Cryopyrin-associated periodic syndrome

The syndromes within CAPS overlap clinically, and patients may have features of more than one disorder. In a retrospective cohort of 136 CAPS patients with systemic involvement from 16 countries, Age of onset is typically in infancy or early childhood. In 57% of cases, CAPS had a chronic phenotype with symptoms present almost daily, whereas the remaining 43% of patients experienced only acute episodes. Up to 56% of patients reported a family history of CAPS. Previous studies confirm these symptoms, although the exact reported rates vary. ==Pathogenesis==

Cryopyrin-associated periodic syndromes are associated with a gain-of-function missense mutation in exon 3 of NLRP3, the gene encoding cryopyrin, a major component of the interleukin 1 inflammasome. In keratoendotheliitis fugax hereditaria, the mutation occurs in exon 1. The mutation in NLRP3 leads to aberrant constitutive formation of this inflammasome. Up to 170 heterogenous mutations in NLRP3 have been identified. Some reports suggest rare mutations are more frequently associated with a severe phenotype, and some mutations are associated with distinct phenotypes, probably reflecting the differential impact of the mutation on the activity of the inflammasome in the context of individual genetic background. Inheritance of these disorders is autosomal dominant with variable penetrance. ==Diagnosis==

Because CAPS is extremely rare and has a broad clinical presentation, it is difficult to diagnose, and a significant delay exists between symptom onset and definitive diagnosis. There are currently no clinical or diagnostic criteria for CAPS based solely on clinical presentation. Instead, diagnosis is made by genetic testing for NLRP3 mutations. Acute phase reactants and white blood cell count are usually persistently elevated, but this is aspecific for CAPS. ==Treatment==

Since interleukin 1β plays a central role in the pathogenesis of the disease, therapy typically targets this cytokine in the form of monoclonal antibodies (such as canakinumab), binding proteins/traps (such as rilonacept), or interleukin 1 receptor antagonists (such as anakinra). These therapies are generally effective in alleviating symptoms and substantially reducing levels of inflammatory indices. Case reports suggest that thalidomide and the anti-IL-6 receptor antibody tocilizumab may also be effective. ==References==