeth Size 2—(31 ⫻ 41 mm) standard films that are used for imaging adult posterior teeth. However, when size 1 films are not available, the size 2 adult films can be placed vertically and used for imaging adult anterior teeth. Bitewing radiographs Routinely adult size 2 IOPAR is used for taking bitewing radiographs. However, size 0 can be used in very small Figure 3

children and size 1 can be used in children. In some instances a longer film (size 3) is used in adults, which measures 53 ⫻ 26 mm. Occlusal radiographs The occlusal film measures 57 ⫻ 76 cm in dimension. It is three times larger than a size 2 IOPAR film.

EXTRAORAL FILMS These films are called screen films or indirect films as the radiographic film is placed between two intensifying screens within a cassette. Screen films are employed in extraoral radiography such as orthopantomograph, lateral cephalograph, skull views, TMJ views, and lateral oblique views of the mandible. Extraoral films are usually available in three sizes: (i) 6 ⫻ 12 inches (orthopantomography), (ii) 8 ⫻ 10 inches (all other skull radiographs: PNS, PA view, lateral cephalogram, etc.) and (iii) 6 ⫻ 8 inches (TMJ views, lateral oblique).

Cassettes

Occlusal film

IOPAR film size 2

IOPAR pedodontic film size 0

Various film sizes, namely, the occlusal, size 2 adult film and size 0 child or pedo film

Cassettes are light tight containers, which help in maintaining a uniform and intimate contact between the film and the intensifying screens. Cassettes are available in various sizes and shapes conforming to the various sizes of radiographic film (6 ⫻ 8 inches, 8 ⫻ 10 inches and 6 ⫻ 12 inches). These are usually made of plastic or thin metal. Basically extraoral film cassettes are available in two specifications, namely, rigid and flexible cassettes. 1. Rigid cassettes These are made of thin metal framework. The surface on the exposure side is made up of plastic and the non-exposure surface has metal clamps, which help in

Figure 4 A

B

C

(A) Intensifying screens within an extraoral cassette. (B) Extraoral film cassette of the size 8 ⫻ 10 inches. (C) Film cassette for orthopantomography of the size 6 ⫻ 12 inches

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Figure 5

Figure 6 X-ray beam Phosphor layer Film

Reflecting layer Base

Composition of intensifying screen. Courtesy: Dr Jaideep Shekhar

locking the cassette so as to ensure an intimate contact between the film and the intensifying screens (Figure 4A–C). Rigid cassettes are easy to handle and protect the screen, however they are expensive and may break on impact. 2. Flexible cassettes These are made up of flexible plastic and used for orthopantomography. These are delicate and may tear with regular use. These are also difficult to load and unload in the darkroom setting. However, these are comparatively cheaper than rigid cassettes and require less room for storage.

Intensifying Screens Intensifying screens are used in pairs and are positioned on either side of a double emulsion film. Composition of intensifying screen Intensifying screens are made of four principal components: the base, reflecting layer, phosphor layer and the coat (Figure 5). Base The base of the intensifying screen is made up of the same material that is used in an intraoral film, i.e. polyethylene terephthalate. The base is usually 0.25 mm in thickness. The base acts as a supportive material. Reflecting layer It is made up of titanium dioxide. It is placed between the base and the phosphor layer. It helps in reflecting back on to the phosphor layer any light that is emitted by it. However, the reflecting layer may add to the unsharpness of the resultant image.

Grid

are some of the salts that are used. The presence of these salts has led to the naming of intensifying screens as salt screens. However, rare earth materials are used these days such as terbium activated gadolinium oxysulfide and thulium activated lanthanum oxybromide. Coat The coat is made up of plastic and has a thickness of 8 ␮m. It provides protection to the underlying phosphor layer. As the coat is made up of plastic it can be easily cleaned. It should be ensured that the coat is free from scratches and dirt.

Grids (Figure 6) During a radiographic exposure, almost 30% of the scattered photons (formed as a result of Compton scattering) leave the site imaged and exit the body. These scattered photons will result in the formation of dark areas on the radiograph, which interfere with the diagnostic quality of the radiographic image. However, the use of grids increases the patient exposure by two-fold. Therefore, grids should be used only when contrast on a radiograph is really necessary. As the grid contains radiopaque absorbing materials, the exposure time has to be doubled when using a grid. If the exposure time is not changed, the resultant radiograph might show multiple thin white lines, which minimize the density of the radiograph. These lines that are seen on the radiographic image are called grid lines.

Phosphor layer Radiosensitive phosphor salts are incorporated into this layer of the intensifying screen. Inorganic salts such as calcium tungstate, zinc sulfide, and zinc cadmium sulfate 722

Composition A grid is made up of alternating strips of lead (radiopaque material) and plastic (radiolucent material) spacers (Figure 7).

Chapter 27 – Radiographic Films and Accessories

The effectiveness of the grid is calculated by its grid ratio. Higher the grid ratio, greater is the efficiency of the grid in removing the scattered radiation.

Figure 7

Grid ratio It is the ratio of the thickness of the grid (t) to the width of the radiolucent spacer material (d). A grid ratio of 8 or 10 is most preferred. Grid ratio = t/d

Patient

Types of grid t

d

Grid Receptor

Grid—line diagram

Grids are made with varying number of pairs of spacer and absorber material for every square inch. Grids with 80 or more line pairs per inch do not show radiolucent grid lines on the resultant image.

1. 2. 3. 4. 5.

Linear grid Focused grid Pseudo focused grid Crossed grid Moving grid or Potter–Bucky diaphragm.

Functions Grids are placed between the object to be imaged and the image receptor system (film) to preferentially minimize the amount of scattered radiation reaching the film. Grids reduce film fog from scattered radiation, thereby increasing the contrast of the resultant image.

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CHAPTER

28

Radiographic Techniques Gail F Williamson, Kıvanç Kamburog˘lu*, Suman Jai Sanghar, Jai Sanghar N, Rinky Nacchyon, Apeksha Mainali, Ravikiran Ongole, Praveen BN

CONVENTIONAL IMAGING

➧

Intraoral X-ray Machine X-ray Beam Angulation and Alignment Radiographic Infection Control Radiation Safety and Protection Preliminary Procedures Intraoral Radiographic Techniques Intraoral Radiographic Procedures Common Intraoral Technique Errors

Extraoral Radiography

➧

TMJ Radiography

➧

Transcranial View

➧

Transpharyngeal View (Parma Projection, Macqueen-Dell Technique)

➧

Transorbital View

➧

Lesser Known/Forgotten Extraoral Radiographic Techniques

Technique Landmarks for Positioning in Skull Radiography ➧

Townes’ Method or AP Axial Projection May Method Axiolateral Oblique Projection Modified Parietoacanthial Projection Acanthioparietal Projection ‘Reverse Waters’ Method’

Posteroanterior Projection Occipitofrontal Projection PA Mandible PA Cephalometric Rotated PA View

➧

Standard Occipitomental view

➧

30ⴗ Occipitomental

➧

Parietoacanthial View (Waters’ View)

➧

Parietoacanthial View (Open Mouth Waters’ View)

➧

Modified Parietoacanthial Projection (Modified Waters’ View)

➧

Acanthoparietal Projection (Reverse Waters’ Method)

➧

Submentovertex View (Base or Full Axial Projection, Schuller Method)

➧

Lateral View

➧

Lateral Cephalometry

➧

AP Axial Projection (Townes’ Method)

➧

Reverse Townes’ View

Lateral Oblique View Lateral Oblique of the Body of the Mandible and Maxilla Lateral Oblique of the Ramus of the Mandible Bimolar Projection

Intraoral Radiography

➧

Panoramic Radiology Origin of Panoramic Radiology Concepts of Panoramic Imaging Characteristics of Ghost Images Indications of Panoramic Radiograph Disadvantages and Limitations

SPECIALIZED IMAGING Computed Tomography (CT) Working Principle Computed Tomographic Scanner Assembly Advantages of CT Disadvantages of CT Uses of CT in Dentistry

Dentomaxillofacial Cone-Beam Computed Tomography (CBCT) Historical Background

*Dr Kıvanç Kamburog˘ lu is grateful to Tomoloji Dentomaxillofacial Radiology Center and Gulhane Military Medical Academy, Dentomaxillofacial Radiology Center, Ankara for their support. 724

Chapter 28 – Radiographic Techniques

Fundamentals of CBCT Advantages and Disadvantages/Limitations of CBCT CBCT Clinical Applications

Magnetic Resonance Imaging Historical Perspective Principles of Magnetic Resonance Imaging MR-contrast Agents Methods for Obtaining Spatial (Tomographic) Resolution of MR Signals Uses for MRI Advantages Disadvantages Common Artifacts in MRI

Nuclear Medicine Radiopharmaceuticals Bone Scanning Salivary Gland Scans

Main Indications for Ultrasound in the Head and Neck Advantages Over Conventional X-ray Imaging Disadvantages Artifacts

Sialography Indications of Sialography Procedure Injection of the Contrast Medium Phases of Sialography Contraindications of Sialography

Arthrography Uses of Arthrography Types of Arthrography Procedure Limitations Complications

Thermography (Thermal Imaging or Infrared Imaging)

Ultrasonography Principle Different Types of Scans Different Types of Scanners Used Instrumentation Doppler Ultrasound

CONVENTIONAL IMAGING INTRAORAL RADIOGRAPHY Gail F Williamson Intraoral radiography is an important tool for proper diagnosis and treatment. Intraoral radiographs allow the clinician to view the teeth and supporting structures revealing conditions that may not be apparent clinically. Intraoral radiography is accomplished by placement of a small image receptor (IR) inside the mouth behind the teeth and structures of interest with the X-ray beam aligned externally over the corresponding area. Available intraoral receptors include radiographic film, rigid digital sensors and photostimulable phosphor plates. Intraoral radiography involves the acquisition of periapical and bitewing images that can be combined to form surveys. Periapical radiographs record the entire tooth or several teeth and the surrounding structures including the apical regions, the trabecular bone, the periodontal ligament space and the lamina dura. By contrast, bitewings record the crowns, proximal contacts of the teeth and the alveolar bone crests. Typically, a complete

Liquid Crystal Thermography Electronic Infrared Telethermography Patient Preparation Procedural Requirements Indications

or full-mouth survey consists of 14–16 periapicals and 2–4 posterior bitewings (Figure 1A, B). In addition to periapicals and bitewings, occlusal radiographs can be taken to record a broad region of either the maxilla or mandible. In most instances, occlusal images are supplemental views taken to record a larger area or to localize an object. Intraoral radiographs can be combined with or augmented by extraoral radiographs. In extraoral radiography, both the receptor and X-ray source are housed outside the oral cavity. Extraoral radiography requires specialized equipment and can be accomplished with intensifying screen-film combinations or with digital imaging systems. The panoramic image is the most common extraoral projection which provides a more complete view of the maxilla and mandible, the maxillary sinuses and the temporomandibular joints (TMJ) (Figure 2). Cephalometric radiography is more task-specific and includes a variety of skull projections. The most common application of cephalometric radiography is the lateral skull projection used in orthodontics. The lateral skull view is used to evaluate structures, monitor growth and development and track treatment progress. Cone-beam computed tomography (CBCT) is the most recent addition to extraoral dental imaging. CBCT is 725


indicated when three-dimensional (3D) imaging is necessary to evaluate and plan treatment in situations such as implant placement, failed endodontic treatment, pathological conditions, difficult surgical procedures and evaluation of craniofacial anomalies.

Intraoral X-ray Machine The typical intraoral dental X-ray machine used to expose intraoral receptors operates at 60 or 70 kilovolts (kV), 4–8 milliamperes (mA) with variable exposure time

Figure 1 A

settings (Figure 3A, B). Kilovoltage controls the penetrating power of the X-ray beam and image contrast or differences in darkness. Milliamperage and time control the number of X-rays and image density or the overall darkness of a radiographic image. Most intraoral X-ray machines have fixed kilovoltage and milliamperage settings which permit adjustment of the exposure time only. The length of the exposure time is dependent on a number of factors including the kilovoltage and milliamperage settings, collimation of the X-ray beam, patient size, area of interest and the type of receptor. Collimation restricts the size of the X-ray beam, reduces patient exposure and improves image quality by reduction of scatter radiation and minimizing penumbra production. Collimation is accomplished with open-ended position indicating devices (PIDs) that are either circular or rectangular in shape and vary in length from 20 to 40 cm (Figure 4). Long rectangular collimation restricts the X-ray beam and

Figure 2 B

A typical full-mouth survey consists of 14–16 periapicals and 2–4 bitewings. (A) Full-mouth survey taken with size 2 film receptors. (B) Full-mouth survey taken with size 1 and 2 film receptors

Panoramic image demonstrating the maxilla, mandible, dentition and TMJ

Figure 3 A

B

(A) Intraoral dental X-ray machine control panel. (B) X-ray head and PID; HeliodentPlus Sirona Dental Systems, Inc., Long Island City, New York

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reduces the volume of tissue exposed on the skin surface the most and, therefore, is recommended for periapical radiography and bitewing radiography when practicable. When selecting the exposure time, consideration should be given to the overall size of the patient as well as the area of interest. Recommended exposure time settings are designed for the average adult patient. For adult patients smaller than average, the exposure time for each area can be reduced by one step and for larger than average, increased by one step. Exposure time settings for children are considerably less than for adults and frequently can be accessed by selecting a child icon on the control panel

Figure 4

(Figure 3A). Exposure time increases as the survey progresses from the anterior to the posterior regions of the mouth. Digital receptor exposures follow these same general principles but the time settings are lower for each area when compared to film. The speed of the receptor has an influence on the exposure time as well. Speed indicates the sensitivity of a receptor to X-rays; the faster the receptor, the less the radiation required to produce a diagnostic image. Currently, F-speed is the fastest film available for intraoral radiography, providing significant dose reduction and comparable performance compared to D-speed film. Digital receptors, both rigid sensors and phosphor plates, provide equal or greater dose savings than F-speed film with equivalent diagnostic utility. Intraoral X-ray machines manufactured today are compatible with film, rigid sensors and phosphor plates.

X-ray Beam Angulation and Alignment

Collimation restricts the size of the X-ray beam and the area of patient skin exposure. It can be accomplished with a variety of devices including PIDs, metal devices that clip into ringed instruments or that slide onto a PID. Rectangular collimation is optimal

The vertical angulation of the X-ray beam varies and is dependent on the tooth, dental arch, oral anatomy and intraoral technique used. Vertical angulation is adjusted by moving the X-ray head and PID up or down. Positive vertical angulations are used for maxillary periapicals and bitewings and negative vertical angulations are used for mandibular periapicals. Positive vertical angulations position the X-ray head above horizon with the PID directed downward while negative vertical angulations position the X-ray head below horizon with the PID directed upward (Figure 5A, B). Most dental X-ray machines have an angle meter on the X-ray head to indicate the degree of the vertical angulation with horizon designated as 0. Vertical angulation controls the length dimension of the recorded image. Errors in vertical angulation produce images that either shorten or lengthen the actual vertical dimension of the structures.

Figure 5 A

B

Vertical angulation. (A) Positive vertical angulation is used for maxillary periapicals as demonstrated by this premolar placement. (B) Negative vertical angulation is used for mandibular periapicals as demonstrated by this incisor periapical placement

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Figure 6

Figure 7

Outer canthus Pupil of eye Ala of nose Tip of nose

Infection control barriers for intraoral image receptors Mentum

The horizontal angulation is adjusted by moving the X-ray head and PID anteriorly or posteriorly (forward or backward) along the horizontal plane. The horizontal angulation is directed proximally for all intraoral views and follows the curvature of the dental arches. This places the X-ray beam perpendicular to the horizontal plane of the teeth of interest. Errors in horizontal angulation result in overlapping of the proximal surfaces of the teeth and width distortion such that the teeth contacts and alveolar bone crests cannot be properly visualized. In order to expose the entire receptor, the center of the X-ray beam, known as the central ray (CR), is directed toward the middle of the receptor which is represented externally by facial anatomic points as illustrated in Figure 6. Failure to properly center the X-ray beam over the receptor produces a partial image. The unexposed portion is called a ‘cone cut’, a term that dates back to the time when closed cones were used rather than open-ended PID collimators to direct the X-ray beam. Closed cones are no longer used as they produce excessive scatter radiation that significantly increases the radiation dose delivered to the patient.

patients and the dental professional. For the clinician, this involves the use of personal protective equipment (PPE) including clinical attire, eyewear, a mask and gloves to avoid contact with patient’s oral fluids. For radiographic equipment, this involves pre-cleaning, disinfection and preferably, coverage with plastic barriers before seating the patient and initiating radiographic procedures. An environmental protection agency (EPA)-registered hospital disinfectant with intermediate-level activity should be used to prepare radiographic equipment and environmental surfaces. Barriers must be changed between patients but when barriers are not used, the equipment and environmental surfaces must be pre-cleaned and disinfected between patients. Disposable or radiographic instruments that can be heat-sterilized should be used for intraoral radiography. Intraoral digital receptors that cannot be heat-sterilized must be covered with a FDA (Food and Drug Administration)cleared barrier (Figure 7) and cleaned and disinfected with an EPA-registered hospital disinfectant with intermediatelevel activity between patients. Protective plastic barrier envelopes are used to cover radiographic film and phosphor plates during placement in the mouth (Figure 7). After exposure, contaminated external barrier must be disinfected before dropping the film or plate out of the barrier in preparation for processing. It is best to consult manufacturer instructions for guidance on digital receptor handling and disinfection practices.

Radiographic Infection Control

Radiation Safety and Protection

Standard infection control procedures must be utilized when taking intraoral radiographs. During radiographic procedures, the clinician can be exposed to a variety of pathogens through direct contact with the patient’s oral fluids or by contact with contaminated radiographic equipment and work surfaces. The primary goals of infection control are to prevent cross-contamination and the transmission of disease between patients and between

ALARA (As Low As Reasonably Achievable) is the guiding principle in radiation safety and protection. It is the ethical and professional obligation of dental professionals to keep the radiation dose delivered to the patient to a minimum. Although the risk of intraoral radiography is thought to be very small, it is not risk-free and the effects of radiation are cumulative. The measures most effective in dose reduction include the use of selection criteria, fast film or digital

Central ray entry points are facial anatomic landmarks designed to help the clinician align the central ray to the center of the image receptor inside the mouth

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Table 1

Selection criteria guidelines

Patient type

Child primary dentition

Child mixed dentition

Adolescent dentition

Adult dentate/artially

Adult edentulous

New patient

Bitewings if contacts closed occlusals

Bitewings/panoramic

Bitewings/panoramic FMS when indicated

Bitewings/panoramic FMS when indicated

Individualized Based on exam

Recall high caries risk

Bitewings at 6–12 month intervals




Not applicable

Recall low caries risk





Not applicable

Recall for periodontal patient

Selected PAS/BWS as needed




Not applicable

Growth and development

Only when indicated

Only when indicated

Panoramic or PAS for 3rd molars

Not applicable

Not applicable

Other

Only in a special situation or circumstance

PAS: Periapicals; FMS: Full mouth survey; BWS: Bitewings.

receptors for intraoral radiography, rare earth screen-film combinations or digital receptors for extraoral radiography, rectangular collimation of the X-ray beam and patient shielding. The clinician should practice radiation safety measures to avoid occupational exposure and to comply with the maximum permissible dose (MPD) limit. The annual dose limit is 50 millisieverts (mSv) and the lifetime dose limit is 10 mSv multiplied by the clinician’s age in years. However, the clinician should strive to completely avoid any occupational exposure. Compliance is easily achieved by not standing in or near the X-ray beam or in its path; not holding the X-ray head or PID in place; not holding the receptor in the patient’s mouth or holding the patient in position. If assistance is needed to stabilize a patient, the parent or guardian should be asked to assist, provided with a radiation shield and given instructions on how to restrain the dental patient. During exposure, the clinician should stand behind a wall barrier or 2 meters away and slightly greater than a right angle to the X-ray beam. Personal radiation dosimeters are commercially available to track occupational exposure and are recommended for pregnant clinicians who expose dental radiographs.

Preliminary Procedures Before radiographs are prescribed, a complete medical and dental history must be taken, reviewed and the chief complaint identified. The dentist should examine the dentition to determine if radiographs are indicated. If radiographs are necessary, the type and number of projections should be identified. The American Dental Association (ADA) and the FDA have established guidelines for the selection of dental radiographic examinations in the United States. Dental radiographs should be prescribed according to

these guidelines and taken for diagnostic and treatment purposes only. Selection criteria guidelines are based on the evidence of disease patterns and information obtained from the patient’s medical and dental history, clinical signs and symptoms of disease, risk factors, age and dentition, and new or recall patient status. Only bitewing radiographs are recommended on time-based regimens as determined by patient risk factors for caries. See Table 1 for a summary of these guidelines. Typically, radiographic procedures are delegated to qualified dental staff (dental assistant and/or dental hygienists) for completion. Once the appropriate survey has been determined, the patient should be prepared for the procedure. Facial jewelry, intraoral prostheses and eyeglasses should be removed and safely stored. The patient should be protected with a lead apron and thyroid collar, provided with an explanation of the purpose of the examination and given instructions to elicit cooperation (Figure 8). Preferably, the patient is seated in an upright position with the midline centered and the occlusal plane parallel to the floor for maxillary periapicals and bitewings and the chin raised so that the mandibular arch is parallel to the floor for mandibular periapicals. The exposure time should be set for the area before placement of the receptor inside the mouth. When ready for exposure, the clinician should practice radiation safety measures to avoid occupational radiation exposure. Once the survey is acquired, proper processing techniques should be followed as dictated by the selected image receptor. The clinician must ensure that the processed radiographic images are properly arranged in the film mount or computer image template according to the ADA standard. This standard involves labial mounting and viewing of radiographic images according to the patient’s right and left sides of the dentition. Attention to correct tooth order, proper location of surrounding anatomical structures and

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Figure 8

Figure 9

Paralleling technique requires placement of the receptor parallel to the teeth with the central ray directed at a right angle to both the teeth and receptor Dental patients should be shielded with a lead apron and thyroid collar during intraoral radiographic procedures

Figure 10 observation of restorative treatments and/or missing that match from periapical to periapical and/or periapical to bitewing will ensure accuracy of arrangement.

Intraoral Radiographic Techniques There are two techniques that can be utilized for taking periapicals radiographs: the paralleling technique and the bisecting angle technique. The paralleling technique is preferred because it produces the most accurate and representative images of the teeth and surrounding structures. The bisecting angle technique is considered a secondary or alternate technique when paralleling technique cannot be accomplished due to intraoral anatomy or other patient factors. Bisecting angle technique produces images with inherent distortion because the buccal and lingual aspects of the teeth and alveolar bone are not projected evenly. This distortion must be taken into consideration when interpreting the radiographs for caries and alveolar bone loss.

A variety of ringed paralleling technique instruments are commercially available. The instruments depicted here have bite blocks designed to hold rigid digital receptors. XCP DS®, Dentsply Rinn, Elgin, Illinois

horizontal and vertical angulation and centering of the X-ray beam (Figure 10). There are a variety of ringed instruments commercially available with designs for all three types of intraoral receptors. Proper assembly and parallel receptor placement to the area of interest are necessary for optimal results. A standard bite-block can be used for the paralleling technique as long as the clinician has the skill to align the PID accurately.

Paralleling technique The paralleling technique requires placement of the receptor parallel to the tooth or teeth of interest both in the vertical and horizontal planes. The X-ray beam is directed so that it strikes both the tooth and the receptor at a right angle (Figure 9). Typically, the paralleling technique is accomplished with ringed instruments that aid the clinician in establishing the correct object to receptor relationship,

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Bisecting angle technique The bisecting angle technique is based on Cieszynski’s rule of isometry or the geometry of equilateral triangles. This rule states that two triangles are equal if they share a common side and two equal angles. Applied to periapical radiography, a tooth and its projected image will be equal in length if the X-ray beam is directed at a right angle to the


Figure 11

Figure 12

Many types of bisecting angle instruments are commercially available for film, rigid sensors and phosphor plate receptors. Snap-A-Ray® Xtra, Stabe Biteblock® and Eezee-Grip® Digital sensor holders are shown from left to right. Dentsply Rinn, Elgin, Illinois

Bisecting angle technique directs the central ray at a right angle to the plane that divides the angle formed by the teeth and receptor

Table 2

Figure 13

Bisecting angle technique

Periapical view

Maxillary

Mandibular

Incisor

40 to 50

5 to 15

Lateral-canine

40 to 50

5 to 15

Premolar Molar

25 to 35 20 to 30

10 to 15 5 to 5

Approximate vertical angulations

common side or bisecting plane that divides the triangle into two equal halves or equilateral triangles (Figure 11). Care must be taken to accurately determine the bisecting plane to avoid errors in vertical angulation. Approximate vertical angulations used for each periapical are listed in Table 2. The horizontal angulation and centering of the X-ray beam remain the same as with the paralleling technique. There are instruments commercially available for the bisecting angle technique for both film and digital receptors (Figure 12). Bisecting angle technique requires more technical skill and as such, more retakes tend to occur than with the paralleling technique. Image receptors As previously mentioned, intraoral radiographs can be taken with three different types of intraoral receptors: radiographic film, rigid digital sensors or photostimulable phosphor plates. All three receptors are considered approximately equivalent in their ability to record dental disease states; caries, periodontal disease and periapical pathoses. Intraoral image receptors range in sizes from 0 to 4, however, the range of sizes depends

Radiographic film ranges from size 0 to 4. Depicted in the front row are the size 2 bitewing, size 3 bitewing and size 1 periapical films. In the back row are the size 4 occlusal, size 0 periapical and size 2 periapical films. Carestream Dental LLC, Atlanta, Georgia

on the type and manufacturer of the receptor. Periapical receptor sizes include 0, 1 and 2 and bitewing receptor sizes include 0, 1, 2 and 3. Size 0 is most commonly used in pediatric imaging and the size 4 receptor is for adult occlusal radiography. Radiographic film Radiographic film is the traditional medium for recording intraoral images (Figure 13). It consists of a blue-tinted plastic base material coated with a double emulsion of gelatin and silver halide crystals, predominantly silver bromide. The film has a dot convexity that indicates the exposure side and aids in proper arrangement and mounting of the processed radiographs. The film is wrapped with an internal black paper with a lead foil on the rear or non-exposure side and covered externally with either a plastic or paper material to protect the emulsion from light and moisture. The exposure side of the film packet is white and the non-exposure side is two-toned

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Figure 14 A

B

Rigid wire dental sensors. (A) Size 2 and 1 rigid digital sensors. Schick CDR Elite, Schick Technologies, Inc., Long Island City, New York. (B) Digital molar periapical image

with colors used to indicate speed and single or double film packet. Once exposed to radiation, the emulsion captures and stores the latent image until the image is made visible by chemical processing. Those silver halide crystals exposed to radiation are reduced to metallic silver by the developer solution reducing agents and form the radiolucent components of the image. The non-exposed, undeveloped silver halide crystals are removed by the fixer solution clearing agent and become the radiopaque components of the image. Typically film-based images are processed by automatic processing systems that develop, fix and dry radiographic film in approximately 5.5 minutes. The processed radiographs are ready for arrangement and mounting after exiting the processor. Care must be taken to properly maintain the processor utilizing regular solution replenishment, cleaning and solution change regimens. Processing errors are a common cause of retakes in filmbased imaging. Direct digital receptors Direct digital receptors are rigid, wired receptors in the form of the charge-coupled device (CCD) or complimentary metal oxide semi-conductor (CMOS) detector (Figure 14A, B). The primary difference between the two devices is the manner in which the latent image is transferred to the read-out amplifier for display. The active image area is smaller compared to film or phosphor plates so the area of coverage is slightly diminished. These rigid devices are area arrays composed of a matrix of pixels with each pixel functioning as an electron well. When the sensor is exposed to radiation, the energy that penetrates through the structures is deposited in the electron well in that location. The intensity of the energy or signal determines the brightness or density of the image in each area. The digital data is processed by the computer and the 732

visible image can be viewed on the monitor almost instantly. Rigid digital sensors are reusable receptors that cannot be sterilized. As indicated previously, they must be properly disinfected and covered with a barrier to avoid direct contact with oral fluids. When positioning the receptor in the mouth, the wire should be oriented toward the occlusal plane for vertically placed anterior periapicals and directed anteriorly for horizontally placed posterior periapicals. Direct digital receptors require less radiation exposure than film. The amount of exposure reduction is related to the speed of the comparison film. Typical exposures for the average patient range from 0.04 to 0.06 second in the anterior sextants to 0.08–0.12 second in the posterior sextants. Refer to the X-ray machine user manual for recommended exposure times. Errors associated with rigid digital receptors are welldocumented in the dental literature. Common errors include vertical angulation errors with foreshortened images and crown cut-offs, placement errors, horizontal overlap, cone cuts and problems related to patient discomfort. The rigid nature of the receptor requires strict attention to the details of placement, intraoral technique and accurate alignment of the X-ray beam. A cotton roll can be placed on the bite-block to avoid crown cut-off and reduce patient biting pressure. To reduce patient discomfort, place rigid receptors closer to the midline where the mouth has greater depth. Commercially available foam tissue cushions and topical anesthetic agents are useful in reducing discomfort and minimizing the gag reflex. The primary advantages of direct digital receptors are rapid image acquisition and immediate image display while the disadvantages are the rigid, wired construction and related placement and discomfort difficulties.


Figure 15 A

B

Phosphor plate receptors. (A) Size 0, 1, 2 and 4 phosphor plates. The opposite side or emulsion side is directed toward the X-ray source. ScanX® Phosphor Storage Plates, Air Techniques, Inc., Melville, New York. (B) Phosphor plate premolar periapical

Photostimulable phosphor plates Photostimulable phosphor plates (PSPs) or storage phosphor plates (SPPs) are wireless digital receptors that handle similar to film (Figure 15A, B). A separate plate is needed for each exposure and a processing step is required before the images can be viewed on the computer monitor. Phosphor plate receptors have a single emulsion coated on the exposure side of the plate composed of europium-activated barium fluorohalide. Rather than an identification dot, plate receptors have a letter or number to identify the exposure side of the receptor. Care must be taken to prevent abrasion, crimping or creasing of the emulsion to avoid permanent image artifacts and frequent plate replacement. Once the plate is exposed, the latent image is stored in the emulsion until the plate is scanned by a helium laser beam (Figure 16). When the phosphor plate is scanned, it emits light in proportion to the exposure received. The light detected by the photomultiplier is converted from analog-to-digital data and the visible image is displayed on the monitor for viewing. The scanning takes several seconds causing a slight delay between image capture and display. Before reuse, the plate must be erased by white light to remove any remnant image. Typically, the plate is erased prior to exit from the scanning unit. The primary advantages of the phosphor plate are its thin, wireless construction while the disadvantages are susceptibility to emulsion scratches producing artifacts and delayed image viewing.

Intraoral Radiographic Procedures Periapical radiography Periapical images provide information about tooth morphology, apical proximity to anatomic structures, abnormalities

Figure 16

Exposed phosphor plate receptors must be scanned by a helium laser beam to digitize and display the visible image. ScanX Intraoral Scanner, Air Techniques, Inc., Melville, New York

of the teeth and supporting structures such as carious lesions, periodontal bone loss and periapical and bony pathoses. Periapical radiographs can be taken in any area of the mouth. There are classic placements for the incisor, canine, premolar and molar teeth as outlined in Table 3. When taking a full-mouth survey, it is best to take the anterior periapicals first. This allows the patient time to adjust to the procedure before taking the posterior periapicals 733


Table 3

Periapical and bitewing techniques

Head position: midsagittal plane perpendicular and occlusal plane parallel to floor Projection

Teeth recorded

Horizontal angle

Vertical angle

Central ray

Maxillary incisor periapical

Central incisor teeth centered

Proximal between central incisors

Parallel to teeth long axes

Tip of nose

Maxillary lateral-canine periapical

Lateral and canine teeth centered

Proximal between lateral & canine


Ala of nose

Maxillary premolar periapical

Distal of canine, 1st & 2nd premolar, 1st molar

Proximal between premolar teeth


Pupil of the eye to mid-cheek

Maxillary molar periapical

1st, 2nd & 3rd molar; 2nd molar centered

Proximal 1st & 2nd molar teeth


Outer canthus to mid-cheek

Premolar bitewing

Canine distal, 1st & 2nd premolar, 1st molar

Proximals between premolar teeth

5

Pupil of eye to occlusal plane

Molar bitewing

1st, 2nd & 3rd molars; 2nd molar centered

Proximals between 1st & 2nd molar teeth

5

Outer canthus to occlusal plane

Head position: midsagittal plane perpendicular and mandibular arch parallel to floor

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Mandibular incisor periapical

Central incisor teeth centered

Proximal between central incisors


Center of chin

Mandibular lateralcanine periapical

Lateral and canine teeth centered

Proximal between lateral & canine


Center of chin corner

Mandibular premolar periapical

Canine distal, 1st & 2nd premolar, 1st molar

Proximal between premolar teeth


Pupil of the eye to mid-mandible

Mandibular molar periapical

1st, 2nd & 3rd molar; 2nd molar centered

Proximal 1st & 2nd molar teeth


Outer canthus to mid-mandible

Diagram


which tend to be more difficult for some patients. Anterior periapicals are placed in the vertical dimension with the receptor identification dot or marker located in the coronal aspect of the image. For adult patients, the size 1 or 2 receptor can be used. The size 1 receptor is preferred for narrow or crowded dental arches. Anterior periapicals are used to record the central incisor, lateral incisor and canine teeth (Figure 17). Posterior periapicals are oriented in the horizontal dimension and are used to record the distal aspect of the canine, premolar and molar teeth (Figure 18). For adult patients, the size 2 receptor is the standard for posterior projections.

Figure 17

Bitewing radiography Bitewing radiographs are most frequently taken in the posterior regions of the mouth of the premolar and molar teeth for the detection of proximal caries and alveolar bone loss (Figure 19A, B). For adult patients, the size 2 receptor is preferred. Bitewings can be oriented in either the horizontal or vertical plane with the receptor positioned parallel to the teeth crowns. Horizontal bitewings are the most common but vertical bitewings are taken particularly when moderate or greater alveolar bone loss is present. Anterior bitewings can be taken to view bone levels in the anterior segments of the mouth as well (Figure 20). A size 1 receptor is used to capture incisor and lateral-canine bitewing views. The clinician can select traditional tabs or instrument holders to accomplish the bitewing survey.

Figure 18

Anterior mandibular periapicals of the incisor and canine teeth

Posterior maxillary periapicals of the premolar and molar teeth

Figure 19 A

B

Bitewings can be taken with a ringed instrument or with a tab. (A) Bitewing taken with the tab bitewing technique. (B) Tab bitewing survey

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Figure 20

Vertical anterior and posterior bitewing survey

Table 4 Topographical occlusal technique Projection

Head position

Placement

Maxillary anterior

Occlusal plane parallel & midsagittal perpendicular to the floor

Horizontal or vertical in anterior region

60

0.5 cm above tip of nose

Maxillary posterior


Vertical toward side of interest

55

2 cm below pupil of the eye

Mandibular anterior

Occlusal plane at 45 angle; midsagittal perpendicular to the floor

Horizontal or vertical in anterior region

15

Center of the mentum

The vertical angulation used for tab bitewings ranges from 5 to 10. The most common error associated with bitewing radiography is horizontal overlap which can render the image non-diagnostic. Occlusal radiography There are two basic types of occlusal projections that can be taken: topographical and cross-sectional. Topographical occlusals provide a broad view of a segment of the maxilla or mandible. Cross-sectional occlusals are used to localize objects or to view the buccolingual dimensions of the dental arches. The most common occlusal projections are topographical taken in the anterior segments of the dental arches. Adult occlusal radiographs are taken with a size 4 intraoral receptor. The only film and phosphor plate receptors available are size 4. The receptor can be positioned horizontally or vertically as needed to accommodate the mouth size and arch width. Topographical occlusals Topographical occlusals are based on the bisecting angle technique. Topographical occlusals have the appearance of a large periapical view of the teeth and surrounding structures. Typical applications include recording bilateral impactions of the permanent canine teeth, mesiodens or large periapical or bony lesions. Topographical occlusal projections can be applied to pediatric 736

Angulation

Central ray

imaging by using a size 2 receptor and reduction of the exposure time. In addition, anterior periapical views can be taken using topographical occlusal technique when mouth opening is limited or the arch is extremely narrow or crowded. In these instances, a size 2 receptor is oriented vertically. Table 4 summarizes the basic technical aspects of topographical occlusal projections. Topographical maxillary anterior occlusal The patient’s head is aligned with the occlusal plane parallel to the floor and the midsagittal plane perpendicular to the floor. The receptor can be positioned horizontally or vertically dependent on the mouth size and arch width. With the mouth opened slightly, the receptor is placed against the maxillary occlusal surfaces with the dot convexity toward the palate and positioned labially. The patient bites together lightly to secure the receptor. The approximate bisecting angle for this projection is 60 with the horizontal angle directed through the proximal contacts of the maxillary central incisors. The central ray of the X-ray beam enters through a point located just above the tip of the nose. Generally, the exposure time is the same time as the maxillary incisor periapical for the selected receptor (Figure 21A, B). Topographical maxillary posterior occlusal As with the anterior occlusal, the patient’s head is positioned with the occlusal plane parallel to the floor and midsagittal


Figure 21 A

B

Topographical maxillary anterior occlusal. (A) Clinical photograph. (B) Occlusal image

Figure 22 A

B

Topographical maxillary posterior occlusal. (A) Clinical photograph. (B) Occlusal image

plane perpendicular to the floor. The receptor is oriented vertically toward the side of interest and placed against the occlusal surfaces of the maxillary teeth with the dot placed anteriorly. The receptor should extend approximately 1 cm beyond the buccal surfaces of the posterior teeth and inserted posteriorly until it contacts the anterior ramus. The receptor is maintained in position by light patient biting pressure. A 60 vertical angulation is used with the horizontal angle directed through the premolar teeth contacts and the central ray entering about 2 cm below the pupil of the eye. This projection will record one quadrant of the maxillary teeth and alveolar ridge (Figure 22A, B). Topographical mandibular anterior occlusal For the mandibular projection, the patient’s head is tilted back until the

occlusal plane is at a 45 angle above horizon. The clinician can align the X-ray head at a 45 angle to use as a comparison to check for proper head position. The occlusal plane should be parallel to the open end of the PID. The midsagittal plane is positioned perpendicular to the floor. The receptor can be positioned horizontally or vertically as needed. With the mouth opened slightly, place the receptor against the occlusal surfaces of the mandibular teeth with the dot convexity toward the tongue and positioned labially. The patient bites together lightly to secure the receptor. The approximate bisecting angle for this projection is 15. The horizontal angle is directed through the proximal contacts of the mandibular incisor teeth and the central ray is directed through the center of the mentum. The exposure time is the same time as the mandibular incisor periapical for selected receptor (Figure 23A, B). 737


Figure 23 A

B

Topographical mandibular anterior occlusal. (A) Clinical photograph. (B) Occlusal image

Table 5

Cross-sectional occlusal technique

Projection

Head position

Placement

Angulation

Central ray

Maxillary


Horizontal or vertical in anterior sectant

Long axes plane of the anterior teeth

1 cm posterior to bregma

Mandibular anterior

Occlusal & midsagittal plane perpendicular to the floor

Vertical toward side of interest

Long axes of posterior mandibular 3 cm posterior to mentum & teeth; 90 to receptor 3 cm lateral to midline

Mandibular posterior

Occlusal & midsagittal plane perpendicular to the floor

Horizontal or vertical in anterior sextant

Long axes of anterior mandibular teeth; 90 to receptor

Cross-sectional occlusals Cross-sectional occlusals are most commonly taken for the purposes of object localization or to view the buccolingual aspect of the dental arches. Cross-sectional occlusal technique directs the central ray at a right angle to the receptor. The maxillary cross-sectional occlusal requires an X-ray machine capable of 90 kV to enable penetration of the calvaria. Table 5 summarizes the essential technical aspects of cross-sectional occlusal projections. Cross-sectional maxillary occlusal The patient’s head and receptor are positioned in the same manner as the other maxillary occlusal projections. The vertical angulation is determined by directing the X-ray beam through the long axes of the anterior teeth. The horizontal angulation is centered with the midsagittal plane and the central ray enters the skull 1 cm posterior to bregma, the junction of the sagittal and coronal sutures. This projection produces an unusual horseshoe-shaped image, for it depicts all of the maxillary teeth through the long axes dimension end-on-end. To produce a maxillary cross-sectional image, the exposure factors should be set at 90 kVp, maximum mA, and a 1-second exposure. The exposure is dependent on the selected receptor (Figure 24A, B). 738

Midline of the floor of the mouth

Cross-sectional mandibular anterior occlusal The patient’s head is positioned such that the occlusal plane is nearly perpendicular to the floor or as far back as possible with the midsagittal plane perpendicular to the floor. The exposure surface of the receptor should be placed against the occlusal surfaces of the mandibular teeth. Approximately 1 cm of receptor extends beyond the labial surfaces of the anterior teeth with the patient biting gently to secure its position. The central ray is directed perpendicular to the receptor and through the midline of the floor of the mouth. The cross-sectional anterior occlusal is useful for evaluating expansion of the anterior mandible or localizing a salivary stone in the sublingual gland (Figure 25A, B). The exposure time is the same time as the mandibular incisor periapical for selected receptor. Cross-sectional mandibular posterior occlusal For this projection, the patient’s head is tilted back so that occlusal plane is nearly perpendicular to the floor with the midsagittal plane perpendicular to the floor. The receptor is positioned vertically toward the side of interest and as posterior as possible. The exposure surface of the receptor is placed against the occlusal surfaces of the mandibular teeth. Approximately 1 cm of the receptor extends beyond


Figure 24 A

B

Cross-sectional maxillary occlusal. (A) Clinical photograph. (B) Occlusal image

Figure 25 A

B

Cross-sectional mandibular anterior occlusal. (A) Clinical photograph. (B) Occlusal image

the buccal surfaces of the posterior teeth with the patient gently biting to maintain its position. The central ray should be directed perpendicular to the receptor and centered 3 cm posterior to the mentum and 3 cm lateral to the midline. This projection records one quadrant of the mandibular teeth through the long axes dimension. The cross-sectional posterior occlusal is useful for evaluating mediolateral expansion of the posterior mandible or localizing a salivary stone in the submandibular gland (Figure 26A, B). The exposure time is the same time as the mandibular molar periapical for selected receptor.

Common Intraoral Technique Errors The clinician must have the ability to evaluate intraoral images for diagnostic quality and be able to identify, understand and correct errors to keep retakes to a minimum and

eventually learn how to avoid them altogether. A diagnostic periapical depicts the area of interest including the entire length of the teeth from the crown to the root apices with at least 3–4 mm of bone surrounding the apices and open proximal contacts. The image should have adequate contrast and density and be free of technical errors. A diagnostic bitewing displays the area of interest, the proximal surfaces of the maxillary and mandibular teeth crowns and the alveolar bone crests. Like periapicals, adequate contrast and density and absence of technical errors are necessary components of a quality image. When evaluating a full-mouth survey, every apex and every proximal surface should be visible somewhere within the composite of images. A number of technical errors can be produced when the parameters of intraoral technique are not properly followed. Common errors encountered in intraoral radiography include 739


Figure 26 A

B

Cross-sectional mandibular posterior occlusal. (A) Clinical photograph. (B) Occlusal image

Table 6

Common technical errors

Error

Description

Correction

Foreshortening

Structures shorter than normal; vertical angle too steep

Decrease the vertical angle of the PID

Elongation

Structures longer than normal; vertical angle not steep enough

Increase the vertical angle of the PID

Horizontal overlap

Proximal surfaces of the teeth are superimposed onto each other with width distortion

Direct the horizontal angle through the proximal contacts of the teeth for each view

Cone cut

Central ray of the X-ray beam is not aligned with the middle of receptor producing a partial image or cut

Direct the central ray toward the center of the receptor using facial landmarks or ringed instruments

Improper placement

The teeth or area of interest are cut-off because the receptor is not placed in the right location

Follow the placement guidelines to include all structures required on a particular view

Underexposure

Image is too light or faint because patient size was underestimated, exposure time set too low or the exposure incomplete

Evaluate the patient size, set the correct time for each view and hold down the exposure button until the exposure is complete

Overexposure

Image is too dark or dense because patient size was overestimated or exposure time set too high

Evaluate the patient size, set the correct time for each view

placement, vertical angulation errors, horizontal overlap, cone cuts and exposure errors. A discussion of these common errors follows. Table 6 summarizes common errors and their corrections.

are dot reversal and a light image from lead foil absorption of the X-rays. Backward plate placement results in reversal of the letter or number identifier. Vertical angulation

Receptor placement The most common technical error regardless of the type of receptor is placement. Each periapical and bitewing placement requires inclusion of specific structures on each view. When the expected structures are not recorded, retakes may be necessary to gain the missing information. In addition to incorrect location, portions of the teeth such as the crowns or apices can be cut-off and necessitate a retake (Figure 27). Backward placement of film and plate receptors is possible as well. Hallmarks of backward film placement 740

Vertical angulation errors result in either foreshortening or elongation of the teeth and surrounding structures. When the vertical angulation is too steep, the structures are diminished in length or foreshortened (Figure 28). This error is corrected by decreasing the vertical angulation. Elongation produces the opposite result with lengthened structures as a result of inadequate or not enough vertical angulation (Figure 29). Correction of elongation requires an increase in vertical angulation to return the structures to normal length.


Figure 27

Mandibular premolar periapical receptor placement error in which the apical portions were cut-off the image

Figure 28

Maxillary incisor periapical with image foreshortening caused by over-angulation in the vertical plane

Horizontal overlap Proximal overlap is the primary error that occurs when the horizontal angulation is misdirected (Figure 30). Diagonal rather than perpendicular entry of the X-ray beam to the horizontal planes of the teeth causes superimposition of the proximal surfaces from one tooth onto the next. The proximal surfaces of the teeth and alveolar bone margins are obscured from view and the structures are distorted in width as well. This error is especially egregious on bitewings as it limits or prevents assessment of the teeth for proximal caries and alveolar bone loss. The open end of the PID should be horizontally parallel to the buccal plane of the teeth of interest to direct the X-rays through the teeth contacts (Figure 31).

Figure 29

Mandibular incisor periapical demonstrating elongation caused by under-angulation in the vertical plane

Figure 30

Premolar bitewing with proximal overlap due to improper horizontal angulation

Cone cuts A cone or PID cut is the direct result of misalignment of the central ray (Figure 32). When the central ray is not directed to the middle of the receptor, a portion of the receptor is not exposed and no image is produced in that region. Cone cuts can occur on any aspect of a radiographic image. The use of the classic receptor placement for each view and central ray alignment with external entry points will help eliminate cone cuts. Ringed instruments with beam guides eliminate this error when properly assembled. Exposure A variety of exposure errors can occur that diminish the diagnostic quality of a radiographic image. Improper 741


Figure 31

The horizontal angulation should be aligned so that the X-rays are directed through the proximal contacts of the teeth on both periapicals and bitewings

Figure 33

A faint image of a maxillary molar periapical due to underexposure of the receptor

Figure 34 Figure 32

Cone cut error on a mandibular premolar periapical. The central ray was positioned too high relative to the center of the receptor and central entry point

selection of the exposure time for the subject or area of interest can produce an underexposed low density image with a faint appearance (Figure 33) or an overexposed highdensity image with a dark appearance. Neither is desirable and both could result in retakes. With digital imaging systems, dark images can be corrected with the imaging software as long as the image is not completely black. However, very light images cannot be corrected by the software because not enough exposure was received by the receptor to form the image. Film and plate receptors can be doubleexposed producing an overly dark superimposed image which requires two retakes (Figure 34). 742

A double exposure occurs when a film or plate receptor is exposed twice. It produces a dark image with superimposed structures which require two retakes

Intraoral radiography is indispensable for proper diagnosis and treatment of dental patients. A variety of intraoral projections can be taken to visualize the teeth and surrounding structures including periapicals, bitewings and occlusals. Intraoral radiographs should be prescribed by the dentist according to selection criteria guidelines to ensure that the benefit of the examination outweighs the risk. The clinician must have the requisite knowledge and skill to effectively manage the patient and competently conduct all aspects of the imaging procedure. Adherence to the tenants of radiographic technique will maximize the diagnostic result while at the same time minimize patient radiation exposure through retake prevention.


EXTRAORAL RADIOGRAPHY

As the term extraoral suggests, it is a technique in which the image receptor is placed outside the mouth during the X-ray exposure.

examined. Such an amount of scatter radiation induces a deterioration of the image quality, reducing the contrast, and it would eventually reduce the diagnostic quality. Though grids minimize scatter radiation and improve the quality of the resultant radiograph, they will also remove some of the primary radiation and thus require the radiation exposure to be increased.

Technique

Landmarks for Positioning in Skull Radiography

Extraoral radiography, in contrast to the intraoral radiography, is made with indirect exposure films, where the film is placed inside a tight cassette between intensifying screen on either side and then the exposure is made after proper positioning of the patient with reference to the long axis of the cassette.

The basic localization points and planes of the skull (all of which can be either seen or palpated) are used in radiographic positioning (Figure 35). Accurate positioning of the skull requires a full understanding of these landmarks. The planes, points, lines, and abbreviations most frequently used in skull positioning are as follows:

Suman Jai Sanghar, Jai Sanghar N

Image receptors Image receptors used here are otherwise known as screen films or indirect exposure films, as they are used along with intensifying screens. These screens emit visible light on exposure to X-rays. The emitted visible light will in turn expose the films. Due to the variation in the properties of intensifying screens, proper screen-film combination must be used as recommended by the screen and film manufacturer so that the emission characteristics of the screen match the absorption characteristics of the film. Dimensions of the films used in skull radiography are 8 10 inches and for lateral oblique views, it is 5 7 inches. Intensifying screens Due to density of the skull, intensifying screens must be used to minimize the amount of radiation to the patient, which also helps in reducing the scattered radiation. Intensifying screens permit a good radiograph to be produced with the patient receiving a much lower dose of radiation.

❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍

Midsagittal plane (MSP) Interpupillary line Acanthion Outer canthus Infraorbital margin External acoustic meatus (EAM) Infraorbitomeatal line (IOML) Orbitomeatal line (OML) Acanthiomeatal line (AML) Mentomeatal line (MML).

MSP The midsagittal or median plane divides the body into right and left halves. This plane is important in accurate positioning of the cranium since, for every frontal or lateral position, the MSP is either perpendicular to, or parallel to, the plane of the film. Interpupillary or interorbital line It is the line connecting either the pupils or the outer canthi of the patient’s Figure 35 Glabelloalveolar line

Speeds of intensifying screens 1. Fast screens Thick layer of relatively large crystals used, maximum speed is attained but with some sacrifice in image detail. 2. Slow screens or high definition screens A thin layer of relatively small crystals are used; detail is the best, but speed is slow necessitating a higher dose of ionizing radiation. 3. Medium screens Medium thick layer of medium sized crystals in order to provide comprise between speed and definition. Grids The grid is usually used to reduce scatter radiation, which causes a decrease of the image contrast. The amount of scatter radiation reaching the film would be several times the primary radiation, depending on the part of the body

ine al l eat l line lom eata m o Orbit Infraorbitomeatal line Acan thiom eatal M en line to me at al lin e

Nasion

el lab

G

External acoustic meatus Angle of mandible (gonion)

Acanthion

Mental point

Illustration depicting various radiographic planes for positioning of the skull

743


eyes. When the head is placed in a true lateral position, the interpupillary line must be exactly perpendicular to the plane of the film. Acanthion It is the midline point at the junction of the upper lip and the nasal septum. IOML It is the line formed by connecting the middle of the infraorbital margin to EAM. It is otherwise known as anthropological baseline or Frankfurt line. OML It is a line located between the outer canthus and the EAM. This is also known as radiographic baseline or canthomeatal line. This line is angled approximately 10 to the anthropological baseline. AML It is a line formed by connecting the acanthion to the EAM. MML It is the line formed by connecting mental point (midpoint of the triangular area of the chin) and EAM. Positioning terminology To describe a skull projection, it is necessary to state the relative positions of the skull planes to the image receptor and the central ray relative to skull planes/image receptor.

