The spectrum of manifestations in DSP (desmoplakin) SR6 domain mutations: immunophenotyping and response to ustekinumab

Paller, A. S.; Czarnowicki, T.; Renert-Yuval, Y.; Holland, K.; Huynh, T.; Sadlier, M.; McAleer, M. A.; Tran, G.; Geddes, G. C.; Irvine, A. D.; Guttman-Yassky, E.

J Am Acad Dermatol. 2017 Oct 27


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 DSP, the gene encoding desmoplakin, and to target therapy based on the molecular pathogenesis. METHODS: Immunophenotyping was performed using the blood and skin of a girl with SR6 region DSP mutations causing erythroderma/ichthyosis and cardiomyopathy. RESULTS: Based on the discovery of Th1 and Th17/IL-23 skewing in the skin and Th17/IL-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 one 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.

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