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Biologic agents are rapidly emerging as an effective therapy to treat autoimmune and other chronic diseases. The use of these agents is poorly characterized, resulting in a lack of guidance for dental practitioners. Case reports of oral adverse events have begun to emerge. However, their scope and frequency have not been summarized and analysed to date. The objective of this review was to characterize the literature on oral adverse effects associated with biological therapy when used for autoimmune and inflammatory disorders.This review was developed in accordance with scoping review recommendations. Search strategies were developed and employed for six databases. Studies were selected using a systematic search process but with broad inclusion of study types given the paucity of information available. Reports of oral adverse events were analysed descriptively according to agent, mechanism of action, underlying disease, and oral adverse effect observed.Our search returned 2080 articles and 51 met our inclusion criteria, of which most were case reports. The most frequent adverse effects included angioedema, oral lichenoid lesions, osteonecrosis of the jaw, and oral infections. There were also cases of oral malignancies associated with use of biologic agents. Less common effects such as pigmentation were also described.Oral adverse events have been reported in patients on biologic therapy, albeit in small numbers to date. This limits the generalizability of these results, which should not be used to generate a clinical guideline as they are based primarily on case reports. However, this study presents the first review characterizing the adverse effects observed. Large multi-center studies will be necessary to further define the oral and dental complications caused by biologic agents.

Diseases of the oral cavity present with varying degrees of mucosal changes, ranging from erythema, atrophy or ulceration to white or hyperkeratotic areas or pigmentation. These are frequently chronic and can occur because of underlying systemic disease. Diagnosis can be challenging because of similarities in clinical presentation between different conditions. The most common presentations include mucosal ulceration and abnormalities of the lips and tongue. Ulceration represents a full-thickness breach in the epithelium. This can result in pain and difficulty with eating, drinking, speech and maintaining oral hygiene. The wide range of causes of oral ulceration includes trauma, recurrent aphthous stomatitis, lichen planus, immunobullous disease, drugs and erythema multiforme. Lesions on the tongue can be caused by primary oral disease or secondary to systemic disease. Abnormalities include nutrient-deficient glossitis, geographic tongue, burning mouth syndrome and, more rarely, amyloidosis. The lips can be affected by skin diseases such as eczema (exfoliative cheilitis) and actinic damage or conditions with potential systemic involvement such as orofacial granulomatosis. The priority with mucosal lesions is to exclude carcinoma, as early detection and treatment significantly decreases morbidity and mortality. This article reviews these disorders and their distinguishing features and highlights the importance of history-taking, clinical examination and further investigation in making a definitive diagnosis.

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: Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, the prognosis of pemphigus was almost always fatal. Due to its rarity, only few randomized controlled therapeutic trials are available. Recently, rituximab has been approved as first-line treatment for moderate and severe pemphigus vulgaris in Europe and the USA.Objectives: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology (EADV) has initiated a throughout update of the guideline for the management of patients with pemphigus. Results: The guidelines for the management of pemphigus were updated and the degree of consent among all task force members was included. The final version of the guideline was consented by the European Dermatology Forum (EDF) and several patient organisations.

Introduction\ud \ud The United Kingdom and Ireland teachers of Human Disease/Clinical Medical Science for Dentistry (HD/CMSD) group continue to work together and most recently collaborated to review current and future assessments.\ud Materials and methods\ud \ud The first part of the review of assessments in HD/CMSD took place at a face‐to‐face meeting with presentations from delegates on assessments in their home institutions. The second and larger part comprised an online survey where all eighteen schools in the UK and Ireland participated.\ud Results\ud \ud All schools had some element of formative assessment, and the majority had a stand‐alone summative assessment at the end of the HD/CMSD teaching block. Most schools had a written paper and practical elements to their assessments, most commonly a combination of a multiple‐choice type question combined with an objective structured clinical examination (OSCE). There was a trend towards the use of single best answer (SBA) questions and a willingness amongst participants to share a question bank. All schools incorporated elements of HD/CMSD in their final examinations.\ud Discussion and Conclusion\ud \ud This collaboration promoted the sharing of developments in assessment for HD/CMSD and demonstrated a willingness to cooperate between institutions. Assessment in HD/CMSD in the UK and Ireland continues to be refined by those responsible for its content and delivery, and assessment methods are progressing following evidence‐based best practice.

