{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T12:25:16Z","timestamp":1744028716704},"reference-count":20,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T00:00:00Z","timestamp":1532044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006389","name":"Universit\u00e9 de Gen\u00e8ve","doi-asserted-by":"publisher","award":["UF1024"],"award-info":[{"award-number":["UF1024"]}],"id":[{"id":"10.13039\/501100006389","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients treated with vemurafenib for metastatic melanoma often develop skin lesions similar to those observed after exposure to dioxin\u2010like compounds. We previously called these lesions <jats:styled-content style=\"fixed-case\">MADISH<\/jats:styled-content> (metabolizing acquired dioxin\u2010induced skin hamartoma) when analysing a case of acute dioxin poisoning.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We performed a clinical trial aimed at comparing the skin lesions observed under vemurafenib treatment with <jats:styled-content style=\"fixed-case\">MADISH<\/jats:styled-content> in order to bring to light a possible crosstalk between vemurafenib and dioxin pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this case series study, we explored the histological aspect of skin lesions in 10 cases treated with vemurafenib for malignant melanoma. We also analysed the ability of vemurafenib and tyrosine kinase inhibitors to induce dioxin\u2013AhR pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All patients had skin lesions diagnosed as \u2018non\u2010inflammatory acneiform eruption\u2019 by dermatologists. These were predominantly facial with notable retroauricular involvement and clinically compatible with chloracne\/<jats:styled-content style=\"fixed-case\">MADISH<\/jats:styled-content> when assessed by dioxin expert. Histological analysis showed mostly comedone\u2010like lesions and dermal cysts containing epithelial wall with basal or lateral epithelial projections and lamellar keratinization and alterations of remaining sebaceous glands. The expression of <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A1, a gene highly induced following dioxin exposure, was not observed in these lesions. Vemurafenib and the tyrosine kinase inhibitors erlotinib and gefitinib did not induce <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A1 activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Although the skin lesions under vemurafenib treatment were morphologically similar to <jats:styled-content style=\"fixed-case\">MADISH<\/jats:styled-content>, the absence of <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A1 expression in dermal cysts of patients and the absence of <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A1 activation by vemurafenib led us consider that these skin lesions were different from true <jats:styled-content style=\"fixed-case\">MADISH<\/jats:styled-content> and not mediated by a crosstalk of AhR signalling, but rather to a hyperactivation of <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\u2010Akt pathway as a consequence of vemurafenib treatment. A strong expression of <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A1 in the epithelial wall of dermal cysts must be required, parallel to the morphology of the lesions, to make the diagnosis of <jats:styled-content style=\"fixed-case\">MADISH<\/jats:styled-content>, the hallmark of an exposure to dioxin\u2010like\/chloracnegen compounds.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.14945","type":"journal-article","created":{"date-parts":[[2018,3,25]],"date-time":"2018-03-25T01:49:16Z","timestamp":1521942556000},"page":"1368-1372","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>RAS<\/scp>opathic comedone\u2010like or cystic lesions induced by vemurafenib: a model of skin lesions similar but not identical to those induced by dioxins <scp>MADISH<\/scp>"],"prefix":"10.1111","volume":"32","author":[{"given":"G.","family":"Kaya","sequence":"first","affiliation":[{"name":"Department of Dermatology University Hospital of Geneva Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Saxer\u2010Sekulic","sequence":"additional","affiliation":[{"name":"Department of Dermatology University Hospital of Geneva Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Kaya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Geneva Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O.","family":"Sorg","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Geneva Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Boespflug","sequence":"additional","affiliation":[{"name":"Department of Dermatology Centre Hospitalier Lyon Sud Lyon 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