Search

In many disorders, skin and/or mucosal changes are dominated by blisters, wounds, or erosions. While these changes can be observed during infective, traumatic, metabolic, or inflammatory processes, these are normally clinical hallmarks of the disruption of the cytoarchitectural stability of the skin. Several proteins, such as those located in the dermal-epidermal junction zone and forming the hemidesmosomes, or those forming epidermal desmosomes are crucial for the maintenance of skin integrity. Defective function may be genetically determined due to impaired or absent production of specific proteins (i.e., epidermolysis bullosa) or due to autoimmune disorders that lead to the production of autoreactive antibodies targeting desmosomal or hemidesmosomal skin antigens. The latter group of diseases are classically named autoimmune blistering diseases of the skin. These can be divided in the pemphigoid group, where antigens are components of the hemidesmosomes, and pemphigus group, where desmosomal proteins are targeted. In this review, we provide a short vademecum of autoimmune skin disorders that are associated with skin fragility., Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: F. Solimani, D. Didona und M. Hertl geben an, dass kein Interessenkonflikt besteht. Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien. Für Bildmaterial oder anderweitige Angaben innerhalb des Manuskripts, über die Patient/-innen zu identifizieren sind, liegt von ihnen und/oder ihren gesetzlichen Vertretern/Vertreterinnen eine schriftliche Einwilligung vor., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background and Objectives: The coronavirus SARS-CoV-2, which is the cause of COVID-19 disease in infected patients, has led to an ongoing worldwide pandemic. Although SARS-CoV-2 vaccination had a dramatic positive effect on the course of COVID-19, there has been increasing evidence of adverse effects after SARS-CoV-2 vaccination. This meta-analysis highlights the association between SARS-CoV-2 vaccination and de novo induction or aggravation of inflammatory and autoimmune skin diseases., Material and Methods: A systematic meta-analysis of the literature on new onset or worsening of inflammatory and autoimmune diseases after SARS-CoV-2 vaccination was performed according to the PRISMA guidelines. The search strategy included following terms: "COVID-19/SARS-CoV-2 vaccine bullous pemphigoid/pemphigus vulgaris/systemic lupus erythematosus/dermatomyositis/lichen planus/leukocytoclastic vasculitis." Moreover, we describe representative cases from our dermatology department., Results: The database-search in MEDLINE identified 31 publications on bullous pemphigoid, 24 on pemphigus vulgaris, 65 on systemic lupus erythematosus, nine on dermatomyositis, 30 on lichen planus, and 37 on leukocytoclastic vasculitis until June 30th, 2022. Severity and response to treatment varied among the described cases., Conclusions: Our meta-analysis highlights a link between SARS-CoV-2 vaccination and new onset or worsening of inflammatory and autoimmune skin diseases. Moreover, the extent of disease exacerbation has been exemplified by cases from our dermatological department., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Bullous pemphigoid is an autoimmune blistering disease caused by autoantibodies against components of the cutaneous basement membrane zone. Autoantibodies lead to complement-dependent and -independent inflammation and blistering. Blister fluid is a valuable biologic resource, as it provides insight into both systemic and local microenvironment responses. Here, we utilized liquid chromatography with tandem mass spectrometry to characterize the bullous pemphigoid blister fluid proteome. We then depleted exosomes to better understand the exosomal versus non-exosomal proteome. We identified 339 proteins in the blister fluid of bullous pemphigoid patients. Gene ontology demonstrated enrichment of several key biologic processes including innate immune response, neutrophil degranulation, platelet degranulation, and complement activation. Exosome depletion resulted in a significant decrease in normalized reporter intensities of 192 proteins, consistent with our observation of a large number of exosomal proteins found in the blister fluid. We then compared the bullous pemphigoid blister fluid proteome to prior proteomic datasets in suction blister fluid, snake bites, and thermal burns, identifying 76 proteins unique to bullous pemphigoid. These include major basic protein, eosinophil peroxidase, galectin-10, and the immunoglobulin epsilon heavy constant region, consistent with tissue eosinophilia. We lastly validated several previously reported blister fluid exosomal components. Blister fluid in bullous pemphigoid contains a mixture of numerous biologic processes. While many of these processes are shared with blistering from alternative causes, we have identified several notable features unique to bullous pemphigoid., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Autoimmune bullous diseases (AIBD) comprise a group of organ-specific autoimmune diseases which are characterised by the production of autoantibodies against adhesion molecules and structural proteins of skin and mucosae. Depending on the target protein, AIBD are classified into intraepidermal (pemphigus group) and subepidermal (pemphigoid group, epidermolysis bullosa acquisita, dermatitis herpetiformis) blistering disorders. Depending on the clinical entity, patients can develop blisters, pustules, erosions, and erythema on the skin and mucosae., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Paraneoplastic skin manifestations associated with malignancies are extremely polymorphous. Clinicians should be familiar with paraneoplastic dermatoses to establish an early diagnosis of the underlying neoplasm. Lack of familiarity with cutaneous clues for internal malignancies may delay diagnosis and treatment of cancer. In this review, we describe several paraneoplastic autoimmune dermatoses, including paraneoplastic autoimmune multiorgan syndrome, paraneoplastic bullous pemphigoid, and paraneoplastic dermatomyositis.