Chronic hyperplastic candidiasis (CHC) clinically presents with white plaques involving the post-commissural buccal mucosa and less frequently, the tongue. Common risk factors include xerostomia, smoking, post-chemotherapy or radiotherapy, antibiotic use, vitamin deficiency and immunosuppression. Here, we present a case of CHC secondary to secukinumab. A 38-year-old man presented with a 6-month history of asymptomatic white plaques involving the lateral tongue and buccal mucosa. The medical history included chronic plaque psoriasis controlled with secukinumab 300 mg monthly, initiated 6 months prior to presentation. Intraoral examination revealed dense homogenous keratosis involving the right and left posterior lateral tongue and posterior buccal mucosa. Histopathological examination was consistent with chronic hyperplastic candidiasis. Special stains for fungal hyphae were positive. In situ hybridization for EBV were negative. Serology was negative for HIV. He was managed with fluconazole 100 mg daily for 1 week and placed on a prophylactic antifungal regime of chlorhexidine 0.2% mouthwash to reduce overall Candida load; however, the white plaques remained unchanged. He subsequently discontinued secukinumab and switched to certolizumab, resulting in complete resolution of oral candidiasis. In psoriasis, dysfunction in the cytokine pathway results in excessive production of IL-17A. Secukinumab, a next-generation anti-IL-17A biologic, is being used more commonly to manage moderate–severe plaque psoriasis. Clinicians should be aware of the risk of development of candidiasis as a potential complication of secukinumab due to the concurrent role of IL-17 in innate and adaptive immunity against Candida. Early recognition of oral Candida lesions with diagnostic biopsy is paramount to exclude dysplasia.

Objective. To assess the evidence for treatment of oral involvement of pemphigus and pemphigoid with biologics.Study Design. This systematic review used a comprehensive search strategy to identify literature describing oral involvement of pemphigus or pemphigoid treated with a biologic agent. The primary outcome measures were efficacy and safety of biologic therapy.Results. Inclusion criteria was met by 154 studies including over 1200 patients. Treatment of pemphigus with a total of 11 unique biologic agents and 3 unique combinations of agents is reported. Five randomized controlled trials (RCT) were included in the final analysis that investigated infliximab, IVIg, rituximab and autologous platelet-rich plasma therapy for pemphigus vulgaris. Three non-RCT studies reported on successful rituximab or IVIg therapy for mucous membrane pemphigoid. Studies demonstrated considerable heterogeneity in agent, methods, and quality.Conclusions. Evidence clearly describing oral tissue response to biologic therapy is sparse. Two RCTs support use of rituximab, one supports use of IVIg, and one pilot study suggests intralesional injection of autologous platelet-rich plasma aids healing of oral PV lesions. As oral lesions of pemphigus and pemphigoid can be refractory to systemic therapy, drug trials including biologic therapies should document details regarding response of the oral lesions to therapy.

Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02., Frontal fibrosing alopecia (FFA) features lichenoid cutaneous inflammation and scarring hair loss. Here, Tziotzios et al. identify four genetic loci associated with FFA by GWAS followed by Bayesian fine-mapping, co-localisation and HLA imputation which highlights HLA-B*07:02 as a risk factor.

Introduction Dermatitis herpetiformis (DH) is a chronic, pruritic, gluten-induced skin disorder characterized by subepidermal granular IgA deposition and a variable degree of enteropathy identical to that seen in coeliac disease. So far, there has been no European consensus about the management of DH. Methods The guidelines were created by small subgroups of a guideline committee consisting of 26 specialists from various medical fields and one patients' representative. The members of the committee then discussed the guidelines and voted for the final version at two consensus meetings. The guidelines were developed under the support of the European Academy of Dermatology and Venereology (EADV) and in collaboration with the European Dermatology Forum (EDF). Results The guidelines summarize evidence-based and expert-based recommendations (S2 level) for the management of DH (see Appendix). Conclusion These guidelines will improve the quality of management of DH and support dermatologists in their diagnostic and therapeutic decisions.

To assess whether a panel of serum pemphigoid autoantibody tests could be used to confirm an immunopathologic diagnosis of mucous membrane pemphigoid (MMP) in direct immunofluorescent negative (DIF-) MMP patients.Prospective cross-sectional study.Seventy-six patients with multisite MMP with 45 matched control participants.Enzyme-linked immunosorbent assays (ELISAs) for BP180 and BP230 (MBL International), immunoglobulin A (IgA) A and immunoglobulin G indirect immunofluorescence (IIF) on human salt-split skin and the keratinocyte footprint assay for anti-laminin 332 antibodies.Sensitivity and specificity of autoantibody detection and significant differences for individual tests and test combinations for MMP involving different sites.All DIF- patients (24/73 [31.8%]) had either ocular-only disease or ocular involvement in multisite disease. Serum pemphigoid autoantibodies were detected in 29 of 76 MMP patients (38.2%) compared with 3 of 45 control participants (6.7%). Autoantibody reactivity detected by any 1 or more of the tests was present in 6 of 24 DIF- patients (25%) compared with 22 of 49 DIF positive (DIF+) patients (44.9%). Ocular-only MMP serum reactivity was not significantly different for any test or test combination compared with control participants, whereas DIF- multisite ocular MMP differed for 1 ELISA and 3 of 7 test combinations. By contrast, for DIF+ nonocular MMP patients, all the individual tests, apart from IgA IIF, and all test combinations were significantly different compared with those for control participants. For the entire MMP cohort, the sensitivity of all individual tests was low, having a maximum of 21.05% for BP180 reactivity but increasing to 38.16% for an optimal test combination. Disease activity was associated strongly with positive serologic findings.Pemphigoid serum autoantibody tests did not provide immunopathologic evidence of MMP in ocular-only MMP patients but showed limited value in DIF- multisite ocular MMP patients. The requirement for immunopathologic confirmation of MMP by autoantibody detection is inappropriate for DIF- ocular-only MMP patients, resulting in missed diagnoses, delayed therapy, and poor outcomes. Alternative diagnostic criteria for ocular-only MMP are required to exclude the other causes of scarring conjunctivitis until more sensitive and specific immunopathologic tests become available.

