Contact leukoderma following irritant contact dermatitis to an isopropanol-based hand rub: A consequence of rigorous hand hygiene.
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ABSTRACT:
SUBMITTER: Sinha S
PROVIDER: S-EPMC7754559 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
Contact leukoderma following irritant contact dermatitis to an isopropanol-based hand rub: A consequence of rigorous hand hygiene.
Sinha Surabhi S Sardana Kabir K
Contact dermatitis 20201201 5
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Project description:BackgroundThe 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 inflammasome-targeting treatment strategies for irritant contact dermatitis.MethodsA 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.ResultsDisulfiram 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).ConclusionWe 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.
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Project description:BackgroundA hallmark of Euphorbia myrsinites (EM), a member of the widespread perennial Euphorbia species, is the extrusion of a poisonous, latex-like sap irritant to the skin and eye after contact. The exact mechanisms underlying these effects have not been unraveled so far.ObjectivesThe aims of the study were to allocate EM sap-induced phytodermatitis to irritant or allergic contact dermatitis (ACD) and to investigate mechanism(s) causing keratinocyte damage.MethodsCutaneous effects of EM sap on healthy human skin were investigated by clinical scoring and reflectance confocal microscopy analyses and compared with ACD. In addition, the effects of sap exposure to keratinocytes were analyzed in vitro using histological analyses and flow cytometry.ConclusionsWe report on 2 cases of EM sap-induced phytodermatitis. Patch testing with fresh EM sap induced dermatitis in 100% of the tested sites with a clinical course following a decrescendo pattern. Compared with ACD, the lesional phenotype was more severe and epidermal disruption was more pronounced. Exposure of human skin tissues and cultivated keratinocytes to EM sap in vitro resulted in a dose-dependent increase in keratinocyte apoptosis. The reported findings support the primarily toxic irritant nature of EM sap-induced phytodermatitis. The contribution of ingenol mebutate to (nontoxic) proinflammatory effects remains to be elucidated.
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Project description:PurposeIrritant contact dermatitis (ICD) is a major cause of occupational disease. The aim was to review the relation between exposure to occupational irritants and ICD and the prognosis of ICD.MethodsThrough a systematic search, 1516 titles were identified, and 48 studies were included in the systematic review.ResultsWe found that the evidence for an association between ICD and occupational irritants was strong for wet work, moderate for detergents and non-alcoholic disinfectants, and strong for a combination. The highest quality studies provided limited evidence for an association with use of occlusive gloves without other exposures and moderate evidence with simultaneous exposure to other wet work irritants. The evidence for an association between minor ICD and exposure to metalworking fluids was moderate. Regarding mechanical exposures, the literature was scarce and the evidence limited. We found that the prognosis for complete healing of ICD is poor, but improves after decrease of exposure through change of occupation or work tasks. There was no substantial evidence for an influence of gender, age, or household exposures. Inclusion of atopic dermatitis in the analysis did not alter the risk of ICD. Studies were at risk of bias, mainly due to selection and misclassification of exposure and outcome. This may have attenuated the results.ConclusionThis review reports strong evidence for an association between ICD and a combination of exposure to wet work and non-alcoholic disinfectants, moderate for metalworking fluids, limited for mechanical and glove exposure, and a strong evidence for a poor prognosis of ICD.
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