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The study of psoriasis has yielded fundamental new insights into immunologic regulation and innovative therapies in a way that few other diseases have. In this review, we summarize the main features of current psoriasis research with emphasis on pathophysiological processes and the milestones in the approval of various biologics and small molecule drugs. Thus, through psoriasis research, we are gaining a better understanding of the interplay between the components of the innate and adaptive immune systems. New therapeutics interfere with crucial regulatory networks. Based on current knowledge, we outline what we believe to be some of the most important future research directions and therapeutic and clinical developments in psoriasis. These span multiple areas, ranging from the study of genetic, epigenetic, cellular, and immunological mechanisms to studies of particular clinical forms of psoriasis, individual systemic effects of the disease and its treatment, and the incorporation of large connected data sets and artificial intelligence. The goal is to understand psoriasis holistically, from the molecular to the organismic and societal levels, in order to develop individualized prevention and treatment strategies. Despite impressive progress, psoriasis research must continue to evolve at both the smallest and largest scales to comprehensively address the needs of both physicians and patients., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Background and Objectives: Darier disease (DD) and Hailey-Hailey disease (HHD) are rare disorders caused by mutations in the ATPase, Sarcoplasmic/Endoplasmic Reticulum Ca 2+ Transporting 2 (ATP2A2) and ATPase Ca 2+ Transporting Type 2C, Member 1 (ATP2C1) gene, respectively, which lead to a disturbance of calcium metabolism in keratinocytes. Clinically, this is reflected by an impairment of keratinization. Histologically, acantholysis with variable degrees of dyskeratosis and parakeratosis is observed. Both diseases can usually be differentiated clinically, histopathologically and genetically. However, their routine distinction might be challenging since some patients do not harbor ATP2A2 or ATP2C1 mutations. To solve this diagnostic challenge, we studied the differential expression of two proteins of store-operated calcium entry (SOCE), stromal interaction molecule 1 (STIM1) and calcium release-activated calcium modulator 1 (ORAI1), by immunohistochemistry., Patients and Methods: Five individuals with ambiguous diagnostic findings and eight controls with an unambiguous diagnosis were studied clinically, histologically, genetically, and by immunohistochemistry for STIM1 and ORAI1., Results: DD patients consistently showed a cytoplasmic STIM1 expression while patients with HHD revealed a membrane-associated staining pattern. In contrast, ORAI1 did not show a differential expression pattern., Conclusions: Our data suggest subcellular compartmentalization of STIM1 as novel biomarker for the distinction of the two disorders., (© 2022 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Ticks, particularly hard ticks (Ixodidae), which are among the most important vectors of dangerous infectious agents, feed on their hosts for extended periods of time. With this lifestyle, numerous adaptations have evolved in ticks and their hosts, the pharmacological importance of which is increasingly being recognized. Many bioactive substances in tick saliva are being considered as the basis of new drugs. For example, components of tick cement can be developed into tissue adhesives or wound closures. Analgesic and antipruritic salivary components inhibit histamine or bradykinin, while other tick-derived molecules bind opioid or cannabinoid receptors. Tick saliva inhibits the extrinsic, intrinsic, or common pathway of blood coagulation with implications for the treatment of thromboembolic diseases. It contains vasodilating substances and affects wound healing. The broad spectrum of immunomodulatory and immunosuppressive effects of tick saliva, such as inhibition of chemokines or cellular immune responses, allows development of drugs against inflammation in autoimmune diseases and/or infections. Finally, modern vaccines against ticks can curb the spread of serious infections. The medical importance of the complex tick-host interactions is increasingly being recognized and translated into first clinical applications. Using selected examples, an overview of the mutual adaptations of ticks and hosts is given here, focusing on their significance to medical advance., (© 2022 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Background: The association of atopic dermatitis (AD) and allergic contact dermatitis has been a matter of considerable uncertainty. Study results range from lack of any association to increased sensitization for multiple allergens, but fail to identify consistent allergen associations., Objective: We studied a large patch test cohort of patients stratified by their atopic skin diathesis using the Erlangen Atopy Score (EAS), independent of active skin disease., Methods: Retrospective multi-center data analysis from five departments of dermatology in Germany with 4,509 patients. Patients were grouped as "no atopic skin diathesis" (n = 2,165) and "atopic skin diathesis" (n = 1,743), according to EAS., Results: Significantly