Amy S Paller1, Tali Czarnowicki2, Yael Renert-Yuval2, Kristen Holland3, Thy Huynh4, Muriel Sadlier5, Maeve A McAleer6, Gary Tran4, Gabrielle C Geddes7, Alan D Irvine8, Emma Guttman-Yassky2. 1. Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address: apaller@northwestern.edu. 2. Department of Dermatology, Mount Sinai School of Medicine, New York, New York. 3. Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin. 4. Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 5. Paediatric Dermatology, Our Lady's Children's Hospital Crumlin, Dublin, Ireland. 6. Paediatric Dermatology, Our Lady's Children's Hospital Crumlin, Dublin, Ireland; National Children's Research Centre, Dublin, Ireland. 7. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin. 8. Paediatric Dermatology, Our Lady's Children's Hospital Crumlin, Dublin, Ireland; National Children's Research Centre, Dublin, Ireland; Clinical Medicine, Trinity College Dublin, Dublin, Ireland.
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.
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.
Authors: Perry M Elliott; Aris Anastasakis; Angeliki Asimaki; Cristina Basso; Barbara Bauce; Matthew A Brooke; Hugh Calkins; Domenico Corrado; Firat Duru; Kathleen J Green; Daniel P Judge; David Kelsell; Pier D Lambiase; William J McKenna; Kalliopi Pilichou; Alexandros Protonotarios; Jeffrey E Saffitz; Petros Syrris; Hari Tandri; Anneline Te Riele; Gaetano Thiene; Adalena Tsatsopoulou; J Peter van Tintelen Journal: Eur J Heart Fail Date: 2019-06-18 Impact factor: 15.534
Authors: Tejas P Joshi; Hannah Y Wang; Prazwal Athukuri; Sarah Bohac; Morgan A Farr; Darien Hinson; Justin A Kahla; Nasim Khalfe; Dylan B McBee; Rachel Stroh; Nicole Walters; Vicky Ren Journal: Am J Clin Dermatol Date: 2022-05-23 Impact factor: 6.233