Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Aug 1;156(8):907-911.
doi: 10.1001/jamadermatol.2020.1019.

Secukinumab Therapy for Netherton Syndrome

Isabelle Luchsinger  1   2 , Nicole Knöpfel  1   2 , Martin Theiler  1   2 , Mathilde Bonnet des Claustres  3   4 , Claire Barbieux  3   4 , Agnes Schwieger-Briel  1   2 , Corinne Brunner  2   5 , Davide Donghi  6 , Michael Buettcher  7 , Barbara Meier-Schiesser  8 , Alain Hovnanian  3   4   9 , Lisa Weibel  1   2
Affiliations

Secukinumab Therapy for Netherton Syndrome

Isabelle Luchsinger et al. JAMA Dermatol. .

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.
Figure 1.. Clinical Response Following Secukinumab Therapy in the 2 Pediatric Patients With Netherton Syndrome
Figure 2.
Figure 2.. Ichthyosis Area and Severity Index (IASI) Score, 5-D Itch Scale, and Dermatology Life Quality Index (DLQI) Before and 3 and 6 Months After Treatment With Secukinumab
The IASI scores range from 0 to 48, with higher scores indicating maximum erythema and scaling; for the 5-D itch scale, from 5 to 25, with higher scores indicating maximum pruritus; and for the DLQI, from 0 to 30, with higher scores indicating maximum impairment.
See this image and copyright information in PMC

Comment in

References

    1. Chavanas S, Bodemer C, Rochat A, et al. . Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet. 2000;25(2):141-142. doi:10.1038/75977 - DOI - PubMed
    1. Furio L, Hovnanian A. Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy. Biol Chem. 2014;395(9):945-958. doi:10.1515/hsz-2014-0137 - DOI - PubMed
    1. Versteegh JJ, Dulfer K, Stuvel K, Pasmans SG, Utens EM. Netherton syndrome; neuropsychological and psychosocial functioning of child and adult patients and their parents. J Health Psychol. 2018;21:1359105318790052. doi:10.1177/1359105318790052 - DOI - PMC - PubMed
    1. Roda Â, Mendonça-Sanches M, Travassos AR, Soares-de-Almeida L, Metze D. Infliximab therapy for Netherton syndrome: a case report. JAAD Case Rep. 2017;3(6):550-552. doi:10.1016/j.jdcr.2017.07.019 - DOI - PMC - PubMed
    1. Fontao L, Laffitte E, Briot A, et al. . Infliximab infusions for Netherton syndrome: sustained clinical improvement correlates with a reduction of thymic stromal lymphopoietin levels in the skin. J Invest Dermatol. 2011;131(9):1947-1950. doi:10.1038/jid.2011.124 - DOI - PubMed

Publication types

MeSH terms