Response pathways of the metabolic and the immune system have been evolutionary conserved, resulting in a high degree of integrated regulation. Insulin is a central player in the metabolic system and potentially also in the homeostasis of the skin. Psoriasis is a frequent and often severe autoimmune skin disease, clinically characterized by altered epidermal homeostasis, of which the molecular pathomechanisms are only little understood. In this study, we have examined a potential role for insulin signaling in the pathogenesis of this disease. We show that IL-1β is present in high quantities in tissue fluid collected via microdialysis from patients with psoriasis; these levels are reduced under successful anti-psoriatic therapy. Our results suggest that IL-1β contributes to the disease by dual effects. First, it induces insulin resistance through p38MAPK (mitogen-activated protein kinase), which blocks insulin-dependent differentiation of keratinocytes, and at the same time IL-1β drives proliferation of keratinocytes, both being hallmarks of psoriasis. Taken together, our findings point toward insulin resistance as a contributing mechanism to the development of psoriasis; this not only drives cardiovascular comorbidities, but also its cutaneous phenotype. Key cytokines inducing insulin resistance in keratinocytes and kinases mediating their effects may represent attractive targets for novel anti-psoriatic therapies.

Altogether these results suggest a role for mTOR signalling in the epidermal changes leading to the psoriatic phenotype. mTOR inhibition might be a mode of action to explore in developing innovative antipsoriatic drugs.

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ZusammenfassungDie Onychomykose ist eine Pilzinfektion des Nagelorgans und betrifft sowohl Finger‐ als auch Zehennägel. Sie wird in Europa vor allem durch Dermatophyten verursacht. Die Diagnostik erfolgt mittels direktmikroskopischer, kultureller und/oder molekularer Methoden aus Nagelmaterial (Nagelspäne). Eine Lokaltherapie mit antimykotischem Nagellack wird bei leichten oder mäßig ausgeprägten Nagelinfektionen empfohlen. Bei mittelschwerer und schwerer Onychomykose wird empfohlen – falls keine Kontraindikationen bestehen – stets oral (systemisch) zu behandeln. Eine antimykotische Kombinationstherapie – oral und topisch – sollte dabei angestrebt werden. Ziel dieser Aktualisierung der deutschen S1‐Leitlinie ist es, Auswahl und Durchführung von geeigneter Diagnostik und Therapie zu vereinfachen. Die Leitlinie wurde unter Berücksichtigung aktueller internationaler Leitlinien und den Ergebnissen einer Literaturrecherche durch die Experten der Leitlinienkommission erstellt. Die Leitlinienkommission besteht aus Mandatsträgern der Deutschen Dermatologischen Gesellschaft (DDG), des Berufsverbandes der Deutschen Dermatologen (BVDD), der Deutschsprachigen Mykologischen Gesellschaft (DMykG), der Deutschen Gesellschaft für Hygiene und Mikrobiologie (DGHM), der Deutschen Gesellschaft für Kinder‐ und Jugendmedizin e.V. (DGKJ), der Arbeitsgemeinschaft pädiatrische Dermatologie (APD) und der deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI). Methodisch wurde die Leitliniengruppe durch die Division of Evidence‐based Medicine (dEBM) begleitet. Die Leitlinie wurde nach einem umfangreichen internen und externen Review durch die beteiligten Fachgesellschaften freigegeben.

Summary Onychomycosis is a fungal infection of the fingernails and toenails. In Europe, tinea unguium is mainly caused by dermatophytes. The diagnostic workup comprises microscopic examination, culture and/or molecular testing (nail scrapings). Local treatment with antifungal nail polish is recommended for mild or moderate nail infections. In case of moderate to severe onychomycosis, oral treatment is recommended (in the absence of contraindications). Treatment should consist of topical and systemic agents. The aim of this update of the German S1 guideline is to simplify the selection and implementation of appropriate diagnostics and treatment. The guideline was based on current international guidelines and the results of a literature review conducted by the experts of the guideline committee. This multidisciplinary committee consisted of representatives from the German Society of Dermatology (DDG), the German‐Speaking Mycological Society (DMykG), the Association of German Dermatologists (BVDD), the German Society for Hygiene and Microbiology (DGHM), the German Society of Pediatric and Adolescent Medicine (DGKJ), the Working Group for Pediatric Dermatology (APD) and the German Society for Pediatric Infectious Diseases (DGPI). The Division of Evidence‐based Medicine (dEBM) provided methodological assistance. The guideline was approved by the participating medical societies following a comprehensive internal and external review.