The spectrum of manifestations in desmoplakin gene (DSP) spectrin repeat 6 domain mutations: Immunophenotyping and response to ustekinumab

Abstract

Background: The immune abnormalities underlying the ichthyoses are poorly understood.

Objective: To determine the immunophenotype of an ichthyosis resulting from mutations in the spectrin repeat 6 (SR6) domain of desmoplakin gene (DSP) and target therapy on the basis of molecular pathogenesis.

Methods: Immunophenotyping was performed by using the blood and skin of a girl with SR6 region DSP mutations causing erythroderma/ichthyosis and cardiomyopathy.

Results: On the basis of the discovery of T helper 1 and T helper 17/interleukin 23 skewing in the skin and T helper 17/interleukin 22 skewing in blood, ustekinumab therapy was initiated. Ustekinumab was also administered to a boy with an SR6 region DSP mutation and ichthyosis without cardiomyopathy. Both children responded despite previous poor responses to immunosuppressants and retinoids.

Limitations: Small number of patients and immunophenotyping in only 1 patient.

Conclusion: An understanding of the molecular basis of inflammation in rare cutaneous disorders can lead to targeted therapy, which promises to be more beneficial than broad immunosuppressants.

Keywords: Carvajal syndrome; EKC syndrome; SAM syndrome; Th1; Th17; ichthyosis; keratoderma; orphan disease; personalized medicine; pustular psoriasis; therapeutic repurposing; therapy; ustekinumab; woolly hair.