Background: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo‐like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life.Objectives and methodology: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence‐based or rely on expert opinion. The degree of consent among all task force members was included.Results: Treatment depends on the severity of BP and patients' comorbidities. High‐potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B‐cell‐depleting therapy and intravenous immunoglobulins may be considered in treatment‐resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations.Conclusions: The guidelines for the management of BP were updated. They summarize evidence‐ and expert‐based recommendations useful in clinical practice.

Background: Various antigen-specific immunoassays are available for the serological diagnosis of autoimmune bullous diseases. However, a spectrum of different tissue-based and monovalent antigen-specific assays is required to establish the diagnosis. BIOCHIP mosaics consisting of different antigen substrates allow polyvalent immunofluorescence (IF) tests and provide antibody profiles in a single incubation.Methods: Slides for indirect IF were prepared, containing BIOCHIPS with the following test substrates in each reaction field: monkey esophagus, primate salt-split skin, antigen dots of tetrameric BP180-NC16A as well as desmoglein 1-, desmoglein 3-, and BP230gC-expressing human HEK293 cells. This BIOCHIP mosaic was probed using a large panel of sera from patients with pemphigus vulgaris (PV, n = 65), pemphigus foliaceus (PF, n = 50), bullous pemphigoid (BP, n = 42), and non-inflammatory skin diseases (n = 97) as well as from healthy blood donors (n = 100). Furthermore, to evaluate the usability in routine diagnostics, 454 consecutive sera from patients with suspected immunobullous disorders were prospectively analyzed in parallel using a) the IF BIOCHIP mosaic and b) a panel of single antibody assays as commonly used by specialized centers.Results: Using the BIOCHIP mosaic, sensitivities of the desmoglein 1-, desmoglein 3-, and NC16A-specific substrates were 90%, 98.5% and 100%, respectively. BP230 was recognized by 54% of the BP sera. Specificities ranged from 98.2% to 100% for all substrates. In the prospective study, a high agreement was found between the results obtained by the BIOCHIP mosaic and the single test panel for the diagnosis of BP, PV, PF, and sera without serum autoantibodies (Cohen’s κ between 0.88 and 0.97).Conclusions: The BIOCHIP mosaic contains sensitive and specific substrates for the indirect IF diagnosis of BP, PF, and PV. Its diagnostic accuracy is comparable with the conventional multi-step approach. The highly standardized and practical BIOCHIP mosaic will facilitate the serological diagnosis of autoimmune blistering diseases.

Background: Autoimmune bullous diseases (AIBD) are rare disorders characterized by autoantibody formation against components of adhesion molecules; in pemphigoid diseases (PD), these are proteins of hemidesmosomes and basement membrane, important for cell‐matrix adhesion in skin and/or mucous membranes. Incidences of these diseases vary considerably between different populations.Objectives: To establish a registry prospectively recruiting all AIBD patients in a geographically well‐defined region in Northern Germany (Schleswig‐Holstein).Methods: Only patients with verified disease (by clinical presentation, histology, direct and/or indirect immunofluorescence and /or ELISA) living in Schleswig‐Holstein were included. Incidences of PD were estimated based on the total number of inhabitants in Schleswig‐Holstein, stratified by birth year and sex.Results: Of 67 patients with PD [35 male, 32 female, mean age 75 (standard deviation 14.3 years)], 83% were patients with bullous pemphigoid [n = 56, 28 male, 28 female, mean age 78 (SD 9.9)]. The resulting crude incidences were 23.4 patients/million/year for all pemphigoid patients, 19.6 patients/million/year for bullous pemphigoid (age‐standardized 16.9 patients/million/year) with a strong increase in bullous pemphigoid patients in the age group of 85–90 years with 262 patients/million/year. Incidences for bullous pemphigoid were higher in urban compared to rural areas. Other PD (mucous membrane pemphigoid, linear IgA disease, anti‐p200 pemphigoid) were less frequent with crude incidences of 2.1, 1.0 and 0.7 patients/million/year, respectively.Conclusions: This study prospectively analyses the incidence of PD in a carefully defined geographical area. The highest incidence among PD patients was found for bullous pemphigoid. The incidence of bullous pemphigoid is considerably increased compared to previous reports and reveals regional differences. Further studies are needed in order to clarify these findings.

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.

Anti-p200 pemphigoid is an autoimmune blistering disease that often resembles other pemphigoid disorders. We developed a test for the detection of autoantibodies against laminin β4, an autoantigen in anti-p200 pemphigoid, to facilitate its diagnosis. The test demonstrated excellent sensitivity and specificity, making it a valuable tool for diagnosing this disease and distinguishing it from similar skin disorders.

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially life-threatening autoimmune blistering diseases. Treatment is based on long term immunosuppression with high doses of glucocorticosteroids in combination with potentially corticosteroid-sparing agents and/or rituximab. Immunoadsorption (IA) has emerged as fast acting adjuvant treatment option. To assess the clinical efficacy of IA in addition to best medical treatment. Multicentre (26 centres from Germany and Austria) randomised controlled trial in 72 patients with newly diagnosed, relapsed or chronic active PV or PF (34 females, 38 males, aged 42-72 years) comparing best medical treatment (BMT) (prednisolone 1.0 mg/kg/d plus azathioprine or mycophenolate) to adjuvant IA (BMT+IA). Central 1:1 randomization was done at the coordinating centre for clinical trials (KKS) Marburg. The primary endpoint was analyzed using Kaplan-Meier and Cox regression methods. The study was ended prematurely due to safety concerns after random allocation of 72 patients to BMT+IA (n=34) or BMT (n=38). The primary endpoint, time to complete remission on therapy, was not significantly different between the groups (p=0.39; HR 1.35 (95%CI: 0.68–2.69). The cumulative dose of prednisolone was significantly lower in the BMT+IA compared to BMT alone (difference -1,214; 95%CI, -2,225 - -70; p=0.03). In a post hoc analysis, patients with more extensive PV/PF showed a tendency towards a shorter time to remission in the BMT+IA group compared to the BMT group (HR=1.87, p=0.17 in patients with baseline PDAI ≥ 15). While more adverse events were observed in patients of the BMT group (29 vs. 25), severe adverse events were more frequent in patients of the BMT+IA group (17 events in 10 patients vs. 11 events in 8 patients). In this study, adjuvant IA did not show a shorter time to clinical remission but a corticosteroid-sparing effect. In patients with extensive PV/PF, post hoc analysis suggests that adjuvant IA may possibly lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.