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Brief Report
May 27, 2020

Secukinumab Therapy for Netherton Syndrome

Author Affiliations
  • 1Pediatric Skin Center, Department of Dermatology, University Children’s Hospital Zurich, Zurich, Switzerland
  • 2Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland
  • 3Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1163, Laboratory of Genetic Skin Diseases, Imagine Institute, Paris, France
  • 4Paris University, Paris, France
  • 5Pediatric Skin Center, Skin and Wound Management, University Children’s Hospital Zurich, Zurich, Switzerland
  • 6Dermatology Practice, Centro Medico Bellinzona, Bellinzona, Switzerland
  • 7Division of Pediatric Infectious Diseases, Children’s Hospital Lucerne, Lucerne, Switzerland
  • 8Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
  • 9Department of Genetics, Necker Hospital for Sick Children, Paris, France
JAMA Dermatol. Published online May 27, 2020. doi:10.1001/jamadermatol.2020.1019
Key Points

Question  Is inhibition of the interleukin 17 signaling pathway an effective therapeutic strategy for patients with Netherton syndrome, a severe and difficult-to-treat genetic condition with high disease burden?

Findings  In this case series, 4 patients with Netherton syndrome were treated with secukinumab, followed by reductions in redness and scaling, relief of pruritus, and improvement in quality of life, particularly in those with the erythrodermic phenotype.

Meaning  This study suggests that anti–interleukin 17 therapy may be a promising option for Netherton syndrome.

Abstract

Importance  Netherton syndrome (NS) is a rare, severe genetic disorder of cornification with high morbidity. Treatment for NS has been notoriously difficult. Recent studies showed an upregulated helper T cell (TH) 17/interleukin 23 (IL-23) pathway in NS, suggesting the possibility of treatment strategies that target IL-17.

Objective  To evaluate the clinical response of NS to treatment with the IL-17 antagonist secukinumab.

Design, Setting, and Participants  This case series study reports the experience of compassionate use therapy with secukinumab in 4 patients with severe NS, including 2 children, from December 1, 2018, to December 1, 2019, with 3 patients still undergoing treatment at the time of final analysis. Data were analyzed from December 1, 2018, to December 1, 2019.

Main Outcomes and Measures  Expression of IL-17 in the skin was evaluated by immunohistochemical analysis, and serum cytokine concentrations were measured using a commercially available assay. Treatment response was assessed using the Ichthyosis Area and Severity Index (IASI) total score, including measures of erythema and scaling, the Dermatology Life Quality Index (DLQI), and the 5-D itch scale.

Results  In all 4 patients (age range, 9-27 years; 3 male and 1 female), immunostaining with an IL-17A antibody showed an increased number of positive cells in lesional skin. Cytokine assessment in serum samples revealed increased levels of CCL20. Treatment duration with secukinumab was 3 to 12 months at the time of this report. After 3 months of therapy, IASI scores were reduced by 44% to 88%, DLQI scores were reduced by 40% to 76%, and 5-D itch scale scores were reduced by 27% to 62%. This outcome was sustained at the 6-month follow-up. Two patients with an erythrodermic phenotype showed marked improvement of all parameters. A refractory palmoplantar eczematous eruption occurred in 2 patients, and a candidal nail infection developed in 2 patients. No severe adverse events were reported.

Conclusions and Relevance  This initial case series reporting the use of anti–IL-17 therapy in NS demonstrated marked cutaneous improvement, particularly in 2 pediatric patients with erythrodermic phenotypes. Further studies are needed to evaluate the long-term benefit of this potential treatment modality.

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