❍

❍ ❍ ❍

❍

❍

Radiation protection Routine radiation protection measures should be applied. The most effective method of dose reduction is a careful technique to avoid the need for repeat radiograph. Radiographic techniques 1.

Fronto-occipital projections The central ray enters the skull through the frontal bone and exits through the occipital bone. 2.

Positioning errors

1. 2.

Rotation—occurs when the MSP is not parallel to the film. Tilt—occurs when the interpupillary line is not perpendicular to the film.

3.

Submentovertex (base or full axial projection, Schuller method)

4.

Lateral view Modifications ❍ Lateral cephalometric

Patient preparation ❍

Before starting any examination, the identity of the patient must be checked by the radiographer.

Figure 36

Illustrations showing the position of the mid-saggital plane

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Standard occipitomental Modifications ❍ 30 occipitomental ❍ Parietoacanthial projection (Waters’ view, PNS view) ❍ Open mouth Waters’ view ❍ Modified parietoacanthial projection (modified Waters’)

Oblique projections The central ray is projected at some angle to the median plane and the coronal plane.

Rotation and tilt are two of the most common positioning errors (Figure 36):

Posteroanterior (PA) projection (0) Modifications ❍ Caldwell projection (15) ❍ 20 PA projection ❍ PA mandible ❍ PA skull ❍ PA cephalometric ❍ Rotated PA view

Occipitofrontal projections The central ray enters the skull through the occipital bone and exits through the frontal bone.

Lateral projections The central ray passes along a coronal plane at right angles to the MSP.

Ensure that all metal objects are removed from the patient, for example, hair clips and hairpins, jewelleries, spectacles, hearing aids. Bunches of hair often produce artifacts and thus should be untied. If the area of interest includes the mouth, then denture (if removable) should be removed. The patient should be provided with a clear explanation of any movements and film positions associated with the normal operation of the skull unit. If needed, foam pads, Velcro straps can be used as accessories for stabilizing the patient. Forty-five degree triangular pads are very useful for immobilizing children. Individual side markers are essential for skull radiography.

5.

Acanthoparietal projection (reverse Waters’ view)

6.

AP axial projection (Townes’ method)

7.

Reverse Townes’ method

8.

Lateral oblique ❍ Ramus of the mandible ❍ Body of the mandible

9.

TMJ projections ❍ Transcranial ❍ Transpharyngeal ❍ Transorbital.


POSTEROANTERIOR PROJECTION

Figure 37

Occipitofrontal Projection Occipitofrontal projections can be taken with different degrees of beam angulation. The choice of the angulation depends on the anatomy, which needs to be demonstrated. 10°

CR

Indications ❍

❍ ❍ ❍ ❍ ❍

Fractures of the body, angle or ramus of the mandible, displacement of fractures especially in a mediolateral direction. Le Forte I fracture of the middle third of the face. Gross displacement of the zygomatic buttress. Displacement of the teeth in alveolar fractures. Cysts or tumors in the rami, showing expansion of the bone in the mediolateral direction. Deformity of the mandible or the maxillofacial area.

Skull position for PA view showing the central ray directed perpendicularly through the occiput to exit the nasion

Figure 38 CR 15°

Film placement Cassette with the film is placed perpendicular to the floor, with long axis vertically in a cassette holding device. Patient positioning ❍

The nose and the forehead of the patient should touch the cassette, a position which places the OML (radiographic baseline) perpendicular to the cassette. ❍ Mid part of the frontal bone is positioned in the center of the cassette. ❍ MSP is positioned perpendicular to the cassette, which is accomplished by adjusting lateral margin of orbit or EAM equidistant from the edges of the cassette. Central ray For PA projections, when frontal bone is of primary interest, the central ray is directed perpendicularly, through the occiput to exit the nasion (Figure 37). Variations of PA projections 15 PA

Caldwell method.

Indication For depiction of the ethmoid and frontal sinuses that include both orbits. Patient positioning is same as that for PA projection except for the central ray projection, which is directed at a caudal angle of 15 to the canthomeatal line (Figure 38). The resultant radiograph will demonstrate the superior border of the petrous ridge projected onto the lower third of the orbit. 20 PA Similar to the above technique the caudal angulation alone can be changed to 20–25 which helps in better visualization of the orbit, as the petrous ridges will be projected inferiorly as the angulation is increased.

Skull position for 15 PA Caldwell view showing the central ray directed at a caudal angle of 15 to the canthomeatal line

PA Mandible Indication The indication of this technique is to demonstrate the transverse or oblique fracture of the body and rami of the mandible, not evident in other projections. Cassette and patient positioning is the same as that for PA projection except that the central ray is directed perpendicular to the cassette and centered in the midline through the cervical spine at the level of the angles of the mandible. Limitation of this technique is that the central body of the rami is not well shown because of the superimposed spine.

PA Cephalometric Cephalometric radiography ensures standardization and reproducibility of the images. Indications ❍ ❍ ❍

To assess the position of unerupted canines. To evaluate the asymmetry of facial bones. For pre- and post-operative assessment of jaws for both orthodontic and orthognathic procedures. 745


Film positioning

Patient positioning

Cassette with the film is placed perpendicular to the floor, with long axis vertically in a cassette holding device.

❍

Patient positioning ❍

MSP should be placed vertical and perpendicular to the film. ❍ Only nose should touch the film, so that the OML is parallel with the floor which makes the radiographic baseline to be at 10 with the film. ❍ Head is immobilized using ear pieces inserted into the EAM. ❍ Film adjusted with lips centered on the film.

Patient’s nose and chin are placed in contact with the midline of the cassette. ❍ The head is then adjusted to bring the orbitomeatal baseline to 45 angle to the cassette. ❍ MSP is perpendicular to the cassette. Central ray Central ray is directed perpendicular to the film through the occiput making its exit through the anterior nasal spine. The final image should be such that the petrous ridge must appear below the floor of the maxillary sinus.

Central ray

30ⴗ OCCIPITOMENTAL

It is directed perpendicular to the film through MSP at the level of the bridge of the nose.

Indications ❍

Rotated PA View Indications ❍ ❍

To demonstrate calculi in the parotid gland. To evaluate cysts and tumors involving the ramus of the mandible which may have mediolateral expansion.

Technique ❍ ❍ ❍

The film is positioned same as that of the PA view. The head is rotated 10 toward the side of interest. This positioning rotates the bones of the back of the skull away from the side of the face under investigation. ❍ The central ray is directed perpendicularly along the side of the face.

To demonstrate fractures of the middle third of the face, orbital floor. ❍ Blow-out fracture of the orbit. ❍ Fractures of the zygomatic arches.

This projection demonstrates the lower orbital margins and the orbital floor. The zygomatic bones and arches are opened out compared with the occipitomental projections as this technique uses a different angulation thereby enabling detection of certain bony displacements. Film placement Cassette with the film is placed perpendicular to the floor, with long axis vertically in a cassette holding device. Patient positioning ❍

Indications

Patient’s nose and chin are placed in contact with the midline of the cassette. ❍ The head is then adjusted to bring the orbitomeatal baseline to 45 angle to the cassette. ❍ MSP is perpendicular to the cassette.

❍

Central ray

STANDARD OCCIPITOMENTAL VIEW

Diagnosis of pathologic conditions affecting air sinuses, especially the maxillary antra. Examples: tumors, cysts, fluid levels. ❍ Fractures of the middle third of the facial skeleton. This position shows the floor of the orbits in profile, the nasal region, the maxillae, the inferior parts of the frontal bone, the zygomatic bone and zygomatic arches, with their entire length superimposed over a small part of the image. Film placement Cassette with the film is placed perpendicular to the floor, with long axis vertically in a cassette holding device. 746

The tube head is angled 30 caudally and centered along the midline, such that the central ray exits at the level of the lower orbital margins. In a severely injured patient, a modified 30 reverse occipitomental view can be taken. Here the cassette is positioned vertically against the vertex of the skull supported with foam pads so that MSP is perpendicular to the film and to the table, also to OML. The tube is angled 20 to the horizontal (toward the floor) and centered to the symphysis menti in the midline.


PARIETOACANTHIAL VIEW (Waters’ View)

PARIETOACANTHIAL VIEW (Open Mouth Waters’ View)

Indications This technique is useful for the evaluation of maxillary sinuses and it also demonstrates frontal sinuses, ethmoidal sinuses, orbit, zygomaticofrontal suture and nasal cavity. In Waters’ technique the neck is hyperextended enough to place the dense petrosae immediately below the maxillary sinus floor. Film placement Cassette with the film is placed perpendicular to the floor, with long axis vertically in a cassette holding device. Patient positioning The patient’s neck is hyperextended and centered over the cassette perpendicular to the acanthion. The patient’s chin is placed resting over the cassette and adjusted so that MSP is perpendicular to the plane of the cassette. The head is adjusted so that the OML forms an angle of 37 from the plane of cassette (Figure 39). Central ray Perpendicular to the cassette exiting at the acanthion. ❍

Too much of angulation results in foreshortening of maxillary sinus and the antral floors are not demonstrated. ❍ When the neck is not fully extended, the petrosae are projected over the inferior portion of the maxillary sinus and obscure the underlying pathologic process, if present.

Figure 39

This method provides an excellent demonstration of the sphenoidal sinuses. The beam is projected through the open mouth and is done for patients who cannot be placed in position for submentovertex view. Film placement Cassette with the film is placed perpendicular to the floor, with long axis vertically in a cassette holding device. Patient positioning It is similar to the positioning in Waters’ view, except that the patient is asked to slowly open the mouth widely. MML will not be perpendicular as in Waters’.

MODIFIED PARIETOACANTHIAL PROJECTION (Modified Waters’ View) Indication The modified Waters’ method is a good projection to demonstrate ‘blow-out’ fractures. Although the parietoacanthial (Waters’) projection is widely used, this technique is modified by making the patient to extend his/her neck to a lesser degree. This method is referred to as ‘shallow Waters’ ’. In this method, OML is adjusted to form an approximately 55 angle with the plane of the cassette (Figure 40A, B). The resulting radiograph demonstrates the facial bone with less axial angulation than with the Waters’ method.

ACANTHOPARIETAL PROJECTION (Reverse Waters’ Method) Indication Reverse Waters’ method is used to demonstrate the facial bones when the patient cannot be placed in a prone position.

37°


CR

Skull position such that OML forms an angle of 37 from the plane of cassette

MSP is placed perpendicular to the plane and also in the midline of the cassette. ❍ Neck is extended so that the OML forms a 37 angle with the plane of the cassette (Figure 41) by raising the chin up. ❍ If necessary, a support is placed under the patient’s shoulders to help extend the neck. ❍ MML is approximated perpendicular to the plane of cassette. Central ray It enters the acanthion which is parallel with MML. 747


Figure 40 A

B

55°

CR CR 35°

Illustrations showing the skull position and entry of central ray for the modified Waters’ view

Patient positioning

Figure 41

❍

The patients shoulders are raised and the neck is hyperextended to bring the vertex of the skull in contact with the cassette. ❍ The head is adjusted to bring the EAM equidistant from the edges of the cassette (Figure 42). ❍ The MSP should be at right angles to the cassette. ❍ The OML should be as near as possibly parallel to the cassette. Central ray

37°

Illustration showing the skull position such that the OML forms a 37 angle with the plane of the cassette

Structures seen Reverse Waters’ demonstrates superior facial bone. The image is similar to that obtained with Waters’ method, but facial structures are considerably magnified.

SUBMENTOVERTEX VIEW (Base or Full Axial Projection, Schuller Method) Indications ❍ ❍ ❍

748

To demonstrate fractures of the zygomatic arches. For visualization of the base of the skull. To evaluate the angle of inclination of the head of the codyle.

The central ray is directed at right angles to the OML and centered midway between the EAM. This projection is contraindicated in patients with suspected neck injuries, especially suspected fractures of odontoid region. Though this technique is described in supine position, seated upright position is more comfortable because the upright position allows a greater freedom in positioning patients body to place the IOML parallel with the cassette. Jug handle view It is a modification of submentovertex view (SMV) projection, wherein the whole length of the zygomatic arch is demonstrated in profile against the side of the skull and facial bones from which this view derives its name. The modification done here is a decrease in the exposure factors.

LATERAL VIEW

Film placement

Indications


❍

Backward displacement of fractures of the middle third of the facial bones.


Figure 42

Figure 43

CR

Skull position showing entry of central ray

❍ ❍

Foreign body in the airway. To evaluate the posterior walls of the antrum, for its integrity.

CR

Illustration depicting entry of central ray for lateral skull view

❍ ❍

To assess the skeletal pattern. For tracing and scanning points necessary for orthodontic procedures.

Film placement

Film placement



Patient positioning

Patient positioning

❍

❍ ❍ ❍

The cassette is supported vertically against the side under examination, so that the center of the cassette is 2.5 cm inferior to the outer canthus of the eye. ❍ MSP is parallel to the cassette by ensuring that the interorbital line is at right angle to the cassette and the nasion and external occipital protruberance are equidistant from the margins of the cassette.

❍ ❍

Central ray It is directed horizontally to a point 2.5 cm inferior to the outer canthus of the eye (Figure 43).

❍

This technique is often reserved for gross trauma as the facial structures are superimposed. If lateral view is taken for a suspected foreign body in the eye, then additional collimation and alteration in the centering point will be required.

❍

Sagittal plane is vertical and parallel to the cassette. Frankfort plane should be horizontal. The head is immobilized by guiding the ear pieces carefully into the EAM. Metal circular markers within the ear pieces allow the operator to rapidly recognize the centering of the cephalostat. The nose support is positioned over the nasion. A wedge-shaped filter is positioned so that it will be superimposed on the face with the thick edge placed anteriorly for demonstration of the soft tissues. The patient is instructed to close his/her mouth and to bite together on his/her back teeth (centric occlusion). Lips should be relaxed.

Central ray Horizontal beam is centered on the EAM.

AP AXIAL PROJECTION (Townes’ Method) LATERAL CEPHALOMETRY This is a standardized true lateral projection of the skull. Indications ❍

To visualize the relationship of the soft and hard tissues of the face. ❍ To assess the position of the teeth in relation to each other and to the hard tissues and adjacent structures.

Indications ❍ ❍

To visualize the occipital area of the skull. Demonstrate the ascending rami of the mandible and condyles of both sides.

Film placement Cassette with the film is placed perpendicular to the floor, with long axis vertically in a cassette holding device. 749


❍

Figure 44 CR 30°

CR

The patient is then asked to keep his/her mouth wide open. By doing so, the condylar heads move out of the glemoid fossae.

37°

Central ray The central ray is aimed upward from below the occiput so that the central ray forms an angle of 30 to the horizontal, and is centered through the condyles.

LATERAL OBLIQUE VIEW Illustrations depicting patient head position and entry of central ray for Townes’ method

Patient positioning ❍ ❍ ❍ ❍

❍

Patient is positioned such that the posterior aspect of the skull rests on the cassette. Patient’s head is adjusted so that the MSP is perpendicular to the midline of the cassette. Flex the patient’s neck enough to place the OML perpendicular to the midline of the cassette. When the neck cannot be flexed, the neck is adjusted so that the IOML is perpendicular and has the central ray angulation to be increased by 7 (Figure 44). The cassette is positioned so that its upper margin is at the level of the highest point of cranial vault. This will place the center at or near the level of foramen magnum.

Central ray Directed through the foramen magnum at a caudal angle of 30 to the OML or 37 to IOML. Central ray enters approximately 2½ inches above the glabella and through the level of EAM.

REVERSE TOWNES’ VIEW

The lateral oblique radiograph is an extraoral projection that reveals a larger area of the jaws than intraoral radiography. Indications ❍

When intraoral views are unobtainable in patients having trismus or severe gagging. ❍ To detect unerupted teeth or impacted molars. ❍ Fractures of the angle or the body of the mandible. ❍ Pathologic conditions affecting the jaws. General imaging principles ❍

The head is rotated to ensure that the area under examination is parallel to the film. ❍ The film and the median plane are not parallel. ❍ The central ray is perpendicular to the film but oblique to the median plane.

Lateral Oblique of the Body of the Mandible and Maxilla This projection shows the dentition in the premolar/molar region of the maxilla and mandible, the inferior cortex of the mandible, and the angle and ascending ramus of the mandible. Position of patient and cassette

This projection shows the condylar heads and necks.

❍

Indications

❍

❍ ❍

❍

Fractures involving the condylar necks. Developmental anamolies involving the condyle, such as condylar hypoplasia or hyperplasia.

Film placement Cassette with the film is placed perpendicular to the floor, with long axis vertically in a cassette holding device.

❍ ❍


Patient positioning is similar to that in PA projection (forehead–nose position). ❍ OML should be at right angles to the film. 750

❍ ❍

The patient is made to sit with the head supported. The median plane is vertical. A 5 7-inch cassette is used. Film markers should be used to indicate the side. The cassette is positioned against the patient’s cheek overlying the region of the mandible under investigation, with the lower border parallel to the inferior border of the mandible but lying at least 2 cm below it. The cassette in this position is stabilized by the patient. The patient’s head is rotated to the side of interest. This positions the contralateral ascending ramus forward and increases the area between the neck and the shoulder to provide space for the X-ray tube. The chin is raised slightly to increase the space between the posterior aspect of the mandible and the cervical spine. The patient is asked to protrude the mandible.


Central ray

Indications

❍

❍

Central ray is directed at a point 2 cm below and behind the angle of the contralateral side of the mandible. ❍ The central ray is perpendicular to the plane of the film. If the superimposition of the hyoid bone onto the body of the mandible is to be avoided, then a downward beam angulation of 10 can be chosen.

To demonstrate the destruction of the condyles due to degenerative changes. ❍ To assess the degree of movement of the joint. Film placement A 5 7-inch cassette is used. Film markers should be used to indicate the side. ❍ The cassette with the film is placed on the side of interest, with the TMJ being centered over the cassette. ❍ The cassette in this position is stabilized by the patient. ❍

Lateral Oblique of the Ramus of the Mandible

Patient positioning

This projection gives an image of the ramus from the angle of the mandible to the condyle.

❍

MSP is parallel to the plane of the film.

Central ray Position of patient and cassette ❍ ❍ ❍

❍

❍ ❍

The patient is made to sit with the head supported. The median plane is vertical. A 5 7-inch cassette is used. Film markers should be used to indicate the side. The cassette is positioned against the patient’s cheek overlying the ascending ramus and the posterior aspect of the condyle of the mandible under investigation. The cassette is positioned such that its lower border is parallel with the inferior border of the mandible but lies at least 2 cm below it. The patient is instructed to support the cassette in this position. The mandible is extended as far as possible.

Central ray ❍

The central ray is directed posteriorly with upward angulation of 10 toward the center of the ramus of the mandible on the side of interest. ❍ The X-ray tube is positioned on the contralateral side of the mandible at a point 2 cm below the inferior border in the region of first or second molar.

Bimolar Projection This technique is used in orthodontic practice. It shows both left and right oblique lateral views on one film. The technique incorporates a hinged lead shield to prevent exposure of the other side of the film.

❍

The central ray is directed at an angle of 25 (positive angulation) from the opposite side, through the cranium and above the petrous ridge of the temporal bone. ❍ The horizontal angulation can be individually corrected for the condylar long axis, or an average 20 anterior angle may be used. Transcranial, transpharyngeal and transorbital views should be taken in both close and open mouth positions, to assess the range of condylar movements.

TRANSPHARYNGEAL VIEW (Parma Projection, Macqueen-Dell Technique) This technique provides a sagittal view of the medial pole of the condyle. Indications ❍ ❍ ❍

To visualize the head and neck of the condyles. Developmental anamolies of the condyle neck. To detect grossly displaced fracture of the condyle.

Film placement A 5 7-inch cassette is used. Film markers should be used to indicate the side. ❍ The cassette with the film is placed on the side of interest, with the TMJ being centered over the cassette. ❍ The cassette in this position is stabilized by the patient. ❍

Patient positioning

TMJ RADIOGRAPHY

❍

TRANSCRANIAL VIEW

Central ray ❍

It is a view that aids in visualizing the sagittal view of the lateral aspects of the condyle and temporal component.

MSP is parallel to the plane of the film.

The beam is directed superiorly at an angle of 5 through the sigmoid notch of the opposite side, and 7–8 from the front, centered over the TMJ of the opposite side. 751


TRANSORBITAL VIEW It provides an anterior view of the TMJ, perpendicular to the transcranial and transpharyngeal projections. Indications ❍ ❍

To visualize condylar neck fractures. To detect degenerative changes or anamolies affecting the condyle.

Dorsal sellae and posterior clinoid processes Occipital bone Posterior portion of the parietal bone.

Positioning of the patient The patient is asked to stand in an upright position. Arms are placed in comfortable position. Shoulders are made to lie in the same horizontal plane. The midsagittal plane of the body is centered to the center of the image receptor (Figure 45A).

Film placement

Positioning of the part

A 5 7-inch cassette is used. Film markers should be used to indicate the side. ❍ The cassette with the film is placed behind the skull on the side of interest.

Patient’s head is adjusted such that midsagittal plane is perpendicular to the midline of the IR. Patient’s neck is flexed such that the OML is 30 to the central ray. IR is positioned such that its upper margin is at the level of the highest point of cranial vertex (Figure 45B).

❍

Patient positioning The patient’s head is tilted downward 10, so that the canthomeatal line is horizontal. Central ray Central ray is oriented downward approximately by 10 and laterally approximately 30 through the ipsilateral orbit, centered over the TMJ of interest. If the condylar motion is limited, then only the neck is visible due to superimposition of the temporal component on the condylar head. This view is rarely being used now, due to unwanted radiation exposure to the eyes. In addition to the above-mentioned techniques for viewing the TMJ, reverse Townes’ view and submentovertex projections can be used to assess the TMJ.

LESSER KNOWN/FORGOTTEN EXTRAORAL RADIOGRAPHIC TECHNIQUES There are many lesser known techniques in maxillofacial imaging which can be used as powerful tools for demonstrating a large variety of craniofacial structures. Although new paradigms for X-ray imaging techniques have emerged, they may not be economic and readily feasible to be used in many health centers. In such cases, some of these techniques can still be used as a standard procedure for demonstrating various craniofacial structures.

Townes’ Method or AP Axial Projection This method demonstrates: ❍ ❍ 752

❍ ❍ ❍

The petrous pyramids Posterior portion of the foramen magnum

Central ray The central ray is directed through the foramen magnum at a caudal angle of 30 to OML. It enters approximately 2½ inches (6.3 cm) above the glabella and passes through the level of EAM (Figure 45C). Structures shown are: ❍ ❍ ❍

Symmetric image of the petrous pyramids Posterior portion of the foramen magnum Dorsal sellae and posterior clinoid processes projected within the foramen magnum ❍ Occipital bone ❍ Posterior portion of the parietal bones.

May Method When a patient with suspected fracture of zygomatic arch comes to the department, radiographs that are usually advised for these patients are submentovertex view, Schuller’s method and sometimes Waters’ view as well. But there are always chances of superimpositions of other structures on the zygomatic arch when these methods are used. Thus, when a radiographic view of zygomatic arch is required, the alternative method would be May method, also known as ‘tangential projection’. This method demonstrates: ❍ ❍ ❍ ❍

Zygomatic arch Temporal process of zygomatic arch Temporal bone Useful in patients who have depressed fractures or flat cheek bones.

Positioning of patient The patient is asked to stand in an upright position. Arms are placed in comfortable position, shoulders are made to lie in the same horizontal plane. The midsagittal plane of the body is centered to center of the image receptor (Figure 46A).


Figure 45 A

B

C

30°

CR

(A) Position of patient in Townes’ method. (B) Upright radiograph. (C) Upright radiograph with central ray directed 30 degrees to OML

Figure 46 B

A

C

15° top of head tilt

15°

CR

(A) Position of the patient in May method. (B) Upright radiograph. (C) Central ray in May method

Positioning of the part Neck is extended such that the IOML is as parallel with the plane of the IR as possible. Chin is rested on the IR. The midsagittal plane is rotated approximately 15. Top of the head tilted away from the side being examined 15. It is ensured that the central ray is tangent to the lateral surface of the skull. The central ray skims across the lateral portion of the parietal bone and the mandibular angle to project the zygomatic arch onto the IR (Figure 46B). Central ray The central ray is directed perpendicular to the IOML and passes through the zygomatic arch at a point approximately 1½ inches posterior to the outer canthus. The IR is centered to the central ray (Figure 46C).

Structures shown are: ❍ ❍ ❍

Zygomatic arch free of superimposition Temporal process of zygomatic arch Temporal bone.

Axiolateral Oblique Projection Another lesser known technique is the axiolateral oblique projection, also known as original law method. This method can otherwise be called ‘double tube angulation’. This method demonstrates: ❍ ❍ ❍ ❍ ❍

Mandibular condyle Mastoid cells Lateral portion of the petrous pyramid Superimposed internal and external acoustic meatuses Mastoid emissary veins. 753


Figure 47 B

A

15°

CR

(A) Position of the patient and direction of central ray in axiolateral oblique projection/ original law method. (B) Upright radiograph

Positioning of the patient Patient is positioned with the head in a true lateral position, the flexion of the patient’s head is adjusted such that the interpupillary line is perpendicular to the plane of the image receptor; and the IOML and midsagittal plane are parallel with the IR plane (Figure 47A).

Also useful for good projection demonstration of blowout fracture.

Position of the patient The patient is placed in prone position. The midsagittal plane of the patient’s body is centered to the midline of the image receptor (Figure 48A).

Central ray

Position of the part

Central ray is directed 15 caudal and 15 anteriorly. It enters approximately 2 inches posterior to and 2 inches above the uppermost EAM and exits the downside mastoid process. The IR is centered to the central ray. The structures shown are (Figure 47B):

❍

❍ ❍ ❍ ❍ ❍

Mandibular condyle Lateral portion of the petrous pyramid Superimposed internal acoustic meatus Mastoid emissary veins when present Mastoid cells.

Modified Parietoacanthial Projection This method demonstrates: ❍ ❍

❍ ❍ ❍ ❍ ❍ 754

❍

Facial bones with less axial angulation than with the Waters’ method Petrous ridges projected immediately below the inferior border of the orbits at a level midway through the maxillary sinus Maxillary sinus Zygomatic bone Inferior orbital margin Nasal septum Mandible

The patient’s head is rested on the tip of the extended chin. The neck is extended to a lesser amount than done in Waters’ method. OML is adjusted to form approximately 55 angle with the plane of the IR, with the average patient’s nose about 3/4 inch away from the IR. The head is adjusted so that the midsagittal plane is perpendicular to the plane of the IR. The IR is centered at the level of the acanthion (Figure 48B).

Central ray The central ray is directed perpendicular to exit the acanthion (Figure 48C). The structures shown are: ❍ ❍ ❍ ❍ ❍

Petrous ridges Zygomatic bone Inferior orbital margin Nasal septum Mandible.

Acanthioparietal Projection ‘Reverse Waters’ Method’ This method is used to demonstrate: ❍

Superior facial bones


Figure 48 B

A

C

55°

CR 35°

(A) Position of patient in parietoacanthial projection. (B) Upright radiograph. (C) Central ray

Figure 49 B

A

C

CR

37°

(A) Patient positioning in acanthioparietal positioning. (B) Upright radiograph. (C) Central ray

❍ ❍ ❍ ❍

Orbit Zygomatic bone Maxillary sinus Petrous ridge.

Position of the patient The patient is seated in upright position. The midsagittal plane of the body is centered to the midline of the cassette (Figure 49A). Position of the part The patient’s chin up is brought up. The extension of the neck is adjusted so that the OML forms 37 with the plane of the IR. The OML is made perpendicular to the plane of the IR. The patient’s head is adjusted such that

the midsagittal plane is perpendicular to the plane of the IR (Figure 49B). Central ray The central is directed perpendicular to enter the acanthion and centered to the IR (Figure 49C). The structures shown are: ❍ ❍ ❍ ❍ ❍

Superior facial bones Orbit Zygomatic bone Maxillary sinus Petrous ridge.

Thus, the ‘forgotten’ techniques overcome the limitations of newer techniques in terms of economics and feasibility, and venture should be undertaken to refresh the forgotten 755


techniques and bring them into use today as well. These techniques can still be used as a standard procedure for demonstrating various craniofacial structures.

Figure 50

PANORAMIC RADIOLOGY Panoramic radiology is considered a curvilinear variant of conventional tomography, in which a single tomographic image of facial structures includes both maxillary and mandibular dental arches and their supporting structures. Panoramic radiography is derived from the word ‘panorama’ which refers to an unobstructed or complete view of a region in every direction. The term ‘orthopantomography’ was coined by Paatero and Sairenji which is derived from ortho—straight or correct, pan (abbreviation for panorama), tomo—tomography is the imaging of depth of tissue layers without the interference of tissue above and below that plane of tissue.

Origin of Panoramic Radiology In the early days of the development of panoramic radiology, various experiments were carried out on the placement of the X-ray source (intraoral/extraoral and stationary/ moving source), placement of the film (adapted intraorally, lingual to teeth, or placed extraorally by adapting the film to the jaws) and patient’s position (stationary/rotating chair). Dr H Numata, a Japanese, in 1933, devised a technique to image the jaws by placing an intraoral film and an extraoral source of X-rays with a slit collimator which rotated about the patient’s head to image the jaws. In his technique the patient was stationary. In 1943, Horst Beger devised a prototype of the panoramic machine where the film was adapted extraorally on the jaws and the source of X-rays was placed intraorally. In 1946, Dr YV Paatero, experimented with a stationary X-ray source and the patient seated in a revolving chair. He called this technique parabolography. In the present day panoramic imaging techniques, the patient is stationary and the X-ray source and the cassette carrying the film are rotated about the patient’s head. The X-ray source and cassette drive/carriage assembly are incorporated into a C-arm. These machines have an optional cephalostat attachment that can be used for imaging the skull such as lateral cephalograms, Waters’ views, anteroposterior view, submentovertex view, etc. (Figure 50). Many of the panoramic machines have the option of using digital receptors such as charged-couple device (CCD) and photostimulable phosphor (PSP) system instead of filmbased technology.

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Panaromic machine with the cephalostat attachment

Concepts of Panoramic Imaging Technique and imaging principles 1.

2. 3.

4. 5.

Patient is advised to remove all metallic objects in the head and neck region such as hair clips, nose rings, ear rings, chains, spectacles, removable dental appliances, etc. Patient is instructed to wear a lead apron (Figure 51). An extraoral panoramic film (5 12 inches) is loaded into a designated panoramic rigid plastic backed cassette of the same size (Figure 52). The loaded cassette is placed into the cassette carriage assembly. Patient may either be seated or standing facing the radiographer (Figure 53). Patient is positioned such that his/her jaws are within the imaginary focal trough. This can be achieved by asking the patient to stand erect with the neck extended and the chin supported by the chin rest (this helps in establishing the vertical height). The anteroposterior position can be achieved by asking the patient to bite in the groove in the biteblock. The bite will also help in relieving the teeth from occlusion thereby preventing any cuspal overlaps. Apart from these measures, the machines have inbuilt light-beam guides that can be used for orientating the head of the patient to coincide with the midline in the sagittal plane, ala tragal line and a line


Figure 51

Figure 53

Patient standing upright facing the radiographer Individual wearing a lead apron devoid of metallic objects in the head and neck region

Figure 54

Figure 52

Panoramic cassette 5 12 inches

6.

7.

8.

of reference running along the corner of the mouth (canine) and ala of the nose (Figures 54 and 55). Exposure parameters are set. Most panoramic machines are equipped to operate between 54–85 kVp, 1–16 mA and 16 seconds exposure for adults and 14 seconds in the child mode. Patient is instructed to place his/her tongue against the roof of the mouth and remain still during the entire exposure cycle. The operator stands behind the lead screen and initiates the exposure by pressing the exposure timer switch which is also referred to as the ‘dead man’s switch’ as the timer needs to be pressed for the entire duration of the 14- or 16-second cycle.

Patient’s chin positioned on the chin rest and anterior teeth biting in the groove on the bite rod

Working principle In rotational panoramic radiography, the patient is stationary and the X-ray source (tube head) and the cassette carriage assembly (connected to each other via a C-arm), rotate around the patient’s head (Figure 56). As the C-arm rotates, the X-ray tube head and the cassette carriage assembly (Figure 57) rotate in the same direction, whereas the film along with the cassette moves in a direction opposite to movement of the tube head. The rate of the film movement is adjusted such that it matches with the speed of the slit shaped beam imaging the patient. A narrow beam of X-rays (facilitated by a slit collimator within the X-ray tube head) sweeps across in a horizontal

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Figure 55

Figure 57

Cassette carriage assembly

Cassette with film

Cassette carriage assembly Light beams showing the midsagittal plane and ala tragal line

Figure 58 Figure 56 Center of rotation C-arm

Cassette carriage assembly

X-ray source X-ray tube head

Film within film-cassette carriage

Illustration showing moving centers of rotation

X-ray tube head and cassette carriage assembly connected via the C-arm

plane around an intraorally placed invisible pivot (apparent intraoral source) referred to as the center of rotation. In the vertical plane, the X-ray beam sweeps beneath the occipital area with a negative angulation of 4 to 7. Unlike older panoramic machines where there was a fixed center of rotation, machines these days make use of continuously moving center of rotation thereby allowing the image layer to conform to the elliptical shape of the dental arches. The moving centers of rotation if plotted can be traced into a shape of two arcs meeting at the midline

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approximating the lingual aspect of the mandibular symphysis (Figure 58). With the above understanding, in the initial few seconds of exposure, when the X-ray beam is imaging the TMJ on the left side the center of rotation lies near the lingual surface of the body of the mandible of the right side. Futhermore, as different areas of the mandible are imaged, the center of rotation correspondingly relocates conforming to an arc shape. Objects located between the center of rotation and film are imaged well (real images) and those between the X-ray source and center of rotation are blurred (ghost images). All objects that are in the midline such as the cervical spine appear as double images (pair of real images). The panoramic machine is calibrated in such a way that the horizontal and vertical magnification is evenly


Effect of patient positioning in the focal trough on the resultant image

Figure 59

Dotted line enclosing imaginary image layer or focal trough

Illustration showing focal trough

Patient position in the focal trough

Image characteristics

Patient overbites on the bite block. The incisal edges of teeth placed way ahead of the groove on the bite

The mandibular anterior teeth appear narrow and fuzzy and the mandibular ramus and condyles will be superimposed by the image of the cervical spine However, this technique may be employed if the area of interest is the maxillary sinus and the nasal cavity

Patient’s anterior teeth way too short of the bite

Anterior teeth appear horizontally magnified and blurred

Patient is positioned with the chin tipped down too steeply

The area in the mandibular anterior region may appear blurred. Anterior teeth in the maxilla appear elongated and those of the mandible will appear stunted Moreover, the hyoid bone may appear superimposing on the roots of the mandibular premolars and molars and the TMJ region may not be imaged

matched so as to produce a final proportionate image. This is achieved by adjusting the speed of the X-ray tube head with regards to the movement of the film. Concept of focal trough The focal trough is also referred to as the image layer which is roughly elliptical in shape to conform to the morphology of the dental arches. The image layer is narrower toward the anterior teeth. Some authors describe the focal trough as the ‘plane of acceptable detail’. It is a three-dimensional imaginary curvilinear zone, in which objects when positioned, will be imaged well. All objects beyond this image layer may not be imaged or seen as distorted and blurred images (Figure 59). When the object of interest is positioned well within this image layer, the vertical and horizontal dimensions will match, resulting in a sharply defined image.

Characteristics of Ghost Images All objects that lie between the source of X-ray beam and center of rotation are projected as ghost images. These are seen as blurred images on the opposite side of the radiograph away from the real image, similar structure as the real image, positioned at the higher level on the radiograph when compared to its real counterpart and they are relatively more vertically blurred than horizontally. Common ghost images seen on the orthopantomograph (OPG) are those of metallic objects such as ear rings, hair clips and anatomic structures such as the cervical spine, hyoid bone, angle of the mandible including the lower border, etc.

A ‘smile-line’ is created Patient is positioned with the chin lifted up

The occlusal plane in the resultant image either appears flat or as a reverse curve. This has been referred to as a ‘sad line’ or a frown However, this technique of patient positioning may be used to improve imaging of mandibular anterior teeth

Improper midline orientation of the patient within the focal trough

Posterior teeth out of the focal trough will appear broad and exhibit proximal overlap, whereas on the contralateral side the teeth will appear slender

Patient’s neck is slumped and not straight and extended

A vertical opaque shadow is seen obscuring the midline structures

Patient instructed to swallow and hold the tongue against the hard palate

This technique will prevent superimposition of the pharyngeal air space over the roots of the maxillary anterior teeth

Indications of Panoramic Radiograph 1.

2. 3. 4. 5.

Used a screening radiograph to evaluate the gross pathologies or developmental disorders affecting the jaws and teeth. Patient’s with limited mouth opening or in individuals who cannot tolerate the intraoral film (severe gag reflex). Evaluation of multiple impacted or supernumerary teeth. Evaluation of the eruption status of teeth. Evaluation of the size and extent of bony pathologies such as cysts, tumors, fibro-osseous lesions, etc.

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6.

Assessment of the fractures of the jaws, especially the mandible (however maxillary and mandibular midline fractures may not be appreciated). 7. Evaluation of the TMJ (condylar pathologies such as fractures, hyperplasia, degeneration and changes in the morphology of articular eminence). 8. Although OPG is not the ideal imaging technique for visualization of the maxillary sinus, the floor, medial and posterior walls can be appreciated. 9. Gross evaluation of the interdental bone height and pattern in periodontal disease. 10. Evaluation of styloid process.

Disadvantages and Limitations 1.

2. 3.

4.

5.

Midline structures and the pathologies in the region may not be appreciated because of the superimposition of the cervical spine. Pathologies in the premolar region may be obscured because of the proximal surface overlap in that region. Finer details such as incipient carious lesions, minimal interdental bone loss, trabecular pattern may not be appreciated as the radiograph has poorer resolution compared to an intraoral radiograph. Panoramic radiograph cannot be taken in individuals with cervical spine injuries and gross maxillofacial injuries that may limit ideal position into the focal trough. Young children, mentally challenged and unconscious patients may not be ideal candidates for this imaging technique.

SPECIALIZED IMAGING COMPUTED TOMOGRAPHY (CT) It is also referred to as computed axial tomography, computed tomographic scanning, axial tomography and computerized transaxial tomography. Godfrey Hounsfield and Allan Cormack were instrumental in the development of CT and were awarded the Nobel Prize in Medicine in 1979 for their efforts. This radiographic technique blends the principles of thin layer radiography (tomography) with the use of a computer to synthesize the image (computed).

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The intensity of the X-ray beam exiting the body is determined by: a. b. c.

The energy of the X-ray source The distance between the source of X-rays and the detector The attenuation of the beam by materials in the object being scanned.

Although a single source and a single-detector array can produce a single scan, the efficiency of the scanning system can be increased multiple folds by using multiple X-ray beams and equivalent number of detectors. Each scan produces a penetration or absorption profile. However, construction of the image requires profiles obtained at different angles through the patient under study. The X-ray source and detector assembly are rotated around the patient (3,600) to produce multiple profiles of the particular site of interest. The X-ray beam attenuation is collected in a grid like pattern called matrix. Each square in the matrix is made up of a pixel (picture element), which represents the X-ray attenuation of a small finite volume of tissue called voxel (volume element). The typical image matrix for most CT scanners is 512 512 pixels. Each pixel represents a calculation of the actual attenuation of the X-ray beam by constituents within the body. A number (CT number or Hounsfield unit [HU]) is designated for each pixel corresponding to the degree of beam attenuation (Table 7). The CT numbers generally range from 1000 to 1000. By convention, water is designated the number 0. However, some scanners may differentiate between CT numbers that range from 2000 to 6000, but most monitors may display only 256 gray-scales and the human eye can perceive only 64 shades of gray. Since the CT numbers represent attenuation or density, the computer constructs an image by printing the numbers

Table 7

CT numbers for commonly imaged tissues

Tissue

CT number

Air

–1000

Lung

–200

Fat

–100

Water

0

CSF

15

Working Principle

Blood

20

The computed tomographic image is initiated by a process called scanning. Beams from one or several small X-ray sources are passed through the body and intercepted by one or more radiation detectors. These radiation detectors produce electrical impulses that are proportional to the intensity of the X-ray beam emerging from the body.

Gray matter

40

White matter

45

Muscle

50

Medullary bone

300

Cortical bone

1000


or by assigning different shades of gray to each number thereby transforming a string of numbers into an image.

contacts the detector array, thus improving CT image quality.

Computed Tomographic Scanner Assembly

Patient support couch

Though CT scanners are available in different system configurations, they all have the same basic components:

The patient support couch helps in stabilizing the position of a patient during a CT scan. The couch must be made of a low-molecular-weight material such as carbon filter to ensure that the path of the X-ray beam is not altered before or after it traverses the patient. The couch is motorized so that the movement of the patient for slice acquisition is smooth controlled and reproducible. The angle of the patient couch can be altered to capture images in different planes. The angulation of the patient is reported as ‘tilt’ on the printout of the image.

1. 2. 3. 4.

Gantry Patient support couch Computer Control console.

Gantry The gantry is made up of the detector array, patient support couch, and the X-ray tube or source. The gantry can be tilted up to 300. The facility to tilt helps in excluding structures from the scan that may degrade the final image (e.g., metallic dental restorations). Detector array The detector is made up of multiple discrete cells or detectors. Each of these detectors acquires specific information for each slice of the scan and transmits it to the computer. The present fourth generation CT scanners have up to 2,400 detectors. The detectors contain either a crystal scintillation detector or a gas-filled detector. Commonly used scintillation detectors are manufactured with cesium iodide (CsI), bismuth germanate or cadmium tungstate (CdWO4). These solid-state detectors are coupled optically to a photodiode. Solid-state detectors exhibit detection efficiency that approaches 100% but cannot be packed closely together. Gas-filled detectors contain either xenon or a xenon– krypton mixture. These gases have a high atomic number, are inert, and display minimal afterglow. The gas is contained under high pressure in the detector array. The individual gas-filled detectors can be placed closely together; the gas, however, in the detector only produces approximately 50% detector efficiency. Regardless of the material used to capture information, the spacing of each discrete detector coupled with their detection efficiency determines the efficiency of the scanner and the ultimate spatial resolution. X-ray source The X-ray source for the currently available scanners consists of an X-ray generator and an X-ray tube. The X-ray generator is designed to produce a high milliampere (up to 400 mA) beam at a nearly continuous rate. The large amount of heat generated through continuous beam production necessitates the use of a large rotating anode and fairly large focal spot. The X-ray beam is collimated before it traverses through the patient (pre-patient collimation) and at the detector array (post-patient collimation). The pre-patient collimation decreases the radiation dose to the patient. The post-patient collimation reduces the amount of scattered radiation that

Computer The rapidity of capturing the image, acquiring data, and larger matrix size (512 512) necessitates the use of highspeed computers. Modern CT scans require computers that can solve up to 30,000 equations simultaneously. The time it takes the computer to generate a visible image after data acquisition is termed ‘reconstruction time’. Reconstruction time for a single slice is usually about 1 second. These computers can constitute up to one-third the cost of a CT scanner. Control console The control console allows the operator to select the parameters of the CT scan, view the image as they are being generated. Many consoles have two monitors so that the technician and the radiologist can manipulate the image as the data is acquired. Image data is stored into the computer so that it can be formatted later into a number of ways. Data is stored either on magnetic tapes or disks. Most CT images are viewed on a film. The electronic data from each view is transferred onto a film using laser cameras. The most common film format is 14 17 inches and may contain 4–15 images.

Advantages of CT ❍

Multiplanar imaging—image acquisition in crosssectional or in other planes. ❍ Greater geometric precision—CT solves the problem of superimposition by allowing the clinician to view a series of thin sections (1.5–10 mm) thick depending on the anatomic site. ❍ Manipulation of the acquired image—the radiographic contrast and brightness can be adjusted based on the requirement. ❍ Soft tissue imaging—helps in separating subtle tissue contrast differences (as low as 0.5%). 761


❍

Helps in distinguishing objects of subtle differences in density such as between blood and fat, blood and CSF.

Disadvantages of CT ❍ ❍

Expensive. Patient’s exposure to radiation—CT is considered a high radiation dose technique (depends upon region imaged, number of slices, thickness of slice and kVp). For a head scan the effective dose has been calculated as 2–4 mSv and 5–15 mSv for a body scan. A mid skull dose for a PA view (PA skull) or Townes’ view is about 3–5 mGy, whereas a mid skull dose of about 34–55 mGy is seen with a CT. ❍ Production of artifacts, especially when metallic restorations are located in the plane of tissue being scanned. These streak type artifacts may obscure radiographic findings in the CT scan and render it useless for diagnosis.

Uses of CT in Dentistry ❍

❍ ❍

❍ ❍ ❍ ❍ ❍

Evaluation of the presence and extent of clinically suspected pathology in the head and neck region including cysts, tumors and infections. Detection of the extension of disease process into the paranasal sinuses, base of skull and orbit. Determination of the location, extent and displacement of maxillofacial skeletal fractures, including detection of subdural and epidural hematomas. Salivary gland imaging. Evaluation of potential implant sites using 3D image reconstruction. Evaluation of the components of the TMJ. CT-guided fine needle aspiration biopsies. Virtual surgeries.

DENTOMAXILLOFACIAL CONE-BEAM COMPUTED TOMOGRAPHY (CBCT) Radiology has always been a tremendous asset in clinical dentistry. Intraoral imaging, whether digital or film, continues to provide the best spatial resolution of any imaging method currently available. However, because spatial information is lost when it is collapsed into a two-dimensional (2D) image, in many cases, two or three intraoral radiographs taken from different angles are recommended. The clinical diagnostic capacity of intraoral radiography is influenced by a number of variables, including beam angulation, exposure time, receptor sensitivity, processing, viewing conditions, superimposition of anatomic structures and lesion

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location. Panoramic radiography, in which images of both jaws are obtained through the synchronous rotation of an X-ray source and image receptor around a stationary patient can provide broad coverage of both jaws and teeth, but without the anatomical detail available with intraoral radiography. Moreover, due to the distance between the radiation source, object and image receptor, there is a magnifying factor associated with image formation, and projection geometry results in image distortion and a marked overlapping of tooth crowns. In order to reduce the level of image distortion and ensure that image quality is not affected by ghost images, accurate preparation and positioning of patients is needed. In contrast to both intraoral and panoramic techniques, which by their nature are incapable of capturing information about the third dimension of teeth and adjacent structures, and can thus provide only limited information about lesion origin, size and location, medical CT devices are able to provide 3D images of the dentomaxillofacial region. However, high patient doses, high cost and lack of availability precludes the routine use of medical CT in dentistry. In response to the high demand for a technique that could provide 3D data at a lower cost and with lower radiation doses than the conventional CT used in medical radiology, CBCT was developed and introduced specifically for dentomaxillofacial imaging.

Historical Background Computed tomography (‘tomography’ is derived from the Greek words tomos, meaning ‘slice’ or ‘section’, and graphia, meaning ‘describing’) was introduced in 1972 by the engineer Godfrey Hounsfield and the physicist Allan Cormack. In 1979, Cormack and Hounsfield, who had worked independently to develop CT, were jointly awarded the Nobel Prize in Physiology or Medicine for their work on the tomographic principles used in computing the spatial distribution of a physical quantity of an object examined from different directions and transferring this data into easily readable images. CT represented the first practical medical application of the tomographic principle in the field of medicine, providing high-contrast images without superimposition of adjacent anatomic structures. The first clinical CT scanners, installed between 1974 and 1976, were dedicated to head-imaging only, and ‘whole body’ systems became available in 1976. Several hours were needed just to acquire the raw data necessary to produce a single image ‘slice’, and several days were required to reconstruct an image from this raw data. Great improvements have since been achieved in speed, patient comfort and resolution. Today, more anatomy can be scanned in less time, which helps to eliminate artifacts from patient motion and provides excellent diagnostic image quality at the lowest possible effective doses.


Figure 60 A

B

X-ray source

X-ray source

Translation

Translation Rotation

Rotation Object

Object

Detector Detector

C

D

X-ray source

X-ray source

E Object

Helical X-ray beam path Detector

Detector

(A) First generation. (B) Second generation. (C) Third generation. (D) Fourth generation. (E) Helical CT. Evolution of CT scanners from the original design

CT scanners have developed over four generations from the original design in which both X-ray source and detector revolved around the patient to one in which a fixed circular array detects the remnant beam originating from a revolving X-ray tube. First generation scanners used parallel pencil beams of X-rays for data acquisition and required both translation and rotation of the beam source and a single-detector apparatus (Figure 60A). Second generation scanners also operated in a translation-rotation mode, but employed multiple detectors that captured a small, fanshaped beam in an attempt to reduce scan time (Figure 60B). With third generation scanners, scan time was further reduced through the use of a single-detector arc in conjunction with fan-beam X-ray geometry (Figure 60C), and with the fourth generation design, stationary detectors were distributed along a full circle to form a detector ring, with only the X-ray source in orbit (Figure 60D). From 1974 to 1987, CT scanners employed high-voltage cables wrapped around an elaborate set of rotating drums and pulleys to transfer power to the X-ray tube. A rotating frame or gantry, would spin 360 in one direction to produce an image or slice, and then spin 360 in reverse to produce a second slice. Between each slice, the gantry would come to a complete stop, and the patient table would be moved forward by an increment equal to the slice thickness. In the mid-1980s, the elaborate X-ray cable-and-drum

system was replaced by an innovation called the ‘power slip ring’, which transferred electric power from a stationary source onto the continuously rotating gantry. The innovation of the power slip ring led to the introduction in 1989 of a helical CT, in which the patient moves continuously through the gantry while the X-ray source moves simultaneously down and around the patient in the same direction (Figure 60E) to acquire a continuous helix of data. By combining data acquisition with continuous movement of the patient through the gantry during scanning, multiple image slices can be captured quickly, reducing exposure time and artifact motion. The most recent technological advancement in CT acquisition occurred in 1998, when the single row of detectors was replaced with multiple rows arranged along the long axis of the human body. This increased the width of the volume acquired in each rotation, resulting in a more efficient use of the X-ray beam. Contemporary CT multidetector scanners possess detector arrays with between 4 and 512 rows of detectors. In current practice, most systems use a combination of helical and multidetector technology; however, despite the reduced scan times of multidetector helical CT (MDCT), radiation doses are still relatively high, as are the costs. Over time, concerns over detector costs, radiation and acquisition time led to the development of CT scanners in which the fan-beam is replaced by cone-beam geometry.

