The spectrum of manifestations in desmoplakin gene (DSP) spectrin repeat 6 domain mutations: Immunophenotyping and response to ustekinumab - 28/02/18
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.
Le texte complet de cet article est disponible en PDF.Key words : Carvajal syndrome, EKC syndrome, ichthyosis, keratoderma, orphan disease, personalized medicine, pustular psoriasis, SAM syndrome, Th1, Th17, therapeutic repurposing, therapy, ustekinumab, woolly hair
Abbreviations used : CIE, DCWHKTA, EKC, IASI, IFN-γ, IL, NS, OMIM, SAM, SR6, Th
Plan
Drs Paller and Czarnowicki contributed equally to this article. |
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Supported in part by the Foglia Family Foundation Endowment (ASP). |
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Disclosure: Dr Paller is a consultant with honorarium for Amgen, Celgene, Dermira, Eli Lilly, GSK-Stiefel, Novartis, Pfizer, Regeneron/Sanofi, and Valeant and an investigator for Galderma, Janssen, Novartis, and Regeneron/Sanofi. Dr Holland is a consultant with honorarium for Amgen and Pfizer and an investigator for Regeneron/Sanofi and Eli Lilly. Dr Irvine is a consultant with honorarium for AbbVie, Chugai Pharma, Genentech, and Sanofi Regeneron. Dr Guttman-Yassky is a consultant with honorarium for Regeneron/Sanofi, Merck, Stiefel/GSK, Pfizer, Genentech, Bristol-Myers Squibb, Galderma, Celgene, Leo Pharma, Janssen, Medimmune, Dermira, Anacor, AnaptysBio, Glenmark, Novartis, Abbvie, Sun Pharma, Mitsubishi Tanabe, Vitae, Allergan, Almirall, Puricore, Asana Biosciences, Gilead, Concert, Immune, Kyowa Kirin, Ziarco, DS Biopharma, Escallier, and DBV Technologies; she is an investigator for Regeneron/Sanofi, Pfizer, Abbvie, Celgene, Medimmune, Dermira, Glenmark, Novartis, Vitae, Asana Biosciences, Innovaderm, Immune, Leo Pharma, Galderma, and Eli Lilly. Drs Czarnowicki, Geddes, Renert-Yuval, Huynh, Sadlier, McAleer, and Tran disclosed no conflicts of interest. |
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Reprints not available from the authors. |
Vol 78 - N° 3
P. 498 - mars 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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