Background:The pathogenesis of contact dermatitis, a common inflammatory skin disease with limited treatment options, is held to be driven by inflammasome activation induced by allergens and irritants. We here aim to identify inflammasometargeting treatment strategies for irritant contact dermatitis. Methods:A high content screen with 41,184 small molecules was performed using fluorescent Apoptosis associated speck-like protein containing a CARD (ASC) speck formation as a readout for inflammasome activation. Hit compounds were validated for inhibition of interleukin (IL)-1β secretion. Of these, the approved thiuramdisulfide derivative disulfiram was selected and tested in a patch test model of irritant contact dermatitis in 25 healthy volunteers. Topical application of disulfiram, mometasone or vehicle was followed by application of sodiumdodecylsulfate (SDS) for 24 h each. Eczema induction was quantified by mexameter and laser speckle imaging. Corneocyte sampling of lesional skin was performed to assess inflammasome-mediated cytokines IL-1β and IL-18.Results: Disulfiram induced a dose-dependent inhibition of ASC speck formation and IL-1β release in cellular assays in vitro. In vivo, treatment with disulfiram, but not with vehicle and less mometasone, inhibited SDS-induced eczema. This was demonstrated by significantly lower erythema and total perfusion values assessed by mexameter and laser speckle imaging for disulfiram compared to vehicle (p < 0.001) and/or mometasone (p < 0.001). Also, corneocyte IL-18 levels were significantly reduced after application of disulfiram compared to vehicle (p < 0.001). Conclusion:We show that disulfiram is a dose-dependent inhibitor of inflammasome pathway activation in vitro and inhibitor of SDS-induced eczema in vivo.Topical application of disulfiram represents a potential treatment option for irritant contact dermatitis.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Wir möchten hier über den Fall einer 50-jährigen Frau mit Hauttyp IV nach Fitzpatrick berichten, die sich im September 2016 mit bilateralen, symmetrischen, lividroten, juckenden supraorbitalen Hautschwellungen und dem Verlust beider Augenbrauen in unserer Hautklinik vorstellte (Abbildung 1 ). Die Hautläsionen hatten in den letzten vier Monaten an Größe zugenommen. Im Jahr 2009 hatte sich die Patienten die Augenbrauen aus kosmetischen Gründen tätowieren lassen. Anamnestisch bestand seit 2002 eine Hypothyreose, die mit 50 mg Levothyroxin tgl. behandelt wurde, eine chronische Gastritis, die mit 30 mg Pantoprazol tgl. behandelt wurde, und seit 2013 eine entzündliche papulo-pustulöse Rosazea, die unter einer topischen Therapie kontrolliert verlief. Die Patientin hatte sich einer Cholezystektomie bei vesikulärer Lithiasis und 2016 einer Ektomie eines pleomorphen Adenoms der Parotis unterzogen. InteressenkonfliktKeiner.