Netherton Syndrome: A Comprehensive Literature Review of Pathogenesis, Clinical Manifestations, and Therapeutic Strategies.

Netherton syndrome (NS) is a rare, autosomal recessive genodermatosis resulting from mutations in the SPINK5 gene, which encodes the LEKTI (Lympho-Epithelial Kazal-type-related inhibitor) protein. This deficiency leads to dysregulated epidermal protease activity, primarily of kallikrein-related peptidases (KLKs), causing severe skin barrier defects, abnormal desquamation, and a complex immune dysregulation involving the T2 and T17 pathways. Clinically, NS is characterised by a triad of ichthyosiform erythroderma (often evolving from congenital ichthyosiform erythroderma to ichthyosis linearis circumflexa); pathognomonic hair shaft abnormalities, such as trichorrhexis invaginata ("bamboo hair"); and atopic manifestations with elevated serum IgE.