Variability of clinical symptoms of cryopyrin-associated periodic syndrome within the family

Cryopyrin-associated periodic syndrome is a group of autoinflammatory diseases caused by mutations in the NLRP3 gene, which lead to uncontrolled inflammasome activation and, consequently, excessive production of the proinflammatory cytokine interleukin 1β. Diagnosis is challenging, since many patients have a heterogeneous multisystem clinical picture. This publication presents a familial case of the disease with variability of manifestations from “blurred” and asymptomatic to a detailed clinical picture with multisystem involvement (persistent inflammatory activity, fever and urticaria associated with cold exposure, erythema nodosum, poly- and monoarthritis, uveitis, aphthous stomatitis, scrotal ulcers, and headache). Two patients had an atypical presentation of symptoms with predominant involvement of the joints, eyes, and oral mucosa, due to which one of them was initially given an alternative diagnosis of Behcet’s disease (syndrome). Genetic testing made it possible to identify a pathogenic mutation in the NLRP3 gene, verify the diagnosis, and promptly prescribe pathogenetic therapy with an interleukin 1 inhibitor, which is necessary to prevent irreversible organ damage (amyloidosis, sensorineural hearing loss, vision loss, etc.) and reduce the burden of the disease.