Orofacial Granulomatosis: Clinical and Immunological Studies

Gibson, John (1998) Orofacial Granulomatosis: Clinical and Immunological Studies. PhD thesis, University of Glasgow.

Abstract

Orofacial granulomatosis (OFG) is assuming increasing importance in the practice of Oral Medicine. This is particularly true in the west of Scotland where over 400 patients with the condition have been identified over a 10 year period. This study has analysed the clinical and immunological parameters in 301 patients with orofacial granulomatosis in an attempt to understand the underlying aetiopathogenesis and to develop a protocol for the investigation and management of such patients. During the study, 140 patients were identified with OFG, 45 patients with gastrointestinal Crohn's disease (CD) (20 having a pre-existing diagnosis; 25 having the diagnosis established during the study), ten patients with Melkersson-Rosenthal Syndrome (MRS), and six patients with sarcoidosis. Gastrointestinal symptoms were found to be of practical value in identifying patients who may have gastrointestinal Crohn's disease. Similarly, systemic examination of patients yielded findings which aided differentiation of CD and OFG. An immunological (allergic) basis for OFG has been postulated in this study. Despite similar compliance scores and follow-up periods between the two groups (CD and OFG), dietary and environmental exclusion advice for substances identified on positive skin testing led to statistically significant differences in changes of both final symptom and sign scores. Further weight to the allergic basis for OFG was added with the overall levels of IgE demonstrated by RAST testing being significantly higher in the OFG group (82.4%) over the CD group (58.6%). In addition, levels of IgG directed against unidentified proteins in the sera of the OFG group, comparable to coeliac disease and significantly higher than control groups, further strengthen the likelihood of immunological reactivity in the OFG group. The consistent HLA haplotype (A2/3 B7 DR2/3/4) and results of lymphocyte studies suggest an immunological mechanism to the clinical presentation in OFG patients. The results of this study would suggest that the antigen may be dietary in origin. However, the negative findings in searching for Mycobacterium paratuberculosis require further analysis; the use of fresh tissue from orofacial biopsies instead of paraffin-processed sections would be a most appropriate next step using PCR technology. Laboratory findings were also of practical value in differentiating the disease categories. Whereas haemoglobin concentrations and serum vitamin B12 levels were not statistically different between the groups, the mean corpuscular volume (lower in CD), ESR (higher in CD), whole blood folate, and serum ferritin (mean lower in CD) were statistically significant in highlighting differences between CD and OFG. Biochemical parameters were largely redundant, with urea and electrolytes and calcium, albumin and phosphate levels revealing no real differences between the diagnostic groups. Analysis of histological data revealed that patients with CD were much more likely to have lymphoedema (p=0.004) and/or granulomata (p=0.012), alone or in combination, on mucosal biopsy than patients with OFG. However, 20.0% of CD biopsies and 30.9% of OFG biopsies had no granulomas present; but only 6.7% of CD biopsies and 16.7% of OFG biopsies had no lymphoedema present. It therefore seems inappropriate to persist with the title Orofacial Granulomatosis, a histopathological term used to describe a clinical entity, and the alternative of Orofacial Lymphoedema is suggested on the basis of clinical findings alone. The clinical findings in patients with OFG led to the helpful concept of Major and Minor diagnostic criteria for Orofacial Lymphoedema, with Major criteria being present in >30% of patients and Minor criteria being present in 7-29% of patients as follows: Major: Chronic lower lip swelling 52.2% Chronic upper lip swelling 51.2% Mucosal oedema and cobblestoning 48.8% Aphthous ulceration 39.2% Mucosal tags 31.2% Full-thickness gingivitis 30.2% Minor: Chronic facial swelling 27.0% Angular cheilitis Fissured tongue Non-aphthous ulceration Papillary hyperplasia 26.2% 11.3% 7.3% 8.0% The diagnosis would be based on 2 major criteria (i.e. present in at least 60.4% of patients) or 1 major plus 3 minor criteria (i.e. present in at least 56.8% of patients). On the basis of this study, OFG, sarcoidosis and Crohn's disease are distinct clinical entities. OFG, or more appropriately Orofacial Lymphoedema, OFL, would appear to be primarily allergic in its pathogenesis (Type IV or delayed hypersensitivity), as would Melkersson-Rosenthal Syndrome. Overall, 45 out of 301 patients in this study population had, or developed, evidence of gastrointestinal Crohn's disease - some 15% over a 10-year period. The successful use of technetium-labelled leucocyte scanning of the gastrointestinal tract to identify gastrointestinal CD in patients with OFL in the paediatric population has been demonstrated in this study.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: David Wray
• Keywords: Dentistry, Medicine
• Date of Award: 1998
• Depositing User: Enlighten Team
• Unique ID: glathesis:1998-74792
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 13 Nov 2019 15:58
• Last Modified: 13 Nov 2019 15:58
• URI: https://theses.gla.ac.uk/id/eprint/74792