pediatrics
Hereditary Cryopyrin Associated Periodic Syndromes (Cryopyrinopathies)
Introduction
The hereditary cryopyrin-associated periodic syndromes are a group of autosomal dominant autoinflammatory conditions characterized by recurrent episodes of fever and inflammatory symptoms; they include familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and neonatal-onset multisystem autoinflammatory disease. Diagnosis is clinical. Treatment is with interleukin-1 inhibitors. Hereditary cryopyrin-associated periodic syndromes (CAPS) represent a spectrum of clinically overlapping autoinflammatory diseases. They are due to Mutations in theNLRP3gene encoding the protein cryopyrin, which mediates inflammation and interleukin-1 beta (IL-1 beta) processing Cryopyrin activity is augmented, triggering increased release of IL-1 beta from the NLRP3 inflammasome; the result is inflammation and fever. Familial cold autoinflammatory syndrome(FCAS) typically causes a cold-induced urticarial rash accompanied by fever, conjunctivitis, and sometimes arthralgias. The condition often appears in the first year of life. (MWS) causes intermittent fevers, urticarial rash, joint pain, and progressive sensorineural hearing loss; 25% of patients develop renal Amyloidosis . Neonatal-onset multisystem autoinflammatory disease(NOMID) tends to cause joint and limb deformities, facial deformities, chronic aseptic meningitis, cerebral atrophy, uveitis, papillary edema, delayed development, and amyloidosis, in addition to fever and a migratory urticarial rash. As many as 20% of patients die by age 20 if untreated. CAPS = cryopyrin-associated periodic syndromes; FMF = familial Mediterranean fever; NOMID = neonatal-onset multisystem inflammatory disease; PFAPA = periodic fevers with aphthous stomatitis, pharyngitis, and adenitis; TRAPS = tumor necrosis factor receptor–associated periodic syndrome. Adapted fromSag E, Bilginer Y, Ozen S: Autoinflammatory diseases with periodic fevers.Curr Rheumatol Rep19(7):41, 2017. doi: 10.1007/s11926-017-0670-8 