The autoimmune blistering disorders present with variable frequency in the oral cavity. Recognition of their key clinical features at presentation is important as there are many causes of oral ulceration. Careful history-taking, clinical examination, an understanding of pathogenesis and appropriate investigations are essential. With the exception of the rare genodermatoses that may lead to blistering and oral ulceration, the majority of patients have an acquired disorder. These include the rare autoimmune blistering diseases mucous membrane pemphigoid (MMP), pemphigus vulgaris (PV), linear IgA disease (LAD), epidermolysis bullosa acquisita (EBA) and paraneoplastic pemphigus (PNP). Important clinical differential diagnoses include erythema multiforme (EM) which may be mistaken for PV in appearance while oral lichen planus (LP) may be indistinguishable from MMP. Angina bullosa haemorrhagica (ABH) may also present with tense haemorrhagic bullae and in the absence of diagnostic tests, requires an astute clinical diagnosis based upon the history. Newer laboratory techniques have facilitated identification of target antigens and epitopes in the autoimmune blistering diseases particularly in MMP. Current interest is in whether these relate to clinical presentation and outcomes. There has also been recent investigation in to the use of saliva as an alternative medium to serum for the diagnosis of oral vesiculobullous lesions. Assessment of disease severity and measurement of QOL at presentation and at subsequent follow up, is paramount to interpreting therapeutic response. Furthermore, combining these scores with serological and/or salivary biomarkers is valuable in the assessment of clinical response. Here we discuss mucous membrane pemphigoid (MMP) and its important differential diagnoses.

Autoimmune blistering diseases are a heterogeneous group of about a dozen complex disorders that are characterized by intraepidermal (pemphigus) and subepidermal blistering (pemphigoid diseases and dermatitis herpetiformis). The Pathogenesis of Pemphigus and Pemphigoid Meeting, organized by the Departments of Dermatology in Lübeck and Marburg and the Institute of Anatomy and Cell Biology, Munich, was held in September 2016 in Munich. The meeting brought together basic scientists and clinicians from all continents dedicating their work to autoimmune blistering diseases. Considerable advances have been made in describing incidences and prevalences of these diseases and linking comorbidities with autoantibody reactivities and clinical variants, for example, dipeptidyl peptidase-IV inhibitor-associated noninflammatory bullous pemphigoid. Although new entities are still being described, diagnosis of most autoimmune blistering diseases can now be achieved using standardized and widely available serological test systems. Various experimental mouse models of pemphigus and pemphigoid disease are increasingly being used to understand mechanisms of central and peripheral tolerance and to evaluate more specific treatment approaches for these disorders, such as molecules that target autoreactive T and B cells and anti-inflammatory mediators, that is, dimethyl fumarate, phosphodiesterase 4, and leukotriene B4 inhibitors in pemphigoid disorders, and chimeric antigen receptor T cells in pemphigus. Very recent experimental data about the immunopathology and the determinants of autoantibody formation and keratinocyte susceptibility in pemphigus were discussed. With regard to cellular mechanisms leading to the loss of cell-cell adhesion, new ideas were shared in the field of signal transduction. Major steps were taken to put the various partly contradictory and controversial findings about the effects of pemphigus autoantibodies and other inflammatory mediators into perspective and broaden our view of the complex pathophysiology of this disease. Finally, two investigator-initiated multicenter trials highlighted doxycycline and dapsone as valuable medications in the treatment of bullous pemphigoid. © 2017 The Authors

Background Anagen effluvium with reversible scalp alopecia is a known side effect of chemotherapy. However, there are an increasing number of reports in the literature documenting permanent alopecia in patients treated with taxanes. Objective We sought to describe the clinicopathologic features in breast cancer patients who underwent treatment with taxanes and adjuvant hormonal chemotherapy. Methods We reviewed the clinical and histopathologic information of a cohort of 10 patients treated with taxanes and adjuvant hormonal chemotherapy. Results We have observed 3 types of clinical patterns of alopecia (types A, B, and C), and have validated the histopathologic features showing alopecia areata–like and female pattern hair loss. Limitations The study was based on a small sample size and retrospective retrieval of clinical information and histopathologic review of posttreatment slides. Conclusions We hypothesize a clinicopathologic model of hair follicle cycle disruption in response to the chemoinflammatory and hormonal insults to the hair follicles resulting in permanent alopecia. Clinicopathologic correlation is paramount to the understanding of the morphobiologic pathways in chemotherapy-induced alopecia caused by taxanes and adjuvant hormonal treatment.