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First adapted for potential clinical use in 1982 at the Mayo Clinic Biodynamics Research Laboratory, the initial interest in CBCT was focused primarily on applications in angiography, radiotherapy and mammography. A practical conebeam algorithm for tomographic reconstruction of 2D projection data was first illustrated by Feldkamp et al who instead of a fan-beam reconstruction formula, used a convolution back-projection formula to directly reconstruct a 3D density function from a set of 2D projections. The formula provided convenient computation with useful properties and relatively small errors in many practical applications, and today, a modified Feldkamp algorithm is the reconstruction algorithm most frequently used in dentomaxillofacial CBCT. Despite the fact that the original Feldkamp back-projection algorithm was published in 1984, CBCT units dedicated to dentomaxillofacial radiology could not be marketed for another 15 years because economic X-ray tubes, high-quality detector systems and sufficiently powerful personal computers were unavailable. Eventually, in 1999, the first dentomaxillofacial CBCT (DMCT) unit, the NewTom DVT 9000, designed by Attilio Tacconi and Piero Mozzo and produced by QR, Inc. of Verona, Italy, was introduced in Europe and was followed in 2001 by the introduction in Japan of the 3D Accuitomo-XYZ Slice View tomography system (J Morita Mfg Corp., Kyoto, Japan). A spate of revolutionary CBCT applications reached the dental market in the 2000s, marking the beginning of a new era in the field of dentomaxillofacial radiology. New technological specifications and settings include multiple field of views (FOVs) and voxels that can better address a variety of specific tasks and imaging which can be conducted with the patient in supine, seated, or standing positions. There are also several hybrid machines offering CBCT imaging along with panoramic and cephalometric radiography. Table 8 provides specifications of some contemporary CBCT systems, including product, manufacturer and software name; detector type; patient positioning options; FOV and voxel size options; effective doses according to FOV (for adults); and additional features. Figure 61A, B show, respectively, a large FOV CBCT unit (iCAT Next Generation, Imaging Sciences, Hatfield, PA, USA) with a seated patient and a small FOV CBCT unit (Kodak 9000, Carestream, Rochester, NY, USA) with a standing patient. All units are similar in size and shape to a panoramic machine.

Fundamentals of CBCT Whereas conventional CT scanners emit a fan-shaped X-ray beam and require a stack of multiple slices to obtain a complete image, CBCT systems operate by focusing a coneshaped beam on a 2D detector that performs one pass or less around the patient’s head to produce a series of 2D images. A cone-beam algorithm is then applied to this image dataset, allowing the operator to extract planar and curved reconstructions of varying thicknesses in any orientation and to generate accurate 3D images of bone and soft tissue 764

surfaces that can be read on a computer monitor. The use of special algorithms allows not only conventional axial plane reconstructions, but multiplanar, reformatted 2D, 3D and panoramic reconstructions as well. Whereas fan-beam geometry uses primary reconstruction of data to produce axial slices from which orthogonal planar images are generated using secondary reconstruction, cone-beam geometry uses multiple-basis data projections to secondarily reconstruct orthogonal images. Raw primary data consists of a series of single-projection images—individually referred to as basis, frame or raw images—that resemble cephalometric radiographic images, only each image in the series is slightly offset from the next. An image volume is usually calculated and constructed from several hundred 2D basis images, the complete series of which is referred to as the ‘projection data’. The number of individual images comprising the projection data is determined by the frame rate (number of images acquired per second), the completeness of the scan arc (generally 180–360) and the speed of rotation. Figure 62 shows schematic diagram of cone-beam and fan-beam imaging geometries and secondary reconstruction processes. When the X-ray beam passes through different layers of tissues, the transmitted intensity will be equal to the sum of the attenuation values of the various voxels that lie in the specific straight path of the X-ray beam. An average attenuation coefficient value for each voxel in the section is derived from the different rays surrounding the area of interest. By calculating the attenuation value of each voxel, it is possible to differentiate between various tissues in a slice based on their computed attenuation values. Most visualization software offer a default presentation consisting of a series of contiguous, interrelated 2D images in three orthogonal planes (axial, sagittal and coronal). Figure 63 shows schematic diagram of axial, coronal and sagittal planes and corresponding CBCT images. In contrast to medical CT, in which data is usually transferred from an acquisition workstation to a separate console for formatting, with CBCT, both image acquisition and visualization are generally performed on the same computer. X-ray generation Medical CT systems utilize high-power X-ray generators to acquire large volumes of data at high speeds, which requires high X-ray energy. Typically, CT systems operate in a range of 80–140 kVp, with a maximum power of 20–100 kW; however, these systems can only be operated at maximum power for a limited time, usually from 30–60 seconds. CBCT systems operate at 80–120 kVp, with most units functioning at the lower end of this range, which does not differ substantially from the operating parameters of panoramic radiographic equipment. Although CBCT and CT have similar focal spot sizes (0.5–0.8 mm), unlike CT, many CBCT systems possess a stationary anode, with a tube current generally within the range of 1–20 mA, which

Table 8

Specifications of some contemporary CBCT systems, including product, manufacturer and software name; detector type; patient positioning options; FOV and voxel size options; effective doses according to FOV (for adults); and additional features

Company

Model

CBCT image detector

Patient positioning

Field of view diameter/height

Voxel size options

Estimated effective doses for adult (ICRP 2007)

Software

Extra features

Quantitative Radiology, Verona, Italy

NewTomVGi CBCT

Amorphous silicon flat panel

Standing Seated Wheelchair

Five FOVs from 6 6 cm to 15 15 cm

From 0.075 to 0.30 mm

15 15 FOV (194 Sv) (Pauwels et al, 2012)

NNT viewer

• Safe beam* • Pulse system** FS: 0.3 mm†

Quantitative Radiology, Verona, Italy

NewTom 5G CBCT

Amorphous silicon flat panel, 20 25 cm

Supine

Five FOVs from 6 6 cm to 18 16 cm

Ultra high: 0.075 mm; High: 0.15 mm; Low: 0.30 mm

Studies are running

NNT viewer

• Safe beam* • Pulse system** FS: 0.3 mm in standard mode FS: 0.15 mm in zoom mode† • Ergonomic, two stage patient chair‡

J. Morita, Kyoto, Japan

Veraviewepocs 3D and Veraviewepocs 3De

CMOS flat panel detector

Standing

Veraviewepocs 3D 4 4 cm; 4 8 cm; 8 8 cm Veraviewepocs 3De 4 4 cm; 4 8 cm

0.125 mm

73 Sv (with 8 8 cm FOV) (Pauwels et al, 2012)

i-Dixel 2.0/One data viewer/ One volume viewer

• Specifically designed for endo, perio and general dentistry. • Dose reduction feature

CBCT Pano/ Ceph options (Hybrid model) 3D Accuitomo 170 CBCT

CMOS flat panel detector

Seated

Nine FOVs ranging between 4 4 cm and 17 12 cm

From 0.08 to 0.250 mm

43 Sv (with the smallest FOV); 50 Sv (with 10 5 cm FOV) (Pauwels et al, 2012)

i-Dixel 2.0/One data viewer/ One volume viewer

High-quality images with low dose

Imaging Sciences, Hatfield, PA, USA

I-CAT Classic CBCT


Seated

16 13–22 cm

Between 0.2 and 0.4 mm

Standard scan 69 Sv (Ludlow and Ivanovic, 2008)

Xoran Cat iCATvision 3DVR

• Quick launch InVivoDental and Dolphin software

Imaging Sciences, Hatfield, PA, USA

I-CAT Next Generation CBCT


Seated

Standard: 16 6, 8, 10, 13 cm Extended: 17 23 cm

From 0.125 to 0.4 mm

87 Sv (with 16 13 cm) (Ludlow and Ivanovic, 2008)

iCATvision InVivoDental 3DVR

720 rotation possible with extended FOV

Vatech, E-WOO Technology, South Korea

PaX-Duo 3D Pano CBCT

Amorphous flat panel

Standing Wheelchair accessible

From 5 5 to 15 13.5 cm

0.08–0.3 mm

FOV (5 5 cm) 42.52 Sv FOV (12 8.5 cm) 120.69 Sv Provided from company. Unpublished

EasyDent/Ez3D

• Auto-switching system between sensors • Pulsed scan**

(Contd...)


J. Morita, Kyoto, Japan

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Table 8

Continued Model

CBCT image detector

Patient positioning

Field of view diameter/height

Voxel size options

Estimated effective doses for adult (ICRP 2007)

Software

Extra features

Vatech, E-WOO Technology, South Korea

PaX-Reve 3D CBCT/Pano/ Ceph

Amorphous flat panel

Standing Wheelchair accessible

From 5 5 cm to 15 19 cm

From 0.08 to 0.25 mm

FOV 5 5 cm 12.16 Sv FOV (15 15 cm) 71.47 Sv Provided from company. Unpublished

EasyDent/Ez3D

• Metal artifact removal • Pulsed scan**

Kodak Dental Systems, Carestream, Rochester, NY, USA

Kodak 9000 3D & 9000c 3D CBCT/Pano/ Ceph

CMOS sensor with optical fiber

Seated Standing Wheelchair

5 3.8 cm single 9 7 3.75 cm stitched

0.076–0.2 mm

5 3.8 cm 19–40 Sv (Pauwels et al, 2012)

Kodak Imaging Software

• Focused small FOV • Stitching#

Kodak Dental Systems, Carestream, Rochester, NY, USA

Kodak 9500 FOV CBCT

Amorphous silicon flat panel


Medium: 15 9 cm Large: 18.4 20.6 cm

0.2–0.3 mm

Medium FOV: 92 Sv; large FOV: 136 Sv (Pauwels et al, 2012)

Kodak Imaging Software

Planmeca Oy, Helsinki, Finland

Promax 3D CBCT/Pano/ Ceph/

Flat panel sensor


8 8 cm, 8 5 cm, 4 8 cm, 4 5 cm

0.1, 0.2, 0.4 mm

30–306 Sv (Qu et al, 2010)

Romexis

• Improved artifact removal • Extraoral bitewing • Stitching#

Planmeca Oy, Helsinki, Finland

Promax 3D Max CBCT

Flat panel sensor


5.5 5 cm to 23 16 cm; full skull: 26 23 cm

0.1, 0.2, 0.4, 0.6 mm

Studies are running

Romexis

• Artifact removal • Full skull scan

Soredex, Tuusulu, Finland

Scanora 3D CBCT Pano

CMOS flat panel

Seated

From 6 6 cm to 14.5 13 cm

0.13–0.35 mm

Largest FOV: 68 Sv (Pauwels et al, 2012)

On Demand

Specific ear, nose, throat imaging possible

Soredex, Tuusulu, Finland

Scanora 3Dx CBCT Pano

CMOS flat panel

Seated

From 5 5 cm to 24 17 cm

0.1–0.5 mm

Not available

On Demand

MyRay, Cefla Dental Group, Imola, Italy

Skyview CBCT

Image Intensifier— CCD sensor

Supine

FOV diameter: 11, 15, 17 cm

0.17, 0.23, 0.33

Largest FOV: 87 Sv (Pauwels et al, 2012)

Myray skyVIEW

Pulsed emission**

Sirona Dental Systems, Bensheim, Germany

Galileos Comfort CBCT Cephalometric

Proprietary Siemens Technology

Standing Seated

15 15 15 cm

0.15–0.3 mm

84 Sv (Pauwels et al, 2012)

Galaxis, Sidexis, Galelios Implant

Galelios surgical guides

*Safe Beam technology reduces radiation level according to patient size. **Pulse system that activates the X-ray source only when needed. †Generally CBCT systems have stationary focal spot (FS) size of 0.5–0.8 mm. ‡NewTom 5G allows the patient to be seated initially and then moved comfortably into a supine position. #Separate scans can be combined to obtain the whole arc. Data is collected from different company sites and articles. Most features are optional and effective dose measurements vary between devices according to settings used.


Company


Figure 61 A

B

(A) Large FOV CBCT unit (iCAT Next Generation, Imaging Sciences, Hatfield, PA, USA) with a seated patient. (B) Small FOV CBCT unit (Kodak 9000, Carestream, Rochester, NY, USA) with a standing patient

Figure 62 Cone-beam

Fan-beam X-ray source

X-ray source Detector Secondary reconstructions

Detector Basis projections

Primary reconstruction

Schematic diagram of cone-beam and fan-beam imaging geometries and secondary reconstruction processes

is much lower than CT and which reduces not only generator power, but also heat production. Finally, most CBCT systems generate a pulsed X-ray beam that coincides with detector activation, which markedly reduces total scan time as well as heat production, which translates into lower radiation doses to patients. Detectors All CBCT systems utilize an area detector to capture and record images. Initially, CBCT detectors were configured

from an image intensifier combined with a charge-coupleddevice (II/CCD) detector, making them large and bulky, and they tended to produce circular basis image areas (spherical volumes) rather than rectangular ones (cylindrical volumes). Nowadays, most CBCT units use flat panel detectors (FPD) comprising a large-area pixel array of hydrogenated amorphous silicon thin-film transistors or in some more recent cases, large, complementary metal oxide semiconductor technology (CMOS) arrays. X-rays are detected indirectly by a scintillator such as thallium-doped cesium iodide or terbium-activated gadolinium oxysulfide, which 767


Figure 63

Sagittal

Axial

Coronal Axial

Coronal Sagittal

Schematic diagram showing axial, coronal and sagittal planes and corresponding CBCT images

Figure 64

Anisotropic x=y≠z

Isotropic x=y=z

spatial-resolving potential than their X-ray intensifier/ charge-coupled device (CCD) predecessors. For each basis image, the detector records incident X-ray photons, collects a charge, and sends a signal to the computer. The speed with which a detector performs this acquisition is called the ‘frame rate’ as mentioned earlier in the section ‘Fundamentals of CBCT’. For most CBCT units, a full rotation usually requires between 5 and 20 seconds (similar to or faster than panoramic radiography), so that each basis image is acquired and sent within milliseconds, and hundreds of basis images are acquired within a single exposure rotation. FPDs have limitations in their performance, including linearity of response to the radiation spectrum, lack of uniformity of response throughout the area of the detector, and bad-pixels. The effects of these on image quality are most noticeable at lower and higher exposures. In order to ensure that these inherent limitations of FPD do not affect image quality, periodic recalibration of detectors is required. Voxels

A comparison of volume datasets obtained anisotropically (left) and isotropically (right)

covers the FPD silicon matrix. This scintillator converts the X-rays to visible light, which is registered by an array of photo-diodes that produce an electrical charge proportional to the incident X-ray energy. FPD arrays afford greater

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A ‘voxel’ describes the smallest distinguishable box-shaped part of a 3D image. In CBCT imaging, voxels are isotropic (equal in all dimensions) and range from 0.4 mm to as small as 0.076 0.076 0.076 mm. Because voxels are isotropic, images can be constructed in any plane with high fidelity. In theory, CBCT can improve the spatial resolution of high-contrast structures in any chosen viewing plane. This superior spatial resolution, i.e. the ability to discriminate


Figure 65 B

A

4 × 4 cm

D

C

6 × 6 cm

E

10 × 10 cm

8 × 8 cm

F

14 × 10 cm

17 × 12 cm

CBCT images of a dry skull obtained using different FOVs of Accuitomo 170 (J Morita, Kyoto, Japan). (A) 4 4 cm; (B) 6 6 cm; (C) 8 8 cm; (D) 10 10 cm; (E) 14 10 cm; (F) 17 12 cm

objects of different attenuation separated by very small distances, is one of the most attractive qualities of CBCT imaging and is largely the result of FPD technology and isotropic data acquisition. CBCT also reduces the negative effects of partial-volume averaging, a characteristic of both conventional fan-beam CT and CBCT imaging that occurs when the voxel resolution of the scan is greater than the spatial resolution of the object to be imaged. In such cases, the pixel is not representative of either the tissue or the boundary, but is given a weighted average of the different CT values. Figure 64 shows a comparison of volume datasets obtained anisotropically (left) and isotropically (right). Field of view Field of view (FOV) is the term used to refer to the scan volume of a particular CBCT unit. FOV is determined by

detector size and shape, beam projection geometry and beam collimation, which limit radiation exposure to a particular region of interest. The availability of different FOVs makes it possible to select the most appropriate FOV for a specific application. CBCT units are classified based on FOV size as small-, medium-, or large-volume units. Because the amount of X-ray scatter, or ‘noise’, decreases with decrease in FOV, small-volume units tend to offer the highest image resolution. Small-volume units are used to scan either a sextant, quadrant or single jaw, medium-volume units are used to scan both jaws, and large-volume units are used to scan the entire head. Because larger FOVs result in higher effective radiation doses, as a rule, smaller FOVs are recommended for dental imaging, with the use of larger FOVs restricted to cases where a wider view is required, such as orthodontic and orthognathic surgery treatment planning. Figure 65A–F shows CBCT images of a dry skull obtained using different FOVs of Accuitomo 170 (J Morita, Kyoto, Japan).

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Table 9

Advantages and disadvantages/limitations of CBCT in routine clinical practice

Advantages Lower radiation doses than conventional CT and beam collimation

Higher radiation doses than 2D imaging

Lower time, space and cost requirements than conventional CT

Less soft tissue discrimination than medical CT

Greater hard tissue definition than medical CT

Limited bone density measurements

Interactive display modes applicable to maxillofacial imaging

Scatter and artifacts created by metal subjects

Interactive treatment planning and computer-aided surgery

Liability

Advantages and Disadvantages/ Limitations of CBCT

basis images acquired, resolution and reconstruction algorithm.

In clinical practice, CBCT possesses a number of advantages over medical CT, such as lower effective radiation doses, lower costs, fewer space requirements, easier image acquisition, higher image accuracy and interactive display modes such as mutiplanar reconstruction that are applicable to maxillofacial imaging. However, the disadvantages of CBCT include higher doses than 2D imaging; the inability to accurately represent the internal structure of soft tissues and soft tissue lesions; a limited correlation with HUs for standardized quantification of bone density; and the presence of various types of image artifacts, mainly those produced by metal restorations, that can interfere with the diagnostic process by masking underlying structures. In addition, liability issues related to CBCT remain unresolved. Table 9 shows advantages and disadvantages/limitations of CBCT in routine clinical practice.

Greater hard tissue definition than medical CT One of the most attractive qualities of CBCT imaging systems is their high spatial resolution, i.e. their ability to discriminate between objects of different attenuations separated by only small distances. CBCT images possess sub-millimeter isotropic voxel resolution ranging from 0.4 mm to as low as 0.076 mm. This superior spatial resolution—a requirement for the accurate depiction of highly detailed small tooth and osseous structures—is made possible by the isotropic acquisition of the CBCT image detector.

Advantages Lower radiation doses than conventional CT CBCT scanners provide adequate image quality for dentomaxillofacial examinations while delivering considerably smaller effective doses than medical CT. Although not available on all CBCT systems, beam collimation, which limits radiation to the area of interest, is a highly desirable function that reduces doses by adjusting the irradiated field according to the FOV. In general, doses range from 13 to 82 Sv for small and medium FOV CBCT, compared to 474–1160 Sv for medical CT. To ensure that optimal doses are achieved, diagnostic and image quality requirements should be evaluated on a case-by-case basis and appropriate exposure parameters and FOVs selected accordingly. Lower time, space and cost requirements than conventional CT Dental CBCTs are compact (4 m2), easy to operate, reasonably affordable and require relatively low maintenance, making them a suitable choice not only for hospitals and medical centers, but also for many dentists in private practice. Scan time is comparable to that of panoramic radiography, varying anywhere from approximately 1–20 minutes, depending upon FOV, number of 770

Limitations/disadvantages

Interactive display modes CBCT data reconstruction capabilities make it possible to reorient images generated in axial, sagittal and coronal planes to realign the anatomical features of the patient. CBCT software also offer various digital enhancement tools, including zoom/magnification, window/level, ability to add annotation and real-time measurement free from distortion and magnification. Three distinct categories of display modes are available—multiplanar reformatted (MPR), ray-sum and volumetric images. MPR modes usually include oblique, curved planar, i.e. distortion-free ‘simulated’ panoramic and serial transplanar, i.e. cross-sectional—image reformation. Ray-sum mode uses images of increasing sectional thickness to create an image slab representing a specific volume of the patient. Ray-sum images can be used to generate simulated projections, such as lateral cephalometric images, that lack the magnification and distortion of conventional X-rays. However, the technique requires the use of the entire volumetric dataset, and interpretation suffers from ‘anatomic noise’, i.e. the superimposition of multiple sections. Volumetric rendering includes two different techniques by which 3D data can be visualized by integrating and selectively displaying large volumes of adjacent voxels. Whereas indirect volume rendering (IVR) involves a complex process that requires the selection and graphic representation of a range of gray-scale intensities at the voxel level, direct volume rendering (DVR) is a somewhat simpler process in which an arbitrary threshold of voxel intensities is selected and all gray values below or above this threshold are eliminated. The most common


Figure 66 A

B

C

D

E

F

CBCT image taken with (iCAT Next Generation, Imaging Sciences, Hatfield, PA, USA): (A) Axial view; (B) Simulated panoramic; (C) Volumetric 3D representation of hard tissue; (D) Serial cross-sectional images; (E) Right generated cephalometric (MIP); (F) Left generated cephalometric (MIP)

DVR technique is maximum intensity projection (MIP), which produces visualizations by evaluating the value of each voxel along an imaginary ray projected from a particular volume of interest toward the eye of the observer, selecting the highest value as the display value and eliminating voxel intensities that are below an arbitrary threshold. Figure 66 shows simulated panoramic and serial cross-sectional images along with volume rendering images. Figure 67 shows the comparison of CBCT ray-sum generated simulated lateral cephalometric image and lateral view of volumetric rendering with superimposition of airway space of the same patient (images created using Invivo software [Anatomage, San Jose, CA]).

Interactive treatment planning and computer-aided surgery CBCT datasets can be exported in standardized 2D or 3D file formats for visualization and further processing with third-party software. This software, as well as software produced by CBCT manufacturers themselves, have increased the clinical applicability of CBCT by, for example, simulating implant placement, bone grafts and orthognathic surgical procedures in a true and accurate virtual environment. The fusion of CBCT images with optical datasets obtained with 3D optical cameras is a relatively new concept that provides a digital cast with an accurate surface to be used or transferred to therapeutic applications via CAD/CAM (computer added design/computer added 771


Figure 67 A

B

Comparison of CBCT ray-sum generated simulated lateral cephalometric image (A) and lateral view of volumetric rendering with superimposition of airway space of the same patient (B). Images created using Invivo software (Anatomage, San Jose, CA)

Figure 68

Implant placement procedure by combining optical digital impression CEREC and Galileos CBCT images (Sirona Dental Systems, Bernsheim, Germany)

manufacturing). Eventually, greater simplification and automation can be expected to lead to more precise dental restorations that can be custom-fit to an individual patient. Figure 68 shows an implant placement procedure by combining optical digital impression CEREC and Galileos CBCT images (Sirona Dental Systems, Bernsheim, Germany). Several CBCT units are also now capable of integrated facial scanning, whereby CBCT acquisition is accompanied by a concomitant 3D laser scan of facial soft tissue that is then overlaid on the bony skull image; the availability of fully integrated, accurate 3D information of both face and bone 772

allows for more effective planning and prediction of treatment outcomes. Disadvantages/limitations Higher radiation doses than 2D imaging CBCT doses, while lower than those from conventional CT, are still significantly higher than those from conventional dental radiography. Differences in CBCT device, FOV, exposure parameters (kVp, mA) and other technical factors result in substantial differences in radiation doses. Dose is strongly related to FOV, which varies according to indication.


Figure 69 A

B

(A) Axial CBCT and (B) MDCT images. Arrows show definitely higher soft tissue contrast in MDCT image compared to CBCT

According to International Commission on Radiological Protection (ICRP) 2007, effective doses range from 19 to 368 Sv, which is higher than the effective doses from full-mouth radiographs (FMX) taken with photostimulable phosphor (PSP) storage and F-speed film with rectangular collimation (34.9 Sv), FMX taken with PSP and F-speed film taken with round collimation (170.7 Sv) and panoramic (CCD) (14.2–24.3 Sv), posterioanterior cephalometric (PSP) (5.1 Sv) and lateral cephalometric (PSP) (5.6 Sv) radiographs. The largest contributors to effective dose from CBCT are remainder tissues (37%), salivary gland (24%) and thyroid gland (21%) tissues. Recent technological improvements have begun to lower doses from CBCT. Most scanners now employ a pulse system, in which the X-ray source is activated only when needed, which is very useful in terms of radiation protection. The use of newer, ‘smart-beam’ and ‘smart-sensor’ technologies, in which the radiation level is set according to the patient size, should also be encouraged as a method of radiation protection. Taking into account the higher radiosensitivity of children, it is imperative that the use of CBCT in children is fully justified over conventional X-ray imaging. Needless to say, conducting ‘routine’ or ‘screening’ imaging before obtaining a medical history and performing a clinical examination is an unacceptable practice. Less soft tissue discrimination than medical CT ‘Dynamic range’ refers to the range of incident signal intensities that can be successfully detected and transmitted as image data. In general, the greater the dynamic range, the better the contrast resolution, i.e. the ability of an imaging system to discriminate differences in tissue attenuation, which varies according to the composition and nature of the tissue imaged. A low power configuration is often associated with increased noise and a smaller dynamic range, resulting in lower contrast resolution. Currently available CBCT

systems in the market are typically described as having soft tissue contrast discrimination of approximately 10 HU, the numeric information contained in each pixel of a CT image which represents tissue density, whereas modern medical CT scanners have contrast resolution of 1–3 HU. This limited contrast resolution remains a barrier to the extension of CBCT technologies into diagnostic imaging, which requires the ability to detect the internal structure of soft tissue. Figure 69 shows the difference between axial CBCT and MDCT images in soft tissue differentiation. Limited bone density measurements Radiodensity, measured in HU is inaccurate in CBCT scans. CBCT gray-scale values cannot provide reliable information on site-specific bone density for purposes such as implant placement because the X-ray attenuation of CBCT acquisition systems currently produces different HU values for similar bony and soft tissue structures in different areas of a scanned volume (e.g. the image value of dense bone at the level of the menton differs significantly from the image value of the same bone at the level of the cranial base). In the absence of such standardization, it is difficult to interpret the gray levels and impossible to compare the values resulting from different machines. A method for establishing attenuation coefficients from which actual HU values can be derived from CBCT has been proposed; however, further research is essential before this can be accepted. Despite its limitations in terms of bone quantity information, evaluation of bone quality from CBCT images has a high correlation with structural analysis of dental implants. Scatter The amount of scatter generated and recorded by cone-beam image acquisition is substantially higher than that of conventional medical CT. In medical CT, collimation at the X-ray source restricts the z-axis coverage of the fanbeam, allowing scatter (sinusoidal lines) from only a thin 773


axial volume of tissue to reach the detector elements during section acquisition. In contrast, CBCT expands the z-axis coverage of the beam, allowing X-ray scatter generated from the entire volume of coverage to reach the detector elements as the image is acquired. This scatter contribution, expressed as scatter-to-primary ratio (SPR), can be as high as 3 in large-volume CBCT systems, compared to 0.2 in conventional medical CT systems. Higher amounts of scatter can reduce diagnostic capabilities by reducing image contrast and increasing both patient dose and image noise, the inhomogeneity of gray levels that occurs as a result of statistical fluctuations in the distribution of X-ray photons registered by the detector. Artifacts A significant limitation to CBCT imaging is the presence of metallic artifacts, i.e. image flaws that are unrelated to the scanned object, which are caused by metal and amalgam restorations and, to a lesser extent, rootcanal filling material and implants. Such artifacts include streaks around materials as well as dark zones that affect the overall quality of the image. Streak artifacts appear as linear hyperdensities that radiate from a metallic object and may extend to the width of the field, affecting visualization of areas even on the opposite side of an image. Beam-hardening artifacts, which appear as dark bands adjacent to high-density structures, may mimic disease. Artifacts originating from root-canal filling material, for example, may mimic root fractures, whereas dark bands around dental implants may mimic loss of osseointegration. Artifacts may also occur as a result of beam-hardening, i.e. the preferential gradual absorption of lower energy X-ray photons as they traverse through layers of tissue, resulting in a gradual increase in the mean energy of the residual beam. Beam-hardening may be more pronounced in CBCT

than in medical CT, mainly because of the lower kVp and thus lower mean energy of the X-ray beam in CBCT systems. Figure 70 shows streak and beam-hardening artifacts in CBCT images. Patient motion is another source of image artifacts. Motion artifacts appear as double-margins around a structure and may increase with increases in scan time, which can be as long as 20–30 seconds. In order to reduce the likelihood of motion artifacts, CBCT units, unlike medical CT, provide specific devices to stabilize the head during examination. Nowadays, CBCT companies are actively developing artifact-reducing algorithms to be used during image reconstruction. These processes, although contributory, are rather slow and may add to the total reconstruction time. More modern approaches attempt to avoid reconstruction errors either by supplementing missing or incorrect information in projection images or by integrating some sort of meta-information into an iterative reconstruction process. All of these methods, however, require massive computational power, which has so far prevented them from being used in daily routine work performed by commercial scanners. Luckily, increasing computational speed and advances in graphics processing units can be expected to overcome this problem. Liability CBCT machines are increasingly being marketed specifically to orthodontists and implantologists or dentists who place implants in private practices. Unlike other advanced medical imaging systems, CBCT scanners are generally owned and operated by non-radiologists who lack the training necessary to interpret CBCT images beyond the confines of their specialty or daily spheres of practice. However, clinicians who order CBCT scans are

Figure 70 A

B

C

(A and B) Axial and (C) coronal CBCT images. Streak artifacts appear as linear hyperdensities that radiate from a metallic object are shown with black arrows. Beam-hardening artifacts, which appear as dark bands adjacent to high-density structures are shown with blue arrows

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responsible for interpreting the entire image volume, given the possibility that incidental findings—the likelihood of which increase when a larger head volume is included in the scan—may have significant health consequences for the patient. With the exception of individuals who have completed a formal program in oral and maxillofacial radiology, most orthodontists and other dental practitioners do not have the necessary expertise to interpret CBCT scans, nor do they feel comfortable in doing so, yet there is no informed consent process or signature waiver that would allow the clinician to interpret only a specific area of an image volume. As a result, the clinician may be considered liable for a missed diagnosis, even one that falls outside the area of his/her expertise. In case of any questions regarding image data interpretation, referral to a specialist in oral and maxillofacial or medical radiology is recommended.

CBCT: Clinical Applications Whereas early CBCT devices were dedicated to implantology and dental imaging, today, applications extend to the face and skull base as a whole. In fact, CBCT has largely replaced conventional tomography for most dental diagnostic tasks and is now commonly used for a variety of purposes in oral implantology, dentomaxillofacial surgery, image-guided surgical procedures, endodontics, periodontics and orthodontics.

Oral implantology The International Congress of Oral Implantologists, Consensus Report cites four different areas in which CBCT can be of use in oral implantology: 1. Diagnostics CBCT can be used in the identification and evaluation of pathology, foreign bodies and defects. 2. Implant planning CBCT images not only have been proven successful when used for linear measurement, but also have been shown to provide reliable 3D information for the assessment of relative bone quality and quantity, 3D evaluation of ridge topography and pre-implantation identification of vital anatomical structures such as the inferior alveolar nerve, mental foramen, incisive canal, maxillary sinus, ostium and nasal cavity floor. This information can be used in the treatment planning process to identify suitable implant sites and to determine whether or not there is a need for surgical procedures, such as sinus lifting and bone augmentation. CBCT is also recommended in sinus grafting operations as a mean of better predicting complications, thereby achieving better surgical outcomes. Figure 71 shows curved and cross-sectional views used to assess implant sites and nerve canal in the mandible. CBCT bone images can also be fused with soft tissue images acquired with digital impression techniques to enhance planning efficiency (Figure 68). 3. Surgical guidance CBCT images have yielded promising results when used for surgical guidance. Commercially

Figure 71

Curved and cross-sectional views used to assess implant sites and nerve canal in the mandible

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Figure 72

Stereolithographic guidance systems constructed for implant placement using implant software StentCad® (Ay Tasarim Ltd., Ankara, Turkey)

available implant simulation software can be used to process CBCT data to provide pre-operative views of anatomical structures in the jaw bone, and the use of a stereolithographic guide can ensure that pre-operatively planned implant positions are accurately transferred to the surgical field. Figure 72 shows stereolithographic guidance systems constructed for implant placement using implant software. 4. Post-implant and/or post-grafting evaluation CBCT can be used to localize implants after placement; to assess boneimplant interfaces; to evaluate demineralized bone and bone transplants; and to identify peri-implant defects. However, it should be noted that metal artifacts caused by implants may complicate assessment and measurement; moreover, keeping in mind concerns over dose, CBCT should only be used if 2D techniques have been unsuccessful. Figure 73 shows cross-sectional CBCT images taken from patients complaining of pain and discomfort in the implant region. Dentomaxillofacial surgery Dentomaxillofacial surgery is important area in which 3D views may become necessary, such as the following: 776

1. Eruption problems CBCT images may help in identifying and localizing impacted or displaced permanent, supernumerary or supplementary teeth, such as third molars and canine supernumeraries. In particular, CBCT images can be used in the pre-surgical assessment of the relationship between third molar apices and the mandibular canal. Figure 74 shows CBCT images taken from a patient prior to surgical extraction of impacted third molar tooth. 2. Oral and maxillofacial pathologies CBCT enables the surgeon to visualize oral and maxillofacial pathologic entities such as benign jaw bone tumors and cysts in three dimensions, thereby assisting in diagnosis as well as in planning appropriate treatment. Figure 75 shows CBCT images of well-defined cystic pathologic lesions. 3. TMJ-related problems CBCT provides information essential to the diagnosis of a variety of TMJ disorders, including osteoarthritis, inflammatory arthritis, trauma and developmental disorders. The ability to provide highresolution multiplanar images with a lower dose than CT is rapidly making CBCT the imaging modality of choice


Figure 73 A

B

C

Cross-sectional CBCT images of patients with pain and discomfort in the implant region that reveal implants mistakenly placed in the maxillary sinus (A), mandibular canal (B) and out of cortical plate (C). Please see arrows (Courtesy: Dr Ilker Cebeci, Tomoloji Dentomaxillofacial Radiology Center, Ankara, Turkey)

Figure 74 A

B

C

D

CBCT images taken from a patient before surgical extraction of impacted right third molar tooth. Conventional panoramic radiograph showing a possible relation between right mandibular molar tooth and mandibular canal (A). CBCT generated panoramic (B) and cross-sectional views show a relationship with third molar apex and mandibular canal (C)

for the evaluation of the osseous components of the TMJ. It is imperative that the clinician evaluate not just the structures of the TMJ, but the entire CBCT volume, as TMJ dysfunction may be accompanied by pathological changes

in adjacent structures, including the mastoid and the external and middle ear, and because pathological conditions such as impacted teeth, dental disease and paranasal sinusitis may mimic TMJ pain and result in misdiagnosis. 777


Figure 75

Patient 1

Patient 2 CBCT images of well-defined cystic pathologic lesions of two different patients

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Figure 76 shows CBCT images of a patient with bone changes in TMJ.

fracture, dental root fracture and anterior maxillary tooth displacement.

4. Craniofacial fractures CBCT has been used to document craniofacial fractures, including mandibular head

5. Tooth autotransplantation CBCT has recently been used to assist in tooth transplantation.


Figure 76

CBCT images of a patient with bone changes in TMJ. Images were reformatted in TMJ mode

Endodontics The use of CBCT in endodontics is increasing rapidly. Units with small FOVs offering high-resolution images of teeth and related structures have been specifically recommended in cases where 2D systems have failed to provide sufficient information regarding the following: 1. Root-canal morphology CBCT images can be used to precisely determine root curvature and to definitively identify accessory canals and other anomalies when conventional imaging has suggested the presence of complex tooth morphology. 2. Periapical pathosis CBCT can assist in the diagnosis of dental periapical pathosis in patients who present contradictory or non-specific clinical signs and symptoms; who have poorly localized symptoms associated with an untreated or previously endodontically treated tooth, with no evidence of pathosis identified by conventional imaging; and in cases where anatomic superimposition of roots or areas of the maxillofacial skeleton are required to perform task-specific procedures. CBCT can also support a diagnosis of pathosis that is non-endodontic in origin, determines the extent of the lesion and identifies its effect on surrounding structures.

3. Pre-, intra- and post-operative assessment CBCT can support pre-surgical case planning by determining the exact location of root apices in relation to adjacent anatomical structures. CBCT can also help in identifying endodontic treatment complications, such as overextended obturation material, separated endodontic instruments, calcified canals and perforations. 4. Dentoalveolar trauma CBCT images can be used in the diagnosis and management of dentoalveolar trauma, especially root fracture, tooth luxation and/or displacement, and alveolar fracture. 5. Root resorption CBCT can be used to localize and differentiate between external and internal root resorption and invasive cervical resorption and other conditions to identify appropriate treatment as well as prognosis. Figure 77 shows CBCT images taken for endodontic purposes. Periodontics CBCT can be used as a supplementary imaging technique in situations where traditional 2D techniques have been 779


Figure 77 A

B

(A) CBCT axial image showing a root fracture line and (B) CBCT sagittal image showing a periapical lesion with bony reaction and maxillary sinusitis. Please see arrows

Figure 78

CBCT image of a cleft palate patient with eruption problems

unable to provide sufficient reliable information for periodontal assessment and treatment. CBCT may play a role in the assessment of marginal bone contours and 3D defects, especially furcations and infrabony defects, in which defect 780

morphology directly influences treatment planning and prognosis. Specifically, CBCT is able to assess buccal and lingual/palatal surface defects better, which are difficult to visualize in 2D imaging.


Orthodontics The use of CBCT in orthodontics has been gaining substantial popularity, although it is primarily recommended in cases where conventional radiography cannot supply satisfactory diagnostic information. This can include assessments of cleft-palate patients, unerupted and supernumerary tooth localization, identification of root resorption caused by unerupted teeth, evaluation of boundary conditions and orthognathic surgery planning. CBCT imaging may also be performed in other cases where it is likely to provide valuable diagnostic information. Figure 78 shows CBCT images of a cleft palate patient with eruption problems. Head and neck Depending on the FOV used, CBCT images may show part or all of the nasal cavity, paranasal sinuses, airway, cervical vertebrae and temporal bone. In fact, specific ear, nose and throat imaging programs have been increasingly included in CBCT systems, suggesting that CBCT may at some point entirely replace medical CT imaging in certain otolaryngology-related applications. For example, an innovative C-arm CBCT system has been used in image-guided surgery of the frontal recess; the technology is portable and provides ‘near-real-time’ imaging to confirm and guide surgical treatment, thereby reducing the risk of disorientation and iatrogenic injury. CBCT has also been found to provide reliable and accurate 3D analysis of the upper airway that can be of help in assessing the presence and severity of obstructive sleep apnea (Figure 67). Imaging of the temporal bone represents another promising area for CBCT, whose high-resolution and nearly artifact-free multi-planar reconstruction images make it possible to precisely assess the intra-cochlear position of the electrode, including visualization of each individual contact. It is this capacity for precision that makes CBCT a perfect candidate for the post-operative assessment and follow-up of cochlear implantation electrodes.

MAGNETIC RESONANCE IMAGING Magnetic resonance imaging (MRI) is a non-invasive method for mapping the internal structure within the body which uses non-ionizing electromagnetic radiation and employs radiofrequency radiation in the presence of carefully controlled magnetic fields to produce high-quality cross-sectional images of the body in any plane.

Historical Perspective The phenomenon of ‘nuclear induction’ later to be termed as nuclear magnetic resonance (NMR) was described independently but almost simultaneously by Bloch and Purcell

and their colleagues in 1946 and for this they were jointly awarded Nobel Prize in 1952. Much later, the term ‘nuclear’ was dropped, it is now commonly referred to as magnetic resonance (MR). In 1971, Damadian noted that in vitro animal tumors had elevated MR relaxation times when compared to normal control tissue and he formed an apparatus and method for detecting cancer in tissue. In 1973, Lauterbur published a paper and showed how MR could be applied to imaging by applying a linearly varying magnetic field across a liquid. Paul C Lauterbur is known as the ‘Father of MRI’. In 1977, human Invivo images were demonstrated by Mansfield and Maudsley. In 1980, multiplanar imaging ability were first demonstrated by Hawkes. In 1992, functional MRI (fMRI) of the brain was introduced by Ogawa.

Principles of Magnetic Resonance Imaging 1. 2. 3. 4. 5. 6.

Nuclear magnetic dipole moment MR scanner Proton magnetization Resonance Relaxation Spin-echo phenomenon.

Nuclear magnetic dipole moment The individual protons and neutrons in the nuclei of all atoms possess a spin or angular momentum. In nuclei with equal number of protons and neutrons with an electrical charge, a magnetic field is generated in nuclei with an electrical charge, a magnetic field is generated in nuclei of unpaired nucleons, causing these nuclei to act as magnets with north and south poles (magnetic dipoles) and having magnetic momentum. The most common of these atoms, the magnetic resonance active nuclei, are hydrogen, carbon, nitrogen, oxygen, fluorine, sodium and phosphorous. Hydrogen atom is the most ubiquitous of these atoms in the body. A hydrogen nucleus consists of a single unpaired proton and therefore acts as a magnetic dipole. MRI is based on magnetic dipole moment. MR scanner The MR scanner consists of a magnet (Figure 79). Inside the bore of the main magnet, there are three sets of coils installed to produce magnetic field gradient, one in the direction of the main field (the z-axis) and two perpendicular to this (the x and y axes). The gradient field strengths over the entire patient are less than 1% of the main field strength and can be rapidly varied in time. Inside the gradient coil assembly, radiofrequency (RF) transmitter/receiver coil is mounted. Surface coil is placed directly on the surface of 781


Figure 79 Gradient coils

Main magnet

RF coil

Couch

y

z x

RF receiver/ transmitter switch

Main magnet power supply

X-gradient power supply

RF pulse generator

Y-gradient power supply

Z-gradient power supply

RF pulse amplifier

Image processor

Central pulse sequence controller

MR scanner

the body that improves the signal-to-noise ratio and the resolution in the final image, but limits the volume that can be examined. Patient is installed on a couch centrally in the bore. Central pulse sequence controller operates the ‘gradient coil power supplies and transmitter-receiver switch’ of the RF coil through the complex sequences used for the various MR-imaging modes. Received radiofrequency signals are analyzed by Fourier transformation which are spatially decoded in the image processor to be displayed as an image, which is a map of the amplitude of radiofrequency signals emitted from small-volume elements, voxels, in an imaginary slice of the patient.

Figure 80 B0 Axis of precession

Axis of spin proton

Proton magnetization Proton exposed to a steady external magnetic field creates a force that will act on its magnetic dipole moment and orient it parallel with the external field, but due to the spin, it does not swing in as a compass needle would do. Instead, it performs a maintained circular movement called precession which has its own axis of spin and rotates at an angle around another axis that is parallel with the external field like toy spinning top in the gravitational field (Figure 80). Magnetic dipole moment of the precessing proton have magnitude and a direction expressed by a vector which is resolved in one component aligned with the axis of precession known as ‘the longitudinal component’. The second component which is oriented perpendicular to the external field and rotating with the frequency of precession is called ‘the transverse component’. Within a magnetic field, all protons precess at the same frequency 782

w External field

Proton spin and precession

which is determined by the strength of the magnetic field and a constant. Relation between these two is expressed by the Larmor equation: F yB0 F precessional frequency, B0 strength of the external magnetic field and y gyromagnetic ratio unit of magnetic field strengthtesla (T). The precessional frequency of protons is 42.58 MHz/T.


Figure 81

Figure 82 Low energy state

z Longitudinal net magnetization vector

z

B0

External field

x–y transversal vectors cancel because out of phase

High energy state

Illustration showing net magnetization vector of protons

Illustration showing proton spin levels

Larmor frequency is not exactly the same for all protons, but may differ by a few ppm (parts per million) depending on the chemical bonds they have established. Larmor frequency of protons in water and in aliphatic fatty acid chains vary. Such differences are designated chemical shifts. Proton spin levels When exposed to the external field, the spin of the proton may be at one of two discrete energy levels. At low spin-energy level, longitudinal component of the magnetic vector points in the same direction as the external field. At the high energy level it points in the opposite direction (Figure 81). The fractional distribution of protons between these two states depends upon temperature and strength of external magnetic field. The difference manifests itself as a net magnetization of the population of protons in the material/tissue within the field. Net magnetization vector is the statistical equilibrium of a huge population of protons, constantly influenced by thermal motion, and shifting between the two spin-energy levels (Figure 82). Resonance When a body part or tissue is installed in a strong, steady and uniform magnetic field of the MR scanner, the equilibrium state is represented by the net magnetization vector which is established within seconds. When disturbed and shifted by a pulse of electromagnetic waves at the Larmor frequency of the protons (42.58 MHz in an IT field) entering perpendicular to the main field, only RF waves (photons) of precisely this frequency will transfer energy by resonance to the precessing protons. This transfer of energy by resonance has two effects on the precessing protons: i.

Protons at the low spin-energy level, having absorbed the energy of a RF photon, shift to the high energy

ii.

level accompanied by a shift in the orientation of their magnetic dipole moments. The magnitude of the longitudinal net magnetization vector as more protons shift to the high energy level. At a certain RF energy input, the longitudinal vector disappears. By further input of RF energy, a surplus of proton is lifted to the high spin-energy level, the longitudinal vector reappears, but in the opposite direction. It forces the protons into coherent precession with the appearance of transverse net magnetization vector which rotates with the Larmor frequency. The net magnetization vector is the resultant of longitudinal and transverse magnetization vectors. Increase in RF energy input increases the longitudinal vector and decreases the transverse vector. The angle between the direction of the main field and net magnetization vector is flip angle.

90 pulse: RF pulse delivering energy just sufficient to tilt the net magnetization vector into the transverse orientation. 180 pulse: RF pulse of twice 90 magnitude causes reappearance of a longitudinal vector, but in the opposite direction, and will also cause the transverse vector to rotate in the opposite direction relative to the main field. The duration of such excitatory RF pulses is in the order of a few milliseconds. Relaxation When RF pulse is turned off, the excited protons return over a period of time to the initial equilibrium state, this is called as relaxation. Recovery of longitudinal magnetization and the decay of transversal magnetization follow different and independent time courses according to simple exponential functions but with different time conducted: i. ii.

T1—Recovery of longitudinal magnetization T2—Decay of transversal magnetization. 783


Table 10

Comparative features of T1 and T2

Table 12

T1

T2

Repetition time (TR)

Echo time (TE)

This is the time at which the longitudinal magnetization has recovered 63% of its equilibrium magnitude

This is the time at which the induced transversal magnetization has decayed 63% of its maximum strength

Duration between repeat RF pulses

Time after application of RF pulse when the MR signal is read Controls the amount of T2 relaxation that has occurred when the signal is collected

Loss of energy whereby those protons that were lifted to the high spin-energy level during magnetization give up this energy and fall back

Loss of phase coherence between the precessing protons has its origin in mutual magnetic interactions between the protons, and between the protons and local field in homogeneities

Time between pulse repetition determines the amount of T1 relaxation that has occurred at the time the signal is collected

Thermal nature with a molecular basis in random collisions with surrounding molecules, collectively called ‘the lattice-thermal relaxation time’ or ‘the spin-lattice relaxation time’

Interactions between nuclei with different spins—‘the spin-spin relaxation time’

T1 longer than T2

Table 11

Pure liquids Solids • Mobile molecules • Molecules fixed • Intrinsic and local • Local intrinsic field field variations are inhomogeneities rapidly fluctuating more permanent and tend to causing protons to average out systematically dephase • Longer (seconds) • Short (milliseconds)

Fat Bone marrow

T1 time (ms)

T2 time (ms)

240–250

60–80

550

50

White matter of cerebrum

780

90

Gray matter of cerebrum

920

100

Muscle CSF (water)

Table 13

Difference between T1 weighted image and T2 weighted image

T1 weighted image

T2 weighted image

Emphasizes T1 value of tissues

Emphasizes differences in T2 values of tissues

Accomplished by use of short TR (300–700 ms) and TE time (20 ms)

Accomplished by use of long TR (2,000 ms) and TE time (60 ms)

Fast T1 time, e.g. Fat-bright Long T1 time, e.g. Water-dark

Short T2 time, e.g. Fat-dark Long T2 time, e.g. CSF/water-bright

To demonstrate anatomy

To identify inflammatory/pathological changes • Other techniques allow the signal from fat or water to be enhanced/ supressed • ‘Fat saturation’—nulls the signal from fat

T1 and T2 relaxation times in a main field of 1.5 T

Tissue type

860–900

50

2,200–2,400

500–1,400

The two relaxation processes reflect two types of interactions between the precessing protons and their surroundings (Table 10). The chemical shift (3 ppm) between protons of water and fatty acids causes rapid decay of transverse magnetization in tissues where fat and ‘watery’ tissue are intimately mixed, e.g. in bone marrow. The mineralized bone tissue has few mobile protons which yield detectable T1 signals in diagnostic imaging. The concentration of protons detectable by MR-imaging in a tissue is spin density/proton density. MR-imaging is directed at detection and visualization of differences in parameters such as T1, T2 or the spin density between different tissues and fluids within the body (Table 11). During the period of relaxation of the magnetized tissues, an electromotive force can be induced in receiver coil as an RF signal in synchrony with the precessing protons. 784

Pulse sequence: basic features

The RF signal is analyzed and encoded to be displayed as an image. Only protons that precess in phase give rise to detectable radiosignals. Thus, to detect differences in T1 between tissues, and to fully exploit differences in T2, complex excitatory pulse sequences are applied. Radiofrequency pulses sequences The components are set by the operator and determine the appearance of the resultant image. Most basic features of a pulse sequence are depicted in Table 12. Tissue contrast Tissue contrast is governed by intrinsic features of the tissues including proton density T1 and T2 times of the issues being imaged and how the TR and TE times are adjusted to emphasize these features, e.g. tissue has high proton density, strong transverse magnetization vector at TE, strong magnetic resonance signal, appear bright on MR image. Conversely, low proton density low transverse magnetization vector at TE weak signal dark on MR-image (Table 13). Spin-echo phenomenon Loss of phase coherence is called as ‘dephasing’ characterized by loss of RF signal due to the spin-spin relaxation (T2) which is an inherent property of the material/tissue.


Figure 83

Figure 84 z

B0 z

90° RF pulse y

MZ

x

y

w

x

Mxymax w

A strong radiosignal emitting at the Larmor frequency

Illustration showing proton magnetization vectors out of phase in the equilibrium state

Figure 85 z

z

180° RF pulse

Mxymax y

y

Mz x

x Mz

w

w

Illustrations showing fanning out of the transverse component after the end of a 90 pulse and the application of a 180 pulse reversing the longitudinal vector

The rate of decay of phase coherence (T2) is always faster because of inhomogeneities in the magnetic field. The other reason is due to ‘external’ disturbance of the measurement can be cancelled by the spin-echo manoeuvre (action) and gradient-echos (reversal of the magnetic gradients). In equilibrium state, all the transverse (Mxy) components of the proton magnetization vectors are out of phase (Figure 83). Sum of the longitudinal components (Mz) are aligned with the main field. A 90 RF pulse flips the longitudinal vector into the transverse plane and forces the transverse components of the proton magnetization vectors to precess in phase. The single resultant Mxy vector is large and emits a strong radiosignal at the Larmor frequency (Figure 84). After termination of the 90 pulse, the transverse component begins to fan out due to small differences in precessional frequency of the individual protons, i.e. T2 relaxation. At the same time the longitudinal vector begins to grow up due to T1 relaxation (Figure 85). A 180 RF pulse reverses the longitudinal vector and the direction of

Figure 86 z

y Mxy

Mz x

w

Illustration showing closing of the fan of vectors

precession faster precessing protons catch up with the slower, i.e. the fan of vectors closes again (Figure 86). At time, TE, the transverse components of the proton magnetization vectors regather and emit again a strong radiosignal. 785


MR-contrast Agents The relaxation times (expressed by T1 and T2) is shortened when paramagnetic substance is targeted to tissue, disturbing admixture of strong magnetic dipoles due to the unpaired electrons in their atoms. Gadolinium (Gd) chelated to DTPA—it is a rare earth element which does not cross the normal blood–brain barrier. This is used to detect defects in this barrier excreted in the urine. It is utilized in urological MR-imaging. Using additional ligands, Gd-chelates may be directed to biliary excretion. Agents based on manganese (Mn) having paramagnetic properties similar to gadolinium have been developed. Gd and Mn based compounds are positive contrast agents because of their influence on the relaxation constants, notably T1, is utilized to produce images (T1 weighted) where the MR signal strength is proportional to the concentration of the agent. Iron oxide particles effectively produce local field in homogeneities. These are negative contrast agents which produce signal voids by strongly shortening T2. After IV administration, it shortens the relaxation time in liver, spleen and bone marrow, but not in tumors lodged in these tissues. This is used for gastrointestinal imaging.

