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Allergy and Oral Mucosal Disease Allergy and Oral Mucosal Disease Shiona Rachel Rees B.D.S. F.D.S. R.C.P.S. A thesis presented for the degree of Doctor of Dental Surgery of the University of Glasgow Faculty of Medicine University of Glasgow Glasgow Dental Hospital & School May 2001 © Shiona Rachel Rees, May 2001 ProQuest Number: 13833984 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 13833984 Published by ProQuest LLC(2019). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 fGLASGOW UNIVERSITY .LIBRARY: \ 1 ^ 5 SUMMARY The purpose of this study was to assess the prevalence of positive results to cutaneous patch testing in patients with oral mucosal diseases and to assess the relevance of exclusion of identified allergens to the disease process. It was also attempted to identify microscopic features that were related to a hypersensitivity aetiology in patients with oral lichenoid eruptions. The analysis was carried out retrospectively in the Departments of Oral Medicine and Oral Pathology in Glasgow Dental Hospital And School and the Contact Dermatitis Investigation Unit in the Royal Infirmary, Glasgow. A total of 1,252 patients with oral mucosal diseases who had been referred to the Contact Dermatitis Unit were assessed, and the prevalence of positive reactions to patch testing and contact urticaria testing in each disease cohort was compared to the prevalence of positive reactions in 100 control volunteers. Sections of specimens from patients with oral lichenoid eruptions were analysed using photographic standards and by counting cells and measuring the sections. The results indicated that patients with oral mucosal diseases were significantly more likely to have demonstrable hypersensitivity to food additives, especially benzoic acid, and perfumes and flavourings, especially cinnamaldehyde, than controls. Dietary avoidance therapy to identified allergens caused improvement in the majority. Patients with oral lichenoid eruptions were significantly more likely to react to mercurial allergens on patch testing than patients with recurrent aphthous stomatitis or orofacial granulomatosis. Microscopic examination revealed that the density of the inflammatory infiltrate was higher in those patients with oral lichenoid eruptions who had one or more positive patch tests or contact urticaria tests. They also had more disruption of the basal cell layer though this was of borderline significance. It was concluded that patch testing and contact urticaria testing, together with the resultant allergen avoidance therapy, are useful adjuncts in the management of oral mucosal diseases. The presence of a florid (in terms of thickness and density) inflammatory infiltrate and disruption of the basal cell layer in cases of oral lichenoid eruptions, suggested that an allergic aetiology was more likely. Ill TABLE OF CONTENTS T itle......................................................................................................................I Summary............................................................................................................. II Table of Contents ..............................................................................................IV List of Tables .............................................................................. X List of Figures ................................................................................ XII List of Publications ........................................................................................ XIV Glossary of Abbreviations .............................................................................. XV Acknowledgements ...................................................................................... XVII CHAPTER 1 LITERATURE REVIEW..................................1 1.1. Allergy: Historical Review and Basic Mechanisms........................1 1.1.1. Historical Review ........................................................................ 1 1.1.2. Basic Mechanisms and Oral Mucosal Immunity .....................9 1.1.2.1. Saliva ......................................................................... 9 1.1.2.2. Mucosa .......................................................................................10 1.1.2.3. Cells............................................................................................11 Antigen Presenting Cells ......................................................11 Lymphocytes .........................................................................12 Eosinophils ............................................................................13 Mast cells and Basophils ......................................................13 1.1.2.4. Cytokines and Mediators ..........................................................14 1.1.2.5. Humoral Mechanisms in Oral Mucosa ................................... 15 1.1.2.6. Cellular Mechanisms in Oral Mucosa .....................................16 1.1.3. Antigens and Allergy Testing .................................................. 18 1.1.3.1. Antigens and the Oral Mucosa .................................................18 Dental home care products ..................................................21 Dental materials and medicaments .....................................22 Metals used in dentistry .......................................................25 Rubber products used in dentistry ......................... 30 Foods....................................................................... 31 Food Additives And Flavouring Agents ............................33 Cosmetics ..............................................................................38 1.1.3.2. Allergy Tests...........................................................................39 Patch testing ......................................................................... 40 1.2. Oral Lichenoid Eruption ....................................................................44 1.2.1. Introduction and Historical Review ........................................44 1.2.2. Classification and Prevalence ..................................................48 1.2.3. Aetiology, Features and Diagnosis .....................................:...52 1.2.3.1. Other Diseases In Relation With OLE ................................... 57 1.2.3.2. Histopathological Features of OLE Lesions .......................... 58 1.2.4. Pathogenesis .............................................................................. 61 1.2.4.1.Immune Pathogenesis ............................................................... 61 1.2.5. Role Of Allergy........................................................................64 1.2.5.1. General .................................................................................... 64 IV 1.2.5.2. M ercury....................................................................................65 1.2.5.3. Comparison O f‘Lichenoid’ and Drug Induced Lichenoid and ‘Idiopathic LP’ Lesions ..........................................................................71 1.2.6. Treatment ....................................................................................76 1.3. Recurrent Aphthous Stomatitis ......................................................79 1.3.1. Introduction ................................................................................ 79 1.3.2. Classification and Features ................................ 81 1.3.2.1 .Minor Aphthae ............................................................. .............81 1.3.2.2.Major Aphthae ...........................................................................82 1.3.2.3.Herpetiform Ulceration ............................................................. 82 1.3.2.4.Beh9et’s Syndrome ....................................................................83 1.3.2.5.Other Systemic Diseases Associated With RAS .................... 84 1.3.3. Aetiology .................................................................................... 86 1.3.4. Pathogenesis ................................................................................88 1.3.5. Role of Allergy ..........................................................................89 1.3.6. Management and Treatment ..................................................... 92 1.4. Angioedema ...........................................................................................95 1.4.1. Introduction ................................................ 95 1.4.2. Classification ................................................................ 97 1.4.2.1 .Hereditary Angioedema ............................................................ 97 1.4.2.2.Acquired Angioedema - (1) Acquired Cl-INH Deficiency ............................................................................................................... 98 1.4.2.3. Acquired Angioedema - (2) Drug and Allergy Related Angioedema and Idiopathic Angioedema ............................................ 99 1.4.3. Treatment ...................................................... 105 1.4.3.1. Hereditary Angioedema and Acquired
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