How to recognise a Behçet's ulcer from other types of oral ulceration? Defining Behçet's ulceration by an International Delphi Consultation.

OBJECTIVES: To define the clinical characteristics of oral ulceration (OU) in Behçet's disease (BD), to allow differentiation from other causes of OU, including aphthous ulcers, by an International Delphi consultation. To develop a clinical guideline on how to recognise BD ulcers. METHODS: Round 1. 40 clinical images of OU in BD, recurrent aphthous stomatitis (RAS), inflammatory bowel disease (IBD) and mucous membrane pemphigoid (MMP) were shown. Participants answered, independently, which images would be consistent with a BD ulcer. Round 2. The results from marking independently were shown. The panel remarked the questions through iteration process. The images not agreed to be a possible BD ulcer were discarded. Round 3. 10 clinical descriptors that may define BD ulcers were suggested. Participants ranked the level of importance for each descriptor on each image presented. Round 4. Participants re-ranked their level of agreement for each descriptor through iteration process. Whether the clinical pictures would be different from RAS was also explored. A final agreement was reached. RESULTS: This study has shown clear differentiation between BD, IBD and MMP ulcers when defining them by phenotype through clinical images only. On the other hand, no differentiation between RAS and BD ulcers was found. The most important clinical descriptors that define BD ulcers have been agreed. CONCLUSIONS: New clinical guidance for Health Care Professionals (HCP) on how to recognise a BD ulcer has been proposed. This should elucidate an earlier diagnosis, quicker access to treatment and control of the disease enhancing patient's quality of life.

Clinical photography: Attitudes among dental students in two dental institutions.

INTRODUCTION: Clinical photography is an important tool in teaching, clinical practice and academia especially for mucosal pathologies. Our aim was to examine differences in attitude towards clinical photography for mucosal pathologies among students. METHODS: Questionnaires about clinical photography were completed by students in dental teaching hospitals in Birmingham (UK) and in Israel (ISR). The questionnaires focussed on the perceived value of clinical photography for a number of purposes and also explored perceived barriers to clinical photography and technology in general. The two departments have different access to clinical photography; in the United Kingdom a separate dedicated photography unit takes all the photographs, whereas in ISR the clinicians take their own photographs. Pearson Chi-squared tests determined statistical significance between categorical variables (P < 0.05). RESULTS: Among the 163 respondents, there were no significant differences in the value of photography between countries or genders. The participants felt that the aims of photography included: teaching (99.4%), monitoring premalignancy (97.6%) and clinician communication (95.8%). More than 90% thought photography should be used for dysplasia and erosive lichen planus cases. Respondents from ISR were more in favour of photographing pathologies including simple leukoplakia, reticular lichen planus, vesiculobullous or pigmented lesions (P < 0.001 compared to the UK). Overall, the main reasons for not using photography were time constraints (25.5%) and access (21.8%). CONCLUSIONS: This study highlights a favourable attitude towards clinical photography for various teaching and clinical indications thereby demonstrating its importance. In order to maximise the benefits of clinical photography, access should be simplified.

Birmingham Behçet's service: classification of disease and application of the 2014 International Criteria for Behçet's Disease (ICBD) to a UK cohort.

BACKGROUND: This study reports on the analysis of the application and diagnostic predictability of the revised 2014 ICBD criteria in an unselected cohort of UK patients, and the ensuing organ associations and patterns of disease. METHODS: A retrospective cohort study was conducted using a database of electronic medical records. Three categories were recognised: clinically defined BD, incomplete BD and rejected diagnoses of BD. We applied the ISG 1990 and ICBD 2014 classification criteria to these subgroups to validate diagnostic accuracy against the multidisciplinary assessment. RESULTS: Between 2012 and 2015, 281 patients underwent initial assessment at an urban tertiary care centre: 190 patients with a confirmed diagnosis of BD, 7 with an incomplete diagnosis, and 84 with a rejected diagnosis. ICBD 2014 demonstrated an estimated sensitivity of 97.89% (95% CI: 94.70 to 99.42) and positive likelihood ratio of 1.21 (1.10 to 1.28). The strongest independent predictors were: Central nervous lesions (OR = 10.57, 95% CI: 1.34 to 83.30); Genital ulceration (OR = 9.05, 95% CI: 3.35 to 24.47); Erythema nodosum (OR = 6.59, 95% CI: 2.35 to 18.51); Retinal vasculitis (OR = 6.25, 95% CI: 1.47 to 26.60); Anterior uveitis (OR = 6.16, 95% CI: 2.37 to 16.02); Posterior uveitis (OR = 4.82, 95% CI: 1.25 to 18.59). CONCLUSIONS: The ICBD 2014 criteria were more sensitive at picking up cases than ISG 1990 using the multidisciplinary assessment as the gold standard. ICBD may over-diagnose BD in a UK population. Patients who have an incomplete form of BD represent a distinct group that should not be given an early diagnostic label. Behçet's disease is a complex disease that is best diagnosed by multidisciplinary clinical assessment. Patients in the UK differ in their clinical presentation and genetic susceptibility from the original descriptions. This study also highlights an incomplete group of Behçet's patients that are less well defined by their clinical presentation.