Methods for Obtaining Spatial (Tomographic) Resolution of MR Signals The final MR-image is a square matrix of pixels containing small-volume element called as voxel in an imaginary ‘slice’ of the patient. Each pixel is given a gray tone value proportional to the amplitude of the radio signal emitted from the corresponding voxel in a defined period of time following a sequence of RF excitations. Scanner gradient These are used to generate image that produce discrete slice of tissue. It is accomplished by using two gradient coils which are required to modify the magnetic field surrounding the patient. X gradient refers to left to right, Y gradiant refers to anterior to posterior, Z gradient refers to head to toe (Figure 87). When one coil is turned on, it creates a gradient in the intensity of magnetic field. Thus, in a 1.5 T scanner, when the Z gradient is turned on, the strength of the magnetic field at the head might be 1.4 T and that of toe is 1.6 T. When this gradient field is applied, the precessional frequency of hydrogen nuclei will vary linearly along the magnetic variant. Accordingly, when the RF pulse is applied, only those nuclei precessing at the same frequency as the applied signal will resonate. This allows selecting the desired slice of tissue along the Z gradient slope of the gradient applied and the bandwidth of the RF pulse determine the 786

Figure 87 y z

x

Illustration depicting the scanner gradient

thickness of the slice location of the signal within the X and Y planes of the selected longitudinal plane derived by switching off the Z gradient coil followed by rapidly turning on the X and Y gradient coils. This sequence alters the phase and precessional frequencies of the nuclei in the selected slice. The resulting magnetic resonance signals from the patient is read out while the frequency encoding gradient is applied. The signal from the patient contains many frequencies that is decomposed by the fast Fourier transformer into amplitude and frequency. This information, which reflects the number of hydrogen nuclei and their T1 and T2 properties at each X and Y location in the selected longitudinal plane is reconstructed into MR images. The phase encoding gradient applied perpendicular to sIice selecting gradient is switched on for short period of time (3–5 ms) after the excitatory RF pulse has been switched off, produces a continuous change in precessional phase across the slice, so that a particular phase derives from particular rows of voxels (horizontal row). The frequency encoding gradient is applied at right angles to both the slice-selecting gradient and the phase encoding gradient-switched on after the phase encoding gradient has been switched off, and is maintained during the period where the RF signals are sampled establishes a continuous increase in precessional (Larmor) frequencies from one edge of the section to the opposite edge, so that a particular frequency derives from a particular row of voxels across the slice (vertical row). The commonly used image matrix is 256 256 pixels. To achieve the same resolution in the X- and Y-directions, the image must be constructed from 256 data samples, recorded with 256 different settings of the phase encoding gradient which is the main reason for the long data aquisition time in MRI compared to CT imaging (Table 14). The amplitude is assigned a gray tone that is proportional to its magnitude and is


Table 14

2.

Differences between CT and MRI

CT

MRI

Ionizing radiation

Radiofrequency

Less expensive

Expensive

Short time

Long time

CI in pregnancy and children

Can be used

Suppression of image not possible

Suppression of certain image possible

5.

Measured in terms of density

Measured in terms of intensity

6.

Two planes—axial and coronal

Multiplanar—oblique view possible

Indicated for trauma patients with acute bleeding

Not for trauma patients

Applicable for fractures

Not for fractures

Contrast used: Iodine, barium

Contrast used: Gd, Mn

For chronic stages

For strokes, edema, initial stage of inflammation, cranial nerves, vessels

Between bones and soft tissues

Between soft tissues

3. 4.

7.

Advantages Best resolution of tissues with low inherent contrast. Uses non-ionizing radiation—non-hazardous. Accurate and rapid localization of intracranial pathologies. No streaking artifacts. High-contrast images achievable.

Disadvantages

Image interpretation

Tissue

T1 image

T2 image

Water

Dark

Very bright

Tumors

Intermediate

Bright

Old blood

Bright

Bright

Fibrous tissue

Dark

Dark

Air

Dark

Dark

Bone calcium

Dark

Dark

Fresh blood

Dark

Dark

Organs

Intermediate

Dark

Fat

Very bright

Bright

displayed as the corresponding pixel in the image. High signal amplitudes appear white while low amplitudes appear black on the gray tone scale. As in CT imaging, ‘window width’ and the ‘window level’ can be varied.

Uses for MRI (Table 15) 1.

1. 2. 3. 4. 5.

CI: Contraindicated

Table 15

Congenital disorders: T1 weighted sequences with coronal and axial images demonstrate abnormalities like cleft lip and palate. Infections: AIDS-generalized cervical lymphadenopathy with cystic lesions in the parotid. Sinusitis: When complicated by serious condition like a tumor, venous sinus thrombosis or an intracranial extension of the infection. Benign tumors: Hemangiomas, lymphangiomas, neurofibromas and schwannomas. Malignant tumors: Diagnosis, staging and monitoring of malignant tumors affecting the head and neck region. TMJ: Articular disk perforations and disk displacements.

For head and neck lesions: T1 weighted images— defining anatomy of the lesion. T2 weighted images— assessing the invasion of the lesion into surrounding structures. Contrast enhanced MRI—extension of the lesion into muscles, brain or blood vessels can be studied. Coronal scan-assessment of lesions involving the base of the skull and the perineural extensions of tumors.

1. 2. 3. 4. 5. 6.

Some patients may complain of mild pain or tingling sensation. Noise produced may cause discomfort to the patient. Contraindicated in patients with cardiac pacemakers. Not used in patients with ferromagnetic substances implanted in the body. Expensive, not easily available. Room used should be free of ferromagnetic materials.

Common Artifacts in MRI Flow effect and movement artifacts in MRI Artifacts occur due to flow in blood vessels and CSF. Depending on the RF pulse sequences applied, the presence of flow may give rise to weaker or stronger signals than expected. Fast flow perpendicular to the section carry away those protons that should have given a signal during the RF signal sampling period. Blood vessel becomes ‘signal void’ and is displayed in black on the image. Protons with strong signals may be carried into the section by flow which disturb the spatial X–Y encoding/decoding leading to artifacts. Wherever flowing blood is imaged the artifacts may be present as streaks through a vessel, extending across the image in the direction of the phase encoding gradient. Artifacts in magnetic resonance image due to motion and use of denture See Table 14. 787


NUCLEAR MEDICINE Nuclear medicine is a diagnostic radiation science utilizing radioactive compounds or tracers having affinities for particular tissues or organs in the body (iodine to the thyroid gland); these are termed as target tissues. The radioactive agents are administered to the patient either orally, intravenous or intrathecally. These agents concentrate in target tissues and emit radiation. These are detected and imaged by a variety of external detectors and imaging systems. This helps in studying the target tissue under static and dynamic conditions. Such studies are called scintigraphic scans, scintiscans or radionuclide scans. When these are utilized for studying bone they referred to as bone scans and when performed for salivary gland they are termed as salivary gland scans. Other scans include heart scans (to identify normal or abnormal blood flow to the heart muscle, measure heart function or determine the existence or extent of damage to the heart tissues after a heart attack); thyroid iodine scans (to analyze the thyroid function and show the structure of the gland. Larger doses of radioactive iodine are used to destroy thyroid nodules in the case of Graves’ syndrome); gallbladder or hepatobiliary scans (to evaluate both liver as well as gallbladder function such as presence of gallstones); lung scans (to evaluate the flow of blood and movements into and out of the lungs, as well as the determination of the presence of blood clots); Gallium scans (to evaluate infection and tumor), brain scans and gastrointestinal scans. Nuclear medicine tests are extremely sensitive to abnormalities in body organs structure and function. Tests using nuclear medicine techniques are more sensitive and specific for disease detection than most tests because they identify abnormalities very early in the progression of a disease, long before the medical problem would be apparent with other diagnostic tests. In 1958, Hal Angler used scintillation camera for imaging the entire system. In 1971, Subramanian and McFee used 99m-Tc (Technetium) labeled MDP (methylene diphosphonate) in bone scanning.

Radiopharmaceuticals These are radioactive agents used in nuclear medicine procedures for imaging. They are produced using nuclear reactors and cyclotrons. Radiopharmaceuticals circulate and concentrate to varying degrees in different organs throughout the body. The localized tracer uptake is dependent on changes in regional blood flow and areas of altered bone physiology and pathology which show an invariable alteration in the osteoblastic and osteoclastic activity. The organs that receive the greatest exposure are referred to as critical organs. For example, in bone scanning the bladder, skeleton and bone marrow receive the highest exposure. 788

Types of radiopharmaceuticals 1. 2.

Radioactive elements/compounds (Technetium-99m, Fluorine-18, Iodine-131) Non-radioactive carrier compound with a radioisotope (Gallium-67 labeled citrate, Iodine-125 labeled polyphosphate and Technetium labeled human serum albumin).

Labeling various phosphate compounds with 99Tc results in the agents concentration in the skeleton hence used in bone scans. Labeling sulfur colloid with 99Tc gives an agent that is taken up by the reticuloendothelial cells of the liver and spleen, hence used in scans of the liver and spleen. Technetium-99m methylene diphosphonate (Tc-99m MDP) is the most widely used radiopharmaceutical. It has a short half-life (6.5 h), hence there is minimal radiation exposure and has superior physical and biological properties. MDP is localized in bone by chemiabsorption onto immature hydroxy apatite crystal within newly formed inorganic matrix and cannot be metabolized by the enzyme system.

Bone Scanning Procedure Ten to fifteen millicuries of 99m-Tc labeled compound is injected IV. A waiting period of 2–3 hours permits the compound to accumulate in the skeleton and to be removed from vascular and soft tissues via the urinary system. The patient is then positioned under the gamma camera and the desired bones are imaged. Whole body radiation dose in bone scan is approximately 0.1–0.5 rad. Working principle Following administration of the radioisotope, they reach the desired organs and emit gamma radiation, which is picked up by the detectors placed outside the body within the gamma cameras. Gamma cameras are devices used to image the radioisotope distribution in the body, within the field of view. It consists of a sodium iodide detector of about 40 cm in diameter. The detector assembly has a collimator which is similar to a grid in radiography. The gamma radiation emitted by the patient passes through the holes in the collimator and reaches the detector, where they are converted into light scintillation. The photomultiplier tubes convert the light into electric pulse which is then passed onto the computer. The computer constructs the distribution of the radioisotopes and displays it on the monitor. Interpretation of bone scans Abnormalities in bone are manifested in a scan mostly as areas of increased tracer concentration or as areas of very


limited uptake. Areas of increased tracer uptake seen as hot spots and cold spots are areas of decreased tracer uptake. In rare instances the entire skeleton will be diffusely hot which is termed as super scans. In a normal scan the tracer will show bilateral, uniform and symmetrical distribution. The normal activity and uptake of the tracer depends on bone mass/density and bone stress in weight bearing areas. Soft tissue and the urinary tract may show some background activity. Clinical applications of bone scans 1. Trauma: Absence of tracer uptake even 24–48 hours after an injury excludes a fracture. Bone scans can help determine the age of a fracture.

Salivary Gland Scans Procedure Patient is advised to lie supine. Intravenously 40–150 megabecquerel (MBq) 99m-Tc pertechnetate is injected. For the next 25 minutes, sequential images are taken at 1 minute intervals. A large field of view gamma camera equipped with a low-energy, high-resolution, parallel-hole collimator is used. Roughly, 15 minutes following the procedure, secretogogue like lemon juice may be given to enhance salivary secretion. The effective equivalent radiation dose to the patient is 0.4–1.6 mSv. Clinical applications for salivary scans

2. Viability of bone grafts: An unsuccessful graft (nonvascularized) appears as a cold spot. On the other hand, osteoblastic activity associated with a vascularized bone graft is seen as a hot spot.

Salivary scintigraphy may be used to assess obstructions in the salivary ducts with or without parenchymal damage, Sjogren’s syndrome, parenchymal impairment after radioiodine treatment in patients suffering from thyroid cancer.

3. TMJ changes: Early articular surface changes of the TMJ can be determined.

ULTRASONOGRAPHY

4. Osteomyelitis: Early detection (1–2 days of symptom onset) of osteomyelitis is represented by the radionuclide hyperactivity. 5. Metabolic bone disorders: Bone disorders such as osteomalacia, hyperparathyroidism and renal osteodystrophy can be assessed. 6. Detection of skeletal metastasis: Carcinoma of the breast, lung and kidney which have a tendency for skeletal metastasis appear as multiple hot spots on a bone scan. 7. Extraosseous localization: 99m-Tc MDP apart from localizing in the skeleton also localizes in several soft tissues lesions such as muscle injuries, myocardial infarct, primary breast lump and lung metastasis from osteosarcoma. Advantages of bone scanning over conventional radiography A bone scan helps in detection of a lesion at the early stage (less than 5% demineralization of bone is adequate), compared to conventional radiographs which require at least 30–50% demineralization of bone. Bone scans can depict the functional state of an organ or tissue whereas conventional radiographic procedures detect the anatomical structure. Limitations In interpreting bone scans of the skull and face, care should be taken to avoid misinterpretation of activity in the mandible and maxillary alveolar ridges which are common sites of uptake due to the frequent dental infections and extraction sites.

The production of sound is the result of periodic changes in the pressure of air against the ear-drum. The periodicity of these changes lie between 1500 and 20,000 cycles per second (Hertz). Human hearing is usually in the range of 20 Hz–20 kHz. Diagnostic ultrasonography uses vibratory frequencies in the range of 1–20 MHz. Sonography comes from a Latin word sonus meaning ‘sound’ and a Greek word graphein ‘to write’. Sonography precisely means imaging with ultrasound. An ultrasound produces a visible image of invisible organs inside the human body (Table 16).

Principle Images with ultrasound are accomplished with pulse-echo technique with the help of transducer. Ultrasound transducers convert electrical energy into ultrasound energy and vice versa. In ultrasonography, sound waves (pulse) generated by the transducer emitted inside the patient will be reflected back (echo) at organ boundaries and within tissues depending on the composition of the matter. These echoes then return to the transducer, where they are converted into electrical energy and then presented on the display of sonographic instruments. The ultrasound instruments processes the echoes and present them as visible dots. The location of each dot corresponds to the anatomic location of the echo-generating structure. Gray-scale image is achieved by different echo-strength and the echo arrival time is used to determine the depth of the structure that produced the echo. The ultrasound instruments processes the echoes and present them as visible dots, which form the anatomic image on the display. Not all the ultrasound pulses are reflected back from any interface. Rather 789


Table 16

Terms associated with ultrasonography

Acoustic impedance

Product of density of the medium propagating the sound and the velocity of propagation

Reflection

The way ultrasound is reflected when it strikes an acoustic interface is determined by the size and surface feature of the interface

Refraction

If the direction of sound changes as it crosses a boundary, then the transmission angle is different than the incidence angle

Attenuation

Reduction in amplitude and intensity of sound as it propagates. It is the result of the combined effects of absorption, scattering and reflection

Anechoic

Without internal echoes; structure is fluid filled and transmits sound easily Example: amniotic cavity, gall bladder

Hyperechoic

Echo producing structure, reflects sound with a brighter intensity Example: gall stones, fat, bone

Hypoechoic

Low level echoes within a structure Example: enlarged lymph nodes

Isoechoic

Very close to the normal parenchyma echogenicity pattern Example: muscles

most of the original pulse continues to be reflected back from deeper interfaces. If process is repeated, but with different starting points for each subsequent pulse, a crosssectional image of the anatomy is built up. Velocity of sound depends on the medium. Sound is attenuated through most bony structures thus velocity is faster in solids whereas it is slow in gas-filled structures such as bowel because it impedes the sound transmission. Contrast agent can also be injected into the circulation to increase echogenicity. Contrast agent contain micro bubbles of gas and they produce strong echoes because impedence of gas is different from that of suspended liquid that enhance echogencity from perfused tissues in grayscale sonography and Doppler ultrasound. For many years, ultrasonography was limited to 2D cross-sectional scan, now it has been extended into 3D scanning and imaging. This requires scanning the ultrasound through many adjacent tissue cross-sections to build up 3D volume of echo-information.

Different Types of Scans 1.

790

B-scan (gray-scale scan) images are produced by scanning the ultrasound through the imaged crosssection (i.e. sending pulses through all regions of the cross-section). B-scan converts the echo-strength into the brightness of each represented echo on the display. (Hence B-scan or brightness scan.)

2.

3.

A-scan images appear as spikes extending upward from the baseline (point of contact of skin and the transducer is representative of the baseline). A-scans, showing the relationship between amplitude and depth are used for measuring the distance between boundaries of tissues with different acoustic properties. These are used to distinguish between solid and cystic lesions. M-scan used to show the motion of cardiac structures. It is a display form that presents depth versus time. Display of changes in echo is useful in evaluation of rapidly moving structure like cardiac valve.

Different Types of Scanners Used 1. Linear scan These cross-sectional images have been produced with vertical parallel scan lines that are so close together that they cannot be identified individually. 2. Sector scan Each pulse originates from the same starting point, but subsequent pulses go out in slightly different directions from the previous ones. This results in a scan which is shaped like a slice of pie. There is a combination of both too, where pulses originate from different starting points but each pulse travels in a slightly different direction than the previous one.

Instrumentation 1. 2.

3.

Transmitter provides high amplitude voltage and controls the rate of pulses emitted by the transducer. Transducers operate according to the principle of piezoelectricity. This principle states that some materials (ceramics, quartz) produce a voltage when deformed by an applied pressure. Piezoelectric crystal used in ultrasonography is lead zirconate titanate. When the transducer receives the electric impulses, the dipoles inside the crystals are realigned to the electric field causing the changes in the thickness of the crystal. This leads to the formation of sound which is transmitted inside the patient. The echo reflected back to the transducers which change in the shape of crystal that results in the production of small oscillating voltages that can be measured or recorded. Receiver and display—after amplification the echo voltages are digitalized, i.e. they pass through analogto-digital converters (ADC). Electric information from image processor drives the display, which produces a visual image.

Coupling agents Even a very thin layer of air between the transducer and the skin surface reflects all the sound, preventing any penetration into the tissue, thus an aqueous gel is applied over


the skin before application of the transducer which eliminates the air layer and facilitates sound passage in and out of the tissue. Coupling agent consists of: 1. 2. 3. 4. 5.

Carbomer—10 g EDTA—0.25 g Propylene glycol—75 g Trolamine—12.5 g Distilled water up to 500 g.

Doppler Ultrasound Echoes produced by moving objects have different frequencies than the pulses sent into the body. This is called the Doppler effect, which is put to use in detecting and measuring tissue motion and blood flow. Color depends on the flow of blood toward or away from the transducer. Colors are always opposite for artery and vein, so if artery is red, vein will be blue or vice versa. This is used to see tissue motion, obstruction and thrombosis. In addition, it can also detect direction, speed and character of blood flow. Color Doppler ultrasonography minimizes the need for biopsy or fine needle aspiration cytology (FNAC). The presence of blood flow signals in the center of node (this indirectly denotes the existence of the converging sinuses) suggests that the node is benign. The presence of peripheral flow suggests a malignant nature (tumors larger than a few millimeters in diameter stimulate the growth of new vessels). It has also been applied to automatic door openers and to burglar alarms.

Main Indications for Ultrasound in the Head and Neck Ultrasound is a very valuable tool in the diagnosis of the head and neck. Optimal ultrasound examination of the superficial structures of the head and neck requires appropriate equipment with high-resolution small part transducers that make use of high frequency ultrasound. Ultrasound sequence between 5 and 20 MHz is used. Either the transducer is used directly on the skin or a silicon stand-off pad is placed between the transducer and the skin to get the ideal contact with the surface, especially in the angle of the jaw and neck. A systematic examination protocol is mandatory for the evaluation of the head and neck. It begins with the examination of the thyroid gland where the instrument is adjusted. The examination is continued along the vascular sheath to the floor of the mouth, tongue, salivary glands and tonsils. Next step is the examination of status of lymph nodes. 1. Cervical lymph nodes The majority of the normal lymph nodes in the head and neck show an axial diameter of 2–5 mm with the exception

of the jugulodigastric and the juguloomohyoid lymph nodes, which are larger and show axial diameter of 8–10 mm and longitudinal diameter of 15–20 mm, normal nodes are difficult to detect because of their high echogenecity, which is similar to that of the surrounding fatty tissues. Reactive lymph nodes Enlarged reactive lymphnodes are most frequently encountered in head and neck, most commonly the submandibular and lateral cervical nodes. The typical sonographic appearance shows a longitudinaloval shape with rounded poles and smooth border. The echogenecity is low and homogenous with hyperechoic periphery. The axial diameter is usually less than 8 mm, whereas the longitudinal diameter can range from 15 to 20 mm. Inflammatory lymph nodes Shape of inflammatory lymph node is longitudinal or ovoid with rounded poles. In addition, they may be round to spherical with smooth borders and display a hypoechoic appearance. The ratio between longitudinal and transverse diameter of lymphnode is termed roundness index (RI). If RI 2 (longitudinal), it indicates inflammatory disease, whereas RI 1.5 (spherical) favors metastatic involvement. In subatue inflammation, the lymph nodes tend to become smaller. In chronic inflammation, they are small, soft, movable, slightly hypoechoic with smooth borders, and have longitudinal shape. Specific lymphadenitis (tuberculosis) They range from large, round, non-echoic to cystic necrotic nodes with blurred borders. Fistulas appear as hypoechoic or non-echoic linear stripes. Primary lymph node disease i. Sarcoidosis (benign) ii. Hodgkin’s and non-Hodgkin’s (malignant) Individual lymph nodes are round to oval and occasionally appear as very large, non-echoic, simulating a cyst. Lymph node metastasis Lymph nodes appear round to spherical, are hypoechoic but occasionally inhomogenously echogenic with loss of hilar definition visible. In case of extranodular involvement, borders are poorly defined. 2. Salivary glands Glands are typically homogenous echogenic structures. Intraglandular and extraglandular ducts can only be visualized using high frequency, high-resolution transducers. Sialadenitis It reveals inhomogenous hypoechogenicity which is more dominant in acute than in chronic inflammation. Sjogren’s syndrome It reveals inhomogenous and hypoechogenicity. In severe cases, multiple cystic lesions appear due to destruction of parenchyma. 791


Sarcoidosis of the parotid glands It reveals multiple small hypoechogenic granulomatous nodules, which are diffusely distributed throughout the gland.

❍

Sialolithiasis It reveals echogenic complex with sound shadowing. Sialoliths which are smaller than 2 mm may not show shadow in sonography. Accuracy of sonography for diagnosis of sialolith is 80–94%.

❍

Sialadenosis It reveals homogenous, echogenic parenchyma extending enlargement of the glands secondary to tumor. Pleomorphic adenoma It reveals homogenous ultrasonic pattern with decreased echogenicity and smooth borders. But occasionally, tumor is hyperechoic with cystic areas of calcification. Cystadenolymphoma It reveals hypoechogenic with smooth border. Hypoechogenicity is homogenous/inhomogenous with cystic areas with multiple septae. ❍

Evaluation of swelling of the neck, particularly those involving the thyroid, cervical lymph nodes or the major salivary glands. Ultrasound is now regarded as the investigation of choice for detecting solid and cystic soft tissue masses. ❍ Detection of salivary gland and duct calculi. 3. Primary soft tissue tumors Hemangiomas and lymphangiomas Echogenicity is variable and depends on the size of cystic compound. They can be hyoechoic or isoechoic but usually are hyperechoic compared to surrounding cervical soft tissues.

❍ ❍

❍

❍ ❍

Advantages Over Conventional X-ray Imaging ❍ ❍

Sound waves are not ionizing radiation. There are no known harmful effects on any tissues at the energies and doses currently used in diagnostic ultrasound. ❍ Images show good differentiation between different soft tissues and are very sensitive for detecting focal disease in the salivary glands. ❍ Technique is widely available and inexpensive.

Cystic hygroma They appear non-echoic.

Disadvantages

Lipoma Fat containing lipomas are relatively hypoechoic. Fibrolipoma reveals high echogenicity with striated feathery appearance.

❍

Carcinoma Most frequent tumor is carcinoma of the tongue. It appears hypoechoic, inhomogenous, space occupying lesion with blurred borders. Sonograpy can evaluate extension across midline and infiltration of the floor of mouth, and relation of tumor to the mandible.

❍ ❍ ❍ ❍

❍

Infections of tongue, floor of mouth. Abscess appears as circumscribed hypoechogenic or non-echogenic, space occupying lesion with irregular border. Central area of abscess contains fluid like pus, thus anechoic and soft tissue remnants, blood vessels or foreign bodies appear echogenic. Aerobic bacteria may produce small bubbles of air, bright reflexes. ❍ Therapeutically in conjunction with the newly developed sialolithotripter, to break up salivary calculi into approximately 2 mm fragments which can then pass out of the ductal system so avoiding major surgery. 792

Ultrasound-guided fine needle aspiration biopsy. Mainly used for detection of subclinical ipsilateral nodes. This helps in accurate analysis of the size of nodes. 18-gauge needle is used for FNAC. Determination of the relationship of vascular structures and vascularity of masses with the addition of color flow Doppler imaging. Detection of foreign bodies in soft tissues. Caries detection: The ultrasonic caries detector consists of a PC-controlled ultrasonic pulse receiver and a probe (diameter 4.5 mm) attached to a handle. The display showed a correct waveform with a recognizable echo, and a thickness value appeared on the monitor. Measurements of the soft tissue thickness using an ultrasonic gingival-thickness meter could help practitioners select the proper orthodontic miniscrew. The meter’s monitor displays the soft tissue thickness. Assessment of blood flow in the carotids and carotid body tumor. Assessment of the ventricular system in babies by imaging through open frontenelles.

Ultrasound had limited use in the head and neck region because soundwaves are absorbed by bone. Its use is therefore restricted to the superficial structures. Technique is operator dependent. Images can be difficult to interpret for inexperienced operators because image resolution is often poor. Real-time imaging means that the radiologist must be present during the investigation. Ultrasonic waves of high intensity ultrasound generate cavitation in liquids.

Artifacts 1.

2.

Section thickness: It results from beam width perpendicular to the scan plane. Echoes are received that originate not only from the center of beam but also from off center. Third dimension volume is visible. Reverberation (multiple reflection): It can occur between the transducer and a strong reflector. Multiple echoes may be sufficiently strong to be detected and cause


3.

4.

5.

6.

7.

confusion on display. The hyperechoic areas are separated at equal interval. Comet tail artifact: When the reflecting surfaces are closely spaced they appear in a form of comet tail. Irregularities of the surface of the lung may cause transient comet tail artifacts. Refraction: Refraction can cause a reflector to be positioned laterally (e.g. abdominal midline) producing two images of single object. The reflector is at 1 but system places it at 2. One real structure is imaged as two artifactual objects. Ghost artifact: In transverse scan, sound rays are refracted at the muscle or fat interfaces in such a way that smaller structures in the abdomen or pelvis may be completely duplicated. Artifact disappears if transducer is angled. Mirror image artifact: Air-filled lung, covered by visceral pleura, causes a highly reflective beam into the chest. Thus, a sonography will produce pattern of bright echoes (mirror image). Gliding sign: Longitudinal image with transducer directly on the ribs appear as curving bright interfaces that cast dense acoustic shadows. The lung surface moves with respiration, thus appear as gliding sign in sonography.

SIALOGRAPHY Sialography is the retrograde injection of contrast agent (usually iodine based) into the ductal system of a salivary gland. In 1925, Barsony introduced the technique of injecting a radiopaque medium (20% potassium iodide) into the ductal system of salivary glands.

Indications of Sialography 1. 2. 3. 4. 5. 6. 7.

To assess the ductal architecture of the salivary glands to assess developmental disturbances. Detection or confirmation of small parotid or submandibular gland sialoliths or foreign bodies. Evaluation of the extent of irreversible ductal damage present as a result of chronic infection. Differentiating between diseases such as chronic sialadenitis, Sjogren’s syndrome and sialosis. Evaluation of fistulas, strictures, diverticula, communicating cysts and ductal trauma. Rarely, as a dilating procedure for mild ductal stenosis. Evaluation of masses within the submandibular or parotid salivary gland in conjunction with a CT scan.

Procedure Armamentarium 1.

Sialographic cannulas (Rabinov cannulas, cannulas designed by Lowman and Bezella)

2. 3. 4. 5. 6. 7.

A set of lacrimal dilators (0000 through 0 caliber) Iodinated contrast agent (oil or water based) 5 ml or 10 ml syringe, guaze pads Secretogogue to stimulate salivary flow such as fresh lemon or 2% citric acid Adequately focused lighting (a headlight unit) High powered magnifying glass.

Preimaging assessment Patient should be asked about the following: 1. 2. 3. 4.

5.

History of allergy to iodine/contrast agents. Medical history about medications. Previous salivary diagnostic tests and the results of the same. Ask the patient whether any thyroid function tests are scheduled in the near future (absorption of iodine across glandular mucosa may interfere with thyroid function tests, in such a case it is recommended that the sialography be deferred after the thyroid tests have been performed). Examine the ductal orifice, if purulent discharge is evident then the procedure should be deferred until the condition has resolved.

Preimaging instructions to the patient 1. 2. 3.

4.

Explain the procedure to the patient. Patient is told to expect a sense of fullness or pressure within the gland during the procedure. The patient should be instructed to indicate to the examiner by means of a predetermined signal, when the injection of the contrast agent is becoming uncomfortable (this is the accepted end point for injecting the contrast agent). Patient should be informed to expect a mild amount of discomfort and swelling of the gland in question, which usually subsides in 24–48 hours.

Technique 1. 2.

3. 4. 5.

Patient is made to lie down in the supine position. Scout radiographs, comprising PA view, PA puffed cheek view and lateral views are taken for the parotid gland and for the submandibular gland; AP view, lateral oblique view and a submentovertex view are taken. The scout radiographs are taken for two reasons: (i) to evaluate for any large calcifications within the salivary glands and they are used as base radiographs against which the sialograph can be compared. The salivary duct orifice is located. Lacrimal dilators are used to dilate the salivary duct orifice. Cannulas are gently maneuvered into the orifice to locate the salivary duct. At this stage, asking the patient 793


6.

to suck on freshly cut lemon will produce saliva aiding in locating the duct orifice. Contrast medium is injected into the salivary duct.

Injection of the Contrast Medium Contrast medium can be injected by three techniques: 1. 2. 3.

Hydrostatic injection technique Distention injection technique Hand injection technique.

Hydrostatic injection technique In this technique, a reservoir is used which contains the contrast media. This reservoir is placed about 70 cm above the patient’s head. This arrangement permits the constant perfusion of the ductal system with a water-soluble contrast agent. This system provides for a uniform pressure during injection without the examiner being physically present in the room. This technique is useful in CT-guided sialography. Distention injection technique Distention sialography involves the hand injection of the contrast media until the gland physically bulges. This usually requires 2.5–3 ml of the contrast media (in normal cases where routine hand injections are used 0.5–0.75 ml is used). This technique was popular in the pre-CT era to evaluate and visualize small peripheral masses within the duct or the gland. This technique is not preferred any more. Hand injection technique This is the most preferred technique for injecting the contrast media into the gland. The contrast media is injected gently using a steady constant pressure. The injection is performed under fluoroscopic observation and stopped immediately when the patient indicates that the injection is becoming uncomfortable. Normally the parotid can accommodate 0.5–0.75 ml of the contrast media and the submandibular gland can accommodate about 0.5 ml of the agent. The filling of the salivary duct and the gland can either be examined under fluoroscopy in real time or routine radiographs can be taken after the contrast media is injected.

Phases of Sialography 1. 2. 3.

Ductal phase Acinar phase Evacuation phase

Ductal phase The ductal phase begins with the injection of the contrast medium and terminates once the parenchyma becomes 794

hazy (reflects the onset of acinar opacification). The ductal phase of the normal parotid sialogram should demonstrate the main duct to be of uniform caliber extending from the ductal orifice to the hilus of the gland. The intraglandular portion of the parotid ductal system should demonstrate a progressive arborization of the secondary and tertiary ducts. This configuration is often described as a ‘leafless tree’ appearance on a sialogram. The ductal phase of the submandibular sialogram can be divided into two substages. The first substage involves the filling of the deep portion of the main duct; the second substage involves the filling of the superficial segment perpendicular to the mylohyoid muscle as well as the remainder of the ductal system. In contrast to the orderly arborization seen in the parotid duct, the submandibular ducts are often noted to terminate abruptly with poor or incomplete filling of the tertiary elements. Acinar phase The acinar phase begins with the completion of ductal opacification and ends when there is a generalized increase in density of the gland. This phase was of special importance in the pre-CT era, when sialography was intended to demonstrate the presence of intraglandular and extraglandular masses. Evacuation phase The evacuation phase of a sialogram provides an estimate of the secretory function of the salivary gland as well as demonstrating or accentuating ductal pathology that might not have been evident on other views. The evacuation phase is divided into two subphases: a. b.

Nonstimulated evacuation of the gland and ductal system Stimulated evacuation of the gland and ductal system.

The evacuation phase evaluated under intermittent fluoroscopy for about one minute, while checking for spontaneous clearing of the contrast agent from the gland. A normally functioning, unobstructed gland should be able to clear nearly the entire contrast agent. The second subphase is an evaluation of the glandular response to stimulation using a sialogogue or 2% citric acid drops placed on the tongue and intermittently monitoring the clearing of the contrast from the gland. The second subphase is performed if a significant amount of contrast is still present in the ductal system after the first subphase. The nonclearing or partial clearing of the gland may be due to a stricture, a sialolith or both or an underlying physiologic abnormality. Post-stimulation views of the gland may demonstrate adequate clearing of the ductal system and intraparenchymal collections of contrast. Small 1–3 mm uniformly distributed collections of contrast agent may be seen as a


result of pseudo sialectases whereas irregularly distributed or larger collections can result from abscess formation or tumor necrosis.

Contraindications of Sialography ❍ ❍ ❍ ❍ ❍

Acute salivary gland infections or patients recovering fom acute infections. Malignant lesions involving the salivary gland. Patient is allergic to contrast agent. Patients who have to undergo thyroid function tests during the period of sialography. Pregnancy (high doses of radiation is used especially for fluoroscopy).

One of the more commonly used approaches involves injection of contrast material into the lower joint spaces, referred to as lower joint space or single contrast arthrography. Perforations of the disk or posterior attachment are demonstrated by contrast material simultaneously flowing into the upper joint space as the lower space is injected. Another variation of the technique involves injecting contrast material into both the spaces and viewing the more central portions of the joint with tomography. Because contrast material is in both joint spaces, the outline of the disk is profiled, showing its configuration and position. The outline of the disk can often be enhanced by using double contrast arthrography. This technique involves injecting a small amount of air along with a small amount of contrast material into both joint spaces, producing a thin coat around the periphery of both joint spaces that highlights the disk and the joint spaces.

ARTHROGRAPHY Arthrography involves injection of a radiopaque contrast material into the joint spaces. The space occupied by the disk can then be visualized lying between the layers of contrast material. Dr Fleming Norgaard, in 1947 was the first to successfully use contrast arthrography. But it was in the 1970s that Wilkes and others introduced and popularaized the technique in the United States.

Procedure 1.

2.

Uses of Arthrography ❍

❍

❍

❍ ❍

Arthrography provides information regarding the soft tissue components, specifically the shape and position of the articular disk. It has been demonstrated that with the addition of tomography, the diagnosis of abnormalities in the position and shape of the disk is accurate. Fluoroscopic observation of the injection may reveal the presence of adhesions, perforations and discontinuities in the capsule and provides a dynamic study of disk movements, also any abnormal accumulation of joint fluid may be evident. Synovial fluid sampling (arthrocentesis) and lavage of the joint can accompany the procedure of arthrography. Arthrography assures a correct pre-operative diagnosis of loose bodies (joint mice). An arthrogram can clearly distinguish the synovial changes of an inflammatory arthritis from an internal derangement resulting from meniscal dysfunction.

3.

4.

5.

6.

7.

Types of Arthrography 1. 2.

Single contrast arthrography Double contrast arthrography

8.

The patient is placed on the fluoroscopic table in a lateral recumbent position with the head tilted on the tabletop. This allows the joint to project over the skull above the facial bones in a manner similar to a transcranial radiograph. Under fluoroscopic guidance the posterosuperior aspect of the mandibular condyle is identified with a metal marker. This area is marked with an indelible pen. Local anesthetic lidocaine is infiltrated into the superficial skin. A 0.75- or 1-inch scalp vein needle and the attached tubing is filled with contrast material and care is taken to eliminate air bubbles. Air bubbles may simulate bodies within the joint space. In a direction perpendicular to the skin and X-ray beam, the 23-gauge needle is introduced in a predetermined region of the condyle with the jaw in the closed position. Advancement of the needle is done under fluoroscopic observation to ensure proper positioning. When the condyle is encountered, the patient is instructed to open the jaw very slightly, and the needle is guided by the feel of the posterior slope of the bony condylar margin. On fluoroscopic observation, the needle will appear contiguous with the posterior condylar outline. Approximately 0.4–0.5 ml of contrast material is injected into the lower joint compartment under fluoroscopic guidance. If the contrast is successfully placed into the lower joint space, the opaque material will be seen flowing freely anterior to the condyle in the anterior recess of the lower joint compartment. The needle is then withdrawn and fluoroscopic videotape images are recorded during opening and closing maneuvers of the jaws. Spot radiographs are obtained during the fluoroscopic procedure. 795


Limitations 1. 2.

periosteum of the condyle and as the joint is distended with contrast material. This discomfort is transient in a majority of cases. If persistent joint pain occurs following the procedure, aspirin or acetaminophen and cold compress application to the affected side is recommended.

Direct medial or lateral displacements are difficult to interpret with arthrography. Cannot be used when the disk is severely deformed.

Complications 1.

2.

3.

4.

5. 6.

7.

8.

THERMOGRAPHY

The rare serious complications associated with arthrography include joint sepsis, allergic reaction to the iodinated contrast medium and hemarthrosis. Pain during and after the procedure, extravasation of the contrast medium, disk perforation and transient facial paralysis are less serious complications of arthrography. The radiation exposure to the patient can be significant, depending on the duration of fluoroscopy and the number of tomographic exposures made. The most frequent complication of the technique is the extravasation of contrast medium into the capsule and soft tissues around the joint, causing pain. Nonionic contrast media will be the agents of choice to minimize this discomfort. Parotitis has been reported following arthrography with large needles and cannulas. Some patients experience a vagal reaction, as a result of increased anxiety during the procedure, this can be managed by administering 0.6 mg of atropine intravenously. Intravasation of contrast material infrequently occurs. Epinephrine in a dose of 0.03 ml (1:1000) per 3 ml of contrast material is recommended because there is a risk of an acute hypotensive episode with intravasation of higher doses. Transient facial paralysis may result from a rapid infiltration of lidocaine. Some patients experience a moderate degree of pain as the needle is placed on the

It is also called thermal imaging or infrared imaging. Thermography is a non-invasive diagnostic imaging procedure that detects, records, and produces an image (thermogram) of a patient’s skin surface temperatures and/or thermal patterns (Figures 88 and 89). The procedure uses equipment that can provide both qualitative and quantitative information on the normal and abnormal functioning of the sensory and sympathetic nervous systems, vascular system, musculoskeletal system, and local inflammatory processes. There are presently two recognized techniques of thermal imaging, namely, electronic infrared telethermography and liquid crystal thermography.

Liquid Crystal Thermography Liquid crystal thermography (LCT) utilizes a range of interchangeable ‘screens’ impregnated with cholesteric methylester derivatives that change color as a function of their temperature. The ‘screens’ are placed on the anatomic surface for development. A 35 mm or polaroid picture of the image is taken for later analysis and archiving.

Electronic Infrared Telethermography Infrared telethermography (IRT) equipment incorporates single or multiple infrared detectors that survey the region

Figure 88 37.0 36.2 35.4 34.6 33.8 33.0 32.2 31.4 30.6 29.8 29.0 °C

Two examples of infrared images of the lateral aspect of the face. Courtesy: Prof Francis Ring, Head of Group, Thermography, University of Glamorgan, UK

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Figure 89

38.5° C 38 36 34 32 30 28 26 25.5° C

Infrared and visual image of a subject with an elevated body temperature. The color alarm clearly shows the parts of the head with a temperature higher than 38C

to be studied in two directions simultaneously. The process does not involve any contact with the surface of the skin.

Patient Preparation ❍

❍ ❍

❍ ❍ ❍

The patient should be instructed not to use lotions, creams, powders, makeup, deodorants or antiperspirants on the body area to be imaged on the day of the examination. The body areas included in the image should not be shaved within 4 hours of the examination. No physical therapy, ultrasound treatment, acupuncture or hot/cold pack should be used 24 hours before the examination. No exercise should be done 4 hours before the examination. Patient should not bathe for an hour before the examination. The area to be imaged should remain completely uncovered of clothing or jewelry.

Procedural Requirements The room should be of adequate size to maintain a uniform temperature. A room approximately 8 10 feet size is adequate to meet these requirements. During the examination, the patient should be positioned relatively equidistant and adequately spaced from each wall. The room should be carpeted. Curtains may be used to prevent outside infrared radiation from entering the room. The room

must be free from drafts. Windows and doors should be adequately sealed to prevent airflow in the area where the patient is positioned. Incandescent lighting should not be used during the examination due to the amount of infrared radiation produced. Standard fluorescent lighting is adequate. The temperature range in the room should be maintained between 18 and 23C. Room temperature transitions during the course of an examination must be gradual so that steady state physiology is maintained and all parts of the body can adjust uniformly. The temperature of the room should not vary more than 1C during the course of a study. The humidity of the room must also be controlled such that there is no air moisture build up on the skin, perspiration, or vapor levels that can interact with radiant infrared energy.

Indications Merla et al (2004) assessed the use of functional infrared imaging in the diagnosis of the myofascial pain. They concluded that functional infrared imaging seemed to distinguish healthy subjects from the patients suffering myofascial pain. Gratt and Anbar (1998) summarized the following clinical applications for thermography in dentistry: 1. 2. 3. 4.

Evaluation of atypical odontalgia Diagnosis of chronic orofacial pain Assessment of TMJ disorders (internal derangement of TMJ) Assessment of inferior alveolar nerve deficit.

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SECTION

XI

Processing of Radiographs and Radiographic Interpretation 29 Latent Image Formation 30 Processing of Radiographic Films 31 Radiographic Faults

801 803 812

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CHAPTER

29

Latent Image Formation Ravikiran Ongole, Praveen BN

Formation of a visible radiographic image is a three-stage process:

2.

1.

3.

Interaction of X-ray beams with the object of interest.

Interaction of the information carrying X-ray beam with the photosensitive silver halide crystals in the film (latent image formation). Chemical action of developing solutions which convert the latent into visible image.

Figure 1 Silver ion

Bromide ion

Sensitivity site X-ray photon

Silver bromide

ee-

X-ray film Interstitial silver ions

e- e- e e-

e-

eee- e e-

Latent image formation. Courtesy: Dr Jaideep Shekhar

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Section XI – Processing of Radiographs and Radiographic Interpretation

FORMATION OF LATENT IMAGE To understand the formation of latent image, one needs to know the composition of an intraoral film. A dental film comprises of an emulsion suspended in gelatinous vehicle that is coated onto a plastic supporting base. The emulsion is composed mainly of photosensitive silver bromide crystals and to a lesser extent silver iodide crystals and very small amounts of free silver ions interspersed in the crystal lattice (interstitial silver ions), iodide ions (produce the physical irregularity in the array of silver and bromide ions) and traces of sulfur compounds, which bind to the surface of the crystals. These sulfur compounds along with the physical irregularities on the surface of the silver halide crystal form the latent image sites.

Steps in Latent Image Formation (Figure 1) 1. 2.

802

X-ray photons pass through the object of interest and carry information to the film. X-ray photons strike the film and interact with the bromide ions primarily (bromide ions are about oneand-a-half times larger in diameter when compared to silver ions).

3.

4.

5. 6.

7.

As a result of Compton and photoelectric effects, electrons are displaced from the bromide ions producing high-speed electrons (recoil electron) and scattered X-ray photons. These recoil electrons travel within the silver halide crystal creating additional bromine atoms, scattered photons and secondary recoil electrons until their energy is dissipated. These recoil electrons get trapped in the latent image site and impart a negative charge to these sites. The free interstitial silver ions which are positively charged are drawn toward the negatively charged latent image sites. Within these sites the silver ion is neutralized resulting in an atom of sliver that gets deposited.

This process repeats multiple times at every single latent site leading to the further deposition of silver atoms which ultimately gives rise to the ‘latent image’. Once these radiographs are placed in the developer solution, the silver atoms in the latent image sites are converted to black metallic silver grains and the unexposed silver halide crystals are removed by the clearing agent in the fixing solution resulting in the formation of a ‘visible image’.

CHAPTER

Processing of Radiographic Films Ravikiran Ongole

Daylight Processor Self-developing Film

Techniques of Film Processing ➧

Manual Processing of Films Darkroom Visual Method Time–Temperature Controlled Method

Following exposure to radiation, the latent image formed on the film is converted to a visible image by a technique referred to as film processing. Radiographic films have been traditionally processed in a darkroom. However, over the years, techniques such as daylight processing, automatic processing and self-developing films have eliminated the need to use a darkroom for processing films.

30

➧

Automatic Processing Working Mechanism Composition of Processing Solutions

Ideal requirements 1.

2.

Darkroom should be spacious enough to permit at least one person to work comfortably and should measure at least 4 ⫻ 5 feet in dimension (Figure 1). An ideal darkroom should have a doorless maze pattern (Figure 2A) or a conch shell design (Figure 2B) to prevent entry of light into working area.

Techniques of Film Processing 1.

2.

Manual processing ❍ Time–temperature method (darkroom technique) ❍ Visual method (darkroom technique) ❍ Daylight processing (darkroom not required) ❍ Self-developing films (darkroom not required) Automatic processing.

Figure 1

MANUAL PROCESSING OF FILMS Traditionally radiographic films are processed in a darkroom. Before one learns the art of radiographic film processing, it is essential to be familiar with the designing of the darkroom and its contents.

Darkroom Radiographic films are sensitive to X-rays and visible light. In order to prevent exposure of the films to visible light it is necessary to process the exposed radiograph in a room specially designed to keep away visible light.

Photograph of a compact darkroom of adequate size

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Figure 2 A

B

Conch shell design

Working area

Doorless maze pattern Working area

(A) Illustration showing the doorless maze pattern of a darkroom. (B) Conch shell design for the darkroom. Courtesy: Dr Jaideep Shekhar

Figure 3

Figure 4

Photograph showing the contents of the darkroom such as the processing tanks, wash basin, drying racks, film holders and safe light

Darkroom infrastructure (Figure 4) An ideal darkroom should contain the following:

Light tight door with a locking mechanism for the darkroom

3.

804

In the event of having a door it should be light tight and should have provisions for locking to prevent accidental opening of the door, which might unnecessarily expose the image receptors to visible light (Figure 3).

1. Processing tanks (master tank with developer and fixer tanks) 2. Safe light 3. Visible light source (tube lights) 4. Working area (to load extraoral film cassettes and unwrap films) 5. Dryer 6. Thermometer and stop clock 7. Storage facility (to store unexposed films)

Chapter 30 – Processing of Radiographic Films

Figure 5 A

B

(A) Master tank with water and containing the developer and fixer solution tanks. (B) Master tank covered with a lid when not in use

8. Exhaust and appropriate ventilation 9. Drying racks 10. Processing solution stirrer and film retrievers. Processing tank The film processing tank is commercially available and made of inert plastic (RinnTM) or can be made custommade out of stainless steel or bricks and mortar (to prevent reaction with the chemicals of the processing solutions). The processing tank should be placed at a convenient height and away from the working area where films are unwrapped or loaded into cassettes. Commercially available tanks comprise of a large master tank and two smaller removable inserts (for the developer and fixer solution) which are placed within the master tank that contains water (Figure 5A). Many of the commercially available master tanks measure 8 ⫻ 10 inches and the smaller tanks hold about 9 liters of the fixer and developer solution. The master tank holds either running water or water stored at room temperature. The temperature of the water in the master tank will help regulate the temperature of the developer and fixer. The water contained in the master tank is also used for rinsing the film during processing. A lid should always be placed over the tank to minimize the oxidation of the processing solutions by atmospheric oxygen and evaporation (Figure 5B).

the films. However, the visible lights may be switched on once the films are placed in the fixer tank. The safe light should ideally be 15 W bulb in the orangered-yellow spectrum of light (Figure 5B) as these colors have the longest wavelength and low penetrating power (X-rays are highly sensitive to blue and green colors). A red GBX-2 filter may be placed over the safe light. One or two safe lights may be used based on the size of the darkroom. One safe light over the processing tanks (ideally on the right hand side or the fixer solution side of the tank) and one over the working area (place where the films are loaded). The safe lights should ideally be placed 4 feet above the working area and processing tanks (Figure 6B). Floating thermometer and stop clock A floating thermometer (Figure 7A) and stop clock are used for the time–temperature method of processing films. The thermometer helps to assess the temperature of the processing solutions so that the duration for which the film should be developed is known. The thermometer is left floating in the water in the master tank prior to the processing (Figure 7B). Alcohol containing thermometer is preferred as mercury containing thermometers may contaminate the processing solutions in the event of a breakage. The stop clock helps to set the exact time for the developing procedure. Drying racks and film hangers

Safe light and visible light illumination Visible light illumination can be in the form of ceiling or wall mounted light source (Figure 6A). However, care should be taken to ensure that these tube lights are switched off during loading the films into cassettes or while processing

Drying racks should strategically be located above the washing area in the darkroom. Once the films are removed from film hangers after drying, the empty hangers should be thoroughly rinsed and left to hang dry over the drying racks (Figure 8). 805


Figure 6 A

B

(A) Photograph showing the visible light mounted on the ceiling. (B) 15 W safe light in the orange-red spectrum of light

Figure 7 A

B

(A) Floating thermometer. (B) Photograph showing the floating thermometer in the master tank containing water

Presence of any remnant fixer solution remaining on the hangers may result in faulty radiographs in the form of light spots. Water droplets on the hangers may produce watermarks on the films, which might obscure diagnostic details in the radiographic image.

Figure 8

Dryer cabinet Wet films following the processing can be dried effectively using cabinet driers, which help in circulating warm air (produced by heaters) around the films thereby hastening the drying process (Figure 9). However, films should not be placed close to the heat source in the cabinet drier as they can get distorted. Alternatively, wall mounted fans over the drying racks can be used. Cabinet driers may also be placed outside the darkroom. Processing technique Film hangers shown drying after use

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Time–temperature method of processing films is the most ideal method of processing films manually. However,


Table 1

Figure 9

Cabinet film dryer

when the facility of temperature controlled processing is not available, the visual method can be employed.

Visual Method In this method, there is no predetermined time for which the film is placed in the developer solution. The exposed film is placed in the developer solution and taken out at regular intervals and examined under safe light for the most calcified/radiopaque structures to be evident. Appearance of radiopaque structures (like the enamel cap, restorations, artificial crowns) indicates the end point of developing time. At this juncture, films are taken out of the developer solution, rinsed in water and placed in the fixer solution. Disadvantage Quality of images is not reproducible as the technique is very subjective.

Time–Temperature Controlled Method The time–temperature method for processing films ensures optimal film quality. Steps in processing the film 1. Ensure that the levels in the developer and fixer tank are adequate (the entire film should submerge into the solutions). 2. Make sure that the solutions are not too old. Depleted developer solution appears brownish black. On an average developer and fixing solutions are changed every 15 days (taking into account that approximately 30 intraoral and 5 extraoral films are processed per day).