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. What's already known about this topic?. There are no validated scoring methodologies for oral mucous membrane pemphigoid (MMP). Proposed disease activity scoring tools for MMP include the Mucous Membrane Disease Area Index (MMPDAI) and the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). The Oral Disease Severity Score (ODSS) has been validated for use in oral pemphigus vulgaris (PV). It has been shown to be reliable and sensitive in both lichen planus (LP) and MMP. What does this study add?. The ODSS has been shown to be a thorough, sensitive and reproducible, yet quick scoring tool for the assessment of oral involvement in MMP. Its versatility for use in oral PV, MMP and LP is an added advantage over other scoring methodologies. What are the clinical implications of this work?. We propose that the ODSS be used as a clinical scoring tool for monitoring activity in oral MMP in clinical practice as well as for use in multicentre studies.

Background Accepted 'standard practice' for the diagnosis of immunobullous disease is a perilesional sample for direct immunofluorescence (DIF). Objectives To compare diagnostic outcomes of a normal buccal punch biopsy (NBPB) with a perilesional biopsy (PLB) for mucous membrane pemphigoid (MMP) and pemphigus vulgaris (PV). Methods A retrospective analysis of 251 DIF-positive patients with MMP and 77 DIF-positive patients with PV was undertaken. Parameters analysed included the intraoral sites of involvement and histopathological, DIF and indirect immunofluorescence (IIF) findings. Results For MMP, PLB was positive in 134 of 143 (93·7%) samples, compared with 129 of 144 (89·6%) by NBPB. The diagnostic sensitivities for PLB (81%, 39 of 48) and NBPB (77%, 37 of 48) among 48 patients who underwent both techniques were not significantly different (P = 0·62). In gingival-only MMP, PLB was positive in 63 of 69 (91%) and NBPB was positive in 63 of 75 (84%). For multisite MMP, PLB was positive in 71 of 74 (96%) and NBPB was positive in 66 of 69 (96%). In gingival-only MMP, biopsies from reflected alveolar mucosa in 17 consecutive patients were positive in 17 of 17 cases (100%). For PV, PLB was positive in 42 of 43 (98%), compared with 42 of 42 (100%) by NBPB. Histopathology was diagnostic in 93 of 134 (69·4%) cases of MMP and 38 of 41 (93%) cases of PV. IIF was positive in 126 of 197 (64·0%) MMP and 68 of 74 (92%) PV patient sera. Conclusions In the largest series of combined oral DIF results in patients with MMP and PV, we have shown that NBPB is equivalent to PLB for the diagnosis of PV and multisite MMP, and is more sensitive than both histology and IIF. What's already known about this topic? The variation in sensitivity of oral biopsy sites for direct immunofluorescence (DIF) in the diagnosis of oral MMP and PV has not been studied in detail in large series of patients. Biopsy can be challenging due to difficult access and fragility of the oral mucosa. The diagnostic biopsy technique is therefore critical. What does this study add? We have shown that a normal buccal punch biopsy (NBPB) from uninvolved oral mucosa is as sensitive as a perilesional biopsy (PLB) for diagnosis of oral PV, and superior to serology and histology. For multisite MMP, NBPB is equivalent to PLB and is more sensitive than serology and histology. The oral punch biopsy technique on uninvolved buccal mucosa tissue is a simple and safe practical method for diagnosing oral PV and MMP.

