An update on investigations of autoimmune diseases affecting orofacial region.

Autoimmune diseases are better diagnosed currently with advances in cellular immunology, molecular biology, and genetics. Clinical diagnosis of systemic and organ specific autoimmune diseases is a challenging task for the Oral physicians and the development of chairside investigation methods has not only saved the time but also cost factor. To understand patient's immune status, the clinical chair side diagnostic aids along with laboratory testing methods are necessary. Laboratory investigations have great importance in detecting, confirming and analyzing the severity, and predicting the prognosis of the autoimmune disease. This article aims to list out the diagnostic methods to diagnose autoimmune conditions and focuses on various diagnostic methods to effectively evaluate autoimmune disease of orofacial region.

Orofacial granulomatosis as a presenting feature of Crohn's disease.

An 11-year-old girl was referred to oral medicine with persistent facial swelling. She was diagnosed with orofacial granulomatosis (OFG) and was treated conservatively for 7 years, with no evidence of systemic illness. Aged 17 she re-presented with a flare up of her OFG, watery diarrhoea and fluctuating febrile episodes. Inflammatory markers were raised and an MR enterogram revealed terminal ileal Crohn's disease. This case highlights that OFG may precede the onset of intestinal Crohn's disease.

Immunophenotype in orofacial granulomatosis with and without Crohn's disease.

OBJECTIVES: The aim of this investigation was to characterise and compare the inflammatory infiltrates in patients with orofacial granulomatosis solely (OFG-S) and OFG with coexisting Crohn's disease (OFG+CD). STUDY DESIGN: Biopsy specimens with granulomas were obtained from patients with OFG-S (n=11) and OFG+CD (n=11) and immunostained with antibodies against CD1a, CD3, CD4, CD8, CD11c, CD20, CD68 and mast cell tryptase, followed by quantitative analysis. RESULTS: Analyses of the connective tissue revealed a significantly higher number of CD3-expressing T cells and CD11c-expressing dendritic cells in the connective tissue of patients with OFG-S compared to patients with OFG+CD. Mast cells displayed a high level of activation, although no significant difference was detected when comparing the two groups. CONCLUSIONS: The results show a different composition of the inflammatory infiltrate in patients with OFG-S compared to patients with OFG+CD. The present observations support that partly-divergent immune mechanisms are involved in these two different subcategories of OFG.

Experience with anti-TNF-α therapy for orofacial granulomatosis.

BACKGROUND: Orofacial granulomatosis (OFG) can be challenging to treat and experience with anti-TNF-α therapy is limited. We report our experience with infliximab (IFX) and adalimumab (ADA) for OFG in 14 patients, the largest reported series to date. METHODS: A review of patients receiving induction and maintenance IFX for OFG +/- Crohn's disease (CD) for active oral disease failing other therapies was performed. Clinical response defined by global physician assessment, aided by oral disease activity scores, was assessed at 2 months, 1 and 2 years. ADA was considered for patients failing IFX. Adverse events were recorded. Predictors of need for anti-TNF-α therapy were determined by comparison with OFG patients not requiring anti-TNF-α from our overall OFG database (n = 207). RESULTS: Fourteen patients (9 men) were treated with IFX [OFG only (n = 7), OFG with CD (n = 7)]. Nine patients received concomitant immunosuppression. Median duration of treatment was 18 months. Shortterm response was achieved in 10/14 (71%) patients. Eight of 14 (57%) and 4/12 (33%) patients remained responsive at 1 and 2 years, respectively. Two patients who failed IFX responded to ADA. Factors predicting need for anti-TNF-α therapy were oral sulcal involvement, intestinal CD and a raised C-reactive protein (CRP). Oral sulcal involvement predicted response at 1 and 2 years. Intestinal CD did not predict response. The only significant adverse event was an IFX infusion reaction. CONCLUSION: IFX provided good short-term response for most OFG patients; however, a significant proportion lost response long term. Adverse events were uncommon. Patients failing IFX may respond to ADA.

Patch testing for food-associated allergies in orofacial granulomatosis.

BACKGROUND: Food-associated allergies, especially to benzoates and cinnamon-related compounds, have been associated with orofacial granulomatosis and both standard and urticarial patch testing have been used to detect such allergies. Elimination diets have also been shown to be effective in some patients. OBJECTIVES: To compare the results of standard and urticarial patch testing in a cohort of patients with orofacial granulomatosis. MATERIALS AND METHODS: Records of 120 cases seen in two hospitals were retrieved and examined for patch test details. RESULTS: Standard patch testing was much less likely to detect allergy to benzoates and cinnamon compounds (7%) than urticarial tests (55%). All urticarial tests that were positive had shown a reaction by 60 min. CONCLUSIONS: Both standard and urticarial patch tests are required to detect food allergies in orofacial granulomatosis. The difficulties of patient self-recording of urticarial tests can be eliminated by retaining patients in the testing unit for professional reading of patches at 60 min.

Subepithelial dendritic B cells in orofacial granulomatosis.

