This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue-bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10-25% of patients laminin 332 is recognized. In 25-30% of MMP patients with anti-laminin 332 reactivity, malignancies have been associated. As first-line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first-line regimens. Additional recommendations are given, tailored to treatment of single-site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high-quality randomized controlled trials.

Background Mucous membrane pemphigoid (MMP) is a rare autoimmune bullous disease predominantly affecting the oral mucosa. Optimal management relies upon thorough clinical assessment and documentation at each visit. Objectives The primary aim of this study was to validate the Oral Disease Severity Score (ODSS) for the assessment of oral involvement in MMP. We also compared its inter- and intraobserver reliability with those of the oral parts of the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Physician's Global Assessment (PGA). Methods Fifteen patients with mild-to-moderately severe oral MMP were scored for disease severity by 10 oral medicine clinicians from four U.K. centres using the ODSS, the oral sections of MMPDAI and ABSIS, and PGA. Two clinicians rescored all patients after 2 h. Results In terms of reliability, the interobserver ODSS total score intraclass correlation coefficient (ICC) was 0.97, MMPDAI activity 0.59 and damage 0.15, ABSIS total 0.84, and PGA 0-72. The intraobserver ICCs (two observers) for ODSS total were 0.97 and 0.93; for MMPDAI activity 0.93 and 0.70 and damage 0.93 and 0.79; for ABSIS total 0.99 and 0.94; and for PGA 0.92 and 0.94. Convergent validity between ODSS and MMPDAI was good (correlation coefficient 0.88). The mean +/- SD time for completion of ODSS was 93 +/- 31 s, with MMPDAI 102 +/- 24 s and ABSIS involvement 71 +/- 18 s. The PGA took < 5 s. Conclusions This study has validated the ODSS for the assessment of oral MMP. It has shown superior interobserver agreement over MMPDAI, ABSIS and PGA, and superior intraobserver reliability to MMPDAI. It is quick and easy to perform.

Linked Articles:Murrell et al. Br J Dermatol 2018; 179:816-817. Ormond et al. Br J Dermatol 2018; 179:872-881.

寻常天胞疮 (Pemphigus vulgaris, PV) 是一种罕见且通常严重的自身免疫性疾病,可在许多部位引起疼痛性水疱,包括皮肤、口腔、鼻腔、咽喉或生殖器。它通过产生针对皮肤或粘膜的有害抗体来做到这一点。口腔通常是该疾病开始的部位,并且可能持续多年受影响。免疫抑制药物可用于治疗 PV, 但为了有效和安全地使用这些药物,临床医生需要一种准确且“可重现”的方法来评估和记录病变的数量和部位。可重现意味着测试可以由另一个人重复进行,且结果将是相同的。因此需使用经过科学验证的评分工具,包括自身免疫性大疱性皮肤病强度评分 (ABSIS) 和天疱疮疾病区域指数 (PDAI) 。这些包括口腔(嘴部)成分,但对于以口腔疾病为主的患者,我们设计了一种特定的口腔疾病严重程度评分 (ODSS),该评分观察口腔中的 17 个部位,但使用起来快速且简单。在这项英国研究中,我们试图验证 ODSS 并将其重现性与 ABSIS、PDAI 和医生全球评估 (Physicians Global Assessment) 评分进行比较。十名口腔医学专家,其中大多数人不熟悉这些方法中的任何一种,每人在一天内对 15 名口腔 PV 患者进行了评分。两名医生对所有 15 名患者进行了重新评分。结果表明, ODSS 既可靠又可重现,并且用于评估口腔疾病至少与 ABSIS 和 PDAI 同样有效(如果不是更好)。通过提供更详细的评估口腔 PV 的方法,我们认为 ODSS 对于长期疾病监测将更加灵敏(准确)。

Pemphigus vulgaris (PV) is a rare and often serious autoimmune disease that causes painful blistering in a number of sites including the skin, mouth, nose, throat or genitals. It does this by producing harmful antibodies that are directed to the skin or mucous membranes. The mouth is a site where the disease often starts and may continue to be affected for many years. Immune suppressant medicines are used to treat PV but in order to use these effectively and safely, clinicians need an accurate and ‘reproducible’ method of assessing and recording the number and site of the lesions. Reproducible means that the test can be repeated by another person and the results will be the same. Scoring tools that have been scientifically validated are therefore used and include the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and the Pemphigus Disease Area Index (PDAI). These include an oral (mouth) component but for patients with predominantly oral disease, we have devised a specific Oral Disease Severity Score (ODSS) which looks at 17 sites in the mouth, yet is quick and simple to use. In this UK study, we sought to validate ODSS and to compare its reproducibility with ABSIS, PDAI and the Physicians Global Assessment score. Ten oral medicine specialists, the majority unfamiliar with any of these methodologies, each scored 15 patients with oral PV on one day. Two clinicians rescored all 15 patients. The results have shown that the ODSS was both reliable and reproducible and was at least as good if not better than ABSIS and PDAI for assessing oral disease. By providing a more detailed method for assessing oral PV, we believe that ODSS will be more sensitive (accurate) for long term disease monitoring.

