Rare but revealing: The first report of familial CAPS in Saudi Arabia

Abstract

Cryopyrin-associated periodic syndrome (CAPS) is a rare autosomal dominant autoinflammatory disease caused by mutations in the NLRP3 gene, leading to interleukin-1β overproduction and systemic inflammation. It is subcategorized into familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), or neonatal-onset multisystem inflammatory disease (NOMID). To the best of our knowledge, this is the first reported familial CAPS in Saudi Arabia. A 28-year-old Saudi male with a lifelong history of recurrent urticaria, polyarthritis, and systemic complaints underwent clinical evaluation, laboratory testing, imaging, and genetic analysis. Family history was reviewed to assess possible hereditary involvement. The patient presented with cold-induced urticaria, inflammatory polyarthritis, chronic sacroiliitis, migraines, tinnitus, and gastrointestinal symptoms. Autoimmune serologies were negative, but C-reactive protein was elevated. MRI revealed bilateral sacroiliitis. Genetic testing identified a pathogenic heterozygous NLRP3 mutation, confirming autosomal dominant CAPS, FCAS subtype. Several relatives reported similar cold-induced symptoms, indicating a familial pattern. This represents the first documented familial CAPS case in Saudi Arabia. CAPS is frequently underdiagnosed due to overlapping features with more common rheumatologic and dermatologic conditions. This case underscores the importance of early recognition, genetic confirmation, and family screening. Prompt initiation of IL-1–targeted therapy is critical to prevent complications and improve quality of life. Increasing clinician awareness is essential, particularly in regions where CAPS has not been previously reported.