SummaryBackground The use of saliva for the diagnosis of pemphigus vulgaris (PV) by enzyme-linked immunosorbent assay (ELISA) using desmoglein (Dsg)3 antigen has not been extensively documented, nor has the detection of serum IgA antibodies to Dsg3. Objectives (i) To establish whether whole saliva might provide a suitable alternative to serum for diagnosing and monitoring PV; (ii) to investigate whether anti-Dsg3 IgA antibodies can be detected in serum and saliva and (iii) to establish whether there is an association between serum or saliva anti-Dsg3 antibodies and disease severity. Methods Precoated Dsg3 ELISA plates were used to test serum and/or saliva for IgG and IgA antibodies. Matched serum and whole saliva samples were collected from 23 patients with PV, 17 healthy subjects and 19 disease controls. All patients with PV, disease controls and six healthy controls provided matched parotid saliva. Results Whole saliva IgG antibodies to Dsg3 were detected in 14 of 23 patients (61%) and serum IgG antibodies were detected in 17 of 23 (74%) with a strong positive correlation. Serum IgA antibodies were detected in 14 of 23 patients with PV (61%) with a combined positivity (IgG and/or IgA antibodies to Dsg3) of 78% (18 of 23). We were unable to show IgA anti-Dsg3 antibodies in either whole or parotid saliva of patients with PV. Sequential samples showed that changes in IgG antibody titres in whole saliva were associated with a change in disease severity scores. Conclusions Assay of salivary IgG antibodies to Dsg3 offers a diagnostic alternative to serum in the diagnosis and monitoring of PV. The role of anti-Dsg3 IgA antibodies requires further elucidation in the pathogenesis of PV.

Pemphigus vulgaris (PV) is an autoimmune blistering disease affecting the skin and mucous membranes. Rituximab, a CD20 chimeric monoclonal antibody, has efficacy in PV management. We report a case of severe oral PV that showed a progressive response to repeated courses of rituximab, culminating in a rapid response within 4 weeks following severe relapse 4 years after initial therapy. It demonstrates the progressively shorter time to achieve partial or complete remission following rituximab infusions, combined with minimal adjuvant therapy over a 7-year follow-up period.

Lichen planus (LP) is a relatively common autoimmune T-cell-mediated disease of unknown aetiology affecting the mucous membranes, skin and nails. Its prevalence varies between 0.5 and 2.2% of the population in epidemiological studies with a peak incidence in the 30–60 years range and with a female predominance of 2:1.1 Mucosal lichen planus tends to follow a chronic course with acute exacerbations. Spontaneous remission of oral lichen planus (OLP) is uncommon, and indeed mucosal LP may become worse with time. In contrast, cutaneous lichen planus may follow a milder clinical course though some variants may be severe such as those affecting the palms and soles and the scalp and the genital tract in females (vulvovaginal gingival LP) where scarring leads to significant complications. It is important to identify those cases that may be drug induced or be associated with a contact allergic or irritant reaction (lichenoid reaction) or the rarer oral presentation of discoid lupus erythematosus. There is a very small risk of malignancy (approximately 1:200 patients/year) associated with oral lichen planus; thus patients should be informed that long term monitoring via their general dental practitioner is appropriate. This review will focus on the clinical presentation and management of oral lichen planus.

A 55‐year‐old woman presented with a 6‐week history of inflammation, pain and paraesthesia involving her left ring finger. The fingernail had been removed 25 days prior to presentation, based on an assumed unresponsive bacterial infection. Her medical history included pemphigus vulgaris (PV), diabetes mellitus and β‐thalassemia trait. There was circumferential inflammation, desquamation and a purulent exudate with erythema at the leading edge of the nail, suggesting an advancing lesion (Fig. 1). Intraorally, there was extensive ulceration on the dorsal tongue and a single ulcer involving the right buccal mucosa. All other skin and mucosal surfaces were unaffected. Comprehensive investigations were undertaken. Bacterial skin swab revealed a heavy growth of Citrobacter koseri. Viral swab was negative. Cortical irregularity of the proximal phalanx was noted on a radiograph, but osteomyelitis was subsequently excluded by magnetic resonance imaging. Serum ELISA studies showed levels of 6 U/mL (negative) for desmoglein (Dsg)1 and 120 U/mL (strongly positive) for Dsg3

BACKGROUND Pemphigus vulgaris (PV) is a rare autoimmune bullous disease, which can present with recalcitrant oral mucosal lesions. Optimal management of PV relies upon careful clinical assessment and documentation. OBJECTIVES The primary aim of this study was to validate the Oral Disease Severity Score (ODSS) for the assessment of oral involvement in PV. A secondary aim was to compare its inter- and intraobserver variability and ease of use with the Physician's Global Assessment (PGA) and the oral scoring methods used in the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and the Pemphigus Disease Area Index (PDAI). METHODS Fifteen patients with mild-to-moderately severe oral PV were scored for disease severity by 10 oral medicine clinicians using the ODSS, the PGA and the oral sections of ABSIS and PDAI. Two clinicians rescored all patients after a minimum 2-h interval. RESULTS Interobserver reliability was assessed using an intraclass correlation coefficient (ICC). For the ODSS total score the ICC was 0·83, for PDAI (oral total activity) 0·79, ABSIS (oral total) 0·71 and PGA 0·7. Intraobserver agreement between initial scoring and rescoring of the same patient by two clinicians demonstrated an ICC for each of 0·97 and 0·96 for ODSS total score; 0·99 and 0·82 for PDAI oral activity; 0·86 and 0·45 for ABSIS total; and 0·99 and 0·64 for PGA. Convergent validity was good, with a correlation coefficient > 0·5 (P < 0·001). The mean ± SD times taken to complete each scoring method were ODSS 76 ± 37 s, PDAI 117 ± 16 s and ABSIS 75 ± 19 s. CONCLUSIONS This study has validated the ODSS for the assessment of oral PV. It has shown superior inter- and intraobserver reliability to PDAI, ABSIS and PGA and is quick to perform.

