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

Br J Dermatol. 2019 Feb;180(2):357-364. doi: 10.1111/bjd.16897. Epub 2018 Dec 2.


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.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Child
  • Child, Preschool
  • Epidermolysis Bullosa Simplex / drug therapy
  • Epidermolysis Bullosa Simplex / genetics
  • Epidermolysis Bullosa Simplex / immunology*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Keratin-14 / genetics
  • Keratin-5 / genetics
  • Male
  • Middle Aged
  • Mutation
  • Pilot Projects
  • Retrospective Studies
  • Skin / cytology
  • Skin / drug effects*
  • Skin / immunology
  • Th17 Cells / drug effects
  • Th17 Cells / immunology*
  • Thalidomide / analogs & derivatives*
  • Thalidomide / pharmacology
  • Thalidomide / therapeutic use
  • Treatment Outcome
  • Young Adult


  • Anti-Inflammatory Agents, Non-Steroidal
  • KRT14 protein, human
  • KRT5 protein, human
  • Keratin-14
  • Keratin-5
  • Thalidomide
  • apremilast