Time–temperature reference chart

Temperature of the processing solutions (Fahrenheit)

Development time (minute)

68

5

70

4.5

72

4

76

3

80

2.5

3. Use a separate stirrer for the developer and fixing solutions and stir the solutions each day in the morning. Stirring will help even distribution of the contents of the solutions and may help in maintaining a constant temperature throughout the solutions. 4. Generally the metal insert containing the developer solution is placed toward the left hand side of the master tank and the fixing solution is placed on the right hand side of the master tank (with the personnel facing the master tank). However, as the inserts are generally not labeled it is wise to check the solutions before processing the films. This can be done by dipping a finger into one of the tanks and gently rubbing the fingertips. The developer solution will feel soapy as it is alkaline in nature. 5. Once the solutions are stirred evenly, the temperature of the solutions is assessed by placing the floating thermometer in the water bath. For intraoral films the manufacturer specified duration of developing can be used. The following time–temperature reference chart may be used (Table 1). 6. Film hanger is selected and ensured that it is dry and does not contain any trace of water or processing solutions. The film packet is opened in the darkroom and the film is clipped onto the hanger. The film thus clipped is drawn out of the film packet thereby ensuring that the film does not come in contact with the fingers of the operator, which might obscure diagnostic details on the resultant radiographic image. 7. Once the film is placed in the developing solution, the stop clock is started. Initially the hanger is gently agitated for a few seconds to eliminate any air bubbles on the film. Later the hanger is placed in the developer tank for the predetermined time based on the temperature of the processing solutions. After the preset time, the hanger holding the film is removed gently and all excess developer solution clinging onto the film is let to drain away into the master tank by holding the hanger over the master tank containing water for a couple of seconds. 8. The film is then placed into the master tank containing water for about 30 seconds. The hanger holding the film should be agitated gently so that all the excess 807


9.

10.

11. 12.

developer solution is removed from the film (this halts the developing process) and the fixer solution is not contaminated by the developer solution (contamination of the fixer solution causes the acidic fixer solution to be neutralized by the alkaline developer solution). Once the films are rinsed, they are placed in the fixer solution for about 4 minutes. The hanger holding the film is agitated at regular intervals to bring the fixer solution to evenly contact the film. After the films are taken out of the fixer solution they are held under running water for about 5 minutes ensuring that all the surfaces of the film come under the running water and remnants of the processing solutions are totally washed away. The film is gently shaken to remove water drops clinging onto the surface of the film. The hanger holding films are then dried using a fan or a cabinet dryer. Dried films are placed in a film mount before interpreting the films using an illuminated viewer box.

Daylight Processor It is essentially a plastic housing with a 15 W bulb. The housing is just large enough to cover three plastic bowls that contain developer, water and fixer solutions. It is like a make-shift arrangement for a darkroom especially for dental clinics and mobile dental clinics. The operator can slide his/her hands via two sleeves provided at the sides of the plastic housing and then unwrap the film. A plastic, tinted see-through lid at the top of the housing enables the operator to see within the plastic case without causing unnecessary light exposure (Figure 10A, B). Under safe light conditions, provided by the 15 W orange-red bulb, the film can be unwrapped, helped with

a single film holder and processed traditionally by dipping the film first into the developer, water and finally the fixing solution. Once processed, the film can be washed outside the housing under running water and subsequently dried.

Self-developing Film These have also been referred to as rapid autodeveloping films. It is essentially a one-piece soft plastic (polyvinyl chloride) pouch designed such that the film is located at one end and a monobath of developer and fixer is located at the other end. Both the ends are connected via a narrow corridor that helps in carrying the processing solutions to the film (Figure 11). During the exposure, the film end is positioned in the mouth with the other end hanging outside the mouth. Once the exposure is made, the pouch is first washed to remove the patient’s saliva. Then the film is developed by holding the monobath end of the pouch upright and rolling it down until the processing chamber ruptures and empties into the corridor. Continuing to roll the pouch ensures that all of the monobath solution travels toward the film end. The user continues to hold the pouch upright and massages the monobath around in the film end of the pouch Figure 11

Self-developing film

Figure 10 A

B

(A) Daylight processing unit. (B) Small cups filled with processing solutions within the daylight processor

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for 50 seconds. When development is complete, the pouch is turned upside down and the monobath is massaged back to its original location at the opposite end. The film end of the pouch is then opened by pulling apart the tabs and the film is removed. The film is rinsed under water to remove the remaining monobath solution.

Circulation-filtration system (Figure 15) The roller-transport system squeezes the chemicals into and out of film emulsion, providing an agitating action, which promotes even processing and increases the speed

Figure 13

AUTOMATIC PROCESSING Automatic film processing refers to the processing of radiographs using machines specifically designed for that purpose. Most automatic processors are not universal (there are separate machines to process extraoral and intraoral films). These processors have inherent limitations with regard to the need for regular maintenance and cost (Figure 12).

Working Mechanism The automatic processor is made up of five basic systems— the transport system, the circulation and filtration system, the replenishment system, the tempering system, and the dryer system.

Roller mechanism within the automatic processor

Figure 14

Roller-transport system (Figure 13) The roller-transport system is composed of a feed tray, a main drive, and a number of rollers called crossovers and racks. As the film is placed in the feed tray, two feed rollers draw the film into the machine (Figure 14). The film moves circularly through a crossover and vertically down in the developer by means of a series of rollers. It moves the same way through the rest of the chemicals.

Film placement slots within the automatic processor

Figure 12

Figure 15

Intraoral film automatic processor

Processing solutions and the roller mechanism within the automatic processor

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of reactions. A circulation-filtration system is used to boost this action. The circulation pump recirculates the solutions through filters, keeping the chemicals properly mixed and clean as well as in a state of agitation.

helps in converting the silver ions into metallic silver at the latent image sites. However, in this process phenidone gets oxidized and becomes inactive. Hydroquinone in the developer solution reduces the oxidized phenidone thereby helping in its reactivation.

Replenishment system As each film passes through the automatic processor, the chemicals are changed slightly. To offset the resulting deficiencies, new developer and fixer in measured amounts are pumped into the solutions via the replenishment tanks attached to the processor. These tanks should be checked weekly and refilled periodically. Tempering system To maintain the desired temperature of the developer and fixer, a heating device and automatic thermostat are used. Water is passed through a mixing valve, so that it is 4⬚F or 5⬚F below the desired temperature, and then heated to the desired temperature by the heating element in the machine. The wash water temperature is controlled by a mixing valve, which mixes the hot and cold water. A thermometer gauge is located between the mixing valve and the wash tank near the mixing valve. Air-dryer system To dry the film, there is a heater to heat the air and a blower to direct the air. An efficient exhaust system ensures that the warm, moist air is removed and only hot, dry air is directed over the films as they move through the rollertransport system.

Composition of Processing Solutions Processing solutions are composed of a developer and fixer solution. Developer solution Function To reduce the silver ions in the exposed crystals of silver halide (latent image) to specks of black metallic silver (diagnostic, visible image). Composition Developer solution contains four constituents, which are dissolved in water. They are: ❍ ❍ ❍ ❍

Developer Activator Preservative Restrainer.

Developer Function It converts the exposed silver halide grains to black metallic silver. It is made up of phenidone and hydroquinone. Phenidone acts as an electron donor and 810

Activator Function Activators help in maintaining the alkaline pH of the developer solution and cause the gelatin of the film to swell thereby helping the diffusion of the developing agents into the emulsion and reach the silver halide crystals. Developer solutions are active at an alkaline pH (approximately 10). This alkaline pH is achieved and maintained by the addition of alkaline agents such as sodium or potassium hydrozide and buffers like sodium carbonate, sodium hydroxide and sodium metaborate or tetraborate. Preservative Function It prevents the oxidation of the developer solution by atmospheric oxygen. It also combines with the oxidized developer solution (appears brown) and forms a colorless soluble compound. The preservative is an antioxidant and is usually sodium sulfite. Restrainer Function It acts as an antifog agent. It minimizes/ restrains the development of unexposed silver halide grains. Potassium bromide or sodium bromide is used as the restrainer in the developer solution. Fixing solution Functions Fixing solution helps in removal of the undeveloped silver halide grains from the emulsion. If the unexposed silver halide grains remain on the film the radiographic image will appear black and will result in a nondiagnostic image. Composition The fixer solution contains four constituents, which are dissolved in water. They are: ❍ ❍ ❍ ❍

Clearing agent Acidifier Preservative Hardener.

Clearing agent Function Dissolves and removes the unexposed silver halide crystals from the emulsion of the film. The removal of the unexposed crystals takes place at a controlled slow pace, however fixing for a prolonged time can lead to a gradual loss of film density (silver grains dissolve in acetic acid of the fixing solution).


Aqueous solution of ammonium thiosulfate is used as the clearing agent. Acidifier Function The acidifier has two important functions. It helps in the diffusion of ammonium thiosulfate into the emulsion and the exit of silver thiosulfate complex from the emulsion. It inactivates remnants of developer solution that is present over the film thereby halting the developing process of any unexposed silver halide crystals during the process of fixing. The acidifier used is acetic acid buffer system (pH of 4–4.5). Preservative Function It prevents the oxidation of the clearing agent. It also combines with the oxidized developer solution, which is carried over to the fixing solution and thereby preventing staining of the film. The preservative used is sodium sulfite or ammonium sulfite. Hardener Function The hardening agents combine with the gelatin and prevent damage to the gelatin during handling of the film. It also reduces the swelling of the emulsion thereby

limiting water absorption, which helps in drying the film faster. Aluminum salts are used as hardeners. Comparison between manual and automatic processing Manual processing

Automatic processing

Darkroom is required

Use of darkroom eliminated

Technique sensitive

Non-technique sensitive as the films are processed automatically

Direct exposure to hazardous processing chemicals

No direct exposure to hazardous chemicals

Films need to be manually dried

Films are dried automatically

Processing solutions need to be manually prepared

Processing solutions are available readymade

Longer time for processing

Short processing time

Negligible maintenance—need to clean the tanks and replace fresh solutions every 2–3 weeks

Regular maintenance—need to clean rollers and servicing gear mechanism

Relatively inexpensive (not considering the construction of a darkroom)

Expensive

Universal for intraoral and extraoral radiographs (provided the tanks are large enough)

Separate processors are required for extraoral and intraoral radiographs

Penny Test Penny test or coin test is used to assess the safe light condition in the darkroom. It is a known fact that radiographic film is sensitive to visible light and X-rays. Excessive exposure to safe light or an improper safe light condition can lead to exposure of the film resulting in film fog. Procedure 1. 2. 3.

In the darkroom, an exposed film is removed from the film packet and placed on the working bench in an area where films are usually unwrapped. A coin is placed on the film and left in place for a few minutes (usually the time it takes for a film to be unwrapped and clipped onto a film holder for processing. Process the film as usual. If the image of the coin is seen on the processed film then the darkroom does not have optimum safe lighting.

Test to Determine the Quality of the Processing Solutions Over a period of time the processing solutions deteriorate and need to be changed. On an average the processing solutions need to be changed every 2 weeks (depending on the number of films processed per day). A practical method of evaluating the solutions can be done by exposing a dental radiograph and using freshly prepared solution to process this film. The film can then be used as a reference film. All successive films processed can be compared with this film for contrast and density. Loss of image contrast and density is an indicator for solution change.

811

CHAPTER

31

Radiographic Faults Ravikiran Ongole, Praveen BN

➧ Errors in Film Storage and Handling

➧

Film Fog Emulsion Peel and Scratched Film Dark Spots or Lines Static Electricity Artifact Nail Marks or Kink Marks ➧

➧

Artifacts

A radiograph is considered ideal when it is dimensionally accurate, covers the area of interest completely and has optimum density and contrast. When the above criteria are not met the radiograph is termed faulty. A faulty radiograph is non-diagnostic and necessitates retaking the radiograph which leads to unnecessary patient exposure.

ERRORS IN FILM STORAGE AND HANDLING

Causes of faulty radiograph

Film Fog

Radiographic faults can occur at any stage in the radiographic process, right from handling and storing of films to the processing. The causes for radiographic faults can be categorized as:

The overall appearance of the radiograph is dark. The radiographic image will show decreased image contrast and detail and as some authors believe they appear as though the radiographs are being viewed through a fog thereby obscuring the image (Figure 1).

❍ ❍ ❍ ❍ 812

Blank Radiograph Dark Radiograph Light Radiographs Film Fog Insufficient Contrast Yellow or Brown Stains Partial Image Blisters on the Film White Spots Dark Spots on the Radiograph Light Spots on the Radiograph Emulsion Wash Away Reticulation of Emulsion Hyporetention Dyschroic Fog No Image/Blank Radiograph

Errors in Film Placement and Projection Technique Herring Bone Effect, Tyre Mark Pattern, Raised Diamond Markings/Knurled Effect Cone Cut Slanting of the Occlusal Plane Apical Ends of the Teeth Not Imaged (Partial Image) Crown Portion of Teeth Not Imaged (Partial Image) Overlapped Image Fore-shortened Image Elongated Image (Total) Elongated Image (Partial) Blurred Image

Errors in Exposure Parameters and Processing Technique

Errors in film storage and handling Errors in film placement and projection technique Errors in exposure parameters and processing technique Artifacts.

These can occur prior to the radiographic exposure and after the processing especially before the film is completely dry.

Causes ❍

Films stored at high temperatures and humidity

Chapter 31 – Radiographic Faults

❍ ❍

Outdated films Films exposed to extraneous radiation.

Ideal film storage temperature is between 50⬚F and 70⬚F (10–20⬚C) and between 30% and 50% relative humidity. Any increase is known to cause increased sensitization of the film emulsion. The expiry date of the film packets have to be checked and it is also recommended that the radiology unit stocks only sufficient number of film packets that can be used within 2 months’ time. Extraoral films should be stored in a vertical orientation to prevent pressure artifacts.

Emulsion Peel and Scratched Film Emulsion is coated onto the plastic supportive base of the film and it adheres to the base via a coat of adhesive agent.

However, during the developing process, the emulsion is rendered soft to aid in the rapid diffusion of the developing agents into the emulsion and reacts with the silver halide grains. However, the hardeners in the fixing solution shrink and harden the gelatin to prevent its damage. White lines appear when the soft film emulsion is removed from the film base by sharp objects. Causes ❍

Wet film in contact with finger nails or other sharp objects such as film clips (Figure 2A, B). ❍ Placing wet films on unclean surfaces. ❍ After processing, films must not come into contact with each other until completely dry as the wet emulsions can stick together and peel off the emulsions when they are separated. Care must be taken when placing the film holder in the processing solutions and drier. Avoid contact with other film hangers and with the tank walls.

Figure 1

Dark Spots or Lines Cause Finger print contamination. ❍

Dark finger marks: from improper handling of the film (holding the film with greasy fingers on the surface of the film, especially when the fingers are contaminated with developer solution). ❍ Clear finger marks or white fingerprint marks can be caused by fixer solution or oily substances on the fingers that prevent the emulsion from developing. Fogged radiograph

Films should be held by the edges only.

Figure 2 A

B

(A) Emulsion peel. (B) Scratched film

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Figure 3

Figure 4

Static electricity artifact on a panoramic film Crescent shaped nail mark

Static Electricity Artifact Causes Static electricity artifacts are formed due to the build-up of electrons in the emulsion. They are frequently caused by low humidity/dry weather or static producing objects such as synthetic materials used in uniforms. Moreover, when films are removed from the film packet or the cassette too rapidly in a dry atmosphere, a small charge of electricity can be released producing these artifacts. Static artifacts have two common appearances: tree like and smudges. Tree like artifacts (Figure 3) are produced when films are unwrapped rapidly and appear as black lines running across the film and smudge static electricity is produced by polyester clothing and appear as black smudges on the film.

Nail Marks or Kink Marks

Figure 5 A

B

Appear as a crescent shaped radiolucent finger nail marks (Figure 4). Cause Excessive bending of the film.

ERRORS IN FILM PLACEMENT AND PROJECTION TECHNIQUE Herring Bone Effect, Tyre Mark Pattern, Raised Diamond Markings/Knurled Effect A lead foil is placed within every intraoral radiographic film packet to prevent unnecessary exposure to surrounding structures from the residual X-ray beam and also protects the film from back scatter or secondary radiation that may result in film fog. 814

(A) Radiograph showing the tyre mark or raised diamond pattern. (B) Knurled pattern on a nut

Though the term ‘herring bone pattern’ is widely used, many of the new film packets do not display this pattern on the lead foil, rather the tyre mark (Figure 5A) or knurled pattern (Figure 5B) are common.


Cause

Slanting of the Occlusal Plane

Wrong side (opposite side) of the film exposed to radiation.

A part of the radiographic image appears blank on the radiograph (Figure 6), which confirms to the circular shape of the position indicating device (PID).

The radiographic film should ideally be held in the mouth using an appropriate film holder which stabilizes the film during exposure. Slanting of the occlusal plane is usually seen when the patient attempts to stabilize the film with a finger. Ideally when the film is placed in the mouth the edge of the film should be parallel to the occlusal plane.

Causes

Cause

❍ ❍

Improper placement of the film.

Cone Cut

Improper placement of film Improper placement of the PID (film partially outside the area covered by the PID).

Apical Ends of the Teeth Not Imaged (Partial Image) Ideally the tooth to be imaged should be positioned in the center of the film. Also care should taken during film placement that at least 2 mm all around the tooth of interest should be visible in the resultant radiograph.

Figure 6

Causes ❍ ❍

Insufficient vertical angulation Film not placed sufficiently deep into the palatal vault (Figure 7A) or lingual vestibule ❍ Patient opens mouth just short of the exposure (Figure 7B).

Crown Portion of Teeth Not Imaged (Partial Image) Cone cut

When the film is placed against the tooth in bisecting angle technique, it should be ensured that the edge of the

Figure 7 A

B

(A) Partial image due to improper film placement resulting in the apices of premolars cut-off. (B) Partial image caused due to opening of the patient’s mouth during exposure

815


Figure 8

Film placed too apically resulting in crowns not imaged

film should be placed about 2 mm beyond the cuspal tips or incisal edges of teeth.

Figure 9

Overlapped proximal aspects of teeth due to improper horizontal angulation

Figure 10

Cause Improper placement of film (Figure 8).

Overlapped Image For all practical purposes, the central beam of X-rays should be directed perpendicular to the film and tooth (in paralleling technique) and to the imaginary bisector bisecting the long axis of tooth and long axis of film (in bisecting angle technique) thereby passing through the interproximal contacts between teeth. Causes ❍ ❍

Improper horizontal angulation (Figure 9) Double exposure.

If an already exposed film is re-used by mistake, then the resultant radiograph will show two overlapped images (Figure 10).

Overlapped images due to double exposure

Figure 11

Fore-shortened Image The radiograph exhibits unusually short images (Figure 11). Causes ❍

Increased vertical angulation (bisecting angle technique) ❍ Film not placed parallel to the long axis of the tooth (paralleling technique).

Elongated Image (Total) Unusually long radiographic images are seen (Figure 12). 816

Fore-shortened images


Causes ❍ ❍

Decreased vertical angulation (bisecting angle technique) Film not placed parallel to the long axis of the tooth (paralleling technique).

Elongated Image (Partial) Only part of the image appears elongated. Cause Excessive bending of the film (Figure 13).

placed in the mouth due to the curvature of the palate or lingual arch such as canines, third molars or mandibular anteriors. Receptors can be flexed but should never be bent as that causes creasing of the emulsion, which in turn compromises the quality of the image. Total blurring occurs either due to the movement of the patient or the X-ray tube head (Figure 14A). It is wise to wait for a few seconds after adjusting the X-ray tube head before making an exposure. Also, patients should be instructed to remain still during the exposure. Causes ❍

Blurred Image Blurred images can either be total or partial. Partial blurring occurs when the film gets bent excessively when

Movement of the film or patient during the exposure (image totally blurred) ❍ Excessive bending of the film (image partially blurred, Figure 14B).

Figure 13 Figure 12

Partial elongation due to bending of film during film placement

Elongated images

Figure 14 A

B

(A) Total blurring of image. (B) Partial blurring of image

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Figure 15

Figure 17

Partially blank radiograph

Light radiograph

Figure 16 b.

Processing errors Developer temperature too high Film developed for a longer time Concentration of the developer too high Accidental exposure to light Improper safe lighting.

❍ ❍ ❍ ❍ ❍

Light Radiographs (Figure 17) Causes a.

Exposure errors Insufficient mA, insufficient kVp, insufficient exposure time ❍ Film packet placed with the wrong side facing the X-ray source ❍ Increased film source distance Processing errors ❍ Placed in the developer solution for a short duration of time ❍ Temperature of the developer solution too low ❍ Depleted developer solution ❍ Diluted or contaminated developer solution ❍ Prolonged fixation. ❍

Dark radiograph

ERRORS IN EXPOSURE PARAMETERS AND PROCESSING TECHNIQUE

b.

Blank Radiograph Causes ❍ ❍

Unexposed film (Figure 15) Exposed film dipped into the fixer solution before it was placed into the developer solution.

Dark Radiograph (Figure 16) Causes a.

Exposure errors Excessive milliampere (mA), excessive kilovolt peak (kVp), excessive exposure time ❍ Insufficient film–X-ray source distance

❍

818

Film Fog Causes ❍ ❍ ❍

Improper wattage of the safe light Prolonged exposure of the film to safe light Safe light not at a proper distance from the working place ❍ Light leaks from cracked safe light filters/light from doors and ventilators.


Figure 18

Figure 19

Yellow/brown stains

Insufficient Contrast Causes ❍ ❍

Blisters on the film

Figure 20

Underexposed to radiation Insufficient developing time.

Yellow or Brown Stains (Figure 18) Causes ❍ ❍ ❍ ❍ ❍

Film inadequately fixed Depleted developer solution Depleted fixer solution Film inadequately washed in water Contaminated processing solutions.

Partial Image

White spots

❍

Cause Part of the film not immersed into the developer solution.

These can be avoided by gently agitating the film holders in the processing solutions.

Dark Spots on the Radiograph

Blisters on the Film

Causes

Causes

❍ ❍

❍ ❍

Air bubbles on the film while developing Temperature difference between the developer and fixer solutions (Figure 19) ❍ Increased acidity of the developer solution.

White Spots (Figure 20) Causes ❍

Air trapped on film surface after the film is placed in the processing solutions, air bubbles prevent the chemicals from affecting the emulsion in that area.

Excessive bending of film, fingerprints Film contaminated with the developer solution before the actual processing ❍ Film in contact with another film or tank walls during the fixing procedure.

Light Spots on the Radiograph (Figure 21) ❍

Film contaminated with the fixer solution before the actual processing (remnants of fixing solution present on the hangers for processing will cause this artifact). ❍ Film in contact with the tank wall or another film during the developing process. 819


Figure 21

Figure 23

Light spots on the radiograph

Yellow stain in the film due to hyporetention

Figure 22 Causes ❍ ❍

Inadequate washing Remaining thiosulfate from fixer solution.

Dyschroic Fog Fogging of the radiograph, characterized by the appearance of a pink surface when the film is viewed by transmitted light and a green surface when the film is seen by reflected light. Cause Reticulation of the emulsion

Emulsion Wash Away Radiograph with part of the emulsion lost due to a prolonged washing.

Reticulation of Emulsion Cause Reticulation of emulsion results when a film is subjected to a sudden temperature change between the developer solution and the water bath (Figure 22).

Hyporetention It appears as a yellowish stain on the radiograph that is processed (Figure 23). 820

Exhaustion of the acid content of the fixing solution (incomplete fixation).

No Image/Blank Radiograph Since none of the X-rays reach the film to form the latent image, all the unexposed silver halide grains are removed by the clearing agent resulting in a blank radiograph (Figure 24). Causes ❍

Mechanical problems such as electrical failure, failure to turn on the machine ❍ Improper alignment of the PID or the film.

ARTIFACTS An artifact is a structure or radiographic appearance that is normally not present in the radiograph and is produced


Figure 24

Blank radiograph

by artificial means. It might be considered as foreign body image on the radiograph. The common artifacts are metallic objects in the path of the X-ray beam such as jewelry (Figure 25A, B), dental appliances (Figure 25C, D), etc. or placement of the finger between the X-ray tube and the film (such as using the finger to stabilize the film in the mouth) resulting in a phalangioma (Figure 25E). Prior to taking a radiograph, patients should be instructed to remove all removable metallic objects such as jewelry, prosthodontics appliances (removable partial and complete dentures), spectacles, hair clips, etc. that are in the area to be imaged. These foreign objects may superimpose over image and obscure the findings. Thyroid collars or lead aprons may also be imaged on radiographs.

Figure 25 B

A

D

C

E

(A) Nose stud artifact. (B) Hair clip, nose stud and earrings artifacts. (C) Intraoral appliance. (D) Cast partial denture. (E) Phalangioma

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SECTION

XII

Radiographic Landmarks

32 Intraoral Radiographic Anatomical Landmarks 33 Extraoral Radiographic Landmarks 34 Site Selection, Evaluation and Imaging for Dental Implants

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CHAPTER

Intraoral Radiographic Anatomical Landmarks

32

Ravikiran Ongole

➧ Landmarks Common to Both the Maxillary and

➧

Landmarks Unique to the Maxillary Intraoral Periapical Radiograph

➧

Landmarks Unique to the Mandibular Intraoral Periapical Radiograph

Mandibular Radiographs Teeth Periodontal Ligament Space Alveolar Bone

During the process of interpreting a radiograph the radiologist is expected to identify normal radiographic anatomy, thereby distinguishing normal features from pathology. These normal radiographical anatomical landmarks are unique to each area of the maxilla or mandible and appear either radiopaque or radiolucent. They may be used to identify a specific area of the jaw. For example, the intermaxillary suture is unique to the radiographs of the maxillary central incisors, mental foramen is typically associated with the radiographs of the mandibular premolars etc. On occasions, these landmarks may exhibit some minor variations (such as a bifid mandibular canal) or may not be very evident on a faulty radiograph. The landmarks discussed here are those that are seen in intraoral periapical radiographs.

Teeth Enamel cap, dentin, cementum, pulp. Enamel appears almost snow white and is seen extending from the neck of the tooth, i.e. the cementoenamel junction from one side to the other covering the tooth like a cap (enamel cap). It is the most mineralized structure on the radiograph (90% mineralized) and appears more radiopaque than other structures (Figure 1). Dentin is seen as homogenous radiopacity (less radiopaque than enamel as it is 75% mineralized) and radiographically has the density of bone.

Figure 1

Intraoral radiographic landmarks 1. 2. 3.

Landmarks common to both the maxillary and mandibular radiographs Landmarks unique to the maxillary radiograph Landmarks unique to the mandibular radiograph.

LANDMARKS COMMON TO BOTH THE MAXILLARY AND MANDIBULAR RADIOGRAPHS ❍ ❍ ❍

Teeth—enamel cap, dentin, cementum, pulp Periodontal ligament space Alveolar bone—lamina dura, alveolar crestal bone, marrow spaces and trabecular bone.

Radiograph showing enamel, dentin and pulp. Enamel is the most radiopaque and pulp is radiolucent

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Section XII – Radiographic Landmarks

Figure 2

Dental papilla enclosed by the radiopaque bony crypt in a root yet to be completely formed

Cementum is not appreciated radiographically because the contrast between it and dentin is minimal. Cementum is 50% mineralized. Pulp appears radiolucent. The coronal pulp (pulp chamber) extends inferiorly into the roots, which is referred to as radicular portion of pulp. In a developing tooth, the pulp canal diverges and the walls of the root taper to a knife edge. A small round area of radiolucency is seen at the root tip which is surrounded by a thin layer of hyperostotic bone which is the dental papilla enclosed by the bony crypt (Figure 2).

Figure 3

Radiololucent periodontal ligament space confined between the radiopaque surface of the root and the lamina dura

Figure 4

Periodontal Ligament Space The periodontal ligament space is seen as a radiolucent area between the root surface and the lamina dura. It is seen all around the root extending from the alveolar crest on one side to the other (Figure 3). The width of the periodontal ligament space varies from 0.15 to 0.36 mm; it is generally thinner in the middle third of the root and wider near the alveolar crest and the apical region of the root. However due to projection errors, the periodontal ligament space may not be discernible on some radiographs.

Alveolar Bone Lamina dura, alveolar crestal bone, cancellous trabecular bone. Lamina dura Lamina dura is a radiographic term used to describe alveolar bone proper (cortical bone), which forms the sockets of teeth. It is also considered to be a ‘specialized’ continuation of the cortical plate. Radiographically, lamina dura is 826

Radiograph showing the radiopaque lamina dura surrounding the roots of the teeth

seen as a well-defined radiopaque line that surrounds the roots of teeth in health (Figure 4). The appearance of lamina dura on a radiograph is because of the attenuation of the X-ray beam as it passes through the thin layer of bone tangentially. Usually lamina dura is well-defined. However, on occasions, even in a healthy tooth lamina dura may appear indistinct and diffuse because of an obliquely directed X-ray beam. Lamina dura is generally more radiodense and thick around the roots of teeth under heavy occlusal forces. A double lamina dura is seen when the surfaces of the mesial and distal root are in the path of the central beam of the X-ray. Loss of lamina dura either partially or generalized may indicate the presence of a local periapical pathology or an underlying systemic disturbance.

Chapter 32 – Intraoral Radiographic Anatomical Landmarks

Figure 5

Figure 6

Pointed radiopaque crest of the interdental alveolar bone in the anterior teeth

Flat topped radiopaque interdental bone in the posterior teeth that runs parallel to the cementoenamel junction

Figure 7 A

B

(A) Trabeculae are fine and dense in the maxillary anterior region. (B) Trabeculae are oriented irregularly and bone marrow spaces are relatively

Alveolar crest Crest of the alveolar bone is a radiopaque structure. It is seen as a continuation of the lamina dura (cortical bone). The junction between the alveolar crest and lamina dura is seen as a sharp well-defined angle. Generally the crest of the alveolar ridge is 1.5 mm apical to the cementoenamel junction. In the anterior teeth, the alveolar crest terminates as a pointed projection and in the posterior teeth it appears flat and parallel to the cementoenamel junction (Figures 5 and 6). Cancellous bone It is present between the buccal and lingual cortical plates in the maxilla and the mandible and accounts for most of the bulk of the alveolar bone. The cancellous bone is made

up of a network of radiopaque trabeculae that enclose radiolucent bone marrow spaces. In the maxillary anterior region, the trabeculae are fine and dense and in the posterior region the bone marrow spaces are relatively larger and oriented irregularly (Figure 7A). In the anterior region of the mandible, the trabeculae are fewer in number and oriented horizontally. In the posterior region of the mandible the bone marrow spaces are larger (Figure 7B).

LANDMARKS UNIQUE TO THE MAXILLARY INTRAORAL PERIAPICAL RADIOGRAPH ❍ ❍

Intermaxillary suture Anterior nasal spine 827


Figure 8 A

B

(A) Radiograph of the mandibular anterior region showing less number of trabeculae that are oriented horizontally. (B) Radiograph of the mandibular posterior region showing large bone marrow spaces

❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍

Nasal fossae and floor of the nasal fossae Nasal septum Incisive foramen Tip of the nose shadow Lateral fossa Canine fossa Nasopalatine canal Superior foramina of the nasopalatine canal Nasolacrimal canal Nasolabial fold Inverted Y line of Innes Maxillary sinus Zygomatic process and zygomatic bone Maxillary tuberosity Pterygoid plates Hamular process Coronoid process of the mandible.

Intermaxillary suture/median suture Anatomical location/projection The intermaxillary suture runs from the alveolar crest between the maxillary central incisors to the posterior aspect of the hard palate. It is seen when an intraoral periapical radiograph (IOPAR) is taken for the upper central incisors. Radiographic appearance (Figure 8A) It is seen as a linear radiolucency bounded by radiopaque lines extending from the crest of the alveolar bone between the maxillary central incisors to the anterior nasal spine on an IOPAR. Occasionally it is seen as a V-shaped enlargement at the alveolar crest.

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Figure 9

Radiograph showing the intermaxillary suture as a linear radiolucent line extending from the crest of the alveolar bone between the maxillary central incisors to the anterior nasal spine

fossa. When an IOPAR is taken for the upper central incisors it is located between and roughly 2 cm beyond the periapices of the central incisors. Radiographic appearance (Figure 8B) It is a V-shaped radiopaque structure. Nasal fossae and floor of the nasal fossa

Anterior nasal spine

Anatomical location/projection The inferior portion and floor of the nasal fossae are seen on an IOPAR beyond the periapical regions of the maxillary anterior teeth, when an IOPAR is taken for the upper central and lateral incisors.

Anatomical location/projection Seen on an IOPAR at the junction of the nasal septum and the floor of the nasal

Radiographic appearance (Figure 9) The floor of the nasal fossae appear as well-defined radiopaque lines that


Figure 10

Anterior nasal spine seen as a V-shaped radiopaque structure at the junction of the nasal septum and the floor of the nasal fossa

extend bilaterally on either side of the anterior nasal spine. The radiolucent region above the floor of the nasal fossae is the inferior portion of the nasal fossa.

Figure 11

Radiograph showing floors of the nasal fossae as well-defined radiopaque lines extending bilaterally on either side of the anterior nasal spine and the inferior portion of the nasal fossae are seen as radiolucent areas above the nasal floor

Figure 12

Nasal septum Anatomical location/projection It is seen on periapical radiographs taken in relation to maxillary central incisors. It is a midline structure and seen extending superiorly from the anterior nasal spine. Radiographic appearance (Figure 10) The nasal septum is a sharply defined linear radiopacity, which may generally appear to be deviated from the midline. However, on occasions the image of septal cartilage and the vomer bone may be superimposed over the nasal septum. Incisive foramen Anatomical location/projection Incisive foramen is seen in relation to the middle and apical one-third of the roots of the maxillary central incisors. It is seen on periapical radiographs taken in relation to maxillary central incisors. Radiographic appearance (Figure 11) It is radiolucent and may have various appearances ranging from a smoothly symmetric outline to irregular or ill-defined border and usually smaller than 1 cm in diameter. Tip of the nose Anatomical location/projection The image of the tip of the nose is superimposed over the apical one-third of the roots of the maxillary central and lateral incisors. It is usually seen in individuals with a prominent and bulbous

Radiograph depicting the nasal septum as a sharply defined linear radiopacity extending superiorly from the anterior nasal spine and dividing the nasal fossae

nose tip. The shadow of the tip of the nose is seen when a radiograph is taken for the maxillary central incisors. Radiographic appearance (Figure 12) It appears as a homogenous cup-shaped radiopacity with a definite outline. Lateral fossa/incisive fossa Anatomical location/projection It is seen in relation to the apical region of the maxillary lateral incisor. Radiographs of the lateral incisors will reveal this anatomic landmark. Radiographic appearance (Figure 13) It appears as a diffuse radiolucency. 829


Figure 13

Incisive foramen seen as a well-defined radiolucent area in relation to the middle and apical one-third of the roots of the maxillary central incisors

Figure 14

Figure 15

Lateral fossa seen as diffuse radioluceny in relation to the apical region of the maxillary lateral incisor

of maxillary central incisors, when taken with an increased vertical angulation. Radiographic appearance (Figure 15) They appear as well-defined oval radiolucencies on either side of the nasal septum (superimposed close to the floor of the nasal fossa). Nasolacrimal canal Anatomical location/projection Rarely visualized on a periapical radiograph. When an increased vertical angulation is used, the nasolacrimal canal may be seen in the periapical region of the canine. In maxillary occlusal radiographs, they are seen in relation to the apices of the molars.

The tip of nose shadow is seen as a homogenous cup shaped radiopacity superimposed over the apical one-third of the roots of the maxillary central and lateral incisors

Nasopalatine canal Anatomical location/projection The nasopalatine canal is rarely seen on periapical radiographs. However, they may be evident on radiographs taken in relation to the maxillary central incisors. Radiographic appearance (Figure 14) The lateral walls of the nasopalatine canal appear radiopaque and extend from the incisive foramen to the floor of the nasal fossa.

Radiographic appearance (Figure 16) Well-defined ovoid/ round radiolucencies. Nasolabial fold Anatomical location/projection The nasolabial fold is seen extending across the middle and apical one-third of the roots of the canine and first premolar. It is seen on IOPAR taken on the maxillary canine. Radiographic appearance (Figure 17) The nasolabial fold appears as a linear radiopaque shadow. Occasionally, a zone of increased radiopacity is seen above this shadow which is caused by the superimposition of the buccal mucosa and alveolus. Inverted Y line of Innes

Superior foramina of the nasopalatine canal Anatomical location/projection Generally seen on maxillary occlusal radiographs or on a periapical radiograph 830

Anatomical location/projection The inverted Y line or Y line of Innes is seen when radiographs are taken in the maxillary canine region.


Figure 16

Radiograph showing the nasaopalatine canal at the periapical region of the maxillary lateral incisor

Figure 17

Radiograph reveals superior foramina of the nasopalatine canal as well-defined oval radiolucencies, superimposed close to the floor of the nasal fossa

Figure 18

Maxillary occlusal radiograph showing nasolacrimal canals as well-defined ovoid radiolucencies in relation to the apices of the molars

Figure 19

IOPAR of the maxillary premolar region showing the nasolabial fold as a linear radiopaque shadow extending across the middle and apical one third of the roots of the canine and first premolar

Maxillary sinus Radiographic appearance In relation to the periapex of the canine, the floor of the maxillary sinus and the floor of the nasal fossa cross one another forming an inverted Y, which is referred to as Y line of Innes (Figure 18). Canine fossa Anatomical location/projection Seen at the periapical regions of the maxillary canine (Figure 19). Radiographic appearance Seen as a diffuse radiolucency.

Anatomical location/projection The floor and a minimal portion of the inferior aspect of the maxillary sinus are seen on periapical radiographs taken in relation to the maxillary premolar and molar teeth. Radiographic appearance The maxillary sinus appears as a uniformly radiolucent structure bounded by well-defined thin radiopaque line. The roots of the maxillary molars ‘appear’ to project into the maxillary antrum as a result of the angulation of the X-ray beam (Figure 20). 831


Figure 20

Radiograph showing the inverted Y line of Innes in relation to the maxillary canine-first premolar region

Figure 22

Radiograph of the maxillary first molar reveals the scalloped well-defined radiopaque floor of the maxillary sinus and the radiolucent maxillary sinus

Figure 21 the maxillary sinus in relation to the apices of the molar teeth. It is seen as a U-shaped or V-shaped radiopaque line. The zygomatic bone is seen as a homogenous radiopacity over the apices of the second and third molars, generally obscuring the periapical region. Pterygoid plates and hamular process Anatomical location/projection The pterygoid plates and hamular process are seen distal to the maxillary tuberosity. They are generally seen on intraoral periapical radiographs taken in relation to the third molars. However, in most cases they may not be evident.

IOPAR showing the canine fossa as a diffuse radiolucency at the periapical region of the maxillary canine

In edentulous spaces, the floor of the sinus dips down and lies close to the alveolar ridge (pneumatization of the sinus). Occasionally thin radiolucent lines are seen to traverse the sinus walls. These radiolucent tracks represent the neural and vascular supply of the sinus. Zygomatic process and zygomatic bone Anatomical location/projection The zygomatic bone and the zygomatic process of the maxilla are seen in the periapical regions of the second and third molars. Zygomatic bone is usually seen when an excessive vertical angulation is used. Radiographic appearance (Figure 21) Zygomatic process of the maxilla is seen above the level of the floor of 832

Radiographic appearance (Figure 22) The pterygoid plates are seen as a radiopaque shadow distal to the maxillary tuberosity and the hamular process is evident as a single radiopaque linear structure extending from the inferior aspect of the medial pterygoid plate. Coronoid process Anatomical location/projection The coronoid process of the mandible is usually seen superimposed over the periapical regions of the second and third maxillary molars and sometimes over the maxillary tuberosity region. The position of the image of the coronoid process on the radiograph depends on the extent to which the mouth was opened during the radiographic projection. It is seen when an IOPAR is taken for the upper second and third molars. Radiographic appearance (Figure 23) The coronoid process appears as a homogenous triangular shaped radiopacity with the tip facing the occlusal aspects of the teeth.


Figure 23

IOPAR of the maxillary molars reveals a V-shaped radiopaque structure seen above the level of the floor of the maxillary sinus projecting downward toward the apices of molar teeth

Figure 25

IOPAR of the maxillary third molar showing the mandibular coronoid process as a homogenous triangular shaped radiopacity with the tip facing the occlusal aspects of the upper teeth

Figure 24 Symphysis Anatomical location/projection Seen only in the first year of life. It is seen in the region corresponding to the midline of the mandible. It is seen on the radiographs of the deciduous mandibular central incisors. Radiographic appearance Symphysis appears as a linear radiolucency between the deciduous mandibular central incisors and extending inferiorly to involve the lower border of the mandible (Figure 24). Genial tubercles (mental spine) and lingual foramen Radiograph showing the pterygoid plates as a radiopaque shadow distal to the maxillary tuberosity and the hamular process as a radiopaque linear structure extending from the inferior aspect of the medial pterygoid plate

LANDMARKS UNIQUE TO THE MANDIBULAR INTRAORAL PERIAPICAL RADIOGRAPH ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍

Symphysis Genial tubercles Mental ridge Mental fossa Mental foramen Mandibular canal Mylohyoid ridge Submandibular gland fossa External oblique ridge Inferior border of mandible.

Anatomical location/projection They are generally evident on the periapical radiographs of mandibular central incisors and mandibular occlusal radiographs. Radiographic appearance Genial tubercles are seen on mandibular occlusal radiographs as discrete radiopaque structures measuring about 4 mm in diameter. They are present beneath the apices of the mandibular central incisors in the midline. In periapical radiographs, they are seen as a well-defined radiopaque mass enclosing a circular radiolucent area which is referred to as the lingual foramen (incisal branches of mental nerve exit out of the lingual foramen to innervate the incisor teeth) (Figure 25). Mental ridge Anatomical location/projection Mental ridge is seen superimposed over the apical one-third of the roots of the mandibular central and lateral incisors. It appears to extend 833


Figure 26

IOPAR showing well-defined radiopaque mass (genial tubercles) enclosing a circular radiolucent lingual foramen

from the premolar region up to the central incisors. These are seen in IOPAR taken for the mandibular incisors.

Figure 27

Radiograph of the mandibular incisor region showing two well-defined radiopaque lines extending bilaterally from the premolar region toward the midline

Figure 28

Radiographic appearance Seen as two well-defined radiopaque lines extending bilaterally from the premolar region toward the midline. Mental fossa Anatomical location/projection The mental fossa is an anatomical depression present on the labial aspect of the mandible extending bilaterally from the midline to the lateral incisor and occasionally up to the canine. Radiographic appearance It is seen as a diffuse radiolucent area, which is superimposed over the roots of the mandibular anterior teeth. The mental fossa is bounded superiorly by the alveolar ridge and inferiorly by the mental ridge (Figure 26).

Mental fossa seen as a diffuse radiolucency superimposed over the roots of the mandibular anterior teeth

Mental foramen Anatomical location/projection The mental foramen is usually seen at the periapical regions of mandibular premolars. It is usually present equidistant from the both the lower border of the mandible and the alveolar ridge. Radiographic appearance It appears radiolucent and has a round, ovoid or an elongated shape. It may or may not have a well-defined radiopaque corticated border (Figure 27). Mandibular canal Anatomical location/projection The mandibular canal is usually seen on periapical projection of mandibular molars. The apices of the molar teeth may some times lie close to the canal. 834

Radiographic appearance (Figure 28) It is seen as linear radiolucent canal running along the apices of the molar teeth. The course of the canal is generally lined by thin radiopaque lamellae of bone. Mylohyoid ridge or internal oblique ridge Anatomical location/projection The mylohyoid ridge is seen extending from the third molar region to the premolars usually along the apices of these teeth. Usually seen when radiographs are taken for the mandibular molars. Radiographic appearance (Figure 29) It is generally seen as a well-demarcated radiopaque line below the level of


Figure 29

IOPAR of the mandibular premolar region showing a well-defined radiolucent area at the periapical region of the 2nd premolar

Figure 31

Radiograph showing the mylohyoid ridge as a well-demarcated radiopaque line running along the apical thirds of the mandibular molar teeth

Figure 30 Figure 32

Radiograph of the mandibular molar region showing the mandibular canal as a linear radiolucent canal running along the apices of the molar teeth

the external oblique ridge that runs along the apical thirds of these teeth. External oblique ridge Anatomical location/projection It is seen on IOPARs of mandibular posterior teeth. The external oblique ridge is seen above and parallel to the mylohyoid ridge. Radiographic appearance (Figure 30) The external oblique ridge appears as a linear radiopacity which merges with the alveolar bone as it traverses toward the premolar region and superiorly it continues as the ascending ramus of the mandible.

IOPAR showing the external oblique ridge as a linear radiopacity which continues as the ascending ramus superiorly

Submandibular gland fossa Anatomical location/projection The submandibular gland fossa is an anatomical depression that houses the submandibular gland. It is seen in the periapical region of molar teeth, below the level of the mylohyoid ridge. It is extends up to the premolar region anteriorly and to the ascending ramus posteriorly. It is seen when a radiograph is taken for the lower molar teeth especially second and third molars. Radiographic appearance (Figure 32) It appears as a diffuse radiolucency. 835


Figure 33

Inferior border of the mandible Anatomical location/projection May be seen in any of the projections of the mandibular teeth. It is usually seen when the film is placed deep within the lingual sulcus and the vertical angulation is increased. Radiographic appearance (Figure 33) The inferior border of the mandible is rarely seen on intraoral periapical radiographs. It is evident as a radiopaque strip of uniform thickness (cortical portion) of bone along the inferior edge of the mandible. Radiopaque anatomical landmarks

IOPAR of the mandibular third molar region showing the submandibular gland fossa as a diffuse radiolucency beneath the level of the mylohyoid ridge and mandibular canal

Figure 34

Maxilla

Mandible

Anterior nasal spine Floor of nasal fossa Tip of nose, nasolabial fold Floor of maxillary sinus Zygomatic process of maxilla Zygomatic bone Maxillary tuberosity Pterygoid plates Hamular process Coronoid process

Genial tubercles Mental ridge Mylohyoid ridge External oblique ridge Inferior border of the mandible

Radiolucent anatomical landmarks

IOPAR showing the inferior border of the mandible as a well-defined linear radiopaque strip of uniform thickness of bone along the inferior edge of the mandible

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Maxilla

Mandible

Intermaxillary suture Nasal fossa Incisive foramen Superior foramina of nasopalatine canal Lateral fossa/incisive fossa Canine fossa Nasolacrimal canal Maxillary sinus

Symphysis Lingual foramen Mental foramen Mandibular canal Submandibular gland fossa

CHAPTER

Extraoral Radiographic Landmarks

33

Praveen BN

Figure 1

23

20 22

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21

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24

9

16 8

17 1 19

11 13 18

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6 7 4

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1. External auditory meatus 2. Hyoid bone 3. Dorsum of tongue 4. Hard palate 5. Anterior nasal spine 6. Soft palate 7. Floor of orbit 8. Frontal process of zygoma 9. Nasal bone 10. Nasion 11. Inferior rim of orbit 12. Ethmoid air cells 13. Posterior wall of maxillary sinus 14. Posterior arch of atlas 15. Occipital condyle 16. Mastoid air cells 17. Condyle 18. Articular eminence 19. Base of skull 20. Sella turcica 21. Sphenoid sinus 22. Posterior clinoid process 23. Roof of orbit 24. Clivus

3 2

Lateral cephalogram

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Figure 2 1 2 8 9

3

4 10 5 6

11 7 12 13

14 1. Supraorbital canal 2. Nasal septum 3. Infraorbital margin 4. Ala of nose 5. Zygomatic bone 6. Maxillary sinus 7. Lateral wall of maxillary sinus

8. Frontal sinus 9. Zygomaticofrontal suture 10. Innominate line 11. Inferior orbital fissure 12. Sphenoid sinus 13. Foramen rotundum 14. Mid-palatal suture

Paranasal sinus radiograph

Figure 3 1

2 3 4 3 5 7

14

15 8 16

9 10

13

6

1. Nasal septum 2. Mid-palatal suture 3. Sphenoid sinuses 4. Coronoid process of mandible 5. Ramus 6. Condyle of mandible 7. Clivus 8. Posterior pharyngeal 9. Anterior arch of atlas 10. Dens 11. Occipital condyle 12. Ossicles 13. External auditory meatus 14. Foramen spinosum 15. Foramen ovale 16. Hyoid bone

11 12

Submentovertex (base of skull) view

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Chapter 33 – Extraoral Radiographic Landmarks

Figure 4 2 2

1

3

1. Lateral pole of condyle 2. Superior surface of condyle 3. Medial pole of condyle 4. Coronoid process

4

3

1

4

Open mouth

Closed mouth

Temporomandibular joint (posteroanterior) view—closed and open mouth position

Figure 5

19 18

1

17

2 3

16

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5 15

6 8

9 14 11 13

1. Superior rim of orbit 2. Lesser wing of sphenoid 3. Innominate line 4. Mastoid process 5. Foramen rotundum 6. Pterygoid process 7. Base of skull 8. Maxillary antrum 9. Zygomatic process of maxilla 10. Inferior turbinate 11. Intermaxillary suture 12. Nasal septum 13. Articulation between atlas and axis 14. Coronoid process 15. Infraorbital canal 16. Superior border of petrous 17. Superior orbital fissure 18. Ethmoid air cells 19. Frontal sinus

10

12 7

Posteroanterior view of the skull

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Figure 6

1 1. Condyle head 2. Articular fossa 3. Articular eminence

2 3

Open mouth

Closed mouth

Temporomandibular joint (lateral) view—closed and open mouth position

Figure 7

13

1

2 3

12 4

5 11

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7 6

9 8

Reverse Townes’ view

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1. Foramen magnum 2. Posterior arch of atlas 3. Dorsum sellae 4. Frontal process of zygoma 5. Posterior wall of maxillary sinus 6. Inferior orbital fissure 7. Zygoma 8. Inferior rim of orbit 9. Nasal septum 10. Coronoid process of mandible 11. Condyle of mandible 12. Internal auditory meatus 13. Articular eminence

Chapter 33 – Extraoral Radiographic Landmarks

Figure 8 15

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1. Mandibular canal 2. Inferior border of zygomatic arch 3. Posterior wall of maxillary sinus 4. Floor of maxillary sinus 5. Anterior wall of maxillary sinus 6. Inferior orbital canal 7. Nasal septum

8. Mental foramen 9. Soft tissue of inferior turbinate 10. Pterygomaxillary fissure 11. Coronoid process 12. Condyle 13. Inferior orbital rim 14. External auditory meatus

15. Condylar fossa 16. Articular eminence 17. Real image of hard palate 18. Common meatus of nose 19. Ghost image of inferior edge of contralateral ramus 20. Body of hyoid

Orthopantomogram

Figure 9 27 28 22 25 21

22

21 21

21

21

21 24 26

29

23 30

21. Outline of base and dorsum of tongue 22. Air-space above the tongue 23. Hypoglossal air space 24. Oropharyngeal air space

25. Nasopharyngeal air space 26. External oblique ridge 27. Ghost image of left palate 28. Sigmoid notch

29. Angle of mandible 30. Inferior border of mandible

Orthopantomogram

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CHAPTER

34

Site Selection, Evaluation and Imaging for Dental Implants Muralidhar Mupparapu

Historical Perspectives Indications for Dental Implants Patient Management with Dental Implants

Dental implants are prosthetic devices implanted into the oral tissues either beneath the mucoperiosteal layer or in the bone to provide retention and support for the fixed or removable prosthesis. Although fabrication of dental implants dates back to many decades, the advent of dental root form implants (DRFIs) have paved way for universal acceptance of implants as replacement for lost teeth. The dental implant restorations not only enhance the esthetics for the patients, but also improve the oral function for speech and mastication. Hence, the dental root form implants (Figure 1) gained immense popularity among the dental practitioners as well as the patients in the dental profession. Nothing is more important in the dental implantology than the precise evaluation and placement of the implant structures in the maxilla and mandible. In order to do this effectively, one needs to precisely understand the surgical Figure 1

Upper lip

Implant fixture Crown prosthesis

Diagrammatic representation of the typical implant fixture and the crown properly placed within the maxillary alveolus

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Identification of the Implant Site Selection of the Implant Site Imaging of the Implant Site

anatomy of the maxillofacial region and the anatomical variations that might be encountered. Secondly, they need to grasp the biomechanics of the dental implant material. Fortunately, now, the science behind the dental implantology is strong, backed with research and evidence-based trials. The fruits of the decades of clinical trials using various dental implant materials along with numerous loading protocols have refined the predictability of dental implants for the maxillofacial region.