Introduction Orofacial Granulomatosis (OFG) is a rare chronic inflammatory condition of unknown aetiology, characterised by lip swelling, orofacial erythema and ulceration. A proportion of OFG patients present with perianal disease in conjunction with their oral disease (‘top and tail’ disease). Perianal disease occurs in approximately one-third of Crohn’s Disease (CD) patients and is associated with significant morbidity and a more severe disease course.1Perianal disease has been shown to occur in 12% of patients with ileal CD (L1), 41–92% of colonic CD (L2) and 15% of ileocolonic disease (L3).2 Method We retrospectively analysed a database of OFG patients. Patients with perianal disease were identified and compared to patients without perianal disease. The Montreal classification was used to classify the sites of patient’s CD. We set out to determine how many of our OFG patients had concurrent perianal disease and how many of them developed intestinal CD. Results 263 patients with OFG were identified, of which 208 patients (79.09%) had OFG only and 55 patients (20.91%) had concurrent intestinal CD. 36 patients (13.69%) had intestinal CD and no perianal disease. 19 patients ((7.22%) 13 male, median age 38 (IQR 25–49)) had intestinal CD and concurrent perianal disease. Within the perianal group, all patients had concurrent intestinal CD. The commonest sites were colonic (L2)(8/19; 42.11%) and ileocolonic (L3)(8/19; 42.11%). The ileum (L1) was affected in 1 patient (1/19; 5.26%) and 2 patients had concomitant upper gastrointestinal CD with ileocolonic disease (L3+L4)(2/19; 10.53%). The presence of OFG and perianal disease significantly increased the chances of developing intestinal CD (OR = 222, p = 0.0002, 2-tail Fisher Test). In the perianal group, 11/19 patients (11/19; 57.89%) were diagnosed with CD prior to developing OFG. The median time to diagnosis of OFG was 10 years after the diagnosis of intestinal CD. Conclusion Perianal disease in Crohn’s disease is common and is associated with a more severe disease course.1Perianal disease in OFG patients is less common, however, where it does occur it is always associated with intestinal CD in our cohort. Therefore, these patients should be investigated accordingly. The diagnosis of OFG was usually made later in the course of intestinal Crohn’s suggesting it is a later development. Disclosure of interest None Declared. References Ardizzone S, Porro GB. Perianal Crohn’s disease: overview. Dig Liver Dis. 2007;39:957–958 Schwartz D, Loftus EV, Tremaine WJ, et al. The natural history of fistulising Crohn’s disease in Olmsted County, Minnesota. Gastroenterology 2002;122:875–880

Introduction A small proportion of patients with Crohn’s disease develop orofacial granulomatosis (OFG), a rare, chronic disfiguring condition of unknown aetiology affecting the oral mucosa and perioral region. Previous studies have suggested that alterations in the oral microbiota may be involved in the pathogenesis of OFG. CD2 is a novel probiotic containing Lactobacillus breviswhich has anti-inflammatory properties, primarily via reduced arginine availability. Previous studies have shown that CD2 reduces oral inflammation in chemotherapy-induced oral mucositis, Behcet’s disease and recurrent aphthous stomatitis. Our aim was to evaluate the tolerability and efficacy of CD2 lozenges in reducing oral inflammation in patients with active OFG. Method This was a single-centre prospective open-label observational study. Patients were recruited from a specialist OFG clinic between February and August 2014. Patients with active OFG received an eight week course of CD2 lozenges taken four times per day. Patients were reviewed before and after treatment and disease activity assessed by Oral disease activity score (ODAS), Visual analogue scale (VAS) of oral soreness and Global physician assessment (GPA). Results 28 patients were recruited with 4 patients withdrawing (3 non-compliance, 1 of which had severe learning difficulties; 1 re-classified as aphthous stomatitis). 7 patients failed follow-up leaving 17 patients (9 males) available for final analysis. The median age was 35 years (range 18–70 years) with 5/17 patients diagnosed with concurrent intestinal Crohn’s disease. Before treatment, the median ODAS was 12 (range 2–36), median VAS was 50% (range 0–90%), with 9/17 patients classified as having mild disease, 2/17 moderate and 6/17 severe. Post treatment, the median ODAS was 12 (range 1–34), median VAS was 20% (range 0–70%), with 9/14 patients had mild disease, 7/14 moderate and 1/14 severe. The reduction in the mean ODAS at 2 months was: 15.5–11.9 = 3.6 (p = 0.044). The mean improvement in oral soreness measured by VAS was: 44%–26% = 18% (p–0.003). There were no adverse events, however one patient discontinued treatment due to severe diarrhoea which resolved upon CD2 cessation. Conclusion CD2 appears to be safe, well-tolerated and of benefit in reducing oral inflammation and oral soreness in active OFG. Given the marked improvement in oral soreness, CD2 may have a role in symptom relief in other oral inflammatory conditions. Based on these results, a larger double-blind prospective study is recommended. The treatment shows promise as an adjunct to dietary therapy and an alternative to systemic immunosuppression. Disclosure of interest None Declared.