Over the last 40 years, research in dental schools has moved from a position where clinicians were expected to make a scientific contribution to their fields on their own, to a fruitful multidisciplinary approach to answering basic questions about the disease process. At one time, clinicians hoping to make an academic contribution were expected to learn basic laboratory techniques in order to do so. Indeed, the foundation of current multidisciplinary research was that this approach was relatively successful. However, it became apparent that successful high-impact contributions required expertise that cannot any longer reside in individuals but in groups. Both the scientific questions and the means of addressing them have become increasingly complex and require a wide range of expertise. This applies not only to laboratory-based research but to clinically applied research. The former needs interactions with expert nonclinical scientists and the latter interactions with expert clinicians from different fields in order to maximise the investigation and management of complex clinical diseases. In oral medicine, there are now many examples of both types of multidisciplinary approach, which have resulted in a marked increase in our knowledge of disease mechanisms in mucosal disease which have in turn led to new approaches to treatment.

Vulval Crohn's disease [VCD] is a challenging condition that can occur without gastrointestinal Crohn's disease [GCD]. We reviewed the clinical features and effects of therapy in a cohort of 22 patients with VCD to determine whether the presence of GCD affected the clinical presentation and treatment response. Of these, 64% had GCD and 65% of these presented with GCD prior to VCD. Fissuring, ulceration, and scarring were more common in those with VCD alone. Potent and ultra-potent topical steroids showed benefit in most patients. There was no clear evidence of sustained remission with metronidazole. Azathioprine was the most commonly used oral immunosuppressive agent, with an efficacy of 57%. Patients with both VCD and GCD had a better clinical response compared with those with VCD alone [70% and 25%, respectively]. Infliximab and adalimumab were effective in 56% and 71% of patients, respectively. Excision of redundant tissue was helpful in four patients. The absence of GCD may delay the diagnosis in women who present with vulval symptoms alone. The more active clinical features in those with VCD alone may represent a more aggressive condition, or the severity of the cutaneous disease may have been reduced by immunosuppression taken for GCD. Several patients obtained sustained remission in their GCD with anti-tumor necrosis factor alpha [anti-TNFα] agents while the VCD remained active.

BACKGROUND: Class I human leucocyte antigens (HLA) -A, -B, -Cw and class II HLA-DRB1, -DQB1 alleles were determined in 131 British Caucasian patients with mucous membrane pemphigoid (MMP) using serological and DNA-based methods. OBJECTIVES: To analyse the class I and II alleles expressed in well-defined clinical and immunopathological subgroups of MMP, in order to establish whether specific alleles or haplotypes might in part explain disease susceptibility, clinical sites of involvement or disease severity. METHODS: Subgroups of patients were analysed according to the following clinical criteria: age of onset, sex, sites of clinical involvement (oral, ocular, skin, nasal, genital, pharyngeal, oesophageal, laryngeal, perianal), disease severity and history of autoimmune disease. Subgroups were also analysed according to the following immunopathological criteria: autoantibody profile, the presence of circulating antibasement membrane IgG or IgA antibodies and the detection of target basement membrane zone (BMZ) antigens (BP230 and BP180) by IgG autoantibodies. RESULTS: Class I HLA typing showed no significant disease or subgroup associations. Class II DRB1 typing showed a significantly increased allelic frequency in MMP vs. controls for DRB1*11 (RR = 2.08, Pc < 0.0000056). For DQB1, MMP vs. controls, there was a significantly increased allelic frequency for DQB1*0301 (Pc < 0.00000028) in both males and females; all clinical sites of involvement, with the exception of laryngeal, oesophageal and perianal sites and in patients with detectable circulating anti-BMZ IgG compared with those negative for IgG (P < 0.0096, Pc < 0.019). A positive trend was noted in patients with ocular involvement compared with no ocular involvement and in patients with a clinical score > or = 10 compared with < 10. We found no difference in DQB1*0301 allele frequency between subgroups with or without BP180 or BP230 target antigens. Haplotype frequencies showed an increase in DRB1*04, DQB1*0301 (Pc < 0.000066) and DRB1*11, DQB1*0301 (Pc < 0.000002) among patients compared with controls. CONCLUSIONS: The DQB1*0301 allele confers a predisposition to all subgroups of MMP and may have a role in T-cell recognition of basement membrane antigens, resulting in the production of anti-BMZ IgG autoantibodies. The positive trend between increased allelic expression of DQB1*0301 in patients with ocular disease and in those with a higher clinical score, further suggests a role for this allele in disease severity.

