Management of Netherton syndrome and hereditary angioedema with concurrent biologic therapy: a case report

Abstract

Netherton syndrome (NS) is a rare autosomal recessive disorder caused by SPINK5 mutations, leading to impaired skin barrier function and severe atopic manifestations. Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is a rare autosomal dominant disorder characterised by recurrent bradykinin-mediated angioedema. Their coexistence has not previously been reported, and evidence on combined biologic therapy is lacking. We report a 30-year-old woman with confirmed NS and long-standing HAE-C1-INH presenting with severe pruritus, xerosis, widespread eczema, elevated IgE, eosinophilia, and trichorrhexis invaginata. Dupilumab was initiated to target T helper (Th)2-mediated inflammation. Due to persistent angioedema attacks despite prior prophylaxis, lanadelumab was introduced. Dupilumab improved eczema severity, hyperkeratosis, and hair abnormalities over 13 months. Lanadelumab reduced angioedema attacks by 88.50%, allowing dose spacing while maintaining disease control. No adverse effects or drug interactions were observed. This is the first reported case of NS and HAE-C1-INH successfully treated with dual biologic therapy. Targeting distinct immunological pathways simultaneously may represent an effective and safe strategy for complex rare disease phenotypes.

Keywords

Netherton syndrome / hereditary angioedema / lanadelumab / dupilumab / case report

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