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?
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.
This study suggests that anti–interleukin 17 therapy may be a promising option for Netherton syndrome.
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.
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.
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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Luchsinger I, Knöpfel N, Theiler M, et al. Secukinumab Therapy for Netherton Syndrome. JAMA Dermatol. Published online May 27, 2020. doi:10.1001/jamadermatol.2020.1019
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