Syphilis is on the increase globally. While recognized more frequently in patients with, HIV/AIDS, it is not unusual among immune competent individuals sometimes presenting with unusual manifestations and/or behaviour. This paper reviews the history and clinical features of syphilis and draws attention to the oral manifestations. CPD/Clinical Relevance: Syphilis should be in the differential diagnosis of oral ulcers or unusual oral lesions.

Summary Background Ulcerative lichen planus is an uncommon and severe subtype of lichen planus primarily affecting the oral mucosal surfaces. It may be associated with significant morbidity and often requires immunosuppressive therapy to achieve disease control. There have been no previous reports in which objective outcome measures have been used to assess the efficacy of mycophenolate mofetil (MMF) in severe ulcerative lichen planus. Objective To evaluate the clinical responses of patients with severe ulcerative oral lichen planus who were treated with MMF at a tertiary oral medicine/dermatology centre. Methods This was a retrospective review of oral disease severity scores performed in 10 patients with recalcitrant ulcerative oral lichen planus (vulvovaginal–gingival, n = 8; penogingival, n = 1; oral, n = 1) before and after treatment with MMF therapy. The results were analysed using the Wilcoxon matched pairs signed-rank test. Results The mean duration of MMF treatment was 3·7 (SD ± 2·4) years with a mean follow-up of 4·2 (SD ± 2·7) years. The mean baseline oral disease severity scores (39·1 ± 11·9) improved by 40% after 12–15 months (24·3 ± 11·9, n = 8, P = 0·01) and by 43% after 21–24 months of MMF treatment (22·2 ± 10·4, n = 9, P = 0·01). Of the 10 patients, six achieved remission, one had well-controlled disease and three had partially controlled disease. Two patients who achieved remission successfully discontinued treatment. MMF was well tolerated in all patients. Conclusion Our case series demonstrates the efficacy and favourable side-effect profile of MMF in the treatment of severe ulcerative lichen planus.

Background Mucous membrane pemphigoid (MMP) is an uncommon mucocutaneous immunobullous disorder. Use of saliva for diagnosis by enzyme-linked immunosorbent assay (ELISA) using the noncollagenous (NC) domain 16a of bullous pemphigoid antigen II (BP180) is not well described. Objective To establish whether whole or parotid saliva is a suitable alternative to serum for diagnosis of MMP. Methods Precoated BP180-NC16a ELISA plates were used to test serum, and whole and parotid saliva for IgG, IgA and secretory IgA antibodies. Patients with MMP (n = 64) provided matched serum and whole saliva. In addition 18 of the MMP patients also provided matched parotid saliva. Healthy controls (n = 50) provided matched serum and whole saliva and 6 of these additionally provided matched parotid saliva. An additional 16 disease controls provided matched serum, and whole and parotid saliva. Results In whole saliva, IgG antibodies were detected in 11/64 (17%), IgA in 23/64 (36%) and a combined positivity in 29/64 (45%). In parotid saliva, IgA antibodies were found in 8/18 (44%). Serum IgG antibodies were detected in 27/64 (42%), serum IgA antibodies in 18/64 (28%) and a combined positivity in 33/64 (52%). Combined use of serum and saliva increased detection of specific antibodies by 30%. Control samples were all negative (positive predictive value of 100% for all tests). The negative predictive values were 62% for IgA saliva, 65% for IgG serum, 59% for IgA serum and 56% for IgG saliva. Conclusions IgG and IgA antibodies may provide a suitable diagnostic marker in MMP. Assay of salivary IgA antibodies to NC16a offers a similar diagnostic predictive value to serum.

