The case of a patient with familial cold autoinflammatory syndrome-2 caused by the NLRP12 mutation associated with severe polyarthritis

Familial cold autoinflammatory syndrome-2 (FCAS2) is a rare autosomal dominant disorder caused by pathogenic variants in the NLRP12 gene. It is characterized by recurrent non-pruritic urticaria, arthritis, fever, and elevated inflammatory markers, often triggered by cold exposure. Here, we describe a Polish patient with FCAS2 linked to the NLRP12 c.1054C>T (p.Arg352Cys) variant, who developed severe polyarthritis mimicking juvenile idiopathic arthritis (JIA), yet without fever. Urticarial rashes began at 8 months of age and were initially unrelated to cold, but later became cold-induced. Standard therapies with antihistaminic drugs for urticaria and methotrexate for JIA were ineffective. Due to persistent arthritis and high inflammatory markers, anti-IL-1 therapy (anakinra) was initiated, leading to marked clinical and laboratory improvement, confirming the autoinflammatory mechanism. This case broadens the knowledge of NLRP12-related syndromes and underlines the value of genetic testing in atypical arthritis unresponsive to standard treatment.