Susceptibility to Dermatophytosis in SDR9C7-Nonsyndromic Epidermal Differentiation Disorder: Observation of Cutaneous Inflammation Involving IRF4 and IL-17

J Dermatol. 2026 Jan;53(1):149-154. doi: 10.1111/1346-8138.70048. Epub 2025 Nov 11.

Abstract

SDR9C7-nonsyndromic epidermal differentiation disorder (nEDD) is a form of ceramide synthesis disorder that is known to confer susceptibility to dermatophytosis. Recurrent widespread tinea corporis developed in a SDR9C7-nEDD patient with homozygosity for the Japanese founder variant (c.826C>T, p.Arg276Cys) during apremilast treatment to improve ectropion. Ceramide analysis of the stratum corneum revealed decreased protein-bound ceramides, indicating skin barrier dysfunction. Based on previous studies of decreased Irf4 mRNA in Sdr9c7-/- mice, IRF4 transcription factor-dependent IL-17 production, and the importance of IL-17A/F in mucocutaneous immunity against Candida albicans, we examined the expression of each molecule using immunofluorescence and found for the first time decreased IRF4 and IL17-A/C/F (which were further decreased by apremilast treatment) in SDR9C7-nEDD epidermis. Although further studies are needed to clarify an evaluation of cytokine profiles in SDR9C7-nEDD, which may have immune profiles different from the previously reported IL-17-dominant immune profiles in the major forms of ichthyosis, these findings might have contributed to susceptibility to dermatophytosis in this patient, and it is suggested that the use of apremilast should be avoided in SDR9C7-nEDD.

Keywords: autosomal recessive congenital ichthyosis; corneocyte lipid envelope; phosphodiesterase 4 inhibitor.

Publication types

  • Case Reports

MeSH terms

  • Epidermis / immunology
  • Epidermis / pathology
  • Genetic Predisposition to Disease
  • Humans
  • Interferon Regulatory Factor-4
  • Interferon Regulatory Factors* / immunology
  • Interferon Regulatory Factors* / metabolism
  • Interleukin-17* / immunology
  • Interleukin-17* / metabolism
  • Thalidomide / analogs & derivatives
  • Thalidomide / therapeutic use
  • Tinea* / genetics
  • Tinea* / immunology
  • Tinea* / pathology

Substances

  • Interferon Regulatory Factors
  • Interleukin-17
  • Thalidomide
  • Interferon Regulatory Factor-4
  • IL17A protein, human