Hereditary cryopyrin-associated periodic syndromes (cryopyrinopathies)

[Couch Potatoe]

The hereditary cryopyrin-associated periodic syndromes are a group of autosomal dominant autoinflammatory conditions triggered by cold ambient temperatures; they include familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and neonatal-onset multisystem autoinflammatory disease. Diagnosis is clinical. Treatment is with interleukin-1 beta inhibitors.
Hereditary cryopyrin-associated periodic syndromes (CAPS) represent a spectrum of progressively severe disease.
They are due to

Mutations in the gene 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. The lack of a confirmed genetic mutation does not preclude the diagnosis of CAPS because 40% of patients who have neonatal-onset multisystem autoinflammatory disease, 25% who have Muckle-Wells syndrome, and 10% of who have familial cold autoinflammatory syndrome do not have identifiable mutations based on standard genetic testing. Many of these patients exhibit somatic mosaicism, causing their phenotype.
Typically, familial cold autoinflammatory syndrome (FCAS) causes a cold-induced urticarial rash accompanied by fever and sometimes arthralgias. The condition often appears in the first year of life.
Muckle-Wells syndrome (MWS) causes intermittent fevers, urticarial rash, joint pain, and progressive deafness; 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.