Originally described by Anhalt as paraneoplastic pemphigus in 1990, paraneoplastic autoimmune multiorgan syndrome (PAMS) is a potentially lethal blistering disease, characterized by polymorphous clinical features, including mucocutaneous erosions, blisters, lichenoid papules, and erythemas. Several autoantibodies have been detected in serum of PAMS patients, including antiplakins, anti-alpha-2-macroglobulin like 1, and antidesmogleins autoantibodies. The mortality rate of PAMS is up to 90%. This is due on the one hand to the poor response to treatments and on the other hand to the delay in the diagnosis and to the prognosis of the underlying neoplasia.

Dermatomyositis belongs to a group of rare autoimmune diseases characterized by a variable degree of skin symptoms and myopathy. The clinically diagnostic hallmarks of dermatomyositis are heliotrope rash, Gottron's papules and weakness of the proximal muscles. Along with pathognomonic, characteristic, and compatible cutaneous features, several uncommon and rare skin manifestations have been reported. In addition, new skin lesions have been described in dermatomyositis patients. Furthermore, rare clinical subtypes of dermatomyositis have been reported in the literature, including Wong-type dermatomyositis, characterised by the coexistence of dermatomyositis and pityriasis rubra pilaris with hyperkeratotic, erythematous, follicular confluent papules on the back of the hands along the bony prominences. In addition, plenty of autoantibody subsets have been recently described that are related to distinct clinical features and systemic involvement, such as anti-MDA5 autoantibodies. We reviewed the English- and German-language scientific literature using the key words "dermatomyositis", "autoantibodies", and "clinical features", alone or in combination, focusing on particular cutaneous symptoms and their association with defined autoantibody profiles. Furthermore, we focused on rare subtypes of dermatomyositis, unusual clinical features, and recently described skin lesions.

Autoimmune blistering diseases are characterized by autoantibodies against structural adhesion proteins of the skin and mucous membranes. Extensive characterization of their autoantibody targets has improved understanding of pathogenesis and laid the basis for the study of antigens/epitopes diversification, a process termed epitope spreading (ES). In this review, we have reported and discussed ES phenomena in autoimmune bullous diseases and underlined their functional role in disease pathogenesis. A functional ES has been proposed: (1) in bullous pemphigoid patients and correlates with the initial phase of the disease, (2) in pemphigus vulgaris patients with mucosal involvement during the clinical transition to a mucocutaneous form, (3) in endemic pemphigus foliaceus, underlining its role in disease pathogenesis, and (4) in numerous cases of disease transition associated with an intermolecular diversification of immune response. All these findings could give useful information to better understand autoimmune disease pathogenesis and to design antigen/epitope specific therapeutic approaches.

