Interstitial Granulomatous Dermatitis: Another Clinical Variant

A 70-year-old female patient presented with an eruption consisting of symmetrically distributed erythematous papules around the umbilicus 1 month after the cessation of adalimumab for the treatment of rheumatoid arthritis. Biopsy of a papule showed an interstitial granulomatous infiltrate in the dermis, without deposition of mucin. The lesions cleared only after re-initiation of treatment 2 months later. Interstitial granulomatous dermatitis is thought to be a distinct histopathological pattern, either drug induced or associated with rheumatoid arthritis or autoimmune collagen diseases. In our case, there was a distinct clinical presentation of interstitial granulomatous dermatitis, composed of symmetrically distributed indurated papules around the umbilicus as well as a mild granulomatous reaction pattern

Spectrum of autoimmune bullous diseases in northern Greece. A 4-year retrospective study and review of the literature

Bullous Diseases Unit at the 2nd Department of Dermatology and Venereology, Aristotle University of Thessaloniki was founded with the aim to provide the optimal diagnostic approach and treatment of patients with autoimmune bullous diseases (AΙBD).  We processed all AIBD files of patients diagnosed from 2011 to 2014 in order to record all epidemiological data and therapeutic manipulations during monitoring. 57 patients were diagnosed with intraepidermal and 62 with subepidermal bullous diseases. There were 51 cases (89%) of pemphigus vulgaris (PV) and 6 (11%) of pemphigus foliaceus (PF), whereas 45 (73%) patients were diagnosed with bullous pemphigoid (BP), 9 (14%) with mucous membrane pemphigoid (MMP), 3 (5%) with pemphigoid gestationis (PG), 3 (5%) with linear IgA dermatosis (LAD), 1 (2%) with epidermolysis bullosa aquisita (EBA), and 1 patient with an undefined subepidermal AIBD. The mean age of patients within the pemphigus spectrum was 57 years. In the pemphigoid spectrum, the mean age was 72 years. Comorbidities were reported with increasing frequency, as well as treatment options other than systemic corticosteroids, such as adjuvant immunosuppressive agents, which were used to achieve complete remission. This is a report from a tertiary AIBD Referral Center in northern Greece. Our data from a 4-year period contribute to the completion of the global geographic incidence map of AIBD.  </p

Detection of IgG autoantibodies against desmocollin–3 in Greek patients with pemphigus

Pemphigus is an autoimmune bullous disorder caused by autoantibodies against desmosomal cadherins. The most common clinical forms are pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Among the numerous proteins that are considered responsible for the cohesion of keratinocytes in epidermis, desmocollin-3 (Dsc-3) has been initially reported to participate in epidermal blistering in mice. There have been reports in which autoantibodies against Dsc-3 have been detected. In PV, a limited number of studies found no presence of IgG or IgA autoantibodies against Dsc-3. In this study we examined sera from Greek patients with PV and PF for the presence of IgG autoantibodies against Dsc-3. Immunoblotting for the detection of autoantibodies against Dsc-3 was performed in sera from all cases. Dsc-3 autoantibodies were not detected in either group (PV and PF). Our results confirm the hypothesis that the pathogenic role of Dsc-3 in epidermal blistering in PV and PF remains controversial. </p

Characterization of the skin microbiota in bullous pemphigoid patients and controls reveals novel microbial indicators of disease

Introduction: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. It predominately afflicts the elderly and is significantly associated with increased mortality. The observation of age-dependent changes in the skin microbiota as well as its involvement in other inflammatory skin disorders suggests that skin microbiota may play a role in the emergence of BP blistering. We hypothesize that changes in microbial diversity associated with BP might occur before the emergence of disease lesions, and thus could represent an early indicator of blistering risk. Objectives: The present study aims to investigate potential relationships between skin microbiota and BP and elaborate on important changes in microbial diversity associated with blistering in BP. Methods: The study consisted of an extensive sampling effort of the skin microbiota in patients with BP and age- and sex-matched controls to analyze whether intra-individual, body site, and/or geographical variation correlate with changes in skin microbial composition in BP and/or blistering status. Results: We find significant differences in the skin microbiota of patients with BP compared to that of controls, and moreover that disease status rather than skin biogeography (body site) governs skin microbiota composition in patients with BP. Our data reveal a discernible transition between normal skin and the skin surrounding BP lesions, which is characterized by a loss of protective microbiota and an increase in sequences matching Staphylococcus aureus, a known inflammation-promoting species. Notably, Staphylococcus aureus is ubiquitously associated with BP disease status, regardless of the presence of blisters. Conclusion: The present study suggests Staphylococcus aureus may be a key taxon associated with BP disease status. Importantly, we however find contrasting patterns in the relative abundances of Staphylococcus hominis and Staphylococcus aureus reliably discriminate between patients with BP and matched controls. This may serve as valuable information for assessing blistering risk and treatment outcomes in a clinical setting

European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology – Part I

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients’ autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the ‘Cicatrising Conjunctivitis Assessment Tool’ and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course

European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology – Part I

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients’ autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the ‘Cicatrising Conjunctivitis Assessment Tool’ and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course

European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology – Part II

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

S2k guidelines on the management of paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome initiated by the European Academy of Dermatology and Venereology (EADV).

BACKGROUND Paraneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi-organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease-associated complications, such as bronchiolitis obliterans. OBJECTIVES These guidelines summarize evidence-based and expert-based recommendations (S2k level) for the clinical characterization, diagnosis and management of PNP/PAMS. They have been initiated by the Task Force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology with the contribution of physicians from all relevant disciplines. The degree of consent among all task force members was included. RESULTS Chronic severe mucositis and polymorphic skin lesions are clue clinical characteristics of PNP/PAMS. A complete assessment of the patient with suspected PNP/PAMS, requiring histopathological study and immunopathological investigations, including direct and indirect immunofluorescence, ELISA and, where available, immunoblotting/immunoprecipitation, is recommended to achieve a diagnosis of PNP/PAMS. Detection of anti-envoplakin antibodies and/or circulating antibodies binding to the rat bladder epithelium at indirect immunofluorescence is the most specific tool for the diagnosis of PNP/PAMS in a patient with compatible clinical and anamnestic features. Treatment of PNP/PAMS is highly challenging. Systemic steroids up to 1.5 mg/kg/day are recommended as first-line option. Rituximab is also recommended in patients with PNP/PAMS secondary to lymphoproliferative conditions but might also be considered in cases of PNP/PAMS associated with solid tumours. A multidisciplinary approach involving pneumologists, ophthalmologists and onco-haematologists is recommended for optimal management of the patients. CONCLUSIONS These are the first European guidelines for the diagnosis and management of PNP/PAMS. Diagnostic criteria and therapeutic recommendations will require further validation by prospective studies