Netherton Syndrome: A Case-Based Review of Diagnosis, Management, and Emerging Treatments

Netherton syndrome (NS) is a rare autosomal recessive disorder caused by SPINK5 mutations, leading to LEKTI deficiency and skin barrier dysfunction. It manifests as ichthyosis, trichorrhexis invaginata (bamboo hair), and atopic diathesis, including food allergies, asthma, and elevated IgE levels. Early genetic testing is key for accurate diagnosis and treatment. We report a case of a two-year-old girl initially diagnosed with atopic dermatitis, presenting with severe, persistent skin issues from infancy. The symptoms included dry, scaly, and inflamed skin, along with elevated IgE levels and polysensitization to food allergens. Trichorrhexis invaginata was identified, and genetic testing confirmed NS. Despite treatments with corticosteroids and emollients, the patient continued to experience flare-ups, leading to the use of biological therapy, specifically secukinumab, due to persistent skin barrier dysfunction. NS is often misdiagnosed due to its overlap with atopic dermatitis, especially in early stages. Mutations in SPINK5 vary in severity, influencing treatment outcomes. Current therapies, including corticosteroids, emollients, and immunomodulators, provide limited relief. New treatments like IVIG, retinoids, and biologics (e.g., secukinumab, dupilumab) show promise in managing inflammation and restoring the skin barrier, with secukinumab targeting IL-17A showing significant improvements. The psychosocial impact of NS affects the patient's quality of life, causing anxiety, social withdrawal, and family stress. Early genetic testing, targeted therapies, and psychosocial support are crucial for managing NS. Future research should focus on improving genetic testing accessibility, optimizing combination therapies, and addressing psychosocial challenges.