Importance: Pneumocystis pneumonia (PCP) is a potentially lethal opportunistic infection that primary prophylaxis can help prevent. The risk of prophylactic therapy must be weighed against the incidence of PCP in the patient population. Prophylaxis most frequently involves trimethoprim-sulfamethoxazole, with second-line therapies, including atovaquone, dapsone, and pentamide. The indication for prophylaxis in immunocompromised patients without HIV is less well defined. Previously, an incidence of at least 3.5% has been proposed as a cutoff to justify prophylaxis., Objective: To assess the incidence of PCP in patients with autoimmune blistering diseases receiving no routine prophylaxis., Design, Setting, and Participants: This was a retrospective analysis of patient medical records to determine the incidence of PCP infections. The multicenter study was performed at tertiary care centers that provide care for patients with autoimmune blistering disease in Germany, Italy, Singapore, Israel, and the Netherlands. Patients had a confirmed diagnosis of pemphigus vulgaris/foliaceus, bullous pemphigoid, epidermolysis bullosa acquisita, mucous membrane pemphigoid/cicatricial pemphigoid, or anti-p200 pemphigoid., Main Outcomes and Measures: To determine the incidence of PCP defined as patients with the International Classification of Diseases, Ninth Revision (ICD-9), code 136.3, for PCP, or free text documentation of PCP occurring based on characteristic radiographic findings with elevated lactate dehydrogenase, or hospitalization for pneumonia with bronchioalveolar lavage demonstrating Pneumocystis jiroveci on confirmatory stains., Results: A total of 801 patients with autoimmune blistering diseases were included in this study; their mean (SD) age was 66.5 (17.6) years, and a total of 465 (58%) were female. Only 1 patient developed PCP, resulting in an incidence rate of 0.1%. This incidence significantly fell below the recommended threshold of 3.5% (0.1% vs 3.5%, χ21 = 27.0; P < .001). This incidence was significantly lower than the previously reported incidence of PCP in all immunosuppressed dermatologic patients (0.1% vs 1.3%; χ21 = 8.2; P = .004)., Conclusions and Relevance: Routine Pneumocystis prophylaxis for patients with autoimmune blistering diseases does not seem to be warranted. Patients with autoimmune blistering disease seem to have a lower risk of PCP than the general population of immunosuppressed dermatology patients. Risks of routine prophylaxis include hyperkalemia, hypoglycemia, photosensitivity, thrombocytopenia, and more rare adverse reactions.

Background: An association between autoimmune disease and malignant melanoma (MM) has often been reported in the literature as a positive prognostic factor for MM. Consequently, we evaluated the influence of different autoimmune diseases on the prognosis of MM., Aim: To evaluate the prognosis of patients with MM who also had an autoimmune disorder, whether tumour-associated, paraneoplastic or drug-induced., Methods: Autoimmune diseases were classified and analysed as tumour-associated, paraneoplastic or drug-induced. Patients were enrolled according to their clinicopathological features and matched with control groups. Kaplan-Meier analysis was used to estimate disease-free survival (DFS) and overall survival (OS), and log-rank test was used to evaluate differences between the survival curves., Results: In total, 49 patients with MM and tumour-associated autoimmune disease were included in our analysis. No case of paraneoplastic autoimmune disease was detected. The survival analyses showed a range of results, from a worsening of DFS and OS to a lack of any difference. In a second analysis, we separately analysed patients who developed autoimmune disorders after starting adjuvant therapy with interferon-α; we did not find significant differences between these patients and the untreated patients., Conclusions: Autoimmune disease, whether tumour-associated or drug-induced, was not associated with better prognosis in patients with MM. The results suggest that the reported relationship between autoimmunity and MM may be a result of individual variation in sensitivity to the autoimmune disease, the tumour or the treatments., (© 2014 British Association of Dermatologists.)