دورية أكاديمية
RASopathic comedone-like or cystic lesions induced by vemurafenib: a model of skin lesions similar but not identical to those induced by dioxins MADISH.
| العنوان: | RASopathic comedone-like or cystic lesions induced by vemurafenib: a model of skin lesions similar but not identical to those induced by dioxins MADISH. |
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| المؤلفون: | Kaya G; Department of Dermatology, University Hospital of Geneva, Geneva, Switzerland., Saxer-Sekulic N; Department of Dermatology, University Hospital of Geneva, Geneva, Switzerland., Kaya A; Department of Pharmacology and Toxicology, University of Geneva, Geneva, Switzerland., Sorg O; Department of Pharmacology and Toxicology, University of Geneva, Geneva, Switzerland., Boespflug A; Department of Dermatology, Centre Hospitalier Lyon Sud, Lyon, France., Thomas L; Department of Dermatology, Centre Hospitalier Lyon Sud, Lyon, France., Saurat JH; Department of Pharmacology and Toxicology, University of Geneva, Geneva, Switzerland. |
| المصدر: | Journal of the European Academy of Dermatology and Venereology : JEADV [J Eur Acad Dermatol Venereol] 2018 Aug; Vol. 32 (8), pp. 1368-1372. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 9216037 Publication Model: Print Cited Medium: Internet ISSN: 1468-3083 (Electronic) Linking ISSN: 09269959 NLM ISO Abbreviation: J Eur Acad Dermatol Venereol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Wiley-Blackwell Original Publication: Amsterdam ; New York : Elsevier Science Publishers, c1992- |
| مواضيع طبية MeSH: | Antineoplastic Agents/*adverse effects , Chloracne/*pathology , Epidermal Cyst/*metabolism , Melanoma/*drug therapy , Skin Neoplasms/*drug therapy , Vemurafenib/*adverse effects, Antineoplastic Agents/pharmacology ; Chloracne/etiology ; Chloracne/metabolism ; Cytochrome P-450 CYP1A1/metabolism ; Dioxins/adverse effects ; Drug Eruptions/etiology ; Drug Eruptions/metabolism ; Drug Eruptions/pathology ; Enzyme Activation/drug effects ; Epidermal Cyst/chemically induced ; Erlotinib Hydrochloride/pharmacology ; Female ; Gefitinib/pharmacology ; Hep G2 Cells ; Humans ; Male ; Protein Kinase Inhibitors/pharmacology ; Vemurafenib/pharmacology |
| مستخلص: | Background: Patients treated with vemurafenib for metastatic melanoma often develop skin lesions similar to those observed after exposure to dioxin-like compounds. We previously called these lesions MADISH (metabolizing acquired dioxin-induced skin hamartoma) when analysing a case of acute dioxin poisoning. Objective: We performed a clinical trial aimed at comparing the skin lesions observed under vemurafenib treatment with MADISH in order to bring to light a possible crosstalk between vemurafenib and dioxin pathways. Methods: 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-AhR pathway. Results: All patients had skin lesions diagnosed as 'non-inflammatory acneiform eruption' by dermatologists. These were predominantly facial with notable retroauricular involvement and clinically compatible with chloracne/MADISH when assessed by dioxin expert. Histological analysis showed mostly comedone-like 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 CYP1A1, 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 CYP1A1 activity. Discussion: Although the skin lesions under vemurafenib treatment were morphologically similar to MADISH, the absence of CYP1A1 expression in dermal cysts of patients and the absence of CYP1A1 activation by vemurafenib led us consider that these skin lesions were different from true MADISH and not mediated by a crosstalk of AhR signalling, but rather to a hyperactivation of PI3K-Akt pathway as a consequence of vemurafenib treatment. A strong expression of CYP1A1 in the epithelial wall of dermal cysts must be required, parallel to the morphology of the lesions, to make the diagnosis of MADISH, the hallmark of an exposure to dioxin-like/chloracnegen compounds. (© 2018 European Academy of Dermatology and Venereology.) |
| التعليقات: | Comment in: J Eur Acad Dermatol Venereol. 2018 Aug;32(8):1233-1234. (PMID: 31211462) |
| معلومات مُعتمدة: | UF1024 University of Geneva |
| المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Dioxins) 0 (Protein Kinase Inhibitors) 207SMY3FQT (Vemurafenib) DA87705X9K (Erlotinib Hydrochloride) EC 1.14.14.1 (CYP1A1 protein, human) EC 1.14.14.1 (Cytochrome P-450 CYP1A1) S65743JHBS (Gefitinib) |
| تواريخ الأحداث: | Date Created: 20180326 Date Completed: 20191014 Latest Revision: 20191014 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1111/jdv.14945 |
| PMID: | 29575357 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1468-3083 |
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| DOI: | 10.1111/jdv.14945 |