Periodontitis prevalence and serum antibody reactivity to periodontal bacteria in primary Sjögren's syndrome: a pilot study.

AIMS: The aims of this study were as follows: (i) To assess the prevalence of periodontitis among patients with primary Sjögren's syndrome (pSS) and comparator groups of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). (ii) To perform a pilot study to compare serum antibody responses to 10 oral/periodontal bacteria in these patient groups and a historical comparator group of patients with periodontitis. MATERIALS AND METHODS: Standard clinical periodontal assessments were performed on 39 pSS, 36 RA and 23 OA patients and "In-house" antibody ELISAs for serum antibodies against 10 oral/periodontal bacteria were performed in these groups. RESULTS: Forty-six percent of the pSS group, 64% of the RA group and 48% of the OA group had moderate/severe periodontitis. These frequencies did not reach statistical significance between groups. Raised antibody levels to Prevotella denticola were found in the pSS, RA and periodontitis groups compared to the OA group. Significant between group differences were seen for Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Campylobacter showae. None of these differences were specifically associated with pSS. CONCLUSION: This study showed no increase in periodontitis in pSS patients. Although the P. denticola data are of interest, identifying bacterial triggering factors for pSS will likely require alternative strategies including modern techniques such as microbiome analysis.

TIRAP Ser180Leu polymorphism is associated with Behcet's disease.

OBJECTIVES: The initiating cause of Behçet's disease (BD) is unknown, but an aberrant response to infection has been suggested. In this study, single nucleotide polymorphisms in Toll-like receptors (TLRs) and associated molecules that have a sentinel function at mucosal surfaces were analysed in patients with BD. METHODS: TLR expression was determined by immunohistochemistry in buccal mucosal tissue from patients with BD, in tissue from patients with lichen planus (LP) or pyogenic granuloma (PG) as disease controls, or from healthy individuals. Using SSP-PCR we analysed SNP in CD14, TLR2, TLR4 and TIRAP (TIR domain-containing adaptor protein) in patients with BD from different geographical regions. RESULTS: TLR expression was increased in buccal lesions from patients with BD compared with healthy controls; however, a similar increase was seen in lesion tissue from patients with LP or PG, suggesting that this was a generalized inflammatory response as opposed to a BD-specific response. SNP analysis showed no association between CD14, TLR2 or TLR4 polymorphisms. However, TIRAP 180Leu was significantly associated with BD in UK, but not Middle Eastern, patients. CONCLUSION: TLR expression showed no difference in tissue from patients with BD compared with either disease or healthy controls. Likewise, SNPs in TLR genes were no different from healthy controls. The association with the increased function variant of TIRAP suggests that encounter with a pathogen at mucosal sites will lead to increased cytokine production and tissue damage with persistence of mucosal lesions.

Orofacial manifestations in patients with inflammatory rheumatic diseases.

The main orofacial manifestation of the inflammatory rheumatic diseases is that of Sjögren's syndrome. In addition, there is a constellation of orofacial manifestations of the inflammatory rheumatic diseases, many of which are extra-articular with some constituting presenting signs of the underlying rheumatic disease. This review will discuss the orofacial manifestations in a variety of connective tissue diseases and will also allude to the oral adverse drug reactions that may occur as a consequence of therapy.

Conjunctival Neutrophils Predict Progressive Scarring in Ocular Mucous Membrane Pemphigoid.