Historical Perspectives The treatment options that are available for replacement of single or multiple teeth in the oral cavity are removable partial denture (RPD), fixed partial denture (FPD) and implant prosthesis (IP). The RPDs which were not helpful in the maintenance of existing bone, compromise the esthetic result, need more bulk for cross-arch stabilization, easily trap food debris and plaque, and interfere with the speech and function. Similarly, the FPDs especially promote caries of the abutment teeth but if not well fabricated, lead to plaque retention in the pontic increasing periodontal risk, involve damage to adjacent teeth, fracturing of the porcelain, and have esthetic concerns for the anterior regions. The FPDs are contraindicated when there is poor abutment support, inadequate hard and soft tissues in the esthetic regions and in young patients with large pulp horns. The dental implants would be an ideal alternative for replacement of teeth. Historically, there were three distinct forms of dental implants, namely, the subperiosteal (epiosteal), the transosseous (staple bone or transmandibular) and the endosteal (blade or plate, ramus–frame and root form) types. Dental practitioners should be familiar with the radiographic appearances of older dental implant systems although many

Chapter 34 – Site Selection, Evaluation and Imaging for Dental Implants

CAD/CAM fabrication of the framework, eliminating the need for impressions via surgery. Subperiosteal implants are no longer preferred after the success of endosteal implants although one can occasionally see them in clinical practice with varying degrees of presentation (Beddis et al, 2012).

Figure 2 Posts will remain outside the gingiva as anchors for the new prosthesis

Transosseous implants

Subperiosteal metal framework

The transosseous implants, also known as staple bone implants or transmandibular implants are restricted to the anterior region of the mandible. They penetrate both cortical plates and pass through the entire thickness of the bone.

Mandible Gingiva covering the implant framework

Diagrammatic representation of subperiosteal implant framework and the posts in the edentulous mandible

of them are rarely used after the advent of the dental root form implants. Subperiosteal implants Subperiosteal implants are metallic meshes that are custombuilt to fit over the alveolar processes and are located underneath the periosteum (Mupparapu and Beideman, 2000). Direct bone impressions via surgery would lead to the fabrication of mesh in a laboratory that fits under the mucoperiosteum (Figure 2). The framework normally rests on the mandible with no penetration into the bone. Two surgeries were involved in the fabrication of these implants. First surgery is for the impression and the second surgery is for the placement of the mesh. The first subperiosteal dental implant in the world was placed by George Dahl in Sweden. The first American subperiosteal implants were developed in 1947. Gershkoff and Goldberg placed the first subperiosteal complete denture implant manufactured with Vitallium (Moore and Hansen, 2004). Dr Leonard Linkow of New York made significant changes to the original design by incorporating fenestrations into the buccal peripheral struts which made it possible for the mucoperiosteum to reattach the bone in between these fenestrations. He also holds 35 patents on various designs of subperiosteal and oral implants. Multiple metallic posts extend from the mesh into the oral cavity crossing the mucoperiosteal barrier to support the prosthesis. Mandibular subperiosteal implants have been shown to be successful in many clinical studies and some of the implants reviewed were present in the mouth for more than 10 years. The success rate for these implants varied in many studies with higher success rate for 10-year periods and lower success rates for longer periods (Moore and Hansen, 2004). Computed tomography (CT) scans were also used to allow

Endosteal implants There are three forms of endosteal implants: the root form, the ramus frame and the plate or blade form implants. Blade implants are rectangular in shape similar to a razor blade. These are used over horizontal column of bone. One or more posts usually extend into the oral cavity to permit fixation of the prosthesis. The only blade implants that are seen clinically at present are the previously placed implants that either failed or fractured and the patient reported for treatment. One such example where the blade implant failure led to the osteomyelitis in the mandible is shown in Figure 3. The root form implants can be either cylindertype, screw root type or a combination of both. These implants use the vertical column of bone unlike the blade implants. Types of dental implants available (according to the material used) The following are the commonly used implants according to the type of material used for fabrication: 1. Metallic implants a. Titanium b. Cobalt–chromium–molybdenum alloy with titanium, aluminum, vanadium c. Cobalt–chromium–molybdenum d. Stainless steel e. Zirconium f. Tantalum g. Gold h. Platinum 2. Non-metallic implants a. Ceramics b. Carbon. The most commonly used implants are: 1. Commercially pure (CP) titanium This is light weight, biocompatible and corrosion resistant. The material is many times stronger than compact bone and the modulus of elasticity is five times greater than that of compact bone. This equals the mechanical stress transfer of compact bone. 843


Figure 3

Failing blade implants in the mandibular molar region as seen from the panoramic reformatted image from a Denta-Scan® CT study. On the right is a picture of a premolar blade implant manufactured by Oraltronics, Russia

Figure 4

Facial profile changes after loss of teeth including the collapse of the perioral soft tissues and loss of vertical dimension

2. Titanium–aluminum–vanadium alloy (Ti–6Al–4V) This is stronger and used for small diameter implants.

Indications for Dental Implants Implants are indicated in many situations in patients with partial or full edentulism. They are indicated in patients with a history of difficulty in wearing a removable partial denture or have a long span fixed partial denture. They are also indicated in patients with severe bony changes secondary to prolonged use of complete or partial dentures. The implants are ideal for patients with poor oral muscular coordination and in those with parafunctional habits compromising the stability of the prosthesis. Patients with hyperactive gag reflex, unfavorable number and location of abutments, single tooth loss and those who refuse to 844

wear dentures for psychological reasons are all candidates for dental implants. In patients wearing complete dentures, bite force is decreased from about 200 to 50 psi with decreased masticatory efficiency. Food selection is limited and healthy food intake is decreased among these patients. Hence the dental implants will greatly help them in getting back the normal occlusal function added with the enhanced esthetics. Finally, in patients with tooth agenesis (congenitally missing teeth), the implants are ideally suited. Patients who lost the entire dentition will show significant changes to the facial profile after loss of teeth chiefly due to the alveolar resorption and the loss of vertical dimension (Figure 4). Restoration of function and esthetics would then become the goal for any prosthesis without compromising on the masticatory efficiency.


Patient Management with Dental Implants There are three aspects of patient management that the practitioner should remember when planning treatment for dental implants: 1. Identification of the appropriate site for implant placement via preimplant assessment This requires patient assessment via thorough medical and dental history, laboratory findings and radiographic evaluation of the existing teeth and edentulous ridges. 2. Selection of appropriate dental implant system (DIS) and fabrication of necessary guides for surgery This involves selection of appropriate implant material and imaging software to display the cone beam computed tomographic volumes and a good communication with the laboratory. 3. Planning and designing appropriate abutment This could be easily accomplished via virtual implant selection and placement. The identification of appropriate length and width of the implant fixture would be determined at this stage taking into consideration, the proximity of the nerve canal and/or sinus cavity.

Identification of the Implant Site Selection of the patient Patient selection is a key factor in going forward with the identification of future implant site(s). This essentially boils down to the assessment of the medical and dental status of the patient. If the patient’s medical and dental history precludes a dental implant placement and a good prognosis, then that should be communicated to the patient ahead of time. Systemic health of the patient plays a vital role in the overall selection of the patient. Any medical condition that delays or alters wound healing should be identified first. A good example for this is ‘diabetes mellitus’. Uncontrolled type 1/type 2 diabetes or untreated diabetes usually results in delayed wound healing. Diabetes (type 1 and type 2 combined) affects approximately 25.8 million people in the Unites States alone. There are at least 79 million people who are considered prediabetics (National Diabetes Fact Sheet, 2011, Centers for Disease Control and Prevention [http://www.cdc.gov/diabetes]). Worldwide, as per 2011 World Health Organization estimates, around 346 million people have diabetes (http://www.who.int/mediacentre/ factsheets/fs312/en/index.html). Wound healing occurs as a cellular response to injury and involves activation of keratinocytes, fibroblasts, endothelial cells, macrophages and platelets. Many growth factors and cytokines released by these cell types are essential for coordination and maintenance of healing process (Brem and Tomic-Canic, 2007). Deficiency of any of the above factors would lead to improper and sometimes nonhealing of the extraction site as well as the implanted site.

Since the success of implant therapy is tied to the osseointegration, this is a crucial step in the overall implant therapy. Several medical conditions that would jeopardize the success of an implant should be considered during the screening process. The list (Hwang and Wang, 2006) includes the following absolute contraindications and relative contraindications: Absolute contraindications 1. Recent myocardial infarction or cerebrovascular accident Due to the increased risk of complications following a myocardial infarction (MI) or a cerebrovascular accident (CVA), the dental practitioner must wait until preliminary stabilization. It is recommended that elective dental care is deferred for at least 6 months status post MI or CVA and the patient is medically stable. 2. Valvular prosthesis placement It is essential that the dental practitioner defers placement of implants in these patients for 6 months to 1 year after the cardiac surgery. Anticoagulants would be used depending on whether the valve is bioprosthetic or mechanical in which case, caution should be exercised. 3. Prior history of bleeding Since uncontrolled bleeding stems from a multitude of systemic conditions, patients who are on oral anticoagulant therapy should be carefully evaluated and the bleeding time, international normalized ratio (INR) must be assessed. An INR of 2.2 or lower is recommended for surgical procedures by Fazio and Fang (2003). 4. Immunosuppression If the WBC count falls below 1,500–3,000 cells/mm3 the patient is not considered a good candidate to receive implants as the ability to combat infections, repair or regeneration would be compromised. With a near normal WBC count and a grossly abnormal neutrophil count (less than 2,000 cells/mm3), the normal range being 3,500–7,000 cells/mm3, a medical consultation is necessary before planning dental implants. It is generally considered that when the patient’s CD4 T-cell count measures below 500 cells/mm3, he/she is considered immunosuppressed and appropriate care should be exercised. 5. Active radiation and/or chemotherapy Both ionizing radiation and chemotherapy disrupt hematopoiesis, and implantation should be deferred in such situations as wound healing is delayed. In addition, if the salivary glands are involved in the line of fire, there would be substantial xerostomia which in turn, would contribute to poor oral hygiene and increase in dental caries secondary to xerostomia. Studies have shown that in about 3–35% of patients, spontaneous or traumatic osteoradionecrosis would be a complication (Marx and Johnson, 1987). When the patient is on cytotoxic anticancer drugs, granulocytopenia followed by thrombocytopenia are expected which might lead to infection, hemorrhage, mucositis and pain. Implant 845


therapy should be deferred until after the patient is completely off the cytotoxic medication. 6. Psychiatric disorders If a patient is unable to comprehend and anticipate dental treatment logically, then it is advised not to place implants. Several conditions including psychotic disorders like schizophrenia, severe character associated conditions like hysteria, borderline personality disorders, dysmorphophobia, cerebral lesions, presenile dementia as well as alcohol and drug abuse. Although there are no biological reasons for patients with most of the above disorders to lose implants, there are reported cases of removal of osseointegrated fixtures based on psychiatric factors (Hwang and Wang, 2006). 7. Intravenous bisphosphonate treatment There is enough evidence to date linking bisphosphonate use to either spontaneous or traumatic induction of osteonecrosis of the jaw. Bisphosphonates inhibit bone resorption and hence are used for treatment of osteoporosis, hypercalcemia of malignancy and Paget’s disease. Bisphosphonates may inhibit osteoclast precursors and cholesterol synthesis as well as promote osteoclast apoptosis and osteoblast proliferation. In a large study, among all the different forms of bisphosphonates that were used in cancer patients, pamidronate (Aredia®, Novartis, Basel, Switzerland) and zoledronic acid (Zometa®, Novartis, Basel, Switzerland) stood out as the agents that were associated with most cases of osteonecrosis, majority of them being mandibular necrosis with recent dentoalveolar procedures performed on them (Ruggiero et al, 2004). So far, there are no published studies on the risk stratification of osteonecrosis of the jaws after drug discontinuation. Hence, the risk is omnipresent once the bisphosphonates have been used and even if they are discontinued. Professional organizations like the American Dental Association, the American Association of Oral and Maxillofacial Surgeons and the American Academy of Oral Medicine have issued guidelines regarding the identification and management of bisphosphonate-related osteonecrosis of the jaw. 8. Acute infection The presence of acute infection is an absolute contraindication for oral implant therapy. The soft tissues and bone should be completely devoid of any infection before the implant therapy can be instituted. 9. Morphology of the edentulous bone crest and vestibule Intraoral inspection and palpation may reveal information about the type of ridge, a suspected thin ridge or a flabby ridge, shape of the ridge, muscle insertions, mandibular tori and the floor of the mouth. A radiographic evaluation of the crestal bone is mandatory before treatment planning. A knife-edged ridge often needs correction before inserting implants. A bony plateau must be created that is wide enough to insert implants with an adequate width. This could mean reducing the existing crest by a few millimeters. The depth of vestibule is an important factor to consider. Bone resorption often leads to shallow vestibule. If that is 846

the case, an implant-supported overdenture is more likely to provide greater lip support in such cases, giving more acceptable esthetic result (Wismeijer et al, 2010). Relative contraindications There are situations where the condition lends to a milder, often local complications or loss of implants in a patient (Hwang and Wang, 2007). The following list, although comprehensive may not include every single situation and or condition that might predispose local loss of bone and eventual failure of the implant: 1. Age of the patient Bone growth in the maxilla and mandible is dynamic in growing children and adolescents. The implants simulate an ankylosed tooth in the growing alveolus and might not be able to catch up with the vertical growth of the alveolar process that happens naturally with the other permanent teeth. This might lead to infraocclusion or displacement with time with respect to the natural dentition. It is considered prudent to wait until the completion of skeletal maturation before placement of implants in the younger patients to avoid imperfect fixture positioning and/or stunt osseous expansion. The elderly tend to have greater prevalence of local conditions like the ridge resorption, nerve proximity, xerostomia as well as systemic conditions like osteoporosis, hypertension and diabetes. Although old age does not seem to be a major contributing factor in the long-term survival of the implants, the associated factors might lead to certain complications (Hwang and Wang, 2007). 2. Osteoporosis Osteoporosis is a condition that is prevalent in the fourth or fifth decade in both men and women in which, there is universal reduction in bone mass with no other abnormality. The resorption overtakes deposition of bone. Although it is generally thought to be a risk factor for failure of osseointegration, the clinical studies that were done revealed little effect of this condition on implant success, at least in the lower jaw (Minsk and Polson, 1998). 3. Smoking Studies have shown that persistent tobacco use following implantation lessened the ability of bone or other periodontal tissues to adapt over time and contributing to the failure of treatment after fixture uncovering (Lambert et al, 2000). The authors suggested smoking cessation for all future implant receiving patients. More recent studies that have examined the effect of smoking in patients with treated periodontal disease show mixed results and it is suggested that since smoking appears to reduce implant success especially in the maxilla, smoking cessation before implant rehabilitation might lead to better results (Hwang and Wang, 2007). 4. Diabetes Patients with both type 1 (previously called the insulin-dependent diabetes mellitus or the juvenile onset diabetes) and the type 2 (previously called the non-insulin dependent diabetes mellitus) diabetes mellitus are at risk


for implant failure due to the pathologic changes that are brought about by the disease in the cardiovascular, renal and circulatory systems which in turn lead to changes at local level. The American Diabetic Association recommends a hemoglobin A1C (HbA1C) level less than 7.0% in patients with type 2 diabetes. With appropriate glycemic control, diabetes does not compromise implant success (Hwang et al, 2007). 5. Cardiovascular disease All forms of cardiovascular diseases including the hypertension, coronary artery disease, vascular stenosis, atherosclerosis, congestive heart failure may impair the healing process after implant placement. Although cardiovascular disease leads to physiological alterations, generally, it does not seem to affect the clinical implant success (Hwang et al, 2007). 6. HIV disease Acquired immunodeficiency syndrome remains one of the leading causes of death in the world even though the mortality rate from HIV infection has substantially declined in the past decade due to advent of highly active antiretroviral therapies (HAART). This has become a chronic, manageable disease. In patients with CD4 count of more than 200 cells/mm3, successful osseointegration and function after 4 years was noticed and in patients with CD4 count less than 200 cells/mm3, a regimen of the antibiotic amoxicillin was suggested post-operatively for a successful outcome (Hwang et al, 2007). 7. Hypothyroidism Thyroid disorders generally affect the bone metabolism. Both T4 and T3 regulate several homeostatic processes. Wound healing in both soft tissue and bone is controlled by these hormones. Hypothyroidism decreases bone cell recruitment, maturation and activity, possibly by reducing the circulatory levels of insulin-like growth factor-1; this ultimately suppresses the bone formation as well as resorption. Implant sites healing and osseointegration would be potentially delayed. Even though in theory, the hypothyroid state might lead to potential failure in implant osseointegration, the studies that were done in this area did not present data that corroborate the theory. Hence, it can be concluded that in a well-controlled patient, hypothyroidism has no effect on the survival of the dental implants. 8. Past history of periodontal disease The risks related to implant loss in patients who lost their teeth to periodontal disease are much higher than the patients who lost their teeth to caries or trauma. The patients who lost their teeth as a result of periodontal disease run a higher risk of developing peri-implant infection even if they are completely edentulous (Heitz-Mayfield, 2008).

Selection of the Implant Site Imaging plays a key role in the selection of the site for mandible or maxilla, whether the implant is for a single site or

Figure 5

Diagrammatic representation of the Misch classification using mandibular bone. The short arrow with long arrow head points to the dense cortical bone in D1. The long arrow with short arrow head in D4 points to the generalized fine trabecular bone with absence of cortical bone

for multiple sites. Historically, the most frequently used and available intraoral and extraoral radiographs were used to evaluate the sites receiving the dental implant. Misch classified the bone density to four different groups based on the observed density of the bone (Misch, 1990). ❍

D1 bone (1,250 Hounsfield unit [HU]) bone is composed of almost all cortical bone mass located primarily in the anterior mandible. ❍ D2 bone (850–1,250 HU) bone is composed of a thick crestal layer of cortical bone and coarse trabecular bone underneath the cortical bone. This type of bone can mostly be found in the anterior maxilla and mandible and in the posterior mandible. ❍ D3 bone (350–850 HU) is composed of a porous crestal layer of cortical bone and fine trabecular bone underneath the cortical bone. This type of bone can mostly be found in the anterior and posterior maxilla but also in the posterior mandible. It is also seen after osteoplasty of D2 bone. ❍ D4 bone (150–350 HU) bone is composed of primarily fine trabecular bone and often the absence of cortical bone. This type of bone can mostly be found in the posterior maxilla and poses the greatest challenge in implant placement (Figure 5). Implants usually placed in D1 or D2 bone stand a very good chance of undergoing osseointegration, while the implants placed in D3 or D4 bone either undergo fibrointegration or fail to integrate at all. There are many factors that affect the long-term success or failure of an implant.

Misch classification is a subjective grading of bone density and the site in question might not always fall under a certain category as the bony anatomy is more complex than what appears visually. The visual radiographic analysis has to be augmented with other parameters of bone quality analysis. This might include factors such as the total 847


overall availability of bone and the health of the alveolar bone and number of implants to be placed in the area. They include correct initial placement of the fixture, successful osseointegration of the fixture, and the ability of the surrounding bone to withstand the occlusal and masticatory forces. A properly placed implant fixture can also fail if the occlusal forces are excessive, leading to a breakdown of the bone around the fixture. Hence, it is important to identify the correct occlusal scheme for the patient even before restoring the implant. Three-dimensional and crosssectional reformatted images of the patient’s jaw through the areas of interest demonstrate the spatial relationships of the opposing arches. The cross-sectional images are very helpful in assessing the direction of various force vectors acting on an implant placed and gives the clinician clues for preimplantation bone augmentation surgery (Delbalso et al, 1994). The widely available panoramic radiography and the linear tomography have a very limited value in the assessment of bone quality. Preoperative assessment of bone density is now performed primarily by radiographic means that includes the cross-sectional data. More recently dental CT has become more acceptable standard procedure.

Imaging of the Implant Site Diagnostic imaging is an essential and integral component of the implant treatment planning. Until the late 1980s, conventional radiographic techniques, namely, intraoral, panoramic, cephalometric radiographs have been the accepted standard (Harris et al, 2002). Developments in the cross-sectional imaging techniques such as complex motion tomography, reformatted CT have become available and were found to be useful compared with the previously accepted imaging techniques. Additionally, available proprietary and third party software paved way for the visualization of the third dimension and virtual positioning of the implant in the radiographic volumes before the implant surgery. The European Association for Osseointegration (EAO) recommended that even for single implant site, cross-sectional imaging may be beneficial and allows for more precise treatment planning. For all posterior maxillary and mandibular sites that are partially or fully edentulous, a cross-sectional imaging will provide sufficient information regarding the bone volume and the proximity to the inferior alveolar nerve canal and/or the maxillary sinus. Cross-sectional images will also help in the predictability of prosthetic results and transferring this information to guide the clinician or the implantologist in implant positioning. Special techniques such as zygomatic implants may also dictate the need for additional imaging. Postoperative monitoring cross-sectional imaging is not a part of the routine protocol unless there is a need for such an imaging due to an infection or suspected endangerment of the neighboring vital structures. 848

Figure 6

Edentulous maxillary areas showing alveolar extensions of the maxillary sinus and one of the periapical images of right maxillary molar region showing the presence of a compound odontoma in the right maxillary sinus

Standard periapical radiographs Although standard periapical radiographs have value in the evaluation of single implant sites for the availability of bone in the superior-inferior direction (Figure 6), the evaluation of bucco-lingual width of the bone is not possible with this two-dimensional (2D) imaging technique. The periapical radiographs can be used to identify the areas for possible implant placement and select the appropriate advanced imaging procedure. However, the periapical radiographs can be used for post-placement evaluation of the implants for angulations and evaluation of suspected periimplantitis (Figure 7). Panoramic radiography Panoramic radiographs were used in the past for identification of the implant sites via radiographic markers but lacked the third dimension (Figure 8). The uneven and unreliable magnification of the image as well as the projection artifacts made it impossible to be accurate especially when an implant is being placed close to the mental foramen, mandibular canal or the maxillary sinus floor. This technique became largely outdated after the advent of the crosssectional imaging. The technique still has value for postoperative assessment of the implant fixture similar to the periapical radiographs. Conventional tomography (linear or complex motion cross-sectional tomography) Quint Sectograph was one of the first linear tomographic machines that were available in the United States market


Figure 7

Periapical radiograph of maxillary left first molar region showing the grafted bone in the maxillary sinus and the root form implant in place. The implant appears to be stable with no evidence of peri-implantitis. Courtesy: Dale Rosenbach, DMD

Figure 9

Tomax ultrascan® complex motion tomographic machine

Figure 8 Dental computed tomography

Cropped panoramic radiograph showing the edentulous maxilla and partially edentulous mandible. The two linear opacities above the crestal level in the region of the left mandibular molars are the radiopaque markers (gutta percha) that were used with imaging

when linear tomography became available as a modality in the early 1930s. They were eventually used worldwide. The complex motion tomographic machines were introduced to dental imaging market in the 1990s. The machines like Tomax® (Figure 9) and Commcat® were used successfully for TMJ imaging as well as implant related crosssectional imaging. A digital acquisition charge coupled device camera was available with the Tomax ultrascan but the technology was soon outdated by the introduction of dental CT and eventually by the CBCT.

Multidetector computed tomography (MDCT) is an imaging technique that uses reconstruction mathematics to create images based on a series of radiographs. The initial CT concepts were developed by Alan Cormack and later brought to fruition by a British engineer Godfrey Hounsfield in 1972. The technique was first used to produce crosssectional images of the brain. The radiographic densities of the imaged structures were compared along a scale with the standard densities of water, air and the bone. The units came to be known as Hounsfield units (HU) or CT numbers. The HU has been used for measurement of radiodensity of structures being examined. The numerical scale ranges from air (1,000) to water (0) and to bone (1,000) and upward of 1,000 for even denser structures. The application of HU measurement can decrease the observer bias inherent in the interpretation of plain films. Overall, the HUs are important in an objective determination of bone density. Dental CT and the concepts of curved plane tomography were first published by Schwarz and coworkers in 1987 (Schwarz et al, 1987), which were utilized in the dental CT studies for reformatting the multiplanar and cross-sectional views. In addition, the dental CT programs like the ‘DentaScan’ were able to produce the ‘panoramic reformation’ from the conventional CT datasets (Figure 10). This gained acceptance by the dental practitioners. Even though the CT radiation dose was higher compared to all the previous radiographic modalities, the benefit of accurate placement of implants outweighed any potential risks. 849


Figure 10

DentaScan® software generated CT images. Courtesy: General Electric Company, USA

Cone beam computed tomography (CBCT) Introduced in the mid 90s, this dental specific CT scanning technology became a well-liked imaging technology, mostly due to the smaller footprint of the machines that can be purchased and installed in dental offices. Secondly, the radiation doses were much lower compared to the MDCT scanners, which were located mostly in the hospitals. CBCT is a relatively new technique, which shares some of the basic principles with MDCT. CBCT uses a cone beam instead of a fan shaped beam and all the basis images are acquired in one single pass instead of multiple passes as in MDCT. The acquisition speed and relatively low dose in CBCT lead to increased noise and lower image resolution when compared to MDCT. Hence, utilization of HUs derived from CBCT imaging has come under criticism due to the differences in acquisition of CBCT volumes as compared to the MDCT. The CBCT volumes are acquired via a 360-degree rotation of the X-ray source using a flat panel detector. The raw data as shown in the Figure 11 will be transmitted first back to the workstation. When the technologist confirms the field of view (FOV), the actual acquisition will be completed, and the entire study is stored as digital imaging 850

and communications in medicine (DICOM) format. These DICOM sets (with a file extension of .dcm) are used for reconstruction and display using appropriate software. The acquisition of CBCT volumes and the resultant anatomy is dictated by what is known as the FOV. The scanner’s FOV determines how much of the patient’s anatomy one can visualize. Scanners using flat panel detectors describe the dimensions of their cylindrical FOVs as height by width (H W). Scanners that use image intensifiers and charge-coupled devices (CCDs) as their detectors identify their spherical FOVs as cm3. Figure 12 shows the grouping of the FOVs based on their largest unstitched FOVs. A scanner with large FOV (at least 16 18 cm) will demonstrate at least the roof of the orbits superiorly and the hyoid bone inferiorly. The large FOV scans are used for orthodontic, maxillofacial prosthodontic or oral surgical purposes commonly but can also be used in other situations where there is a need for such a volume (Figure 13). The voxel sizes vary from scanner to scanner and the range is from 0.075 to 0.4 mm. Medium FOV (at least 8 14 cm) scanner capture typically from the infraorbital area superiorly down to lower border of the mandible inferiorly and from condyle to condyle horizontally. These views are


Figure 11

Figure 13

Appearance of a raw CBCT scan volume

Showing the CBCT machine, Kodak 9500® that has multiple FOV settings. Both medium and large FOV settings are available in this machine

Figure 12

Large volume Height: >16 cm Width: >18 cm

Small volume (Limited) Height: >4 cm Width: >4 cm Medium volume Height: >8 cm Width: >14 cm

Diagrammatic representation of large, medium and small volume CBCT field of view (FOV)

used commonly for preimplant assessment in maxilla and mandible and the assessment of maxillary sinuses and the TMJs bilaterally. The range of minimum voxel sizes vary from 0.080 to 0.13 mm and the maximum could be as large as 0.4 mm. Small FOV (at least 4 4 cm) scanners are used for capturing a small area within the mandible or maxilla, usually for preimplant assessment or periodontal or endodontic needs. The minimum voxel sizes here vary from 0.076 to 0.15 mm. Generally, smaller voxel sizes are used in small FOV scanners and larger voxel sizes are used in medium and large FOV scanners. The data volume of the CBCT study depends on the voxel size and to keep the

volumes practical for storage and transmission, optimal voxel sizes are employed. In a recent consensus of the International Congress of Oral Iimplantologists, the use of CBCT implant placement was discussed and the proceedings were recently published (Benavides et al, 2012). It is recommended that the CBCT along with all other radiographic examinations must be justified on an individual need basis for implant planning. The benefits of these examinations must clearly outweigh the potential radiation related risks. CBCT should be used as an imaging alternative in cases where the projected implant receptor site or the bone augmentation sites are suspects for adequacy of bone. When used, the smallest possible volume should be imaged and the entire volume should be interpreted. Implant manufacturers have developed specific designs for their implant fixtures taking into consideration the anatomy, retentive capacity and osseointegration ability of each implant. The implant interface that will face the bone is designed to promote osseointegration with the bone after implants are placed. Hence, the biocompatibility of implant material is very important for the success and long-term prognosis of the implant fixture. Radiographic appearance of screw-type and cylinder-type implants As shown in Figure 14, the implant fixtures are unique to each manufacturer and the type of implant can perhaps be recognized by the radiographic appearance of the fixture. The figure shows various Nobel Biocare’s root form implants. In Figure 15, the cylinder-type implants are noted (IMZ dental implants). The radiographic appearances will be useful in post-operative radiographic identification of the type of implants. 851


Figure 14

Nobel Biocare Replace Select Straight RP [4.3 × 11.5 mm]

Nobel Biocare Nobel Speedy Groovy RP [4.0 × 13 mm]

Nobel Biocare Nobel Speedy Shorty WP [6.0 × 7 mm]

Nobel Biocare Nobel Perfect (View A) [4.3 × 10 mm]

Nobel Biocare Nobel Perfect (View B) [4.3 × 10 mm]

Nobel Biocare Immediate Provisional Implant

Nobel Biocare (Branemark) Self-tapping [3.75 mm]

Nobel Biocare (Branemark) Conical Self-tapping [3.75 × 10 mm]

Nobel Biocare (Branemark) Branemark MK I [3.75 × 10 mm]

Nobel Biocare (Branemark) Branemark MK I [3.75 × 13 mm]

Radiographic appearance of screw-type dental implants manufactured by Nobel Biocare. Courtesy: www.whatimplantisthat.com

Figure 15

IMZ (Attachments Int.) High Cyclinder [4.25 × 11 mm]



IMZ (Attachments Int.) Hex Head [4.0 mm]

Cylinder-type IMZ’s dental implants. Courtesy: www.whatimplantisthat.com

Placement of implants, software manipulation and assessment of osseointegration The anatomy of the site should be thoroughly checked before attempting to measure the area. Typically, the height 852

and the width of the remaining bone are measured. This knowledge will help the clinician choose the implant with appropriate dimensions. In order to make sure that the implant size and placement angulation are predictable, the


clinician uses software that are either provided by the manufacturer or by utilizing the third party software separately via importing the data volume to the software. The implant is ‘virtually’ placed within the volume. Before placing the implant, the mandibular canal is mapped out

Figure 16

The existing complete denture can be used for fabrication of a radiographic guide and a surgical guide. Courtesy: Hani Braidy, DMD

via a process called ‘paint the canal’ using pre-identified coordinates. If a radiographic template/guide (Figure 16) was used before the radiographic examination, then that template can be converted to a surgical template by the laboratory using the information gained from the CT scans.

Figure 17

Lab prepared surgical guide in the patient’s mouth before implant placement. Courtesy: Hani Braidy, DMD

Figure 18

CBCT showing the anterior extension of the mental foramen (arrows) in the edentulous mandible. The CBCT-based cross-sections near the midline demonstrate the ‘lingual foramen’ which would be a blind sac that derives the neurovascular bundle from the lingual nerve and artery

853


The surgical template so formed will have the prefabricated implant guides. A typical surgical guide that has been fabricated using an existing denture is shown in the Figure 17.

The surgeon or the implantologist places the implant fixture using a surgical guide and based on whether the system is one-stage or two-stage, healing abutments would be placed before closure of the wound. Single-stage implants

Figure 19

CBCT cross-sectional views (parasagittal views) of the left mandible showing the ‘dumbbell-shaped’ anatomy and the clear delineation of the mandibular canal and the mental foramen (arrow)

Figure 20

Another instance of preimplant CBCT scan showing the reformatted panoramic view and cross-sectional views of the left molar area. Note the measurements that are directly digitally obtained from the sections

854


Figure 21

CBCT reformatted panoramic view and maxillary anterior cross-sections showing knife-edge shaped ridge

Figure 22

CBCT reformatted panoramic view and maxillary posterior cross-sections showing severely resorbed ridges bilaterally

855


Figure 23

Bone grafting completed in the maxilla bilaterally via sinus lift procedure as shown in the panoramic reconstruction of CBCT and left cross-sectional views of the maxilla

can be loaded immediately and the clinician can make that determination based on the type of implant, anatomy of the implant site and other pertinent factors. The inferior alveolar nerve canal is typically very distinct bilaterally up to the mental foramen. From mental foramen onward medially toward the midline, there are instances where the smaller branches of the mandibular canal continue even after the mental foramen, Figure 18 demonstrates one such example. Trauma to this foramen leads to excessive bleeding from the lingual vessels. A nerve injury in this area might lead to numbness of the sublingual area close to the genial tubercles. Hence, care should be exercised while planning implants in the anterior mandible between the two canines. In the posterior areas of the mandible, the location of the mental foramen and the mandibular canal are important landmarks for identification and measurement of the residual alveolar bone. The bone height and width are carefully measured and the bony anatomy of the ridge and the basal bone is observed for anatomical variations. One such variation could be a ‘dumbbell-shaped mandible’ as shown in Figure 19. If the bone width and alveolar bone direction is misjudged in such situations, it leads to selection of the wrong type of implant and possibly an unsuccessful outcome. During preimplant assessment of the site, the measurements are digitally obtained using the measuring tool provided 856

by the display and enhancement software (Figure 20). The measurements are usually considered 1:1 without any significant magnification or distortion. Hence, the measurements can be translated directly to the selection of appropriate implant sizes. Ridge resorption is noted commonly in the anterior maxilla as shown in Figure 21. Once a knifeedge like ridge is noted, then bone grafting becomes necessary to be able to place root form implants in that region. Posteriorly, if the ridge is severely resorbed (Figure 22) bone grafting can be done via ‘sinus-lift’ procedure and the appropriate implants can be placed using the newly gained bone volume (Figure 23). This has become increasingly common and complications are relatively rare with the improvements in both the technique and the materials used for grafting. If appropriate imaging is not performed before the implant placement, the implant fixtures could be disastrously placed sometimes leading to immediate loss of implants (Figure 24). Adequacy of bone and the quality of the bone is paramount to the success of the root form implant. The effective radiation doses are an important consideration before selecting any radiographic procedure. CBCT examinations should be prescribed only after a thorough patient examination preceded by collection of an equally thorough medical and dental history as was discussed in the beginning of this chapter. The effective radiation doses for CBCT-based procedures are in the range


Figure 24

A SimPlant® study of a patient showing the disastrous outcome of the implant fixtures. Poor planning and lack of preimplant imaging usually leads to such results. Note the displacement of an implant into the left maxillary sinus. Courtesy: Barry E Zweig, DDS

of 30–400 Sv as compared to a panoramic radiograph (2.7–23 Sv) and maxilla-mandibular CT (180–2,100 Sv). These measurements are based on effective radiation dose compilation from various studies. The dose comparisons can be found online at the European CBCT guidelines site for dental and maxillofacial radiology (www.sedentext.eu). Post-operative evaluation of implants and future directions Imaging modalities used in the post-operative evaluation of the dental implant patient include intraoral periapical radiography and panoramic radiography for assessment of

bone healing around the fixture. Three-dimensional imaging is recommended only when complications arise from the placement. A good example would be to evaluate the nerve canal proximity if the patient is symptomatic for nerve injury. In such situations, a limited volume CBCT would be ideal to evaluate the area. Dental implantology and implant imaging are rapidly expanding areas of dentistry. The information presented in this chapter should provide some basic concepts regarding implant selection, imaging and placement strategies for both doctoral and graduate level dental students. However, the reader is encouraged to follow the literature on the subject for a more up-to-date knowledge.

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SECTION

Appendices

XIII

Appendix 1 Appendix 2 Appendix 3 Appendix 4 Appendix 5

Terminologies Summary of Radiographic Pathology Characteristics of Ideal Radiograph Indications for Intraoral Radiography Patient Position for Extraoral Radiography

861 867 871 872 873

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Appendices.indd 859

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APPENDIX

1

Terminologies Ravikiran Ongole

Abrasion Pathologic wearing away of tooth substance due to an abnormal mechanical process, e.g. faulty toothbrushing technique.

Anomaly An irregularity or deviation from normal; an abnormal structure.

Abscess

Antibody An immunoglobulin molecule that reacts with a specific antigen that induced its synthesis. Synthesized by B lymphocytes that have been activated by the binding of an antigen to a cell surface receptor.

Localized collection of pus.

Absorbed dose ‘It is a measure of the total energy absorbed by any type of ionizing radiation per unit mass of any type of matter’. It is given by D ⫽ d␧/dm, where d␧ is the mean energy imparted to matter of mass (dm) by ionizing radiation. The SI unit for absorbed dose is gray (Gy). 1 Gy ⫽ 1 joule per kilogram (J/kg). The traditional unit of absorbed dose is rad (radiation absorbed dose). Acantholysis Dissolution of the intercellular bridges of the prickle cell layer of the epithelium. Acanthosis Hypertrophy or thickening of the prickle cell layer of the skin. Acute

Sudden onset of signs and a short course.

Agenesis organ. Ageusia

Absence or failure of formation of any part or A total lack of taste perception.

Agnosia Inability to classify or contrast odors, although able to detect odors. ALARA ‘As Low As Reasonably Achievable’, means that exposure to ionizing radiation should be kept as low as reasonably achievable, economic and social factors being taken into consideration.

Anosmia

Inability to detect odors.

Antigen Any substance, almost always a protein, not normally present in the body which when introduced to the body stimulates a specific immune response and the production of antibodies. Apoptosis (Greek—falling off) It is defined as programed cell death. The cell gets fragmented into membrane-bound particles that are subsequently eliminated by phagocytosis. Atopy A clinical hypersensitivity state which is subject to hereditary influences, e.g. asthma, eczema. Atresia Absence or closure of a normal body orifice or passage. Atrophy A decrease in the size of a normally developed organ or tissue. Attrition It is the physiological wearing away of tooth substance as a result of tooth-to-tooth contact, e.g. agerelated wearing away of the occlusal/incisal surfaces. Bacteremia

Presence of bacteria in blood.

Analgesia A drug that dulls the sense of pain. It relieves pain without loss of consciousness.

Becquerel (Bq) It is the international unit of radioactivity. It is defined as the number of radioactive decays (disintegrations)/unit of time. 1 Bq ⫽ 60 disintegrations/minute or 1 Bq ⫽ 1 disintegration/second.

Anaphylaxis The immediate immunologic (allergic) reaction initiated by the combination of antigen (allergen) with mast cell cytophilic antibody (chiefly IgE).

Blanching (French—white) It refers to change in color of a tissue to a paler and lighter shade when pressure is applied.

Anaplasia A condition in tumor cells in which there is loss of normal differentiation, organization and specific function. (Adult cells that have changed irreversibly toward more primitive cell types. These changes are often malignant.)

Bulla Elevated blister containing clear fluid and greater than 1 cm in diameter, e.g. pemphigus, pemphigoid. Cachexia This refers to a state of decreased tissue or organ mass resulting from a state of malnutrition or underlying severe debilitating disease. 861

Section XIII – Appendices

Carcinoma in situ The most severe stage of epithelial dysplasia, involving the entire thickness of the epithelium, with the epithelial basement membrane remaining intact. Cellulitis Acute inflammation which spreads rapidly through tissue spaces and along tissue planes. It is usually suppurative in nature. Chancre Painless ulceration formed during the primary stage of syphilis. This infectious lesion forms approximately 21 days after the initial exposure to Treponema pallidum. Cheilitis

Inflammation of the lips.

Cheilosis Condition characterized by fissuring and dry scaling of the vermilion border of lips (usually seen as a feature in riboflavin deficiency). Chloroma Malignant green color tumor occurring anywhere on the body and originating from myeloid tissue. These are associated with myelogenous leukemia. Choristoma Microscopically normal cells that are present in abnormal location. Chronic Slow onset, mild but continuous manifestations and long-lasting, often progressive effects. Congenital Conditions that are present at birth, regardless of their causation. Contusion A bruise; an injury of a part without a break in the skin, characterized by swelling, discoloration, and pain. Consanguinity In genetics, the term is generally used to describe mating or marriages among close relatives. Controlled area It is a limited access area in which the occupational exposure of personnel to radiation is under the supervision of an individual incharge of radiation protection. The reduced exposure in that area is to be ⬍26 mC/kg/week. Curie (Ci) The number of radioactive decays (disintegrations)/unit of time. 1 Ci ⫽ 2.2 ⫻ 1012 disintegrations/minute 1 Ci ⫽ 3.7 ⫻ 1010 disintegrations/second. Cyst It is a pathological cavity filled with a fluid, semifluid or gaseous material but not by pus, which may frequently but not always lined by epithelium. Decay Radioactive decay or the disintegration of the nucleus of an unstable atom by spontaneous emission of energy in the form of high speed particles or electromagnetic waves.

862

Diagnosis, final It is the diagnosis that is arrived at after all the necessary data history, clinical examination and investigations have been collected, analyzed and subjected to a logical thought process. Disintegration

A spontaneous nuclear transformation.

Disorder, congenital It is the disorder which occurs during the development process (intrauterine life). The manifestation of which is seen either at birth or later in life. Disorder, developmental It is the abnormality that occurs during the formative stage of an organ or tissue. Disorder, genetic It is a disorder caused by abnormality in the gene or an abnormality in mutation. Disorder, inherited It is the disorder, which is transmitted through genes to the offspring of the next generation or to subsequent generations. Dose It is the amount of energy absorbed per unit of mass at a site of interest. Expressed in units of rad or gray. Dose equivalent (DE) Absorbed dose multiplied by certain modifying factors. The principle factor is the quality factor (QF), which corrects absorbed dose for relative biological damage for quality factors for: Beta, gamma and X-rays ⫽ 1 Alpha ⫽ 20 1 rad ⫽ 1 rem for beta, gamma and X-ray. Various types of radiation, expressed in units of rem or sievert. a.

b. c.

Deep dose equivalent—applies to the external whole body exposure in terms of dose equivalent at a tissue depth of 1 cm (1,000 mg/cm2). Shallow dose equivalent—applies to the skin at a max. Tissue depth of 0.007 cm (7 mg/cm2). Effective dose equivalent—is the sum of the product of the dose equivalents each weighted by a factor for the tissue organ in question.

Dose, loading A larger than normal dose administered as the first in a series of doses, the others of which are smaller than loading dose but equal to each other. The loading dose is administered in order to achieve a therapeutic amount in the body more rapidly than would occur only by accumulation of the repeated smaller doses. Dose, maintenance The smaller doses which are given after the loading dose are called ‘maintenance’ doses.

Diagnosis, clinical/provisional/tentative It is the diagnosis that is made after thorough case history taking and clinical examination but before any investigations are performed.

Drug, bioavailability The percentage of dose entering the systemic circulation after administration of a given dosage form.

Diagnosis, differential Identification of a particular disease by differentiating it from all other disease processes that may have similar symptoms and signs.

Drug, first pass effect All drugs that are absorbed from the intestine enter the hepatic portal vein and pass through the liver before they are distributed systemically.

Appendix 1 – Terminologies

Drug, half-life The period of time required for the concentration or amount of drug in the body to be reduced to exactly one-half of a given concentration or amount. Dysgeusia

An altered taste sensation.

Dysosmia

Distorted identification of smell.

Dysphagia lowing.

Painful swallowing or difficulty in swal-

Dysplasia An abnormality of development characterized by the loss of normal cellular architecture. Ecchymosis Larger purpuric lesions. Edema Accumulation of excess fluid in the intercellular or interstitial tissue spaces or body cavities. Effective dose (E) It is a radiation quantity used to estimate the risk in humans. It is the tissue-weighted sum of the equivalent doses in all specified tissues and organs of the body, given by the expression: E ⫽ ⌺T WT ⌺RWRDT, R

or

E ⫽ ⌺WT X HT

where HT or WR DT, R is the equivalent dose in a tissue or organ T, and WT is the tissue weighting factor. The unit for the effective dose is the same as for absorbed dose, J kg⫺1, and its special name is sievert (Sv). Epiphora

Tearing from the eye.

Epistaxis

Bleeding from the nose.

Equivalent dose (HT) It is a radiation quantity used to compare the biological effects of different types of radiation on a tissue or organ. The dose in a tissue or organ T is given by: HT ⫽ ⌺WRDT, R where DT, R is the mean absorbed dose from radiation R in a tissue or organ T and WR is the radiation weighting factor. Since WR is dimensionless, the unit for the equivalent dose is sievert (Sv). 1 Sv ⫽ 1 Gy. Traditional unit of equivalent dose is the rem (Roentgen equivalent man). Erosion A shallow defect in the oral mucosa representing a loss of covering epithelium down to, but not involving the stratum germinatum, e.g. erosive lichen planus. Erosion (wasting disease) It is the loss of tooth substance by a chemical process that does not involve known bacteria, e.g. excessive consumption of citrus fruits. Exposure A special radiation quantity of ionization in air from X-rays or gamma rays. It is measured as the amount of charge per mass of air, which is coulombs/kg. Units are expressed in roentgen (R). 1 R ⫽ 2.58 ⫻ 10⫺4 C/kg. External exposure Radiation exposure from a source outside the body.

Exudate Fluid with a high concentration of protein and cellular debris which has escaped from blood vessels and has been deposited in tissues, or on tissue surfaces, usually as a result of inflammation. (Specific gravity can be 1.020 or higher and high protein content can be 1–6 g/dl.) Fascial spaces Potential tissue spaces through which infection spreads easily, e.g. submandibular space, buccal space, pterygomandibular space. Final diagnosis It is the diagnosis arrived at after all the data has been collected, analyzed and subjected to logical thought. Fistula It is an abnormal communicating tract between two epithelial surfaces or organs. A fistulous tract is generally lined with granulation tissue but over a period of time may become epithelialized. Pain in the tongue.

Glossodynia Glossopyrosis

Burning sensation in the tongue.

Granuloma Tumor-like mass of inflammatory tissue consisting of a central collection of macrophages, often with multinucleated giant cells, surrounded by lymphocytes. Granulomatous Pertaining to a well-defined area that has developed as a reaction to the presence of living organisms or a foreign body. The tissue consists primarily of histiocytes. Gray (Gy) The international unit of absorbed dose. 1 Gy ⫽ 100 rad; 1 Gy ⫽ 1 joule/kilogram (J/kg). Hamartoma Abnormal proliferation of tissues of structures native to the part. Hematoma Tumor-like mass produced by coagulation of extravasated blood into tissues from ruptured blood vessels. Hemiparesis Hemiplegia

Weakness on one side of the body. Paralysis of one side of the body.

Hereditary A condition that may be genetically transmitted from parent to offspring. High radiation area It is defined as an area, accessible to individuals, in which radiation levels from radiation sources, external to the body could result in an individual receiving a dose equivalent in excess of 0.1 rem (100 mrem) in 1 hour at 30 cm from the radiation source or from any surface that the radiation penetrates. Hyperemia Presence of an increased amount of blood in a part or an organ. Hyperplasia Enlargement caused by an increase in the number of normal cells. Hypertelorism Abnormal increased distance between two organs or parts. Ocular hypertelorism refers to increased interorbital distance. 863


Hypertrophy Increase in the size or volume of a tissue or organ as a result of enlargement of the cell. Hypogeusia

Substantial loss of all taste sensation.

Hypoplasia Incomplete development of a tissue or organ; a tissue reduced in size because of a decreased number of constituent cells. Hyposmia

Decreased ability to detect odors.

Iatrogenic Adverse condition in a patient resulting from treatment by a physician or surgeon. Id reaction Hypersensitivity reaction to candidal antigen, manifests as vesicular and papular rash on skin of patients with chronic candidiasis. Idiopathic Occurring without known cause. Induration Abnormally hard portion of a tissue with respect to the surrounding similar tissue; often used to describe the feel of locally invasive malignant tissue on palpation. Ischemia A local deficiency of blood due in part to functional constriction or actual mechanical obstruction of a blood vessel. Kerma (K) It is the quotient of the sum of the kinetic energies, dEtr, of all charged particles liberated by uncharged particles in a mass, dm, of material. K ⫽ dEtr/dm

Nevus A small flat elevated pigmented or non-pigmented lesion of congenital origin involving the skin or mucous membrane. Nodule Solid, elevated lesion varying in size from 5 mm to 2 cm, e.g. fibroma. Oral diagnosis It is the art of using scientific knowledge to identify oral disease process and to distinguish one disease process from the others. Oral medicine It is the specialty of dentistry that is concerned with the oral healthcare of medically compromised patients and with the diagnosis and non-surgical management of medically related disorders or conditions affecting the oral and maxillofacial region. Oral medicine specialists are concerned with the non-surgical medical aspects of dentistry. These specialists are involved in the primary diagnosis and treatment of oral diseases that do not respond to conventional dental or maxillofacial surgical procedures. The practice of oral medicine will provide optimal health to all people through the diagnosis and management of oral diseases. Papule Small circumscribed solid elevated lesion varying in size from a pinhead to 5 mm, e.g. Fordyce’s granules. Paraparesis

Weakness affecting the lower extremities.

Kerma is a non-stochastic quantity and dEtr is the expectation value of the sum of the kinetic energies. The unit for kerma is joule per kilogram (J/kg) and its special name is gray (Gy).

Paraplegia

Lesion A morphological alteration of the tissue with objective signs of disease.

Paresthesia It is an altered sensation or abnormal sensation (tingling sensation).

Linear energy transfer (L or LET) It is the average linear rate of energy loss of charged particle radiation in a medium, i.e. the radiation energy lost per unit length of path through a material. That is, the quotient of dE by dl where dE is the mean energy lost by a charged particle owing to collisions with electrons in traversing a distance dl in matter.

Parosmia Altered perception of smell in the presence of an odor, usually unpleasant.

L ⫽ dE/dl

Paresis

Paralysis of the lower limbs.

Slight or partial paralysis.

Paroxysmal

Recurring ‘sudden attacks’ of symptoms.

Parulis A sessile nodule on the gingiva at the site where a draining sinus tract reaches the surface. Petechiae Pinpoint purpuric spots, 1–2 mm in diameter.

The unit of L is Jm⫺1, often given in keV ␮m⫺1.

Phantosmia Perception of smell without an odor present.

Macule It is a circumscribed non-raised area of altered coloration varying in size from a pinhead to several centimeters in diameter, e.g. petechiae, melanin pigmentation in Addison’s disease.

Plaque A circumscribed solid elevated lesion greater than 5 mm in diameter, e.g. leukoplakia.

Metastasis The transport of neoplastic cells to parts of the body remote from the primary tumor and the establishment of new tumors in those sites. Necrosis 864

Neoplasm Abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change.

Death of a cell as a result of disease or injury.

Precancerous condition Generalized state associated with a significantly increased risk of cancer, e.g. Plummer– Vinson syndrome, oral submucous fibrosis. Precancerous lesion A morphologically altered tissue in which cancer is more likely to occur than its normal counterpart, e.g. erythroplakia, leukoplakia.

