Epidermolysis bullosa simplex generalized severe induces a Th17 response and is improved by Apremilast treatment

Castela E, Tulic MK, Rozières A, Bourrat E, Nicolas JF, Kanitakis J, Vabres P, Bessis D, Mazereeuw J, Morice-Picard F, Baty D, Berard F, Lacour JP, Passeron T, Chiaverini C

Br. J. Dermatol. 2018 Jun;

Abstract

PMID: 29932457

BACKGROUND: Epidermolysis bullosa simplex generalized severe is a genetic disorder caused by mutation in KRT5 or KRT14 genes. Usually considered as a mechanical disease, recent data argue for additional inflammatory mechanisms.

OBJECTIVES: The aim of this study was to assess the inflammation in the skin of patients with EBS.

METHODS: A first immunohistochemical retrospective study was performed on frozen skin samples from 17 EBS-gen sev patients. A second multicenter prospective study was conducted on 10 patients with severe EBS-gen sev. Blister fluid and epidermis were processed for immunochemistry analysis and quantitative real time PCR. Cytokine expression was analyzed in blister fluid and compared with controls.

RESULTS: Histological analysis showed a constant dermal perivascular CD4+ lymphocytes infiltrate in skin biopsies of blister (n=17) as well as in rubbed skin (n=5), an epidermal infiltration of neutrophils and eosinophils in 70% of cases and an increased immunostaining for CXCL9 and CXCL10 in blistering skin. High levels of Th17 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.

CONCLUSION: Our study demonstrates the importance of inflammation in EBS-gen sev patients and underlines the key role for Th17 cells in its pathogenesis. In addition, this study provides promising new therapeutic approaches for this disabling disorder. This article is protected by copyright. All rights reserved.