Background Mucous membrane pemphigoid (MMP), a chronic autoimmune subepithelial blistering disease, is associated with circulating IgG and/or IgA autoantibodies against several basement membrane zone antigens. The heterogeneity of clinical presentation and diversity of target autoantigens have contributed to difficulties in characterizing this condition immunologically. Objectives To analyse serum autoantibody profile and HLA class II alleles in MMP patients and to correlate this with the clinical presentation of disease. Methods Well-defined subgroups consisting of 124 patients with MMP were examined for IgG and IgA reactivity with immunoblotting using human epidermal, dermal and placental amnion proteins. The results were further analysed on the basis of detailed clinical (sites of involvement and disease severity) and immunopathological criteria (immunofluorescence study and HLA class II alleles). Results Immunoblot assay revealed that the majority of MMP patients had IgG (93 of 124, 75%) and/or IgA autoantibodies (63 of 124, 51%) to BP180 (including its soluble ectodomains, 120-kDa LAD-1 and 97-kDa LABD97 antigens). Other antigens targeted predominantly by IgG autoantibodies included: BP230 in 34 (27%), beta4 integrin in 26 (21%), and laminin 5 in three (2%). All the BP230+ sera and 23 (88%) beta4 integrin+ sera also reacted with at least one of the BP180 antigens. Over 85% of patients with reactivity to beta4 integrin had ocular involvement. In most cases of MMP, more severe clinical features were associated with antibody reactivity to multiple basement membrane zone antigens, as well as reactivity to multiple BP180 component antigens. Dual BP180/LAD-1 reactivity with IgG and IgA was associated with a more severe phenotype. In addition, the subset-dependent autoantibody reactivity correlated well with specific HLA class II alleles, DQB1*0301, DRB1*04 and DRB1*11. Conclusions Our results confirmed that BP180 is a major autoantigen targeted by the sera of patients with MMP. The disease-prevalent HLA class II alleles and humoral autoimmune response against the particular subsets of antigenic epitope(s) within BP180 ectodomain may contribute to the clinicopathological significance and disease severity of MMP.

Summary Background Pemphigus vulgaris (PV, OMIM 169610) is a severe blistering disorder of the skin and mucous membranes, caused by the production of autoantibodies directed against the epithelial adhesive protein desmoglein 3. Although an association between PV and HLA class II alleles has been established, the genetic factors predisposing to the disease remain poorly understood, the rarity of PV hampering the recruitment of substantial patient cohorts. Objectives To investigate DSG3 as a candidate PV susceptibility gene. Methods We examined five DSG3 single nucleotide polymorphisms (rs8085532, rs3911655, rs3848485, rs3794925 and rs1466379) in two case–control datasets respectively originating from the U.K. (62 PV patients, 154 controls) and northern India (28 patients, 98 controls). Results In the U.K. sample, we observed a significant association between PV and the DSG3*TCCTC haplotype (Fisher's exact test P = 0·002). A related haplotype (DSG3*TCCCC) was associated with PV in the Indian dataset (P = 0·002). We also found that all British and Indian patients bearing DSG3 risk haplotypes carried at least one copy of a PV-associated HLA allele. Conclusions These results suggest that genetic variation of DSG3 may be an additive risk factor predisposing to PV and warrant further investigations of this gene.

SummaryBackground Pemphigus is a group of autoimmune blistering diseases of the skin and/or mucous membranes requiring management with immunosuppressive therapy. The optimal therapeutic regimen would rapidly induce remission and maintain effectiveness with minimal adverse effects in the long term. Objectives The present study describes our experience of the addition of mycophenolate mofetil (MMF) to prednisolone in the management of severe, refractory pemphigus. Methods Patients with active, refractory pemphigus were treated with MMF. Our series included 12 cases of pemphigus vulgaris, four cases of pemphigus foliaceous and one case of paraneoplastic pemphigus. All patients were monitored to assess disease control and mycophenolate toxicity. Results Of the 17 cases, MMF has been of benefit to 12. MMF was well tolerated and there were no treatment withdrawals because of safety concerns. Conclusions We found that MMF permitted a reduction in prednisolone dosage without disease relapse.

We report a case of a primary cutaneous alveolar rhabdomyosarcoma presenting on the lower limb of a 60-year old woman. The tumor was characterized by aggregates of round blue cells in an alveolar growth pattern in the dermis and subcutis, with the additional unique finding of epidermotropism. By immunohistochemistry tumor cells were positive for vimentin, muscle-specific actin, desmin, myogenin, and Myo-D1 with focal positivity for CD56, neuron-specific enolase, and S-100 protein. Staining for pan-keratin, HMB-45, melan-A, epithelial membrane antigen, chromogranin, CD99, leukocyte common antigen, and alpha-smooth muscle actin was negative. Interphase fluorescence in situ hybridization analysis from paraffin-embedded tumor demonstrated the presence of the translocation (2;13)(q35;q14) confirming the diagnosis. Further investigations revealed no tumor in the underlying deep soft tissues, and there was no evidence of metastasis in other organs. A local recurrence associated with a metastasis to a regional lymph node on the right groin was treated with an above-knee amputation and local radiotherapy to the groin area. The patient subsequently developed cutaneous metastases in the amputation stump and died 2 years after initial presentation. This case indicates that rhabdomyosarcoma may rarely present in the skin in adults and should be included in the differential diagnosis of primary cutaneous small round blue cell tumors not only in children but also in this age group.

We report a patient with combined cutaneous and oropharyngeal pyoderma gangrenosum in association with an IgA lambda paraproteinaemia. The differential diagnosis of oral pyoderma gangrenosum is discussed.