Appendix 1 – Terminologies

Prognosis It is the prediction of the course, duration and termination of a disease and the likelihood of its response to treatment. Ptosis

Drooping of the upper eyelid.

Purpura Reddish to purple flat lesions caused by blood leaking into the subcutaneous tissue. They do not blanch on pressure. Depending on their size they are termed as purpura or petechiae. Larger petechiae are purpura.

It accounts for the different degrees of damage produced by equal doses of different radiations. Example: Radiation weighing factor (Wr): for X-rays, gamma rays, beta particles ⫽ 1 Neutrons (range) ⫽ 2–20; alpha particles ⫽ 20. Sarcoma It is a malignant tumor arising from connective tissue. Septicemia

Presence of bacterial toxins in blood.

Pustule It is a vesicular type of lesion containing pus, e.g. pyostomatitis.

Sessile The term describes the base of the lesion which is flat or broad.

Quadriplegic

Sievert (Sv) The special name for the SI unit of equivalent dose, effective dose, and operational dose quantities. The unit is joule per kilogram (J kg⫺1). 1 Sv ⫽ 100 rem; 1 Sv ⫽ 1 Gy ⫻ Wr.

Paralyzed in all four limbs.

Quality factor (QF) A linear energy transfer dependent factor by which absorbed dose is multiplied to obtain a dose quantity, dose equivalent, to indicate the biological effectiveness of absorbed dose. Radiation The emission and propagation of energy through space. Radiation absorbed dose (rad) The energy absorbed per gram of material. It represents the amount of energy that is absorbed by the material of interest, e.g. person, organ, tissue, cells. 1 rad ⫽ 100 erg/g. Radiation area It is an area, accessible to individuals, in which radiation levels could result in an individual receiving a dose equivalent in excess of 0.005 rem (5 mrem) in 1 hour at 30 cm from the radiation source or from any surface where the radiation penetrates. Radiation weighting factor (WR) A dimensionless factor by which the organ or tissue absorbed dose is multiplied to reflect the higher biological effectiveness of high-LET radiations compared with low-LET radiations. It is used to derive the equivalent dose from the absorbed dose averaged over a tissue or organ. Red lesion A non-specific term used to describe any area on the oral mucosa that on clinical examination appears more red than the surrounding tissues and is usually velvety or granular or smooth in texture. Restricted area An area, access to which is limited by the licensee for the purpose of protecting individuals against undue risks from exposure to radiation and radioactive materials. Roentgen (R) It is a unit of radiation exposure in air. It is defined as the amount of X-ray or gamma radiation that will generate 2.58 ⫻ 10⫺4 coulombs (a measure of electrical charge) per kilogram of air at standard temperature and pressure. This can also be defined as the amount of energy absorbed in air. This unit is applied for only X-rays and gamma rays. Roentgen equivalent man (rem) The product of the amount of energy absorbed (rad) times the coefficient of radiation in producing damage. rem ⫽ rad ⫻ (Wr)

Sign Any change in the body or its function, which is perceptible to a trained observer and may indicate a disease. Sinus It is a blind tract that connects a cavity lined by granulation tissue to the epithelial surface. This lining may subsequently become epithelialized. Stochastic effect It is the sub-lethal changes in the DNA of an individual cell and the heritable effects for which the probability of an effect occurs, but not its severity. It is regarded as a function of dose without threshold. Swelling It is a non-specific term used to describe any enlargement or protuberance in the body. Symptom Any change in the body or its function, which is perceptible to the patient and may indicate a disease. Teratoma A true neoplasm made up of a number of different types of tissues, none of which is native to the area in which it occurs. Therapy, curative Treatment directed toward eradication of one or more of the agencies etiologic to the patient’s condition, e.g. use of antibiotics such as penicillin. Therapy, palliative or symptomatic Treatment directed only toward relief of the patient’s symptoms. The natural course of the disease is unaffected. Therapy, restorative Therapy directed at rapid restoration of health, usually regardless of the nature of the original disease; restorative therapy is most frequently given during convalescence, e.g. vitamin supplements. Therapy, substitutive or replacement Treatment directed toward supplying a material normally present in the body, but absent in a specific patient because of disease, injury, congenital deficiencies, etc., e.g. use of hormones. Therapy, supportive Treatment directed toward maintaining the patient’s physiological or functional integrity until more definitive treatment can be carried out, or until the patient’s recuperative powers function to obviate the need for further treatment. 865


Tissue weighting factor (WT) The factor by which the equivalent dose in a tissue or organ T is weighted to represent the relative contribution of that tissue or organ to the total health detriment resulting from uniform irradiation of the body. It is weighted such that: WT ⫽ 1. Tumor Any enlargement, especially one due to a pathological overgrowth of tissue. Ulcer Breach in the continuity of the surface epithelium of the skin or mucous membrane to involve the underlying connective tissue as a result of micromolecular cell death of the surface epithelium or its traumatic removal.

866

Uncontrolled area It is an area where access is neither controlled nor restricted. In an uncontrolled area the shielding should reduce the exposure rate to ⬍ 2.6 mC/kg/week. Vesicle Elevated blisters containing clear fluid and less than 1 cm in diameter, e.g. herpes simplex infection, herpangina, herpes zoster. Viremia Presence of viruses in blood. White lesion Non-specific term used to describe any area of the oral mucosa that on clinical examination appears whiter than the surrounding tissues and is usually raised, roughened or otherwise of a different texture than the adjacent normal tissue.

APPENDIX

Summary of Radiographic Pathology

2

Medha Babshet

Table 1

Radiolucent lesions affecting the jaws Unilocular

Associated with teeth Pericoronal

Periapical

Others

• • • • •

• • • • •

• • • • • • • •

Inflammatory paradental cyst Dentigerous cyst Mural ameloblastoma Keratocystic odontogenic tumor (OKC) Adenomatoid odontogenic tumor (early stage) • Ameloblastic fibroma

Periapical granuloma Periapical cyst Dentoalveolar abscess Periapical scar Periapical cemento-osseous dysplasia (lytic stage)

Not associated with teeth

Traumatic bone cysts Globulomaxillary cyst Incisive canal cyst Lateral periodontal cyst Gingival cyst of adult Cemento-ossifying fibroma (early stage) Residual cysts Squamous odontogenic tumor

• • • • •

Primordial cyst Stafne’s bone cyst Neurilemmoma Traumatic neuroma Post-surgical maxillary cyst

Multilocular Associated with teeth


• • • • • •

• • • • • • • • •

Ameloblastoma Keratocystic odontogenic tumor (OKC) Botryoid odontogenic cyst Odontogenic myxoma Glandular odontogenic cyst Central odontogenic fibroma

Central giant cell granuloma Brown tumor of hyperparathyroidism Cherubism Aneurysmal bone cyst Central hemangioma Arteriovenous malformation Desmoplastic fibroma Metastatic tumors of jaw Focal osteoporotic bone marrow defects

867


Table 2

Radiopaque lesions affecting the jaws Focal

Generalized

Associated with teeth


• • • • • • • • •

• • • • • • • • • • •

Condensing osteitis Idiopathic osteosclerosis Garrey’s osteomyelitis Hypercementosis Periapical cemento-osseous dysplasia Focal cemento-osseous dysplasia Cemento-ossifying fibroma Cementoblastoma Complex odontoma

Table 3

Tori Exostosis Osteomas Foreign bodies Mucosal cysts of maxillary sinus Ectopic calcification Sialolith Rhinolith Calcified lymph node Phlebolith Arterial calcification

• • • • • • •

Florid cemento-osseous dysplasia Paget’s disease Osteopetrosis Albright’s syndrome Gardner’s syndrome Caffe’s disease (infantile cortical hyperostosis) Familial gigantiform cementoma

Mixed radiolucent-radiopaque lesions of the jaws Associated with teeth

868


Periapical

Pericoronal

• Rarefying and condensing osteitis • Periapical cemento-osseous dysplasia (intermediate stage) • Cemento-ossifying fibroma

• • • • • • • •

Odontoma (intermediate stage) Adenomatoid odontogenic tumor Calcifying epithelial odontogenic cyst Calcifying epithelial odontogenic tumor Ameloblastic fibro-odontoma Ameloblastic odontoma Ameloblastic fibrodentinoma Dentinoma

• • • • • • • • • • • •

Chronic osteomyelitis Osteoradionecrosis Focal cemento-osseous dysplasia Florid cemento-osseous dysplasia Fibrous dysplasia Paget’s disease (intermediate stage) Cemento-ossifying fibroma Osteogenic sarcoma Desmoplastic ameloblastoma Osteoblatic metastatic carcinoma Chondroma Chondrosarcoma

Appendix 2 – Summary of Radiographic Pathology

Table 4

Characteristic radiographic findings of jaw pathologies

Characteristic radiographic finding

Jaw lesions

Cotton wool

• • • •

Ground glass

• Hyperparathyroidism • Fibrous dysplasia

Orange peel

• Fibrous dysplasia

Soap bubble appearance

• • • • • • • •

Honeycomb appearance

• Ameloblastoma • Central hemangioma of bone

Tennis racket appearance

• Odontogenic myxoma

Moth eaten

• • • • •

Driven snow

• Pindborg’s tumor (CEOT)

Codman’s triangle Cumulus cloud formation

• Osteosarcoma

Onion peel appearance

• • • • • • • • • •

Garre’s osteomyelitis Calcifying subperiosteal hematoma Ewing’s sarcoma Osteogenic sarcoma Leukemia Syphilis Hypervitaminoses A Caffey’s disease Metastatic neuroblastoma Fracture callus

Sunray (sun burst) appearance

• • • • • •

Osteosarcoma Ewing’s sarcoma Hemangioma (central) Chondrosarcoma Odontoma (rarely) Burkitt’s lymphoma

Hair-on-end

• Sickle cell anemia • Thalassemia • Chronic iron deficiency anemia

Stepladder appearance

• Thalassemia • Sickle cell anemia

Chicken wire appearance of enlarged marrow spaces

• Thalassemia

Paget’s disease Diffuse sclerosing osteomyelitis Florid osseous dysplasia Sclerotic cemental masses

Hemangioma Aneurysmal bone cyst Cherubism Ameloblastoma Giant cell lesion of hyperparathyroidism Central giant cell granuloma Odontogenic cysts like odontogenic keratocyst, follicular and residual Arteriovenous malformation

Burkitt’s lymphoma Chronic suppurative osteomyelitis Lytic variety of osteosarcoma Osteoradionecrosis Osteosarcoma (lytic type)

(Contd.)

869


Table 4

Continued

Characteristic radiographic finding

Jaw lesions

Beaten silver

• • • • • • •

Punched out

• Multiple myeloma • Histiocytosis X • Eosinophilic granuloma

Salt and pepper

• Metastatic lesions • Hyperparathyroidism • Fibrous dysplasia

Floating teeth appearance

• • • • •

Ballooning expansion

• Follicular cyst • Aneurysmal bone cyst

Candle stick appearance

• Progressive systemic sclerosis • Pyknodysostosis

Chalk like appearance

• Osteopetrosis • Hyperparathyroidism • Pyknodysostosis

Egg shell appearance

• Multilocular cyst • Ameloblastoma

Heart-shaped radiolucency

• Nasopalatine cyst

Pear-shaped radiolucency

• Globulomaxillary cyst

Craniofacial synostosis & dysostosis Calcifying subperiosteal hematoma Leukemia Caffey’s disease Metastatic neuroblastoma Hypervitaminoses A Syphilis

Histiocytosis X Squamous cell carcinoma of gingiva Papillon–Lefevre syndrome Advanced periodontitis Cherubism

Other characteristic radiographic findings

870

Bull’s eye appearance

Dilaceration of roots

Moth eaten appearance of crowns of teeth

Amelogenesis imperfecta especially the hypocalcified type

Shell teeth


Thistle tube-shaped pulp chambers in anteriors Flame-shaped pulp chambers in molars

Type II/coronal dentin dysplasia

Ghost-like teeth

Regional odontodysplasia

Trap door sign

Blow-out fracture involving the orbit

Hanging drop/tear drop sign

Herniation of orbital contents into the maxillary sinus

Joint mice

Small calcifications (Loose bodies) within the temporomandibular joint space

APPENDIX

Characteristics of Ideal Radiograph

3


CHARACTERISTICS OF IDEAL RADIOGRAPH Ideal radiograph is one with optimum density and contrast showing all the details which are well defined with minimum or negligible distortion. An ideal radiograph should have optimum visual characteristics (density and contrast), geometric characteristics (sharpness, minimal or no magnification and distortion), record anatomical accuracy of radiographic images and exhibit adequate coverage of anatomic region of interest. A radiograph should record the complete area of interest. For an intraoral periapical radiograph (IOPAR) the full length of root and at least 2 mm of periapical bone should be visible.

a short gray scale. A low contrast radiograph displays many shades of gray and thus exhibits a long gray scale. For all practical purposes, an ideal radiograph is a compromise between high and low contrast.

Sharpness Sharpness is also referred to as detail, resolution or definition. It refers to the capability of X-rays to reproduce distinct outlines of an object or to reproduce the smallest details of an object. Intraoral periapical radiographs have better resolution than panoramic radiograph and computed tomographic scans. Resolution is described as line pairs per mm.

Density

Magnification

Density is the degree of overall blackness or darkness of a dental radiograph. The primary factors that affect density are kilovoltage peak (kVp), milliamperage (mA), exposure time and the source to film distance. Some of the secondary factors the affect density are development characteristics (dark and light radiographs), subject thickness, speed of film, film latitude, use of screens and grids and extent of filtration.

Radiographic image that appears larger than the object it represents, because of the divergent path of X-rays.

Contrast Contrast is difference in the degree of blackness (densities) between adjacent areas on a dental radiograph. A high contrast radiograph is one with very dark and very light areas. Such a radiograph is considered to exhibit

Distortion Distortion is the variation in the true size and shape of the object being recorded. It results from unequal magnification of different parts of the object.

Characteristic Curve Characteristic curve is a graphic plot of relationship between film density and exposure. It is also called H and D curve after Hunter and Driffield.

871

APPENDIX

4


Indications for Intraoral Periapical Radiography

Indications of Bitewing Radiography

❍

❍

❍

❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍ ❍

872

Indications for Intraoral Radiography

Assessment of developmental disturbances affecting the root morphology for diagnosis, exodontia and endodontic treatment Assessment of dental caries and periapical pathology (including status of periodontal ligament space, integrity of lamina dura and bone changes at the periapical region of teeth) Assessment of the periodontal ligament space and interdental bone in periodontal diseases Detection of dento-alveolar fractures Assessment of the quality of the bone prior to placement of dental implants Detection of small cysts and tumors affecting the jaw bones Detection of the presence and position of the impacted teeth (supernumerary, odontomes, etc.) Detection of secondary caries beneath restorations and crowns Detection of foreign material embedded within the soft tissue such as the lip, buccal mucosa Detection of the status of eruption of primary/permanent teeth Assessment of endodontic treatment Assessment of alveolar bone grafts

❍

❍ ❍ ❍ ❍

Proximal regions of three maxillary and three mandibular teeth can be assessed in a single radiograph Detection of incipient proximal caries (however, if the carious lesions is deep, IOPAR should be taken to assess any periapical change) Detection of alveolar crestal bone loss Assessment of ill-fitting/overcontoured crowns Assessment of overhanging restorations Detection of secondary caries

Indications of Occlusal Radiography ❍ ❍

Provides a bird’s eye view of the dental arches Detection of cortical plate changes caused by bony pathology (cysts, tumors) in a buccolingual direction (such as expansion, resorption, pathological fractures, laminar bone formation etc.) ❍ Location of impacted teeth (buccal/lingual position) ❍ Detection of sialoliths (calculi in the ducts of the submandibular salivary gland and sublingual gland) ❍ Detection of symphyseal, parasymphyseal mandibular fractures

APPENDIX

Patient Position for Extraoral Radiography

5

Suman Jai Sanghar, Jai Sanghar N

Figure 1

Figure 2

Posteroanterior view

Posteroanterior Calwell view

OML: orbitomeatal line, CR: central ray. 873


Figure 3

Figure 5

Posteroanterior mandible

Figure 4

Figure 6

Standard occipitomental view

874

30⬚ occipitomental view

Waters’ view

Appendix 5 – Patient Position for Extraoral Radiography

Figure 7

Figure 9

Open mouth Waters’ view

Figure 8

Patient’s head positioning for reverse Waters’ view

Patient’s head position for submentovertex view

Figure 10

Patient’s head position for lateral view projection

875


Figure 11

Figure 13

Patient’s head position for Townes’ view

Figure 12

Patient’s head position for reverse Townes’ view

876

Patient’s head position for lateral oblique view of the ramus

Figure 14

Patient’s head position for transcranial view

Appendix 5 – Patient Position for Extraoral Radiography

Figure 15

Figure 16

Patient’s head position for transorbital view

Patient’s head position for transpharyngeal view

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CHAPTER 16 Barr PN, Brown NC, Hammer JE. Hyperphosphatasia: report of 2 cases with dental findings. Periodontics 1964;2:209–15. Carranza FA Jr, Cabrini RL, Lofrez Otero. Histometric analysis of interadicular bone in protein deficient animals J Periodontal Res 1969;4:292. Cawson RA 1962. The Oral changes in Gargoylism Proceeding of the Royal Society of Medicine 1962;55:1066–77. Charon J, Margenhagen S, Gallin J. Ginvitis and oral ulceration in patients with neutrophil destruction. J Oral Pathol 1985;14:159–5. Corman KS, Crane A, Wang HY, et al. The interleukin I Genotype as a severity factor in adult periodontal disease. J Clin periodontal 1997;24:72–7.

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CHAPTER 17 Al-Dlaigan YH, Shaw L, Smith A. Dental erosion in a group of British 14-yearold, school children. Part I: Prevalence and influence of differing socioeconomic backgrounds. BDJ 2001;190(3):145–9. Aw TC, Lepe X, Johnson GH, et al. Characteristics of noncarious cervical lesions: a clinical investigation. J Am Dent Assoc 2002;133:725–33. Bartlett D, Ganss C, Lussi A. Basic Erosive Wear Examination (BEWE): a new scoring system for scientific and clinical needs. Clin Oral Investig 2008; 12(Suppl 1):S65–8. Epub 2008 Jan 29. Bartlett DW, Shah P. A critical review of non-carious cervical (wear) lesions and the role of abfraction, erosion, and abrasion. J Dent Res 2006;85(4):306–12. Bell EJ, Kaidonis J, Townsend GC. Tooth wear in children with Down syndrome. Aust Dent J 2002;47(1):30–5. Bodecker CF. Local acidity: a cause of dental erosion-abrasion. Ann Dent 1945;4(1):50–5. Centerwall BS, Armstrong CW, Funkhouser LS, et al. Erosion of dental enamel among competitive swimmers at a gas-chlorinated swimming pool. Am J Epidemiol 1986;123:641–7. Chaudhry SI, Harris JL, Challacombe SJ. Dental erosion in a wine merchant: an occupational hazard? Br Dent J 1997;182:226–8. Chikte UM, Grobler SR, Kotze TJ. In vitro human dental enamel erosion by three different wine samples. SADJ 2003;58:360–2. Chikte UM, Naidoo S, Kolze TJ, et al. Patterns of tooth surface loss among winemakers. SADJ 2005;60:370–4.

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CHAPTER 19 Abdelsayed RA, Eversole LR, Singh BS, et al. Gigantiform cementoma: clinicopathologic presentation of 3 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91(4):438–44. Adekeye EO, Edwards MB, Goubran GF. Fibro-osseous lesions of the skull, face and jaws in Kaduna. Nigeria Br J Oral Surg 1980;18:57–72. Agazzi C, Belloni L. Gli odontomi duri dei mascellari: contributo clinicorontgenologico e anatomo-microscopico con particolare riguardo alle forme ad ampia estensione e alla comparsa familiare. Arch Ital Otol 1953; 64(Suppl 16):3–102. Albright F. Polyostotic fibrous dysplasia: a defense of the entity. J Clin Endocrinol 1947;7:307–24. Albright F, Butler AM, Hampton AO, et al. Syndrome characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction, with precocious puberty in females: report of five cases. N Engl J Med 1937;216:727–46. Benjamins CE. Das osteoid-fibroma mit atypischer Verkalkung im sinus frontalis Acta Otolaryngol 1938;26:26–43. Bradley ES Jr, Leake D. Ossifying fibroma involving the maxilla and the mandible; report of a case. Oral Surg Oral Med Oral Pathol 1968;26: 605–14. Cannon JS, Keller EE, Dahlin DC. Gigantiform cementoma: report of two cases (mother and son). J Oral Surg 1980;38:65–70. Daffner RH, Kirks DR, Gehweiler JA Jr, et al. Computed tomography of fibrous dysplasia, AJR Am J Roentgenol 1982;139:943–8. Edwards PA, Corio RL. Benign fibro-osseous lesions of the jaws. Ear Nose Throat J 1984;63:383–92.

CHAPTER 18

CHAPTER 20

Brand HS, Abraham-Inpijn L. Cardiovascular responses induced by dental treatment. Eur J Oral Sc 1996;104:245–52. Carmona IT, Scully C. An update on the controversies in bacterial endocarditis of oral origin. Oral surg Oral Med Oral Pathol Oral Radiol Endod 2002; 93:660–70. Dajani AS, Taubert KA, Wilson W, et al. Prevention of bacterial endocarditis: Recommendations by the American Heart Association. JAMA 1997;277: 1794–801. Demmer RT, Desvarieux M. Periodontal infections and cardiovascular disease: the heart of the matter. J Am Dent Assoc 2006;137(Suppl):14S–20S. Genco R, Offenbacher S, Beck J. Periodontal disease and cardiovascular disease: epidemiology and possible mechanisms. J Am Dent Assoc 2002; 133(Suppl):14S–22S. Glick M. Screening for traditional risk factors for cardiovascular disease: a review for oral health care providers. J Am Dent Assoc 2002;133(3):291–300. Imperiale TF, Horwitz RI. Does prophylaxis prevent postdental infective endocarditis? A controlled evaluation of protective efficacy. Am J Med 1990; 88:131–6.

Aaron Samsula, Alan Menter M. Persistent rash on the face and lips. Proc (Bayl Univ Med Cent) 2003;16(4):488–90. Abaza Nabil et al. The role of labial salivary gland biopsy in the diagnosis of Sjogrens syndrome: Report of Three Cases. J Oral Maxillofac Surg 1993; 51:574–80. Anavi Y, Mintz S. Benign Lymphoepithelial lesions of the sublingual gland. J Oral Maxillofac Surg 1992;50:1111–13. Andrade RE, Hagenk A, Manivel JC. Distribution and immuno phenotype of the inflammatory cell population in the benign lymphoepithelial lesion. Human Pathol 1988;19:932–41. Anhalt JG. Paraneoplastic pemphigus- An autoimmune mucocutaneous disease associated with neoplasia. N Engl J Med 1990;323:1729–35. Anusaksthrin O, Dolby AE. Autoimmunity and periodontal disease. J Oral Pathol 1991;20:101–7. Altman RD, Medsgar TA Jr, Bloch DA, et al. Predictors of survival in systemic sclerosis. Arthritis Rheum 1991;34:403–13. Artlett CM, Smith JB, Jimenez SA: New perspectives on the etiology of systemic sclerosis. Mol Med Today 1999;5(2):74–8.

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CHAPTER 21 Britton WJ, Lockwood DN. Leprosy. Lancet 2004;363(9416):1209–19. de Abreu MA, Michalany NS, Weckx LL, et al. The oral mucosa in leprosy: a clinical and histopathological study. Rev Bras Otorrinolaringol (Engl Ed) 2006;72(3):312–6. Lockwood D. Leprosy. Clin Evid 2006;(15):1079–87. Morgado de Abreu MA, Mota de Avelar Alchorne M, Michalany NS, et al. The oral mucosa in paucibacillary leprosy: a clinical and histopathological study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;[Epub ahead of print]. Ridley DS, Jopling WH. Classification of leprosy according to immunity. A fivegroup system. Int J Lepr Other Mycobact Dis 1966;34(3):255–73. Scollard DM, Skinsnes OK. Oropharyngeal leprosy in art, history, and medicine. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87(4):463–70. Srinivasan S, Nehru VI, Bapuraj JR, et al. CT findings in involvement of the paranasal sinuses by lepromatous leprosy. Br J Radiol 1999;72(855):271–3. Tuberculosis in Canada 2005 Pre-Release a publication by the Public Health Agency of Canada; report accessed at http://www.publichealth.gc.ca/ tuberculosis Jan 2007. WHO facts sheet at http://www.who.int/mediacentre/factsheets/fs104/en/ index.html. Yepes JF, Sullivan J, Pinto A. Tuberculosis: Medical Management update. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;98:267–73.

CHAPTER 22 Alexander WN, Nagy WW. Gonococcal arthritis of the temporomandibular joint. Report of a case. Oral Surg Oral Med Oral Pathol 1973;36(6):809–13. Barsh LI. Molluscum contagiosum of the oral mucosa. Report of a case. Oral Surg Oral Med Oral Pathol 1966;22(1):42–6. Bonci A, Di Lernia V, Lo Scocco G, et al. A patient with primary syphilis of the finger. Acta Derm Venereol 2001;81(5):382–3. Brown TJ, Yen-Moore A, Tyring SK. An overview of sexually transmitted diseases. Part I. J Am Acad Dermatol 1999;41(4):511–32. Bruce AJ, Rogers RS 3rd. Oral manifestations of sexually transmitted diseases. Clin Dermatol 2004;22(6):520–7. Buntin DM, Rosen T, Lesher JL Jr, et al. Sexually transmitted diseases: bacterial infections. Committee on Sexually Transmitted Diseases of the American Academy of Dermatology. J Am Acad Dermatol 1991;25(2 Pt 1):287–99. Buntin DM, Roser T, Lesher JL Jr, et al. Sexually transmitted diseases: viruses and ectoparasites. Committee on Sexually Transmitted Diseases of the American Academy of Dermatology. J Am Acad Dermatol 1991;25(3):527–34. Chaudhary M, Kulkarni M. Molluscum contagiosum in human immunodeficiency virus infected patients. Indian J Dent Res 2008;19(2):155–9. Chue PW. Gonococcal arthritis of the temporomandibular joint. Oral Surg Oral Med Oral Pathol 1975;39(4):572–7. Cohen MS, Shugars DC, Fiscus SA. Limits on oral transmission of HIV-1. Lancet 2000;356(9226):272. Note: References for the Radiology section uploaded on the web link.

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CHAPTER 23 Akca AE, Ucok O, Akar A, et al. The role of lipoid proteinosis in gingival hypertrophy. Quintessence Int 2004;35(7):584–6. Alpoz AR, Coker M, Celen E. The oral manifestations of MaroteauxLamysyndrome (mucopolysaccharidosis VI): A case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:632–7. American Dietetic Association. Position of The American Dietetic Association: Oral health and nutrition. J Am Diet Assoc 1996;96(2):184–9. Ardekian L, Peled M, Rosen D, et al. Clinical and radiographic features of eosinophilic granuloma in the jaws: Review of 41 lesions treated by surgery and low-dose radiotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:238–42. Asaumi J, Konouchi H, Hisatomi M, et al. Two cases of polyostotic eosinophilic granuloma. Dentomaxillofac Radiol 2000;29(6):382–5. Bamji MS. Less recognized micronutrient deficiencies in India. Nutrition Foundation of India. April 1998. Bamji MS, Arya S, Sarma KVR, et al. Impact of long-term low-dose B-complex vitamin supplements on the vitamin status and psychomotor performance of rural school boys. Nutr Res 1982;2:147–53. Banoczy J, Hadas E, Estzari I. Three year results of clinical longitudinal experiments with sorbitol. Caries Res 1981;15:201. Bari AU. Congenital erythropoietic porphyria in three siblings. Indian J Dermatol Venereol Leprol 2007;73(5):340–2. Bazopoulou-Kyrkanidou E, Tosios KI, Zabelis G, et al. Hyalinosis cutis et mucosae: gingival involvement. J Oral Pathol Med 1998;27(5):233–7.

CHAPTER 24 Acharya AB, Sivapathasundharam B. Forensic Odontology, In: Rajendran R, Sivapathasundharam B, (eds). Shafer’s Textbook of Oral Pathology, 5th edn, Elsevier, New Delhi, 1199–227. Acharya AB, Taylor JA. Are a minimum number of concordant matches needed to establish identity in Forensic Odontology? J Forensic Odonto-Stomatology 2003;21(1):6–13. American Board of Forensic Odontology, Inc, ABFO Guidelines and Standards, in: Bowers CM, Bell GL. (eds). Manual of Forensic Odontology, 3rd edn, Printing Specialists, Vermont, 1995;334–41. Arany S, Iino M, Yoshioka N. Radiographic survey of third molar development in relation to chronological age among Japanese Juveniles. J Forensic Sci 2004;49(3):534–8. Austin-Smith D, Maples WR. The reliability of skull/photograph superimposition in individual identification. J Forensic Sci 1994;39(2):446–55. Ball J. The current status of lip prints and their use in identification. J Forensic Odonto-Stomatology 2002;20(2):43–6. Bécart A, Hédouin V, Martin-Bouyer L, et al. The Oral Health Status of Drug Addicts: A Prison Survey in Lille, France. J Forensic Odonto-Stomatology 1997;15(2):27–9. Bilge Y, Kedici PS, Alakoç YD, et al. The identification of a dismembered human body: A multidisciplinary approach. Forensic Sci Int 2003;137(2–3): 141–6. Bockholdt B, Maxeiner H. Hemorrhages of the tongue in the postmortem diagnostics of strangulation. Forensic Sci Int 2002;126:214–20. Borrman HIM, DiZinno JA, Wasén J, et al. On denture marking. J Forensic Odonto-Stomatology 1999;17(1):20–6.

Index

A ABCDE warning signs, 369 Abdominal ultrasonography, 397 Abfraction, 458, 464 Abrasion, 452, 460 Acanthomatous ameloblastoma, 335 Acanthosis nigricans, 227 Accessory cusps, 44 Acid-enzyme theory, 407 Acinic cell adenocarcinoma, 297 Ackerman’s tumor, 366 Acquired immune deficiency syndrome (AIDS), 99 Acquired immunity, 590 Acquired melanocytic nevus, 348 Acrodermatitis enteropathica, 228 Acrodynia, 63 Acromegaly, 536 Acrosclerosis, 601 Actinomycosis, 86 Activated partial thromboplastin time, 498 Acute adrenal insufficiency, 547 Acute dental caries, 413 Acute intermittent porphyria, 642, 643 Acute leukemia, 492 Acute lymphocytic leukemia, 386, 492 Acute lymphonodular pharyngitis, 90 Acute monocytic leukemia, 492 Acute necrotizing ulcerative gingivitis (ANUG), 204, 452 Acute pain, 115 Acute pseudomembranous candidiasis, 135, 154 Acute radiation syndrome, 699 Acute sinusitis, 105 Acute suppurative osteomyelitis, 433 Added filtration, 694 Addison’s disease, 66, 546 Adenocarcinoma, 295, 297 Adenoid cystic carcinoma, 298 Adenomatoid odontogenic tumor, 338 Adherence and adhesions, 247 Adult periodontitis, 442 Aerodontalgia, 118 African Kaposi’s sarcoma, 377 Agammaglobulinemia, 456 Age estimation methods, 669 Agenesis, 266 Aggressive periodontitis, 442 Aglossia, 22

Agnathia, 30 Agranulocytic angina, 491 Agranulocytosis, 455 Ankyloglossia, 23 classification, 23 ALARA principle, 704, 728 Albers–Schönberg disease, 578 Alcohol, 139, 384 Alkaptonuria, 76 Allergic rhinitis, 506 Allergic salute, 507 Allergic shiners, 507 Allodynia, 111 Allowable occupational dose, 704 Amalgam tattoo, 63 Ameloblastic carcinoma, 363 fibrodentinoma, 342 fibroma, 342 fibro-odontoma, 342 fibrosarcoma, 366 sarcoma, 366 Ameloblastoma, 33 Amelogenesis imperfecta, 53, 54, 77 Amine odor test, 632 Amino acids, 635 Amlodipine, 446 Amorphous calcium phosphate, 464 Amputation caries, 401 Amyloid, 642 Amyloidosis, 642 Anaphylaxis, 481 Anatomical variations, 842 Androgens, 445 Andy Gump facies, 255 Anemia, 456, 485 Aneurysmal bone cyst, 322 Angina pectoris, 478 Angiogenesis, 385, 401 Angiolipoma, 355 Angiosarcoma, 377 Angle’s classification of malocclusion, 255 Angular cheilitis (perleche), 155, 156, 487 Anhidrotic ectodermal dysplasia, 222 Ankyloglossia, 23 Ankylosis, 253 Ann Arbor classification, 495 Annual dose limits, 710 Anodontia, 45 Anorexia nervosa, 524

Anorexia, 287 Antemortem radiographs, 657 Anterior median lingual cyst, 323 Antidiuretic hormone, 538 Antihypertensive therapy, 477 Anti-mongoloid eyelids, 646 Antinuclear antibody (ANA), 599 Anti-Saccharomyces cerevisiae antibodies, 624 Antiseptic mouthrinses, 508 Antistreptolysin O titers, 480 Antoni type B cells, 356 Antral polyps, 318 Antrocystectomy, 330 AP axial projection, 752 APECED, 600 Aphthous stomatitis, 211, 591 Aphthous ulcers, 104, 210, 211, 520, 591 Apical periodontal cyst, see Periapical cyst Aplastic anemia, 448 Apnea, 512 Apple-green birefringence, 642 Areca nut, 383, 463 Argyll Robertson pupil, 627 Argyria, 64 Aromatic hydrocarbons, 383 Arrested caries, 412 Arsenic, 63 Arteriovenous malformations, 359 Arthrography, 795–796 Articular capsule, 239 Articular disk, 239, 240, 246 Articular eminence, 239 Artifacts, 820 Aryl hydrocarbon hydroxylase, 383 Ascher’s syndrome, 27 Aschoffs nodules, 480 Ascorbate, 639 Ascorbic acid, 499, 639 Ash leaf macules, 233 Ashboe–Hansen sign, 212 Aspergillosis, 109, 207, 615 Aspiration biopsy, 393 Aspirin, 483, 500 Asteroid bodies, 290, 619 Asthma, 508, 510 Atherosclerosis, 478 Atrophic glossitis, 487 Atrophic lichen planus, 148, 150 Attached gingiva, 210, 312, 346 Attrition, 459, 670

885

Index

Atypical facial pain, 126 Atypical odontalgia, 125 AUPD cells, 552 Aura, 530 Auriculocondylar syndrome, 33 Auspitz’s sign, 221, 234 Autoimmune hepatitis, 527 Autoimmune hypothyroidism atrophic thyroiditis, 539 Hashimoto’s thyroiditis, 539 Autoimmune polyendocrinopathy-candidiasisectodermal dystrophy, 551, 600 Autoimmune theory, 407 Autoimmunity, 590 Avulsion, 673 Azotemia, 514 Aδ fibers, 112

B Bacille Calmette–Guérin (BCG) vaccination, 610 Baclofen, 122 Bacterial pharyngitis, 508 Bacterial sialadenitis, 282 Baelz’s disease, 283 Barodontalgia, 118 Barosinusitis, 119 Barrel-shaped rib cage, 577 Bartholin’s duct, 267 Basal cell adenoma, 293 Basal cell carcinoma, 367 Basal cell nevus syndrome, 342 Battle’s sign, 263 Bay cyst, 320 B-cell immunity, 590 Beam limiting devices, 706 Bean-shaped cyst, 347 Bean-shaped radiopacities, 646 Bearded infant appearance, 584 Beckwith–Wiedemann syndrome, 27 Beedis, 381, 382, 383 Behçet’s disease or syndrome, 31, 216 Bejel, 626 Bell’s palsy, 529 Bence Jones proteins, 497 Benign chondroblastoma, 351 Benign lymphoepithelial lesion, 277, 591 Benign migratory glossitis, 24 Benign mucosal cysts, 317 Benign mucous membrane pemphigoid, 188, 212 Benign osteoblastoma, 351 Benzopyrene, 383 Benzydamine hydrochloride, 25, 401 Beriberi, 640 Bernard–Soulier syndrome, 500 Betel quid chewers, 463 Betel quid lichenoid lesion, 153 Bifid condyles, 33 Bifid tongue, 24 Bilaminar zone, 240 Bilirubin, 61 Biliverdin, 62 Biological indicators, 671 Bird face deformity, 255 Bismuth grip, 63

886

Bisphosphonates, 588 Bite mark procedures, 672 Black beard sign, 588 Black box, 522 Black hairy tongue, 18 Black tarry stools, 523 Blade of grass lesion, 588 Blank radiograph, 820 Blastomycosis, 107, 613 Bleeding time, 498 Bleomycin, 402 Blepharosis moniliformis, 646 Bloch–Sulzberger syndrome, 231 Blood dyscrasias, 440 Blood pressure, 475 Blood studies, 397 Bloody crusted appearance, 191 Blue bloaters, 510 Blue colored sclera, 577 Blue dye, 394 Blue, purple or gray tinted sclera, 577 Blurred image, 817 Bone scanning, 788 Bohn’s nodules, 316 Bollinger’s granules, 88 Botryoid odontogenic cyst, 311 Botryomycosis, 88 Bouin’s solution, 219 Boundary lubrication, 247 Brachytherapy, 400 Bradykinesia, 531 Brazilian pemphigus, 596 Breathlessness, 475, 505 Bremsstrahlung radiation, 688, 689 Breschet–Gorham syndrome, 585 Brim sign, 588 Brittle bone disease, 576 Broad saddle nose, 644 Bronchodilators, 510 Bronchogenic carcinomas, 511 Bronze diabetes, 67 Brown tumors, 516, 543 Bruck syndrome, 578 Brueghel’s syndrome, 532 Brush biopsy, 395, 398 Bruxism, 459 Buccal space, 427, 429 Bulimia, 287 Bulimia-related sialadenosis, see Anorexia Bulimia nervosa, 524 Bull neck appearance, 431 Bulla spreading sign, see Ashboe–Hansen sign Bulldog jaw, 628 Bull’s eye lesion, 190 Bullous impetigo, 84, 193 Bullous pemphigoid, 185, 212, 596 Burkitt’s lymphoma, 496 Burning feet, 514 Burning mouth sensation, 487 Burning mouth syndrome, 127 Burning tongue, 272 Burtonian line, 64 Busse–Buschke disease, 109 Butterfly rash, 84, 598

C Café-au-lait macules, 536 pigmentations, 66 spots, 234, 576 Caffey’s disease, 583 Caffey–Silverman syndrome, 583 Calcifying epithelial odontogenic tumor, 337 Calcifying odontogenic cyst, 312, 339 Calcium, 477 channel blockers, 446 hydroxide, 463 oxide, 463 Calculus, 451 Cameron ulcers, 523 Canalicular adenoma, 293 Cancrum oris, see Noma Candida leukoplakia, see Chronic hyperplastic candidiasis Candidiasis, 101, 140, 153 classification, 154 Canine space, 429 Canker sores, 591 Capillary fragility test, 498 Capillary malformations, 359 Caplan’s syndrome, 594 Capsulitis, 249 Carbamazepine, 122 Carbohydrates, 634 Carbon monoxide, 383, 531 Carbonic acid, 463 Carboxymethylcellulose, 401 Carcinogens, 384 Carcinoma ex ameloblastoma, 364 Carious lesions, 410, 425 Carotenoids, 637 Carotid sheaths, 393 Carpal tunnel syndrome, 537, 540 Cascading waterfall appearance, 58 Casein phosphopeptide, 464 Caseous necrosis, 608, 609 Cat-scratch disease, 89 Causalgia, 311 Caviar lesions, 16 Celiac disease, 53, 214 Cell mediated immunity, 157, 590 Cell rests of Serres, 305 Cemental tears, 452 Cementicles, 470 Cementifying fibroma, 571 Cementoblastoma, 343 Cemento-ossifying fibroma, 571 Cephalometric radiography, 725 Cervical burn out, 461 Cervical enamel extensions, 43 Cervical esophagus, 393 Cervical lymphadenopathy, 508 Cetuximab, 402 Chalky, ground glass, granular and salt and pepper appearance of bone, 516 Chancre, 206, 612, 626 Characteristic radiation, 688, 689 Charcot’s joints, 627 Chediak–Higashi syndrome, 453, 491 Cheilitis glandularis, 283 Cheilitis glandularis apostematosa, 283 Cheilitis granulomatosa, 289, 620

Index

Chelation, 406 Chemical burn, 135 Chemical indicator, 706 Chemo-osteonecrosis, 588 Chemotherapeutic agents, 401 Chemotherapy, 104, 401, 845 Cherubism, 580 Chest pain, 475, 505 Chicken pox, 178, 201 Chicken-wire appearance, 490 Chicken-wire pattern, 351 Chinese script writing, 575 Chlamydial infections, 631 Chloasma, 64 Chloasma gravidarum, 551 Chloromas, 493 Chloroquine, 64, 65 Cholesterol clefts, 320 Cholesterol crystals, 318, 326 Chondroma, 350 Chondrosarcomas, 261, 372 Christmas disease, 503 Christmas tree pattern, 226 Christ–Siemens–Touraine syndrome, see Hypohidrolic ectodermal dysplasia Chromogenic bacteria, 73 Chronic atrophic candidiasis, 155 Chronic bronchitis, 505, 509 Chronic dental caries, 413 Chronic diffuse sclerosing osteomyelitis, 437 Chronic fatigue syndrome, 90 Chronic focal sclerosing osteomyelitis, 436 Chronic myelocytic leukemia, 493 Chronic hyperplastic candidiasis, 154 Chronic irreversible pulpitis, 414, 418 Chronic leukemia, 493 Chronic lymphocytic leukemia, 493 Chronic lymphoid leukemia, 493 Chronic mucocutaneous candidiasis (CMC), 156 Chronic obstructive airway disease, 509 Chronic obstructive pulmonary disease, 509 Chronic osteomyelitis with proliferative periostitis, see Periostitis ossificans Chronic pain, 115 Chronic periapical abscess, 415 Chronic renal failure, 513 Chronic sclerosing sialadenitis, 285 Chronic sinusitis, 105 Chronic suppurative osteomyelitis, 434 Chronological hypoplasias, 52 Chvostek sign, 544 Chylothorax, 586 Cicatricial pemphigoid, 186, 213, 596 Cigarettes, 139, 381, 383 Cigars, 381 Ciprofloxacin, 79 Circumferential caries, 401 Circumscribed morphea, 601 Circumvallate papillae, 16 Cisplatin, 402 Civatte, hyaline, cytoid bodies, 150 Classification and staging system for oral leukoplakia, 138 Classification of ankyloglossia, 23 Classification system for Kaposi’s sarcoma, 377

Clay modeling, 667 Clear or gargoyle cells, 644 Cleft lip, 27 Cleft palate, 27 Cleft tongue, 24 Cleidocranial dysplasia and Maroteaux-Lamy syndrome, 307 Clinical forms of leukoplakia, 140 Closed lock, 248 Clotting mechanism, 497 Clutton’s joints, 628 Cobblestone appearance, 622 Cod fish vertebrae, 578 Codman’s triangle appearance, 371 Codman’s tumor, see Benign chondroblastoma Coffee ground vomitus, 523 Cogan’s lid twitch, 604 Coherent scatter, 695 Cold test, 422 Collagenases, 385 Collarette, 193 Collimators, 694 functions, 694 types, 694 Colloid bodies, 694 clvatte, 694 hyaline, 694 cytoid, 694 Color changes in burned teeth, 661 Colpitis macularis, 631 Comb sign, 522 Commissural lip pits, 26 Complex odontome, 341 Composite odontome, 341 Compound hemangiomas, 358 Compound nevus, 348 Compton effect, 696 Compton scatter, 695 Computed tomography (CT), 760–762 Concept of referred pain, 114 Concrescence, 36 Condensing osteitis, 414 Condylar aplasia, 33 Condylar hyperplasia, 33 Condylar neck fractures, 262 Condyloma acuminatum, 347, 630 Cone-beam computed tomography (CBCT), 762 Cone cuts, 741 Congenital heart disease, 479 hemoglobinopathies, 490 lip pits, 26 rubella syndrome, 91 syphilis, 628 teeth, 46 Congenital aplasia, see Agenesis Congenital epulis of newborn, 355 Congo red staining, 642 Conn’s syndrome, 549 Contact stomatitis, 209 Cooper type scissors, 659 Coronary artery disease, 847 Coronary heart disease, 478 Coronoid hyperplasia, 34 Corrosion, see Erosion Cotton-wool appearance, 438, 588 Cough, 504

Coxa vara, 577 Cowdry type A, 240 CPP-ACP, 464 Cracked tooth syndrome, 466 Cracker sign, 268 Cranial arteritis, 591 Cranial suture pattern, 664 Craniotabes, 638 Crazing, 660 C-reactive protein, 253, 624 Crescent-shaped lesions, 464 CREST syndrome, 603 Cretinism, 539 Cricoid cartilage, 393 Crohn’s disease, 520, 521, 622 Croup, 505 Cryptococcosis, 109, 207 Cullen’s sign, 90 Cushing’s syndrome, 545 Cusp of Carabelli, 44 Cyanosis, 68, 475 Cyclic neutropenia, 455, 492 Cyclosporine, 446 Cylinder–type implants, 851 radiographic appearance, 851 Cystic fibrosis, 511 Cystic hygroma, 326, 792 Cystic PIOC, 364 Cysticercosis, 327

D Dane particle, 526 Dapsone, 611 Dark-field microscopic examination, 613 Darkroom infrastructure, 804 Dark spots, 819 Daylight processor, 808 De Musset’s sign, 627 De novo ameloblastic carcinoma, 364 Dead tracts, 468 Debulking, 399 Decortication, 436 Deep cervical nodes, 12 Deep fascia, 426 Deep fungal infections, 613 Deep hemangiomas, 207 Degenerative joint diseases 358 Demirjian’s method, 250 Dennie–Morgan lines, 670 Dens evaginatus, 41 Dens in dente, 40 Dens invaginatus, 40, 41 Dental attrition, 670 Dental caries, 405 classification, 410 Dental computed tomography, 849 Dental floss, 417, 460 Dental fluorosis, 55, 79 Dental identification, 654 procedure, 655 Dental implants, 842–845 forms, 842 historical perspectives, 842 indications, 844 patient management, 845 post-operative evaluation, 857

887

Index

Dental implants (Contd.) treatment options, 842 types, 843 Dental plaque, 406, 440, 442 Dental records, 657 Dental transposition, 47 Dentifrices, 460 Dentigerous cyst, 306 Dentin dysplasia, 58, 78 Dentinal caries, 414 Dentinal hypersensitivity, 464 Dentinogenesis imperfecta, 55, 56, 77 Denture marking systems, 663 Dermatitis herpetiformis, 180 Dermoid cysts, 327 Desmoglein-I, 181 Desmoplastic fibroma, 344 Developmental cysts, 304 Diabetes, 384, 454, 846 insipidus, 538 mellitus, 288 mellitus-associated gingivitis, 440 mellitus type I insulin dependent (IDDM), 600 Diabetic ketoacidoses, 108 Diascopy test, 68 Digastric muscle, 244 Digital radiography, 707 Dilaceration, 38 Dimple wart, see Molluscum contagiosum Diphtheria, 83 Diphtheritic membrane, 83 Diplopia, 390 Direct digital receptors, 732 Direct target theory, 399 Discal ligaments, 241 Discoid lupus erythematosus, 170 Disinfection, 104 Disk displacement, 248 with reduction, 248 without reduction, 248 Disk thinning and prerforation, 246 Dislocation, 248 types, 249 Displacement of disk–condyle complex, 248 hypermobility, 248 Disseminated form of histoplasmosis, 107 Disseminated intravascular coagulation (DIC), 498 Distodens, 46 Distomolar, 46 Doppler ultrasound, 791 Dose limits, 704 Double lip, 26 Down syndrome, 22, 35, 43, 326 Driven snow patterns, 337 Drug influenced enlargements, 440 Drug influenced gingival diseases, 440 Drug-induced pigmentation, 64 Dry beriberi, 640 Dry mouth, 223, 269, 272 Duchenne muscular dystrophy, 532 Dwarfism, 535 Dyschroic fog, 820 Dysesthesia, 387 Dysgeusia, 518

888

Dyskeratosis congenita, 166, 225 Dysostosis multiplex, 645 Dyspnea, see Breathlessness Dystonia, 532 Dystrophic calcification, 16 Dystrophic epidermolysis bullosa, 194

E Eagle’s syndrome, 122 Eating disorders, 524 Echelon lymph nodes, 393 Ectodermal dysplasia, 222 Edrophonium test, 604 EDTA, 463 Ehlers–Danlos syndrome, 223, 453, 499 Ekman–Lobstein syndrome, 576 Electrical insulating oil, 693 Electric pulp tester, 423 Electromagnetic spectrum, 687, 688 ELISA test, 102 Elongated image, 816 Ely cyst, 251 Emphysema, 509 Enamel caries, 414 Enamel hypoplasia, 511, 516 Enamel pearls, 42 Enameloma, 42 Enchondromas, 350 Endarteritis obliterans, 612 Endemic Kaposi’s sarcoma, see African Kaposi’s sarcoma Endobone, 579 Endocrine glands, 532 Endocrinopathic pigmentation, 546 Energy requirement, 633 Enostosis, 584 Entropion, 195 Enucleation, 330 Environmental enamel hypoplasia, 51 Enzymatic theory, 407 Eosinophilic granuloma, 647 Epidermal growth factor receptor, 402 Epidermoid cysts, 327 Epidermolysis bullosa (EB), 193 types, 193 Epidermolysis bullosa acquisita, 596 Epilepsy, 530 Epiloia, see Tuberous sclerosis complex Epiphora, 390 Epistaxis, 499 Epithelial dysplasias, 143 Epithelial rests of Malassez, 318 Epithelioid macrophages, 605 Epithelioma contagiosum, see Molluscum contagiosum Epithelioma cuniculatum, 367 Epsilon-aminocaproic acid (EACA), 502 Epstein pearls, 316 Epstein–Barr virus (EBV), 385, 450 Epulis fissurata, 354 Erb’s palsy, 584 Erosion, 461 Erosive lichen planus, 147 Eruption sequestrum, 47 Erysipelas, 84 Erythema multiforme, 177, 189

Erythema nodosum, 619 Erythematous candidiasis, see Chronic atropic candidiasis Erythrodontia, 76, 643 Erythroleukoplakia, 141, 142 Erythroplakia, 168 Esophageal reflux disease, 213, 519 Esophageal webs, 487 Estrogens, 445 Ethyl alcohol, 384 Eumelanin, 18 Eustachian tube, 390 Evaginatus odontomas, 41 Ewing’s sarcoma, 376 Examination of temporomandibular joint, 243 Exanthematous diseases/infections, 52 Exertional dyspnea, 475 Exfoliative cytology, 397, 395 Exocrine glands, 532 Exophytic growth, 390 Exostoses, 19, 35 Exposure parameters and processing technique, 818 errors, 818 blank radiograph, 818 dark radiograph, 818 film fog, 818 light radiographs, 818 External resorption, 466 Extraoral films, 721 Extraoral radiographic techniques, 752 axiolateral oblique projection, 753 lesser known/forgotten, 752 acanthioparietal projection reverse Waters’ method, 754 May method, 752 modified parietoacanthial projection, 754 Townes’ method, 752 Extraoral radiography, 743 grids, 743 image receptors, 743 intensifying screens, 743 Extraskeletal chondroma, 350 Extrinsic asthma, 508 Extrinsic cysts, 316, 318 Extrinsic discoloration, 71 Extrinsic stains, 72 Eye to heaven appearance, 581 Eyelid beading, 646 Eyelid twitch response, 604

