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-1β 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 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.

In human subjects imiquimod induces contact dermatitis with the distinctive feature that pDCs are the primary sensors, leading to an IL-23/T17 deviation. Despite these shortcomings, the human imiquimod model might be useful to investigate early pathogenic events and prove molecular concepts in patients with psoriasis.

Fig. 1. Rapid clinical response of hidradenitis suppurativa (HS) to secukinumab treatment. Clinical images of the genital and gluteal region (A) before and (B) after 8 weeks of treatment with the interleukin-17A antibody secukinumab, demonstrating rapid reduction in inflammatory nodules and signs of cutaneous inflammation.

Differential in situ expression of IL-17 in skin diseases Background: 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. Materials & Methods: 289 samples of the 30 most common cutaneous infectious, autoimmune, inflammatory and tumor diseases were stained for IL-17 immunohistochemically. Results: 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. Conclusion: 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.

Generalized pustular psoriasis (GPP) is a chronic, non-communicable inflammatory skin disease which can involve multiple organs and potentially lead to a fatal outcome. GPP is characterized by acute, recurrent flares of sterile pustular lesions on erythematous skin with signs of systemic inflammation also affecting extracutaneous organs. It can be associated with a pre-existing plaque psoriasis or develop independently. Due to its low prevalence, it is defined as an orphan disease. 1-3 In our review article of 2018 "Generalized pustular psoriasis-a model disease for specific targeted immunotherapy," we presented the concept that GPP is an ideal disease to illustrate current problems in the field of inflammatory skin diseases-starting from a precise definition of this heterogeneous disease overlapping with other types of pustular diseases, 4 advances in understanding the

Summary 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.

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