Secukinumab Therapy for Netherton Syndrome

Abstract

etherton syndrome (NS) is a rare autosomal recessive skin disorder caused by mutations in SPINK5 (OMIM 605010), leading to severely impaired skin barrier function. Patients are at risk for complications such as hypernatremic dehydration, impaired thermoregulation, failure to thrive, and sepsis. Skin infections are common, as are allergies, asthma, and increased levels of circulating eosinophils and total IgE. 1,2 Affected individuals have lifelong ichthyosis lineariz circumflexa, associated with erythroderma, and pruritus. 3 Treatment of NS is difficult, with the mainstay being bland emollients. Topical corticosteroids and calcineurin in-hibitors may provide short-term benefit, but the former have a high risk of increased transcutaneous absorption and the latter have a high risk of resultant Cushing syndrome and immune suppression. As for systemic agents, low-dose retinoids, infliximab, and intravenous immunoglobulins have been tried with variable success. [4][5][6][7] Recent studies showed that NS shares an immune profile similar to psoriasis with helper T cell (T H ) 17/interleukin 23 (IL-23) and IL-17/tumor necrosis factor (TNF) synergistic activation. 8-10 Herein we report our experience using the IL-17A antagonist secukinumab in patients with NS. IMPORTANCENetherton 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 (T H ) 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.

Secukinumab for the treatment of SAM syndrome associated with desmoglein‐1 deficiency

“…Novel data show an increase in proinflammatory T helper 17 expression in patients with ichthyosis, thus suggesting that blockage of IL‐17A may be a promising therapeutic approach in this specific group of patients 5–7 . An initial case series reporting the use of anti‐IL‐17 therapy in Netherton syndrome demonstrated marked cutaneous improvement, particularly in two paediatric patients with erythrodermic phenotypes 8 . Detection of IL‐17A‐positive inflammatory cells in situ in the skin of our patient confirmed the involvement of IL‐17A‐producing cells, and provided a rationale for targeted therapy with an anti‐IL‐17A antibody.…”

Netherton Syndrome: Case Report and Review of the Literature

“…Secukinumab, an anti-interleukin 17 A antibody, has been used as well in 4 patients with severe NS, reporting a reduction by 44-88% in the Ichthyosis Area and Severity Index total score after 3 months of therapy, along with a reduction by 40-76% of Dermatology Life Quality Index and by 27-62% in the 5-D itch scale. Sustained improvement was observed at 6-month follow-up [11]. Ustekinumab blocks the p40 subunit of interleukin-12 and interleukin-23.…”

Scalp roof tiles.

“…Early childhood, skin manifestations gradually expressed into diagnostic ILC, with tram like plaques and pathognomonic 2-edged scales. 3 The finding of TI is pathognomonic for NS. Enteropathy, failure to thrive, hypoalbuminemia, and temperature instability have also been reported.…”