F Faces pain scale, 116, 117 Facet, 459 Facial approximation, 667 Facial hirsutism, 643 Facial neuropathies, 628 Facies leprosa, 611 Factitial injury, 452 Falling snowflakes, 328 Familial fibrous dysplasia, see Cherubism Fanconi’s anemia, 488 Fascia, 428, 429 Fascial spaces, 426 Fat soluble vitamin, 636

Index

Fatty acids, 635 Fatty degeneration, 401 Fellatio syndrome, 625 Fergusson, 659 Fever, 598 Fibroma, 345 Fibromatoses, 361 Fibromatosis gingivae, 29 Fibromyalgia, 259 Fibro-osseous lesions, 568 Fibro-osseous metaplasia, 675 Fibrosarcoma, 370 Fibrous dysplasia, 573 Fibrous hyperplasia, 354 Filiform papillae, 19, 24 Film badge monitoring, 713 Film badges, 713 Film placement and projection technique, 814 errors, 814 Film processing, 803 techniques, 803 automatic, 809 manual, 803 steps in processing, 807 visual method, 807 Film receptors, 706 Film storage, 707 Film storage and handling, 812 errors, 812 dark spots or lines, 812 emulsion peel, 812 film fog, 812 nail marks or kink marks, 814 scratched film, 812 static electricity artifact, 814 Films and processing of films, 687 Filters, 694 Finger clubbing, 475, 519 Fish scale appearance, 577 Fishy scale odor, 515 Fissured tongue, 13, 24 Fite method, 611 Fitz–Hugh–Curtis syndrome, 630 Flapping tremors, 525 Floating in air apperance teeth, 647 Floating in space, 395 Floating thermometer, 805 Floating tooth syndrome, 582 Florid cemento-osseous dysplasia, 569 Florid osseous dysplasia, 570 Fluid deprivation test, 538 Fluid level appearance, 105, 106 Fluid-fluid levels, 323 Fluorescent treponemal antibody-absorbed (FTA-ABS) test, 613 Fluorosis, 52 FNAC, 396 Foamy macrophages, 648 Focal cemento-osseous dysplasia, 611 Focal epithelial hyperplasia, 165, 347 Focal reversible pulpitis, 439 Focal sclerosing osteomyelitis, 414 Focal sialadenitis, 271 Focal trough, 759 concept, 759 effect of patient positioning, 759

Fogo selvagem, see Brazilian pemphigus Folate, 385 Foliate papillitis, 168 Folic acid deficiency, 487 Follicular cyst, see Dentigerous cyst Forchheimer spots, 91 Fordyce granules, 11, 29 Foreign body granulomas, 616 Forensic dentistry, 654–678 Fore-shortened image, 816 Fothergill’s disease, 120 Fournier’s molars, 52 Fractionated irradiation, 400 Framed vertebrae, 588 Free radicals, 384 Free-floating desmosomes, 646 Frictional traumatic keratosis, 135 Frontal bossae of parrot, 628 Frontal sinus configuration, 664 Full axial projection, 748 Fulminant hepatitis, 528 Functional capacity, 475 Fusion, 28, 36

G GABHS, 507, 508 Gag reflex, 844 Galacturonic acid, 463 Galvanizing, 464 Gamma rays, 687 Gangrenous, see Noma GAPO, 48 Gardner’s syndrome, 341, 349 Gargoylism, 644 Garrè’s osteomyelitis, 437 Gastroesophageal reflux disease (GERD), 519 Gastrointestinal syndrome, 700 Gate control theory, 114 Gaucher cells, 648 Gaucher disease, 648 Gemination, 36 Generalized seizures, 530 Geniculate neuralgia, 124 Genital wart, see Condyloma acuminatum Geographic tongue, 24 German measles, 91 Gestant odontome, 40 Ghost cells, 365 Ghost images, 759 Ghost-like appearance, 60 Giant cell arteritis, 591 Giant cell fibroma, 360 Giant cell granuloma, 352 Giant cell reparative granuloma, 352 Giant cell tumors, 542 Giant osteoid osteoma, 352 Gigantiform cementoma, 570 Gigantism, 656 Gilchrist disease, 107, 207 Gingival cyst of infants, 305 Gingival diseases modified by medications, 440 Gingival hyperplasia, 483, 644 Gingival recession, 425 Ginglymodiarthroidal joints, 239 Glanders like disease, 85

Glands of Blandin and Nuhn, 267 Glands of von Ebner, 267 Glanzmann’s thrombasthenia, 500 Glenoid fossa, 239 Glomeruloid appearance, 365 Glomerulonephritis, 617 Glossitis, 628, 487 Glossocele, 323 Glossopharyngeal neuralgia, 122 Glucocerebroside, 648 Glucose-6-phosphate dehydrogenase deficiency, 488 Goldenhaar’s syndrome, 33 Golgi tendon organs, 241 Goltz–Gorlin syndrome, 228 Gomori methenamine silver stain, 108 Gonococcal arthritis of TMJ, 631 Gonorrhea, 630 Gorham’s disease, 585 Gorham’s osteolysis, 585 Gorham–Stout syndrome, 585 Gorlin’s sign, 224 Gout, 253 Graft versus host disease, 234 Graham-Little syndrome, 149 Grand mal seizures, 530 Granulocytes, 490 Granuloma, 504, 605 Granuloma pyogenicum, 353 Granulomatous diseases, 511, 605 Graves’ disease, 541 Grids, 708, 722 composition, 722 functions, 723 types, 723 Grinspan syndrome, 149 Grocott methenamine silver stain, 621 Grocott-Gomori methenamine silver, 208 Ground glass appearance, 517, 574 Growth hormone, 535 in children, 535 Guillain–Barre syndrome, 599 Gumma, 207, 613 Gunther’s disease, 643 Gutkha, 381

H Hailey–Hailey disease, 229 Hair-on-end radiographic appearance, 489, 490 Hairy leukoplakia, 102, 516 Hairy tongue, 18 Half value layer, 694 Halitosis, 561 Hallopeau type pemphigus vegetans, 596 Halo-shadow, 438 Hand, foot and mouth (HFM) disease, 179, 204 Hand–Schuller–Christian disease, 647 Hangar-Rose skin test, 89 Hanging teeth, 390 Hansen’s disease, 610 Heart failure, 482 Heartburn, 519 Heat test, 423 Hebra nose, 88

889

Index

Heck’s disease, see Focal epithelial hyperplasia Heerfordt syndrome, 619 Heinz bodies, 488 Heister mouth gags, 659 Helicobacter pylori, 519 Hemangiomas, 68, 357 Hemarthrosis, 501 Hematological diseases, 489 Hematomas, 69 Hematopoietic syndrome, 699 Hemifacial atrophy, 32 Hemifacial hyperplasia, 31 Hemifacial hypertrophy, 31 Hemihyperplasia, 35 Hemochromatosis, 67 Hemodialysis, 481, 517 Hemoglobinopathies, 489, 490 Hemophilia A, B and C, 502, 503 Hemoptysis, 505 Hemorrhage, 662 Hemosiderin, 62 Heparin therapy, 484 Hepatitis, 526 A, 526 B, 526 B surface antigen, 528 C, 527 D, 527 G virus, 527 Hereditary benign intraepithelial dyskeratosis, 165 Hereditary corpoporphyria, 643 Hereditary gingival fibromatosis, 449 Hereditary fibrous dysplasia, see Cherubism Hereditary opalescent dentin, 57 Hermann’s syndrome, 341 Herpangina, 180, 203 Herpes labialis, 201 Herpes simplex viruses (HSV), 175, 385 type 1, 175 type 2, 175 Herpes viruses, 175 Herpes zoster, 178, 203 Herpetic gingivostomatitis, 449 Herpetiform ulcers, 211 Herring bone pattern, 814 Hiatal hernia, 522 High performance laser spectroscopy-laser induced fluorescence (HPLC-LIF), 395 High voltage transformer, 693 Highly differentiated squamous cellcarcinoma, 398 Higoumenakis sign, 235 Hilar lymphadenopathy, 607 Histiocytosis X, 647 Histoplasmosis, 106, 207, 614 Hodgkin’s disease, 495 Homogeneous leukoplakia, 141 Honeycomb like appearance, 243, 374 Honeycomb pattern, 351 Honiton lace, 219 Horizontal overlap, 741 Hormone resistance, 535 Hormones, 533

890

Host modulation, 444 Hot potato voice, 508 Howship’s lacunae, 579 Hoyeraal–Hreidarsson syndrome, 225 HPA axis, 535 Human herpes virus-8, 175, 376 Human immunodeficiency virus (HIV), 92, 285, 385, oral manifestations, 101 structure of HIV-1 virion, 92 transmission, 97 Human papilloma viruses, 385 Humoral immunity, 590 Hunter syndrome, 644 Hurler syndrome, 644 Hutchinson teeth, 613 Hutchinson’s incisor, 52 Hutchinson’s triad, 628 Hyalinosis cutis et mucosae, 646 Hydatid disease, 328 Hydrostatic enlargement of cysts, 305 Hydroxyl radicals, 384 Hyperacusis, 529 Hyperalgesia, 111 Hyperbaric oxygen (HBO), 436 Hypercalcemia, 497, 542 Hypercarotenemia, 637 Hypercementosis, 470 Hyperdontia, 45 Hyperglycemia, 600 Hypermobility, 224, 248 Hyperostosis, 584 Hyperparathyroidism, 542 Hyperpigmentation, 400 Hyperplasia of minor salivary glands, 266 Hypersensitivity, 459 Hypertension, 476, 549 Hyperthyroidism, 540 Hyperuricemia, 253 Hyperventilation, 544 Hypodontia, 45 Hypoesthesia, 111 Hypoglycemia, 540 Hypohidrotic ectodermal dysplasia, see Anhidrotic ectodermal dysplasia Hypomineralized enamel, 50 Hypoparathyroidism, 544 Hypopharynx, 392 Hypophosphatasia, 453 Hypoplastic enamel, 50 Hypoplastic teeth, 640 Hypopnea, 512 Hyposalivation, 267, 268 Hypovolemia, 523

I Ice pack test, 604 Icterus, see Jaundice Idiopathic hypertension, see Hypertension Idiopathic osteolysis, 586 Idiopathic osteosclerosis, 584 Idiopathic thrombocytopenic purpura, 500 IgA, 195, 409 IgG, 409 Image guided radiotherapy (IGRT), 400

Immune granulomas, 605 Immune-mediated granulomatous inflammation, 605 Immunity, 157 Immunomodulators, 184 Impacted teeth, 49 Impetigo, 84 Implant site identification, 845 absolute contraindications, 845 conventional tomography, 848 imaging, 848 panoramic radiography, 848 relative contraindications, 846 selection of the implant site, 847 selection of the patient, 845 standard periapical radiographs, 848 Incinerated teeth, 660 Incineration, 659 Incipient caries, 411 Incontinentia pigmenti, 231 Indirect target theory, 399 Indwelling catheters and stents, 481 Infantile cortical hyperostosis, 583 Infantile osteomyelitis, 436 Infectious arthritis, 252 Infectious mononucleosis, 90 Inflammatory bowel disease, 519 Inflammatory cysts, 304 Infrabony defects, 456 Infrared telethermography (IRT), 796 Infratemporal fossa space, 429 Inherent filtration, 694 Inherited coagulation disorders, 502 Intensifying screens, 707, 722 Intensity modulated radiation therapy (IMRT), 400 Internal replacement, 467 Internal resorption, 466, 467 International normalized ratio (INR), 484 Interstitial glossitis, 613 Intradermal injections, 611 Intramuscular injections, 502 Intraoral films, 719, 720 composition, 720 dimensions, 721 uses, 719 Intraoral herpes, 201 Intraoral radiography, 725 common technical errors, 740 preliminary procedures, 729 procedures, 733 bitewing radiography, 735 occlusal radiography, 736 periapical radiography, 733 selection criteria guidelines, 729 techniques, 730 bisecting angle, 730 common technique errors, 739 paralleling, 730 Intraoral X-ray machine, 691, 693, 726 components, 691 dissipation of heat from, 693 working mechanism of, 693 Intraoral X-ray units, 690 mobile intraoral radiographic units, 690

Index

Intraosseous mucoepidermoid carcinoma, 296, 365 Intravenous bisphosphonate treatment, 846 Intrinsic cysts, 316 Intrinsic discoloration, 81 Inverted pear-shaped radiolucency, 315 Inverted Y line of Innes, 830 Ionization chambers, 712 Ionizing radiation, 384 Iris lesion, 190 Iron deficiency anemia, 210, 486 Iron, 210 Ischemic heart disease, 478 Isotope tracer probe, 394 Ivory-white papules, 645 Ivy bleeding time, 498

J Jadassohn–Lewandowsky syndrome, 225 Jaffe–Lichtenstein syndrome, 574 Jaundice, 68, 525 Jaw resection, 659 Jewels sign, 195 Jigsaw puzzle pattern, 588 Jod–Basedow phenomenon, 540 Joint mice, 251 Jugulo-digastric lymph nodes, 393 Junctional epidermolysis bullosa, 194 Junctional nevus, 348 Juvenile idiopathic arthritis, 251 Juvenile ossifying fibroma, 348, 572 Juxta articular chondromas, 350

K Kaposi’s sarcoma, 69, 376 classification system, 377 Kassowitz’s law, 628 Kawasaki disease, 232 Keratin pearls, 399 Keratoacanthoma, 347 Keratoconjunctivitis sicca, 270 Keratocystic odontogenic tumor, 304, 307, 339 Khaini, 381 Kidney shaped cyst, 316 Kilovoltage, 709 Kissing disease, see Infectious mononucleosis Klestadt’s cyst, 315 Klinefelter syndrome, 326 Klippel–Trenaunay syndrome, 358 Knurled effect, 814 Koebner’s phenomenon, 147 Koenen’s tumors, 233 Kohlschutter-Tonz syndrome, 56 Koiloncychia, 486 Koplik’s spots, 91 Kuttner tumor, see Chronic sclerosing sialadenitis Kvaal’s radiographic method, 672 Kveim test, 620 Kwashiorkor, 635

L Labial salivary gland biopsy, 275 Lacrimal sac, 390 Lacrimo-auriculo-dento-digital (LADD) syndrome, 266

Lagophthalmos, 610 Lamina dura, 825 Langhans type giant cells, 605 Latent bone cyst, 323 Latent image formation, 802 steps, 802 Latent syphilis, 627 Lateral oblique view, 750 Lateral periodontal cyst, 311 Lateral pharyngeal space, 430 Lateral pterygoid muscle, 242 Lateral radicular cyst, 319 Lazy leukocyte syndrome, 453, 456 Lead aprons, 709, 711, 715 Left shift, 492 Legionnaire’s disease (legionellosis), 504 Leiomyoma, 357 Leiomyosarcoma, 377 Lemierre’s syndrome, 90 Leong’s premolar, see Dens evaginatus Leontiasis ossea, 31 Lepra cells, 611 Lepromatous leprosy, 610, 611 Lepromin test, 611 Leprosy, 610 Letterer–Siwe disease, 648 Leucovorin, 402 Leukemia, 447, 455 Leukemia associated gingivitis, 440, 447 Leukemoid reaction, 492 Leukocyte disorders, 455 Leukocytosis, 492 Leukoedema, 13 Leukopenia, 491 Leukoplakia, 137, 225 classification and staging system, 138 clinical features, 140 medical management, 144 Leutic glossitis, 628 Levine’s ionic see-saw theory, 407 Levine’s sign, 478 Levy–Hollister syndrome, 266 Lichen planopilaris, 147 Lichen planus, 172, 189, 218 Lichenoid drug reaction, 152 Lichenoid mucosal reactions, 521 Lichenoid stomatitis, 483 Light spots, 819 Lincoln’s highway, 430 Lincoln’s sign, 588 Linea alba buccalis, 134 Linear ‘en coup de sabre’, 601 Linear accelerators, 400 Linear enamel caries, 411 Linear gingival erythema (LGE), 448 Linear IgA bullous dermatosis, 195 Linear IgA disease, 195 Lines of Zahn, 16 Lingual frenum, 626 Lingual pits 26 Lingual thyroid, 25 Lingual tonsils, 12 Lingual varices, 15, 69 Lip print, 678 Lipids, 635 Lipoid proteinosis, 646

Lipoma, 355 Liposarcoma, 373 Lipschütz bodies, 240 Lipstick sign, 268 Liquid crystal thermography (LCT), 796 Liver disease, 68, 503, 525 functions, 525 Liver metastasis, 397 Localized microdontia, 35 Lockjaw, 85 Löfgren syndrome, 619 Log wheel rigidity, 531 Loose bodies, see Joint mice Loss of taste, 401 Lowenstein tumor, 367 Lower respiratory tract infections, 504, 508 LT ratio, 396 Ludwig’s angina, 428 Lues, 626 Lues maligna, 207, 627 Luminescence, 713 Lumpy jaw, 86 Lupus erythematosus (LE), 170, 600 Luxation, 779 Lyell’s syndrome, 189 Lymph nodes, 495 Lymphatic malformations, 359 Lymphatics, 392 Lymphoid nodules, 595 Lymphomas, 495 Lymphoproliferative syndrome, 491 Lyonization effect/Lyon hypothesis, 54 Lysosomal storage diseases, 641 Lysosomes, 641

M Macqueen-dell technique, 751 Macrodontia, 35 Macroglossia, 22 Macrognathia, 30 Macrophages, 605 Maculopapular lesions, 627 Maculopapular rash, 612 MAGIC syndrome, 215 Magnetic resonance imaging (MRI), 781 advantages, 787 common artifacts, 787 due to motion and use of denture, 787 flow effect and movement artifacts, 787 contrast agents, 786 disadvantages, 787 historical perspective, 781 image interpretation, 787 methods for obtaining spatial resolution, 786 principles, 781 MR scanner, 781 nuclear magnetic dipole moment, 781 proton magnetization, 782 relaxation, 783 resonance, 783 spin-echo phenomenon, 784 uses, 787 Maillard pigments, 79

891

Index

Main d’ accoucheur sign, 544 Major aphthous ulcers, 211 Malignant ameloblastoma, 363 Malignant epithelial odontogenic ghost cell tumor, 365 Malignant hypertension, 477 Malignant melanoma, 368 Malignant schwannoma, 378 Malignant tumors, 261, 380 Mandibular advancement devices, 512 Mandibular buccal bifurcation cyst, 321 Mandibular condyle, 239 Mandibular infected buccal cyst, 321 Man-made radiation, 702 Manual and automatic processing, 811 comparisons, 811 Marasmus, 635 Marble bone disease, 579 Marfan syndrome, 249 Marijuana, 383 Maroteaux–Lamy syndrome, 645 Marsupialization, 349 Mask-like appearance of face, 602 Masseter, 244 Masseter muscle, 241, 258 Massive osteolysis, 586 Masson-Fontana silver stain, 110 Masticatory abrasion, 460 Masticatory space, 429 Matrix metalloproteinases, 444 Maxillary tuberosity, 831 Maximum permissable dose, 703 May–Hegglin anomaly, 500 Mayer mucicarmine stain, 110 McGill pain questionnaire, 116 McGregor line, 578 Measles, 91 Measles-mumps-rubella (MMR) vaccine, 91 Meckel’s diverticulum, 523 Medial pterygoid muscle, 242, 258 Median mandibular cysts, 316 Median rhomboid glossitis, 155, 168 Mediastinal group lymph nodes, 393 Melanin, 62, 18 Melanin incontinence, 29 Melanoacanthosis, see Oral melanoacanthoma Melanocarcinoma, see Malignant melanoma Melanocytic nevi, 62 Melanomas, 369 Melanotic macule 69 Melioidosis, 84 Melkersson–Rosenthal syndrome, 13, 289, 521, 620 Menaquinones, 638 Menstrual cycle-associated gingivitis, 445 Mercury, 661 Mercury poisoning, 63 Merkel cell carcinoma, 552 Mesh-like pattern, 577 Mesiodens, 46 Metabolic disorders, 52, 641 Metachromatic dye, 397 Metastases, 392 Methenamine silver stains, 108 Methotrexate, 402 Michel’s solution, 219

892

Microbial plaque, 442 Microdontia, 35 Microfracture, 464 Microglossia, 22 Micrognathia, 30 Midline cysts, 324 Migratory glossitis, 168 Mikulicz cells, 89 Mikulicz’s disease, 277, 591 Mikulicz ulcer, 211 Milia, 194 Miliary tuberculosis, 607 Mineralocorticoids, 549 Minocycline, 64, 78, 79 Minor aphthous ulcers, 211 Mishri, 381 Mobility, 497 Moderately differentiated squamous cell carcinoma, 398 Modified Waters’ view, see Skull radiography Molar-incisor hypomineralization, 77 Molluscum contagiosum, 629 Monocytes, 490 Monoglandular fever, see Infectious mononucleosis Monomorphic adenoma, 293 Mononucleosis, 450 Monounsaturated fatty acids, 635 Moon face, 546, 635 Moon’s molars, 52 Moorrees’ method, 670 Morquio syndrome, 33 Morsicatio buccarum, 134 Morsicatio labiorum, 135 Morsicatio linguarum, 135 Mosaic pattern, 588 Moth-eaten appearance, 395, 435 Mottled enamel, 52 Mouse-like facies, 602 Mouth mirror test, 268 Mucic acid, 463 Mucocele(s), 278 Mucocutaneous lymph node syndrome, 232 Mucoepidermoid carcinoma, 295 Mucopolysaccharidoses, 454, 644 Mucormycosis, 108, 207, 615 Mucosa-associated lymphoid tissue (MALT) lymphoma, 277 Mucositis, 700 Mucous membrane pemphigoid, 186 Mucous patches, 206, 627 Mucous retention cyst, 316 Mulberry molars, 52, 613 Multidrug-resistant tuberculosis, 609 Multifocal eosinophilic granuloma, 647 Multinucleated giant cells, 582 Multiple endocrine neoplasia (MEN), 552 MEN I, 552 MEN II, 552 MEN III, 552 Multiple mucosal neuroma syndrome, 552 Multiple myeloma, 496 Multiple sclerosis, 531 Munro’s abscesses, 222 Mural growth theory, 304

Muscle splinting, 256 Muscles of mastication, 244 Muscular dystrophy, 532 Muscular hypertrophy, 258 Musculoskeletal disorders, 115 Mushroom fracture, 254 Mushroom-shaped skull, 577 Myasthenia gravis, 532, 603 Mycobacterium tuberculosis, 606 Myocardial infarction, 479 Myofascial pain, 119, 257 Myofibroblastoma, 362 Myositis, 256 Myospasm, 257 Myotomy, 659

N Nanocomplex, 464 Nasal obstruction, 390 Nasopalatine duct cyst, 314 Nasopharyngeal cysts, 323 Natal and neonatal teeth, 46 Natal teeth, 46 Neck dissection, 399 Necrotic pulp, 466 Necrotizing fasciitis, 428 Necrotizing sialometaplasia, 215, 284 Necrotizing stomatitis, see Noma Neisseria gonorrhoeae, 254 Neonatal line, 52 Neonatal lupus erythematosus, 598 Neonatal teeth, 46 Neonatal tetanus, 86 Neospinothalamic tract, 113 Nervus intermedius neuralgia, 124 Neuralgia, 120 Neurofibroma, 356 Neurofibrosarcoma, 378, 379 Neurogenic sarcoma, see Neurofibrosarcoma Neurohypophysis, 538 Neuromelanin, 18 Neurosyphilis, 628 Neurovascular syndrome, 700 Neutropenia, 455, 491 Nevoid basal cell carcinoma syndrome (NBCCS), 304 Nevus cells, 348 Niacin deficiency, 455 Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, 384 Nicotine, 382 Nicotine stomatitis, 136 Niemann–Pick disease, 649 Nifedipine, 447, 483 Nikolsky’s sign, 182, 235 Nitrosamine, see Nicotine Nitrosodiethanolamine, 382 Nitrosoproline, 382 Nociception, 111 Nociceptors, 11, 112 Noma, 87 Noma neonatorum, 87 Noma pudendi, 87 Non-Hodgkin’s lymphoma (NHL), 495 Non-homogeneous leukoplakia, 141 Non-lipid reticuloendothelioses, 647

Index

Non-odontogenic cysts, 314 Non-specific sialadenitis, 281 Non-starch polysaccharides, 634 Non-suppurative osteomyelitis, 433 Noonan syndrome, 326 North American blastomycosis, 207 Nuclear medicine, 788 types, 788 NUG, 449 NUP, 449 Nursing bottle caries, 412 Nutrients, 633 Nutriology, 633

O Obstructive sleep apnea syndrome, 512 Occipital neuralgia, 125 Occlusal enamel pearl, see Dens evaginatus Occlusal radiographs, 395, 721 Occupational exposure, 703 Occupational hazards, 390 Odontecrexis, 119 Odontoameloblastoma, 336 Odontogenic carcinomas, 363 Odontogenic carcinosarcoma, 366 Odontogenic fibroma, 344 Odontogenic keratocyst, 307 Odontogenic myxomas, 344 Odontogenic sarcomas, 365 Odontogenic tumors, 332, 344 Olfactory reference syndrome, 561 Oligodontia, 45 Olympian row, 628 Omohyoid muscle, 399 Oncocytoma, 295 Oncogenes, 386 Opalescent brittle teeth, 577 Open apices method, 671 Open lock, see Dislocation Open mouth Waters’ view, see Skull radiography OPG, 306, 320 Oral contraceptive, 447 Oral hairy leukoplakia, 100, 516 Oral melanoacanthoma, 347 Oral submucous fibrosis, 159 Oral warts, 346 Orofacial digital syndrome, 24 Orofacial granulomatosis, 289, 620 Orofacial pain, 115 Oromandibular dystonia, 532 Oromandibular limb hypogenesis syndrome, 22 Oropharyngeal candidiasis, 509 Oropharyngeal trichomonal infection, 631 Orthokeratinized odontogenic cyst, 307 Orthopnea, 475 Orthostatic hypotension, 563 OSMF, 159, 160, 161 Ossifying fibroma, 348, 571 Osteitis fibrosa generalisata, 543 Osteoarthritis, 251 Osteoarthrosis, 250 Osteoclast, 543, 578 Osteodentin, 640 Osteodystrophia deformans, 587 Osteogenesis imperfecta, 576

Osteogenic sarcoma, 573 Osteoma, 349 Osteomalacia, 455, 638 Osteomyelitis, 431 microorganisms responsible, 432 Osteopetrosis, 578 congenita, 579 tarda, 579 Osteoporosis, 846 Osteoporosis circumscripta, 588 Osteoradionecrosis, 401, 701 Osteosarcoma, 373, 374 Otalgia, 387 Overlapped image, 816 Oxyphilic adenoma, 295 Oxytocin, 538

P Paan, 381, 382 Pacemakers, 484 Pachyonychia congenita, 225 Paget’s disease, 586 Palatal cancer, 590 Palatal rugae, 15, 663 Palatal torus, 19, 20 Paleospinothalamic tract, 113 Pancreatin, 511 Pancytopenia, 226, 488 Panhypopituitarism, 536 Pannus, 252 Panoramic radiograph, 759 disadvantages and limitations, 760 indications, 759 Panoramic radiology, 756 concepts, 756 technique and imaging principles, 756 working principle, 757 origin, 756 Pansinusitis, 105 Papillary cystadenoma lymphomatosum, 294 Papillon–Lefevre syndrome, 453 Paracoccidioidomycosis, 208 Parade ground fracture, 262 Paradental cyst, 320 Paramedian lip pits, 26 Paramolar, 46, 47 Paraneoplastic pemphigus, 184, 185, 596 Parapharyngeal space, 427 Parasitic cysts, 327 Parathyroid glands, 542 Paratracheal lymphadenopathy, 607 Parinaud oculoglandular syndrome, 89 Parkinson’s disease, 278, 531 Parma projection, 751 Parotid enlargement, 290 Parotid papillae, 17 Paroxysmal nocturnal dyspnea, 475 Partial seizures, 530 Pastia’s lines, 82, 508 Patch test, 153 Paterson–Kelly syndrome, 487 Pathological fracture, 395, 396 Pathological wear, 464 Patient shielding, 711 Paul-Bunnell test, 90 Pediatric medicines, 462

Peg lateral, 35 Pel–Ebstein fever, 495 Pellagra, see Niacin deficiency Pelvic inflammatory disease, 630 Pemphigoid, 212, 596, 597 Pemphigus, 212, 596 Pemphigus erythematosus, 596 Pemphigus foliaceous, 181, 596 Pemphigus vegetans, 181, 596 Pemphigus vulgaris, 181, 596 Penny test, 811 Peptic ulcer disease, 523 Percussion test, 466 Perforations, 795 Periadenitis mucosa necrotica recurrents, see Major aphthous ulcers Periapical cemento-osseous dysplasia, 569 Periapical cyst, 318, 416 Periapical granuloma, 416, 419 Periapical pocket cyst, 320 Periodontal disease, 101, 440, 450, 592 Periodontal pain, 118 Periostitis ossificans, 437 Peripheral edema, 475 Peripheral giant cell granuloma, 352 Peripheral ossifying fibroma, 348 Pernicious anemia, 488 Personal protective equipment (PPE), 728 Personnel dosimeter, 713 Personnel shielding, 711 Petechiae, 69 Petit mal seizures, 530 Peutz-Jeghers syndrome, 66 PFAPA syndrome, 215 Phantom bone disease, 585 Pharyngitis, 507 Pharyngotonsillitis, 508 Phenytoin-induced gingival enlargement, 446 Pheochromocytoma, 549 Pheomelanin, 18 Phleboliths, 16 Phoenix abscess, 415 Phosphate, 488 Phosphopeptide, 464 Photoelectric effect, 696 Photographic effect, 713 Photopheresis, 184 Photostimulable phosphor plates, 733 Phycomycosis, 615 Pilocarpine, 288 Pink disease, 63 Pink form, 655 Pink panters, 510 Pink puffers, 510 Pink tooth, 466, 467 Pink tooth of Mummery, 80 Pinta, 626 Pinto’s ligament, 241 Pit and fissure caries, 410 Pituitary dwarfs, 536 Pityriasis rosea, 226 Planck’s constant, 687 Plasmapheresis, 600 Platelet count, 500 Platelet disorders, 499 Platelets, 497

893

Index

Platyspondyly, 578 Pleomorphic adenoma, 291, 792 Pleomorphism, 398 Plumbism, 64 Plummer–Vinson syndrome, 487 Pocket dosimeter, 713 Podophyllin, 103, 630 Polonium, 382 Polyarthritides, 252 Polycyclic aromatic hydrocarbon (tars), 382 Polycythemia, 485 Polycythemia rubra vera, 485 Polyunsaturated fatty acids, 635 Pontiac fever, 512 Poorly differentiated squamous cell carcinoma, 399 Popcorn calcifications, 578 Porphyria, 642 Porphyria cutanea tarda, 643 Portable handheld X-ray unit, 691 Position indicating device (PID), 694, 706, 709 Positive identification, 657, 678 Positron emission tomography, 294 Possible identification, 657, 678 Posterior auricular nodes, 91 Posterior cervical muscles, 245 Postmortem dental examination, 655 Postmortem identification, 655 Postmortem pink teeth, 661 Postmortem radiographs, 657 Postnasal drip, 105 Pregnancy, 445, 462, 550 Pregnancy gingivitis, 551 Pregnancy tumor, 445 Pregnancy-associated gingivitis, 445 Prenatal diagnosis of clefts, 28 Prevotella intermedia, 454 Prickle cells, 398, 399 Primary herpetic gingivostomatitis, 176, 200 Primary HPT, 542 Primary intraosseous squamous cell carcinoma, 364 Primary hypertension, see Hypertension Prinzmetal’s angina, 478 Probable identification, 657 Probe, 394, 395 Processing solutions, 810, 811 composition, 810 developer solution, 810 fixing solution, 810 test to determine the quality, 811 Progesterone, 550 Proliferative verrucous leukoplakia, 142 Proptosis, 390 Prostaglandins, 112 Protective co-contraction, 256 Protein energy malnutrition (PEM), 635 Proteins, 635 Proteolysis-chelation theory, 406 Proteolytic theory, 406 Prothrombin time, 498 Proton pump inhibitors, 269, 523 Protostylid, 44, 45 Protruded tongue, 662 Proximal surface caries, 417 Psammomatoid ossicles, 573

894

Pseudo macroglossia, 22 Pseudomicrodontia, 35 Psoriasis, 165, 221 Psychosomatic factors, 455 Pterygomandibular space, 427, 430 Ptyalism, 63, 278 Puberty-associated gingivitis, 445 Pulmonary tuberculosis, 608 Pulp calcifications, 468 Pulp canals, 42, 459 Pulp hyperemia, see Focal reversible pulpitis Pulpal pain, 116 Pulse oximetry, 424 Pulse rate, 476 Pulse rhythm, 476 Punch biopsy, 398 Punched-out radiolucencies, 497 Purified protein derivative, 609 Pyoderma gangrenosum, 520 Pyogenic granuloma, 353 Pyostomatitis vegetans, 623

Q Qualitative disorders, 491 Qualitative neutrophil defects, 488 Quantitative defects, 485

R Rabbit fever, 83 Racial pigmentation, 17 Radiation, 701 sources, 701 cosmic sources, 702 natural radiation, 702 terrestrial sources, 702 Radiation biology, 690, 697 deterministic effects, 699 of total body radiation, 699 on tissues and organs, 699 effects on living systems, 697 bystander effect, 699 cell cycle effects, 698 direct effect, 697 effects in the developing embryo and fetus, 700 on oral tissues, 700 film exposure and processing, 714 stochastic effects, 699 Radiation caries, 401, 412, 426, 701 types, 701 Radiation dose, 399 Radiation hazards, 685 Radiation-induced cancer, 700 Radiation-induced heritable diseases, 700 Radiation monitoring devices, 713 Radiation physics, 687 fundamentals, 687 electromagnetic radiation, 687 ionizing and non-ionizing radiation, 688 particulate radiation, 687 production of X-rays, 688 radiation, 687 Radiation protection survey, 711 Radiation safety and protection, 701, 728 historical events in, 701

Radioallergosorbent test, 507 Radicular cyst, see Periapical cyst Radiculomegaly, 35 Radiographic evaluation of carious lesions, 425 Radiographic faults, 812 causes, 812 Radiographic film, 731 Radiographic image formation, 801 Radiographic infection control, 728 Radiographic landmarks, 83, 825 common to both the maxillary and mandibular radiographs, 825 extraoral, 837 radiolucent anatomical, 836 radiopaque anatomical, 836 unique to the mandibular radiograph, 825, 833 unique to the maxillary radiograph, 825, 827 Radiographic techniques, 724–797 conventional imaging, 724, 725 extraoral radiography, 724 intraoral radiography, 724 specialized imaging, 724, 760 arthrography, 725 computed tomography (CT), 724 dentomaxillofacial cone-beam computed tomography (CBCT), 724 magnetic resonance imaging, 725 nuclear medicine, 725 sialography, 725 thermography (thermal imaging or infrared imaging), 725 ultrasonography, 725 Radiography, 703 dose limits, 703 patient exposure, 703 reducing dental exposure, 703 Radioisotope scan, 394 Radionuclide imaging, 294, 541, 588 Radiotherapy, 363, 364, 399 Radiotracer, 395, 584 Raman spectroscopy, 395 Rampant caries, 411, 426 Ramsay Hunt syndrome, 124, 125, 179, 529 Ranula, 279 Rapid plasma reagin (RPR), 613 Ras protein, 386 Raspberry like papillomas, 228 Rathke’s pouch, 324 Raw-ham colored lesions, 627 Ray phenomenon, 87 RBC disorders, 210 Reactive leukocytosis, 492 Receptor placement, 740 Recommended dietary allowance (RDA), 633 Recurrent caries, 412, 425 Recurrent erythema multiforme, 190 Red lesion, 134 Red strawberry tongue, 83 Referral pattern for myofascial pain, 258 Regional odontodysplasia, 59 Reiter’s syndrome, 215 Renal failure, 513 Renal osteodystrophy, 516, 542 Renal rickets, 516 Rendu-Osler-Weber syndrome, 69

Index

Reparative dentin, 468 Residual cyst, 320 Respiratory infections, 504 Respiratory tract diseases, 506 Resting and reversal lines, 588 Rests of Malassez, 318, 320, 337, 363 Reticular atrophy of pulp, 468 Reticular forms, 148 Retrocuspid papilla, 14 Retrodiscitis, 249 Retrograde parotitis, 515 Retropharyngeal space, 427, 430 Retrozygomatic space, see Infratemporal fossa space Reverse smoking, 383, 390 Reverse Townes’ view, 750 Reverse Waters’ method, see Skull radiography Rhabdomyoma, 357 RHD, 480 Rheumatic fever, 480 Rheumatoid arthritis, 252, 592, 595 Rheumatoid factor, 253, 600 Rheumatoid synovial fluid, 594 Rhinocerebral zygomycosis, 616 Rhinoscleroma, 88 Rhinoviruses, 506 Rhizomegaly, 35 Rhizomicry, 35 Rhodopsin, 636 Riboflavin deficiency (riboflavinosis), 455 Rickets, 52, 638 Rickety rosary, 638 Riga–Fede disease, 47, 197 Rigor mortis, 659 Risus sardonicus, 85 Rodent ulcer, 367 Root caries, 425 Root dwarfism, 35 Root end cyst, see Periapical cyst Root surface caries, 410, 417, 461 Rootless teeth, 58 Rose bengal staining, 272 Row of tombstones, 183 Rubella, 91 Rubeola, 91 Rugger-jersey sign, 579 Rushton’s hyaline bodies, 319 Russel bodies, 89

S Sabouraud’s agar, 108, 109, 157 Saddle nose, 617, 628 Safe light, 805 Saliva, 267 Saliva swab, 676 Salivary calculi, 280 Salivary dysfunction, 75, 400 Salivary flow rate, 408 Salivary gland scans, 789 clinical applications, 789 procedure, 789 Sandpaper rash, 82 Sandpaper-like exanthema, 508 Sanfilippo syndrome, 645 Sarcoidosis, 289, 618

Saucerization, 436 Scarlet fever, 82 Schaumann bodies, 290, 619 Scheie syndrome, 644 Schirmer’s test, 271, 272 Schuller method, 748 Schwannoma, 356 Scintigraphy, 271, 496, 543 Scintillation, 713 Sclerotic cemental masses, 570 SCOFF questionnaire, 525 Scooped dentin, 464 Scratch test, 81 Screw-driver appearance, 52 Screwdriver edge-shaped central incisors, 628 Screwdriver-shaped incisors, 613 Screw-type implants, 851 radiographic appearance, 851 Scrofula, 608 Scrotal tongue, 13 Scurvy, 499 Secondary aldosteronism, 549 Secondary dentin, 468 Secondary hypertension, 476 Secondary pulmonary tuberculosis, 607, 608 Selenium, 144, 385 Self-developing film, 808 Self-healing carcinoma, 347 Senear–Usher syndrome, 596 Sentinel node, 394 Septic arthritis, 252 Sequelae of pulpitis, 413, 416 Sequestrated bone, 401 Sequestrectomy, 436 Serous non-secretory cyst, 317 Serum alkaline phosphatase levels, 575, 584 Serum bilirubin, 525, 526, 528 Sex hormones, 454 Sexually transmitted diseases, 625 Shagreen patch, 233 Shell teeth, 57 Shepherd’s crook deformity, 575 Shingles, 178, 201 Shovel-shaped incisors, 41 Sialadenitis, 281 Sialadenosis, 287 Sialography, 793, 795 contraindications, 795 indications, 793 injection of the contrast medium, 794 phases, 794 procedure, 793 armamentarium, 793 preimaging assessment, 793 preimaging instructions to the patient, 793 technique, 793 Sialolithiasis, 280 Sialometry, 274, 290 Sialorrhea, 278 Sialosis, 287 Sicca complex, 277 Sicca syndrome, 271 Sickle cell anemia, 489 Sickle cell trait, 489 Siga, 409, 462

Silent thyroiditis, 539, 540 Simian gait, 587 Simmond’s disease, 536 Sinusitis, 104 Sistrunk procedure, 325 Situs inversus, 22 Sjögren’s syndrome, 791 Skin prick test, 507 Skull-photograph superimposition, 666 Skull radiography, 743 landmarks for positioning, 743 patient preparation, 744 planes for positioning of the skull, 743 positioning errors, 744 positioning terminology, 744 radiation protection, 744 techniques, 744 acanthoparietal projection, 747 AP axial projection, 749 bimolar projection, 751 lateral cephalometry, 749 lateral oblique of the ramus of the mandible, 751 lateral view, 748 modified parietoacanthial projection, 747 30° occipitomental, 746 PA cephalometric, 745 PA mandible, 745 parietoacanthial view, 747 posteroanterior projection, 745 rotated PA view, 746 standard occipitomental view, 746 submentovertex view, 748 Slaked lime, 139, 381 Slow virus, 587 SLUDGE syndrome, 604 Sly syndrome, 645 Smoker’s melanosis, 65 Smoker’s palate, 136 Smoking, 452 Smooth surface caries, 410 Snail track ulcers, 207, 613, 627 Snarling face, 603 Snuff, 139, 382 Snuff dipper’s cancer, 366 Soap bubble appearance, 322, 334, 362 Social profiling, 662 Sodium valproate, 446, 566 Solid PIOC, 364 Somatostatin analog, 537 Source to image receptor distance (SID), 708 South American blastomycosis, see Paracoccidiodomycosis Spatula test, 86 Speckled leukoplakia, 219 Sphenomandibular ligament, 241 Spindle-shaped fibroblasts, 582 Splendore-Hoeppli phenomenon, 88 Splenus capitis, 245 Split papules, 206, 627 Spoon-shaped nails, see Koilonychia Squamous cell carcinoma, 364, 398, 399 Squamous odontogenic tumor, 337 Squamous papilloma, 345 St. Anthony’s fire, 84

895

Index

Stable angina, 478 Stafne’s bone cyst, 323 Static bone cyst, 323 Stellate-shaped fibroblasts, 570 Stensen’s duct, 17, 267, 285 Step down transformer, 693 Sterilization, 104 Sternocleidomastoid, 245 Steroids, 186, 509, 533, 580 Stevens–Johnson syndrome (SJS), 191, 216 management guidelines, 512 Still’s disease, 254 Stomatitis medicamentosa, 209 Stomatitis venenata, 209 Strawberry cervix, 631 Strawberry gingivitis, 108, 617, 618 Strawberry tongue, 83, 232, 508 Stress reflux syndrome, 461 Stretch test, 14 Stridor, 428, 505 String of beads sign, 195 Stunted roots, 401, 578 Sturge–Weber syndrome, 40, 45, 68 Stylomandibular ligament, 241 Subacute necrotizing sialadenitis, 283 Subchondral bone cysts, 251 Subcutaneous injections, 580 Subglottic larynx, 393 Sublingual space, 427, 429, 431 Subluxation, 248, 249 Submandibular nodes, 389 Submandibular space, 427, 429, 431 Submental nodes, 393, 394, 429 Submental space, 429 Submerged teeth, 49 Succinic acid, 463 Sucrose chelation theory, 406 Sugar substitutes, 634 Sulcus terminalis, 16 Sulfur colloid, 394, 788 Sulfur granules, 86, 87 Sunray appearance, 362, 371, 374, 375 Superficial fascia, 426 Superficial hemangiomas, 358 Superior joint space, 240, 247 Supernumerary teeth, see Hyperdontia Supine hypotensive syndrome, 551 Supplemental teeth, 46, 47 Suppurative osteomyelitis, 433, 434 Supraclavicular nodes, 393, 608 Supraomohyoid triangle, 394 Suprasternal notch, 325, 393 Sutton’s ulcers, see Major aphthous ulcers Sweet criteria, 121 Swift disease, 63 Swimmer’s erosion, 464 Swiss cheese pattern, 298 Symblepharon, 187, 195, 227 Synovial chondromatosis, 261, 262 Synovial chondrosarcoma, 261 Synovial fluid, 240 Synovial sarcomas, 261, 372 Synovitis, 249 Syphilis, 384, 612, 626 Syphilitic aortitis, 627 Syphilitic osteomyelitis, 628

896

Systemic lupus erythematosus (SLE), 172, 597 Systemic sclerosis, 601

T Tabes dorsalis, 612, 627 Talon cusp, 39, 40 Tam O’Shanter skull, 578 Tanaka’s ligament, 241 Target or double halo appearance, 522 Target lesion, 190 Tars, 382–383 Taurodontism, 42, 43 T-cell immunity, 590 Technetium scan, 394 Teletherapy, 400 Telomeres, 225, 385 Temporal space, 429 Temporalis muscle, 241 Temporomandibular joint (TMJ), 239, 241, 243, 593, 840 arterial supply, 243 examination, 243 radiography, 751 sensory innervation, 243 transcranial view, 751 transorbital view, 752 transpharyngeal view, 751 venous drainage, 243 Temporomandibular joint imaging, 849 Teratoid cysts, 327 Tertiary syphilis, 627, 628 Test cavity, 422 Tetanolysin, 85 Tetanospasmin, 85, 86 Tetanus, 85 Tetracycline, 78, 444 Thalassemia, 490 Thermal burns, 135 Thermography, 796 indications, 797 patient preparation, 797 procedural requirements, 797 techniques, 796 Thermoluminescent dosimetry (TLD) badges, 714 Thiamin deficiency, 455 Thinning of articular disk, 246 Thiocyanate, 383 Third molars in age estimation, 671 Thistle-tube-shaped pulp chamber, 59 Thorny radiation, 585 Thrombocytopenia, 488, 500 Thrombocytopenic purpura, 456, 500 Thrombotic thrombocytopenic purpura, 500 Thyroid collars, 709, 711, 715 Thyroid gland, 538, 539, 542 Thyroid storm, 541 Thyrotoxic crisis, 541 Thyrotoxicosis, 540, 591 Thyroxin, 538, 540 Tic douloureux, see Trigeminal neuralgia Tissue biopsy, 395, 614 TNM staging, 391 Tobacco, 138, 381 Toluidine blue staining, 142, 397

Tongue hemorrhage, 662 Tonsillar pillars, 91, 110, 390 Tonsillitis, 83, 507 Topographical occlusal technique, 736 Tori, 19 Tornwaldt’s bursa, 324 Torus mandibularis, 19, 20 Torus palatinus, 20 Total filtration, 694 Tourniquet test, 498 Townes’ method, 749 Toxic epidermal necrolysis (TEN), 191 management guidelines, 512 Traditional CT, 397 Tram line calcifications, 68 Transcutaneous electric nerve stimulation (TENS), 258, 484 Transient neonatal MG, 603 Transmigration, 48 Trapezius, 245 Traumatic arthritis, 252 Traumatic bone cyst, 321 Traumatic neuroma, 357 Traumatic ulcers, 197, 199 Treacher Collins syndrome, 27, 31, 33 Treponema pallidum, 200, 206, 612, 626 Triangular shaped face, 577 Trichiasis, 195 Trichinosis, 329 Trifid condyles, 34 Trifacial neuralgia, 120 Trigeminal neuralgia, 120–123 Trigeminal neuropathy, 101, 628 Trigger point therapy, 258 Trigger points, 120, 125 Trismus, 85, 428 Trisomy, 22, 43 Trousseau’s sign, 544 True cysts, 303, 304 True macroglossia, 22 TSH, 533, 535, 540 Tuberculoid leprosy, 610, 611 Tuberculosis, 101, 205, 606–611 Tuberculous lymphadenitis, 608 Tuberculous meningitis, 607 Tuberculous osteomyelitis, 205, 608 Tuberous sclerosis complex, 232 Tularemia, 83–84 Tumor markers, see Blood studies Tumor suppressor genes, 143, 386 Tunneling technique, 659 Turner syndrome, 45, 326, 550 Turner’s hypoplasia, 51 Turner’s tooth, 51 Type I collagen, 543, 576, 592 Types of dislocation, 249 Tzanck cells, 176, 177 Tzanck smear, 201, 648 Tzanck test, 183

U Ugly duckling sign, 369 Ulcerative colitis, 214, 520 Ulceronodular disease, 207, 627 Ultrasonography, 789–792 Unicystic ameloblastoma, 336

Index

Unifocal eosinophilic granuloma, 647 Universal precautions, 104 Unstable angina, 478 Upper respiratory tract infections, 506 Urbach–Wiethe disease, 646 Uremia, 514, 515 Uremic fetor, 514 Uremic frost, 515 Uremic gastroenteritis, 514 Uremic stomatitis, 518 Uremic syndrome, 514 Uremic toxin, 514, 517 Usher syndrome, 56, 596 Uto-Aztecan premolar, 44

B1-thiamine, 640 B2-riboflavin, 640 C, 455, 639 D, 455, 637 E, 145, 455 K, 502, 638 Vitamin K deficiency, 503 Volatile sulfur compounds, 444 Von Ebner’s glands, 17 Von Recklinghausen disease of bone, 542 Von Willebrand factor, 497 Von Willebrand’s disease, 503 Vrolik syndrome, 576

W V Vanishing bone disease, 585 Varicella zoster infection, 178, 201 Variegate porphyria, 643 Vascular disorders, 474, 476, 498, 499 Vascular malformations, 68, 357, 358 Velscope and Vizilite plus, 395 Venereal disease research laboratory (VDRL) tests, 613, 628 Venereal diseases, 625 Venereal wart, see Condyloma acuminatum Verapamil, 446 Verocay bodies, 356 Verruca vulgaris, 346 Verrucous carcinoma, 366–367 Verrucous hyperplasia, 346 Verrucous leukoplakia, 138, 141 Vertical angulation, 740 Vietnamese time-bomb, 85 Viral pharyngitis, 507 Visual analog scale (VAS), 116 Vital signs, 482, 550 Vital staining, 395, 397 Vitality tests, 468, 522 Vitamin(s), 636–641 A (retinol), 636 B complex, 455, 640

Waddling, 587 Wallerian degeneration, 529 Wall mounted intraoral radiographic unit, 690 Warfarin, 484, 504 Warthin–Starry method, 89, 613 Warthin’s tumor, 294, 295 Water brash, 278, 519 Water-clear cells, 310 Water lily sign, 328 Water soluble vitamins, 636, 639 Waters’ view, see Skull radiography WBC disorders, 210 Weber and Fechner’s law, 111 Weber’s glands, 267 Weeping lubrication, 247 Wegener’s granulomatosis, 617, 618 Well-differentiated squamous cell carcinoma, 398 Wet beriberi, 640 Wharton’s duct, 267, 280 Wheezing, 505 Whiff test, 631 White blood cells, 490 White coat hypertension, 477 White lesion, 133 White sponge nevus, 166

White spots, 819 White strawberry tongue, 83 Wickham’s striae, 147, 219, 236 Wilms’ tumor, 31 Winchester syndrome, 586 Witkop’s disease, see Hereditary benign intraepithelial dyskeratosis Wood-hard tongue, 646 Wormian bones, 540, 578

X Xeroderma pigmentosum, 226 Xerophthalmia, 271, 636 Xerosis, 636 Xerostomia, 267–270, 700 X-rays, 685, 687, 689 properties, 689 publications, 685 X-ray beam angulation and alignment, 727 X-ray equipment, 706, 710, 712 X-ray photons, 695 X-ray tube, 692 schematic diagram, 692 Xylitol, 276, 634

Y Yaws, 612, 626 Yellow form, 657 Yunis–Varon syndrome, 48

Z Zahn lines, 16 Ziehl–Neelsen stain, 606, 609 Zinc sulfate, 229, 401 Zinsser–Engman-Cole syndrome, 225 Zollinger–Ellison syndrome, 523 Zoster ophthalmicus, 179, 235 Zoster sine herpete, 124, 179 Zygomatic bone, 832 Zygomatic process, 832 Zygomycosis, 615

897

Textbook of Oral Medicine Oral Diagnosis and Oral Radiology

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