# Netherton Syndrome: A Systematic Review of the Challenges of Diagnosis and Treatment

## TL;DR

Netherton syndrome is a rare genetic skin disorder with challenges in diagnosis and treatment, requiring more research for effective therapies.

## Contribution

This paper systematically reviews 30 case reports to highlight diagnostic and therapeutic challenges in Netherton syndrome.

## Key findings

- Biologic therapies improved symptoms and infection rates but did not lead to complete remission.
- Genetic testing is the most reliable diagnostic method but is not always accessible.
- Treatment outcomes vary, emphasizing the need for individualized care and larger studies.

## Abstract

Netherton syndrome is an autosomal recessive genodermatosis caused by biallelic mutations in the SPINK5 gene, a gene that codes for lymphoepithelial Kazal-type-related inhibitor 1 (LEKT1) protein. This disorder is characterized by erythroderma, ichthyosis, hair shaft abnormalities, and immune dysregulation. While there is increasing research and recognition of Netherton syndrome, much remains unknown, with limited knowledge of the history, manifestations, and responses to therapies. The purpose of this study was to review case reports of Netherton’s to draw conclusions from patient demographics, symptoms, treatment, and outcomes. A systematic review of 30 case reports and clinical studies on Netherton syndrome was conducted, including only patient-level clinical data of studies in English. Data were extracted via full-text review, organized into comparative tables, and analyzed for common patterns in symptoms, diagnostic techniques, and treatments. Biologic therapies consistently reduced Netherton syndrome effects with improvements in symptoms and infection rates. No cases of complete remission have been reported from the cases examined. With no standardized treatment in place, larger studies are needed. While biologic therapies have offered improvement of symptoms for patients with Netherton syndrome, remission is still not achievable. Treatment outcomes are variable and require an individualized technique in patient care. Genetic testing is the most valuable for diagnosis, but it is not always accessible. Lack of standardized therapy exhibits a need for larger studies to be conducted in order to improve patient care.