Figurate erythemas - update and diagnostic approach.

Figurate erythemas (FE) represent an etiopathophysiologically heterogeneous group of diseases defined by their characteristic annular erythematous skin lesions. Diagnosis is made primarily by clinical examination together with histological findings; often it is a diagnosis made by exclusion. While some authors discuss FE as clinical reaction pattern rather than distinct clinical entities, others identify four classic FE: erythema annulare centrifugum, erythema gyratum repens, erythema migrans and erythema marginatum. The differential diagnoses of FE are numerous and often challenging. We therefore present a potential diagnostic algorithm for FE that discriminates the differentials according to their temporal evolution and the clinical/histological phenotype of the various subtypes. Since some FE may present with an underlying malignancy, diligent clinicians are needed when dealing with those entities.

Generalized pustular psoriasis-Dawn of a new era in targeted immunotherapy.

Generalized pustular psoriasis (GPP) is a rare, inflammatory skin disease characterized by recurrent flares of pustulation accompanied by systemic symptoms. Due to its acuteness, sufficient diagnosis and treatment are essential, but often face challenges. We recently overviewed various treatment options of GPP utilizing established therapies in psoriasis vulgaris (PsO). Although there is a pathogenic relation to PsO, more and more evidence suggests a predominant involvement of the innate immune system in GPP. Recent discoveries on the genetic background of GPP with underlying mutations in IL36RN, CARD14, AP1S3 and SERPINA3 contributed to a better understanding of the pathogenesis and provide major opportunities in the development of innovative, targeted therapies. The proposed umbrella term "autoinflammatory keratinization diseases" (AIKD) helps to categorize this heterogeneous disease. Finally, we address the problem of insufficient standardized assessment tools and propose a reproducible scoring system also capturing the systemic features of GPP. In summary, GPP is a prototype disease to demonstrate both obstacles and progress in dermatology-currently insufficient definition and diagnostic tools on the one hand side, yet major advances in dissecting disease heterogeneity, opportunities for novel diagnostic techniques and therapeutic decision-making based on molecular events on the other side.

Toll-like receptor 7/8 agonists stimulate plasmacytoid dendritic cells to initiate TH17-deviated acute contact dermatitis in human subjects.

BACKGROUND: A standardized human model to study early pathogenic events in patients with psoriasis is missing. Activation of Toll-like receptor 7/8 by means of topical application of imiquimod is the most commonly used mouse model of psoriasis. OBJECTIVE: We sought to investigate the potential of a human imiquimod patch test model to resemble human psoriasis. METHODS: Imiquimod (Aldara 5% cream; 3M Pharmaceuticals, St Paul, Minn) was applied twice a week to the backs of volunteers (n = 18), and development of skin lesions was monitored over a period of 4 weeks. Consecutive biopsy specimens were taken for whole-genome expression analysis, histology, and T-cell isolation. Plasmacytoid dendritic cells (pDCs) were isolated from whole blood, stimulated with Toll-like receptor 7 agonist, and analyzed by means of extracellular flux analysis and real-time PCR. RESULTS: We demonstrate that imiquimod induces a monomorphic and self-limited inflammatory response in healthy subjects, as well as patients with psoriasis or eczema. The clinical and histologic phenotype, as well as the transcriptome, of imiquimod-induced inflammation in human skin resembles acute contact dermatitis rather than psoriasis. Nevertheless, the imiquimod model mimics the hallmarks of psoriasis. In contrast to classical contact dermatitis, in which myeloid dendritic cells sense haptens, pDCs are primary sensors of imiquimod. They respond with production of proinflammatory and TH17-skewing cytokines, resulting in a TH17 immune response with IL-23 as a key driver. In a proof-of-concept setting systemic treatment with ustekinumab diminished imiquimod-induced inflammation. CONCLUSION: In human subjects imiquimod induces contact dermatitis with the distinctive feature that pDCs are the primary sensors, leading to an IL-23/TH17 deviation. Despite these shortcomings, the human imiquimod model might be useful to investigate early pathogenic events and prove molecular concepts in patients with psoriasis.

