Familial Cold Autoinflammatory Syndrome

Familial cold autoinflammatory syndrome is an autosomal dominant inherited inflammatory disease characterized by episodes of rash, fever, and joint pain following generalized exposure to cold. Attacks usually occur 1–2 hours after exposure and last less than 24 hours. It has been reported primarily in families from North America and Europe, but sporadic cases have also been reported. The diagnosis is based on clinical presentation and can be confirmed by the identification of a NALP3 mutation. No clinical trials have been performed with FCAS patients, but anakinra, an IL-1 receptor antagonist, has been effective at preventing symptoms prior to a cold challenge and as a maintenance medication in several patients. The NALP3 gene, also known as CIAS1, is expressed in peripheral blood leukocytes and chondrocytes and codes a protein also known as Cryopyrin. NALP3 mutations have also been identified in Muckle Wells syndrome and Chronic infantile neurologic cutanaeous articular syndrome. There are several laboratories in Europe and North America where sequencing of NALP3 is performed.