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

TY - JOUR

T1 - Epidermolysis bullosa simplex generalized severe induces a T helper 17 response and is improved by apremilast treatment

AU - Castela, E.

AU - Tulic, M. K.

AU - Rozières, A.

AU - Bourrat, E.

AU - Nicolas, J.-F.

AU - Kanitakis, J.

AU - Vabres, P.

AU - Bessis, D.

AU - Mazereeuw, J.

AU - Morice-Picard, F.

AU - Baty, D.

AU - Berard, F.

AU - Lacour, J.-P.

AU - Passeron, T.

AU - Chiaverini, C.

N1 - Funding: DEBRA France; CHU of Nice, France.

PY - 2019/2/4

Y1 - 2019/2/4

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85058009252

U2 - 10.1111/bjd.16897

DO - 10.1111/bjd.16897

M3 - Article

C2 - 29932457

SN - 0007-0963

VL - 180

SP - 357

EP - 364

JO - British Journal of Dermatology

JF - British Journal of Dermatology

IS - 2

ER -