Cryopyrinopathies: update on pathogenesis and treatment

Cryopyrinopathies are a group of rare autoinflammatory diseases that includes familial cold autoinflammatory syndrome, Muckle-Wells syndrome and chronic infantile neurologic cutaneous articular syndrome (also termed neonatal-onset multisystemic inflammatory disease). These syndromes were initially considered to be distinct disease entities despite some clinical similarities; however, mutations of the same gene have since been found in all three cryopyrinopathies. These diseases, therefore, are not separate but represent a continuum of subphenotypes. The gene in question, CIAS1 (now renamed NLRP3) encodes NALP3 (also known as cryopyrin). NALP3 is an important mediator of inflammation and interleukin 1beta processing. New therapies based on biologic agents that specifically target interleukin 1beta are currently being developed. These new agents have provided very encouraging results for patients with these long-lasting inflammatory conditions--which used to be considered refractory to treatment. The development of therapeutic options for these cryopyrinopathies illustrates effective translation of basic science to clinical practice and the convergence of human genetics and targeted therapies.