Generalized pustular psoriasis - a model disease for specific targeted immunotherapy, systematic review.

Generalized pustular psoriasis (GPP) is a rare, multisystemic skin disease characterized by recurrent episodes of pustulation. GPP can be life-threatening and is often difficult to treat. In the era of precision medicine in dermatology, GPP stands exemplary for both challenges and chances-while new treatments offer great hope, there is urgent need for better definition and stratification of this severe and heterogeneous disease. Our objective was to systematically review the literature for evidence of efficacy of targeted immunotherapy and their mode of action in the context of clinical phenotype, classification and pathogenesis of adult GPP. Classifying GPP is challenging since clinical criteria for description and diagnosis are not consistent between expert centres. We therefore defined diagnostic feasibility of the reviewed cases by assessing four criteria: compatible clinical history, typical dermatological features and/or diagnostic histopathology, consistent clinical pictures and the DITRA status. Pathogenesis of GPP is mediated by pathways that partly overlap plaque type psoriasis, with a more pronounced activity of the innate immune system. Both IL-1 and IL-36 but also IL-17 play a major role in disease formation. We ascertained a total of 101 published cases according to our predefined criteria and identified TNF-α, IL-12/23, IL-17 and IL-1ß as targets for immunotherapy for the treatment of GPP. Of those cases, 61% showed complete response and 27% partial response to targeted immunotherapy. Only 12% experienced weak or no response. These data indicate that specific immunotherapy can be used to effectively treat GPP, with most evidence existing for anti-IL-17 agents.

The Impact and Consequences of SARS-CoV-2 Pandemic on a Single University Dermatology Outpatient Clinic in Germany.

The pandemic outbreak of coronavirus disease 2019 (COVID-19) affects health care systems globally and leads to other challenges besides infection and its direct medical consequences. The aim of this study was to investigate the impact of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic on the university dermatology outpatient clinic (UDOC) of the Technical University of Munich, Germany. We analyzed datasets from 2015 until 2020 extracted from the hospital information system database and our documented outpatient files regarding patient numbers, gender, age, and diagnoses. In 2020, case numbers of outpatient care declined significantly (p = 0.021) compared to previous years and was related to the timing of political announcements answering SARS-CoV-2 pandemic. Additionally, during calendar week 10 to 15-the peak time of the spread of COVID-19 in Germany-the proportion of patients missing their consultation was significantly higher in 2020 than in 2019 (22.4% vs. 12.4%; p < 0.001). Gender-associated differences regarding absences were not detected, but patients aged 85 years or older were significantly more likely to miss their consultation compared to all other age groups (p = 0.002). Regarding different disease clusters, patients with chronic inflammatory skin diseases and infectious and malignant diseases were more likely to miss their consultation (p = 0.006). Noticeably, less patients with malignant diseases, and particularly malignant melanoma, were registered during this pandemic. Our data support the hypothesis that medically constructive prioritization might not be implemented properly by patients themselves. Identifying missed patients and catching up on their medical care apart from COVID-19 will pose an enormous challenge for health care systems globally.

Differential in situ expression of IL-17 in skin diseases.

UNLABELLED: Interleukin (IL)-17 is a key molecule for epithelial immunity and inflammation. OBJECTIVES: To quantify IL-17 expression in situ in a large panel of cutaneous diseases. 289 samples of the 30 most common cutaneous infectious, autoimmune, inflammatory and tumor diseases were stained for IL-17 immunohistochemically. IL-17 expression strongly varied between the diseases, but was conserved within each disease. The major cellular sources of IL-17 were T cells and granulocytes. Skin diseases caused by extracellular microbials were infiltrated by many IL-17+ cells, while intracellular infections were scarcely positive for IL-17. While autoimmune diseases were mostly accompanied by IL-17+ T cells, IL-17+ granulocytes were dominant in neutrophilic dermatoses. Cutaneous diseases show a characteristic pattern of IL-17+ cellular infiltrate. These patterns are relevant for the clinician, since therapeutic approaches targeting differentiation of Th17 cells as well as direct targeting of IL-17 are or will become available.