D2.467 - Management of Netherton syndrome and hereditary angioedema with concurrent biologic therapy: a novel case

Background

Netherton syndrome (NS) is a rare autosomal recessive disorder caused by mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene, leading to lympho-epithelial Kazal-type-related inhibitor (LEKTI) deficiency, impaired epidermal barrier function, ichthyosis linearis circumflexa, trichorrhexis invaginata and severe atopic manifestations. Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is an autosomal dominant bradykinin-mediated disease characterised by recurrent angioedema attacks. The coexistence of NS and HAE-C1-INH has not previously been reported and no evidence exists regarding the concomitant use of dupilumab and lanadelumab in such patients.We describe the clinical course, therapeutic response and safety of dual biologic therapy with dupilumab and lanadelumab in a patient affected by both NS and HAE-C1-INH.

Written informed consent for publication was obtained from the patient.

Case presentation

A 30-year-old woman with genetically confirmed NS and long-standing HAE-C1-INH presented with severe pruritus, xerosis, elevated immunoglobulin E (IgE) levels and widespread eczematous lesions refractory to topical and systemic therapies. Atopic dermatitis severity was assessed using disease activity and quality of life scores. Dupilumab was initiated at standard dosing for atopic dermatitis. Due to persistent abdominal and cutaneous angioedema despite previous prophylaxis with tranexamic acid, stanozolol and plasma-derived C1-INH, lanadelumab was introduced as long-term prophylaxis.

Dupilumab led to progressive improvement in eczema, hyperkeratosis, and hair shaft abnormalities. Disease activity scores decreased at 4 and 13 months; dermoscopy demonstrated longer, smoother and thicker hair with reduced trichorrhexis invaginata. Lanadelumab prophylaxis reduced angioedema attacks by 88.5% compared with the pre-prophylaxis period, allowing a reduction in dosing frequency to monthly administration while maintaining disease control. The patient reported substantial improvement in quality of life. No adverse reactions, safety concerns or interactions between the two biologics were observed during more than 52 weeks of combined therapy.

Conclusion 

This is the first documented case of concomitant NS and HAE-C1-INH successfully managed with dual biologic therapy. Dupilumab improved cutaneous manifestations and hair abnormalities, while lanadelumab markedly reduced angioedema frequency. The combination was safe, well tolerated and associated with significant clinical benefit. As targeted therapies expand, concomitant biologic treatment may represent a valuable therapeutic option for patients with complex rare disease phenotypes requiring simultaneous management of distinct immunologic pathways.