The spectrum of manifestations in desmoplakin gene (DSP) spectrin repeat 6 domain mutations: Immunophenotyping and response to ustekinumab. J Am Acad Dermatol 2018 Mar;78(3):498-505.e2
Date
10/27/2017Pubmed ID
29066275DOI
10.1016/j.jaad.2017.10.026Scopus ID
2-s2.0-85044643075 (requires institutional sign-in at Scopus site) 66 CitationsAbstract
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.
Author List
Paller AS, Czarnowicki T, Renert-Yuval Y, Holland K, Huynh T, Sadlier M, McAleer MA, Tran G, Geddes GC, Irvine AD, Guttman-Yassky EAuthor
Kristen E. Holland MD Associate Professor in the Dermatology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
CardiomyopathiesChild
Dermatitis
Dermatitis, Exfoliative
Dermatologic Agents
Desmoplakins
Female
Genotype
Humans
Hypersensitivity
Ichthyosis
Immunophenotyping
Male
Mutation
Syndrome
Th1 Cells
Th17 Cells
Ustekinumab
