Expanding the Cutaneous Presentation of Blau Syndrome, Response to Treatment, and Correlation With Genetics

Blau syndrome is a rare, autosomal dominant granulomatous disease caused by mutations in the NOD2/CARD15 gene. While the classic triad of arthritis, dermatitis, and uveitis is well known, the full range of cutaneous manifestations remains underexplored.

To expand the understanding of cutaneous findings in Blau syndrome, correlate these findings with NOD2 variants, and evaluate treatment outcomes across organ systems.

A retrospective review of medical records from January 1999 to January 2024 identified 14 patients with Blau syndrome supported by the presence of NOD2 variants. Clinical data on dermatological features, genetics, and treatment responses were analyzed and categorized into specific and non-specific cutaneous findings.

Of the 14 patients with Blau syndrome, 85% (12/14) demonstrated skin involvement. Specific findings included lichenoid or granulomatous papules and nodules (50%, 6/12), while non-specific findings (83%, 10/12) were more diverse, including dermatitis (6/10), chronic urticaria (5/10), ichthyosiform eruptions (4/10), vasospastic disorders (5/10), and oral/genital ulcers (2/10). Skin biopsies in three patients with specific findings revealed non-caseating granulomas. Genetic analysis identified multiple NOD2 variants, though no clear genotype-phenotype correlation was observed. TNF-alpha inhibitors demonstrated efficacy in controlling ocular and joint disease.

Blau syndrome presents with a broader spectrum of cutaneous findings than previously recognized. These findings highlight the importance of dermatological evaluation and a multidisciplinary approach to optimize diagnosis and management.