PURPOSE: Ocular mucous membrane pemphigoid (OcMMP) is a rare autoimmune disorder resulting in progressive conjunctival fibrosis and ocular surface failure leading to sight loss in up to 50%. This study was designed to optimize an ocular surface sampling technique for identification of novel biomarkers associated with disease activity and/or progressive fibrosis. METHODS: Fifty-seven patients with OcMMP underwent detailed examination of conjunctival inflammation and fibrosis using fornix depth measurement. Ocular surface impression cytology (OSIC) to sample superior bulbar conjunctiva combined with flow cytometry (OSIC-flow) profiled infiltrating leukocytes. Profiles were compared with healthy controls (HC) and disease controls (primary Sjögren's syndrome, pSS). Thirty-five OcMMP patients were followed every 3 months for 12 months. RESULTS: Overall neutrophils were elevated in OcMMP eyes when compared to pSS or HC (109 [18%] neutrophils/impression [NPI]; 2 [0.2%]; 6 [0.8%], respectively [P < 0.0001]) and in OcMMP patients with no visible inflammation when compared with HC (44.3 [7.9%]; 5.8 [0.8%]; P < 0.05). At 12 months follow-up, 53% of OcMMP eyes progressed, and this was associated with baseline conjunctival neutrophilia (P = 0.004). As a potential biomarker, a value of 44 NPI had sensitivity, specificity, and positive predictive values of 75%, 70%, and 73%, respectively. Notably, eyes with no visible inflammation and raised conjunctival neutrophils were more likely to progress and have a greater degree of conjunctival shrinkage compared to those without raised neutrophils. CONCLUSIONS: These data suggest that OSIC-flow cytometric analyses may facilitate repeated patient sampling. Neutrophils may act as a biomarker for monitoring disease activity, progressive fibrosis, and response to therapy in OcMMP even when the eye appears clinically uninflamed.

Oral lichenoid drug eruptions: their recognition and management.

Lichen planus is a relatively common, often clinically distinctive, mucocutaneous condition with an uncertain aetiology. One variant of lichen planus is the so-called 'lichenoid drug eruption'. In contrast to idiopathic lichen planus, lichenoid drug eruptions, where practicable, may be managed by substitution of the offending drug. The dental clinician is in a prime position to identify these lesions and liaise with medical colleagues regarding their management. This article reviews oral lichenoid drug eruptions, emphasizing those aspects of relevance to the general dental practitioner.

Architectural characterization of organotypic cultures of H400 and primary rat keratinocytes.

Organotypic epithelial structures can be cultured using primary or immortalized keratinocytes. However, there has been little detailed quantitative histological characterization of such cultures in comparison with normal mucosal architecture. The aim of this study is to identify morphological markers of tissue architecture that can be used to monitor tissue structure, maturation, and differentiation and to enable quantitative comparison of organotypic cultures (OCs) with normal oral mucosa. OCs of oral keratinocytes [immortalized H400 or primary rat keratinocytes (PRKs)] were generated using the three scaffolds of de-epidermalized dermis (DED), polyethylene terephthalate (PET), and collagen gels for up to 14 days. Cultures and normal epithelium were analyzed immunohistochemically and by using the semi-quantitative reverse transcriptase polymerase chain reaction (sq-RT-PCR) for E-cadherin, desmoglein-3, plakophilin, involucrin, cytokeratins-1, -5, -6, -10, -13, and Ki67. The epithelial thickness of OCs was measured in stained sections using image processing. Histological analysis revealed that air-liquid interface (ALI) cultures generated stratified organotypic epithelial structures by 14-days. The final thickness of these cultures as well as the degree of maturation/stratification (including stratum corneum formation) varied significantly depending on the scaffold used. For certain scaffolds, the immunohistochemical profiles obtained recapitulated those of normal oral epithelium indicating comparable in vitro differentiation and proliferation. In conclusion, quantitative microscopy approaches enabled unbiased architectural characterization of OCs. The scaffold materials used in the present study (DED, collagen type-I and PET) differentially influenced cell behavior in OCs of oral epithelia. H400 and PRK OCs on DED at the ALI demonstrated similar characteristics in terms of gene expression and protein distribution to the normal tissue architecture.

Estimating indirect costs in primary Sjögren's syndrome.

OBJECTIVE: To estimate the indirect costs associated with primary Sjögren's syndrome (pSS) compared with rheumatoid arthritis (RA) and community controls. METHODS: Data were obtained from 84 women patients with pSS as part of a study to develop a systemic activity measure, from 87 consecutive women patients with RA attending a hospital clinic, and from 96 women community controls on a general practice list. A modified economic component of the Stanford Health Assessment Questionnaire was used to assess lost productivity. RESULTS: Using a conservative model, the estimated total annual indirect costs (95% CI) were 7677 pound sterling (5560 pound sterling, 9794 pound sterling) for pSS, 10,444 pound sterling (8206 pound sterling, 12,681 pound sterling) for RA, and 892 pound sterling (307 pound sterling, 1478 pound sterling) for controls. Using a model that maximizes the estimates, the equivalent figures were 13,502 pound sterling (9542 pound sterling, 17,463 pound sterling), 17,070 pound sterling (13,112 pound sterling, 21,028 pound sterling), and 3382 pound sterling (2187 pound sterling, 4578 pound sterling), respectively. These were all significantly greater at p < 0.001 for patient groups than for the control group. CONCLUSION: pSS is associated with significantly increased indirect costs equivalent to 69%-83% of that for patients with RA. This needs to be taken into account when evaluating the overall economic consequences of pSS.