more individuals with atopic skin diathesis showed at least one positive patch test reaction to the baseline series compared to individuals without atopic skin diathesis (49.1 % vs. 38.3 %). In logistic regression analyses, atopic skin diathesis was associated with a significantly higher risk of sensitization to methylchloroisothiazolinone/methylisothiazolinone (OR 2.383) and methylisothiazolinone (OR 1.891), thiuram mix (OR 1.614), as well as nickel (OR 1.530), cobalt (OR 1.683), and chromium (OR 2.089)., Conclusions: Atopic skin diathesis proved to be the most important intrinsic risk factor for contact sensitization to few, specific allergens. Past or present AD was a less relevant variable., (© 2021 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Sensitization rates to aeroallergens are rising worldwide. The prevalence is increasing, especially in Western countries. We aimed to investigate (1) sensitization rates and (2) cross-sensitization patterns in skin prick tests (SPTs) for the most relevant inhaled allergens in central Germany over 20 years, adjusted for regional pollen counts., Patients and Methods: This monocentric study evaluated SPTs for tree pollen, grass pollen and house dust mites (HDMs) in 4,315 patients (including children) with suspected airway allergies, from 1998-2017., Results: Sensitization rates to almost all aeroallergens have increased significantly over time, without relevant changes in regional pollen counts. Current sensitization rates in all our symptomatic patients were highest for grass (55.3 %) and rye pollen (59.6 %), with most pronounced increases in HDM sensitization over time (from 37.8 % to the current figure of 50.1 %). However, a low but consistent proportion of tree-sensitized patients (3.6-7.8 %) showed isolated positive SPTs to alder and/or hazel pollen without sensitization to birch pollen., Conclusions: We demonstrate a significant rise in the total number of sensitized patients as well as increases in cross-sensitization between closely related allergens. Individuals with unusual mono-sensitization profiles to common inhaled allergens should be studied in more detail, since these patients are currently excluded from clinical trials for allergen immunotherapy., (© 2020 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Background and Aims: Infantile hemangiomas can be successfully treated by both systemic propranolol and neodymium:YAG (Nd:YAG)-dye laser combination therapy. In this retrospective study, the efficacy and safety of sequential and parallel therapy of complicated hemangiomas treated with both methods were evaluated., Patients and Methods: 30 children with 48 complicated hemangiomas were treated with propranolol and Nd:YAG-dye laser combination therapy. Using photo comparison, the percentage remission rate was evaluated by three investigators on a four-step scale (I: 0-25 %, II: 26-50 %, III: 51-75 % and IV: 76-100 %)., Results: Eleven children received propranolol and laser therapy in parallel (A), twelve children received laser therapy after propranolol (B) and seven children received propranolol after laser therapy (C). Due to emigration abroad, one child was lost to follow-up. A strong improvement (IV) was observed in 23/29 (79.3 %) of all treated children (A: 90.9 %, B 75 %, C 66.7 %). The mean duration of propranolol therapy in all children was 8.6 months (A: 8.9 months, B: 8.2 months, C: 8.9 months). On average, 2.33 laser treatments were performed per hemangioma (A: 1.95, B: 3.2, C: 1.91). Serious side effects caused by propranolol and laser therapy were not observed., Conclusions: Propranolol and Nd:YAG-dye laser combination therapy can be used sequentially or in parallel safely and effectively. They complement each other in a meaningful manner., (© 2020 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

The COVID-19 pandemic caused by SARS-CoV-2 has far-reaching direct and indirect medical consequences. These include both the course and treatment of diseases. It is becoming increasingly clear that infections with SARS-CoV-2 can cause considerable immunological alterations, which particularly also affect pathogenetically and/or therapeutically relevant factors. Against this background we summarize here the current state of knowledge on the interaction of SARS-CoV-2/COVID-19 with mediators of the acute phase of inflammation (TNF, IL-1, IL-6), type 1 and type 17 immune responses (IL-12, IL-23, IL-17, IL-36), type 2 immune reactions (IL-4, IL-13, IL-5, IL-31, IgE), B-cell immunity, checkpoint regulators (PD-1, PD-L1, CTLA4), and orally druggable signaling pathways (JAK, PDE4, calcineurin). In addition, we discuss in this context non-specific immune modulation by glucocorticosteroids, methotrexate, antimalarial drugs, azathioprine, dapsone, mycophenolate mofetil and fumaric acid esters, as well as neutrophil granulocyte-mediated innate immune mechanisms. From these recent findings we derive possible implications for the therapeutic modulation of said immunological mechanisms in connection with SARS-CoV-2/COVID-19. Although, of course, the greatest care should be taken with patients with immunologically mediated diseases or immunomodulating therapies, it appears that many treatments can also be carried out during the COVID-19 pandemic; some even appear to alleviate COVID-19., (© 2020 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)