BACKGROUND: Orofacial granulomatosis (OFG) is a chronic, disfiguring, granulomatous inflammation of the lips and oral mucosa. The pathogenesis is unknown, but it has been linked previously to Crohn's disease (CD) and more recently to dietary sensitivity. The oral mucosa is an immunologically responsive site associated with the generation of protective mucosal and systemic immune responses to vaccination and also hyperresponsiveness to allergens in some individuals. Classically, immune responses in oral mucosa are considered to be mediated by mucosa-associated lymphoid tissues (MALT), secondary lymphoid follicles that are intimately associated with epithelia. METHODS: Immunohistochemistry was used to investigate the inflammatory infiltrate in OFG and control tissue samples. Polymerase chain reaction (PCR), cloning of PCR products, and sequencing were used to characterize the local immunoglobulin gene profile in OFG. RESULTS: We describe large, active, dendritic B cells in oral mucosa that were not associated with any organized lymphoid tissues in the local subepithelial microenvironment. They express activation induced cytidine deaminase, which is essential for immunoglobulin gene diversification by somatic hypermutation and class switch recombination. IgE is also expressed by these B cells. They do not align with any other previously described B-cell subset in secondary lymphoid tissues in terms of morphology, proliferative activity, or phenotype. CONCLUSIONS: These subepithelial dendritic B cells may contribute to the immune responsiveness of the oral mucosa, including IgE-mediated allergic responses. In patients with OFG, further understanding of the role these cells play in oral immunity may lead to novel therapeutic possibilities.

Oral biopsies from patients with orofacial granulomatosis with histology resembling Crohn's disease have a prominent Th1 environment.

BACKGROUND: Orofacial granulomatosis (OFG) is an idiopathic inflammatory disorder of children and young adults whose clinical symptoms include swelling of the lips or face, mucosal nodularity (cobblestoning), mucosal tags, hyperplasia of the gingivae, and aphthous oral ulcers. Whether some OFG patients with clinical and histological characteristics resembling Crohn's disease (CD) are a special group (oral CD) or true CD patients with symptoms reaching all the way to the oral mucosa remains to be determined. METHODS: In this study oral biopsies from 10 patients with OFG were analyzed for the presence of T cells, T-cell subsets, B cells, and macrophages, as well as cytokines (IL-4, IL-10, IFN-gamma, IL-12, and TNF-alpha), chemokines (RANTES and MIP-1alpha), and chemokine receptors (CCR3, CCR5, and CXCR3). For comparison, oral tissues from 7 patients with other granulomatous diseases were included. RESULTS: Compared with the non-OFG group, the OFG group had raised levels of CD4(+) T cells, IFN-gamma, IL-10, and RANTES but reduced levels of CD68(+) macrophages outside the granulomas, whereas within the granulomas the levels of CD3(+) and CD4(+) T cells and of IFN-gamma were raised, but the levels of IL-4 were decreased. These data are indicative of a Th1 environment within the oral OFG tissues, which resembles that already observed in gut CD tissues. CONCLUSIONS: Therefore, it can be concluded that some OFG patients have both histopathological and immunopathological features that resemble those observed in CD patients.

Oro-facial granulomatosis: Crohn's disease or a new inflammatory bowel disease?

BACKGROUND: Oro-facial granulomatosis (OFG) is a rare chronic inflammatory disorder presenting characteristically with lip swelling but also affecting gingivae, buccal mucosa, floor of mouth, and a number of other sites in the oral cavity. Histologically, OFG resembles Crohn's disease (CD), and a number of patients with CD have oral involvement identical to OFG. However, the exact relationship between OFG and CD remains unknown. METHODS: Thirty-five patients with OFG and no gut symptoms were identified from a combined oral medicine/gastroenterology clinic. All underwent a standardized assessment of the oral cavity and oral mucosal biopsy to characterize the number of sites affected and the type of inflammation involved. Hematological and biochemical parameters were also recorded. All 35 patients underwent ileocolonoscopy and biopsy to assess the presence of coexistent intestinal inflammation. RESULTS: Ileal or colonic abnormalities were detected in 19/35 (54%) cases. From gut biopsies, granulomas were present in 13/19 cases (64%). An intestinal abnormality was significantly more likely if the age of OFG onset was less than 30 years (P=0.01). Those with more severe oral inflammation were also more likely to have intestinal inflammation (P=0.025), and there was also a correlation between the histologic severity of oral inflammation and the histologic severity of gut inflammation (P=0.047). No relationship was found between any blood parameter and intestinal involvement. CONCLUSIONS: Endoscopic and histologic intestinal abnormalities are common in patients with OFG with no gastrointestinal symptoms. Younger patients with OFG are more likely to have concomitant intestinal involvement. In these patients, granulomas are more frequent in endoscopic biopsies than reported in patients with documented CD. OFG with associated intestinal inflammation may represent a separate entity in which granulomatous inflammation occurs throughout the gastrointestinal tract in response to an unknown antigen or antigens.