Epidermolysis bullosa simplex generalized severe induces a T helper 17 response and is improved by apremilast treatment

E. Castela, M. K. Tulic, A. Rozières, E. Bourrat, J.-F. Nicolas, J. Kanitakis, P. Vabres, D. Bessis, J. Mazereeuw, F. Morice-Picard, D. Baty, F. Berard, J.-P. Lacour, T. Passeron, C. Chiaverini (Lead / Corresponding author)

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    Background: Epidermolysis bullosa simplex generalized severe (EBS-gen sev) is a genetic disorder caused by mutation in the KRT5 or KRT14 genes. Although it is usually considered a mechanical disease, recent data argue for additional inflammatory mechanisms. Objectives: To assess the inflammation in the skin of patients with EBS-gen sev. Methods: A first immunohistochemical retrospective study was performed on frozen skin samples from 17 patients with EBS-gen sev. A second multicentre prospective study was conducted on 10 patients with severe EBS-gen sev. Blister fluid and epidermis were processed for immunochemical analysis and quantitative real-time polymerase chain reaction. Cytokine expression was analysed in blister fluid and compared with that in controls. Results: Histological analysis showed a constant dermal perivascular CD4 + lymphocyte infiltrate in skin biopsies of both blister (n = 17) and rubbed skin (n = 5), an epidermal infiltration of neutrophils and eosinophils in 70% of cases, and increased immunostaining for CXCL9 and CXCL10 in blistering skin. High levels of T helper 17 cytokines were detected in lesional skin. Three adult patients with EBS-gen sev were treated with apremilast, with a dramatic improvement of skin blistering and good tolerance. Conclusions: Our study demonstrates the importance of inflammation in patients with EBS-gen sev and underlines the key role for T helper 17 cells in its pathogenesis. In addition, this study provides promising new therapeutic approaches for this disabling disorder.

    Original languageEnglish
    Pages (from-to)357-364
    Number of pages8
    JournalBritish Journal of Dermatology
    Issue number2
    Early online date22 Jun 2018
    Publication statusPublished - 4 Feb 2019

    ASJC Scopus subject areas

    • Dermatology


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