CAPS — pathogenesis presentation and treatment of

Authors: Jasmin B KuemmerleDeschner

Publish Date: 2015/05/12

Volume: 37, Issue: 4, Pages: 377-385

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Abstract

The cryopyrinassociated periodic syndrome CAPS is a severity spectrum of rare diseases CAPS comprises the three conditions previously described as familial cold autoinflammatory syndrome FCAS MuckleWells syndrome MWS and neonatalonset multisystem inflammatory disorder NOMID also known as chronic infantile neurologic cutaneous and articular CINCA syndrome The clinical phenotype of CAPS is characterized by systemic inflammation General symptoms are fatigue and fever Local manifestations affect multiple tissues such as skin joints muscles eyes and the central nervous system Distinct clinical features are characteristic for each subphenotype In FCAS these are coldinduced urticaria and fever in MWS systemic amyloidosis and hearing loss and in NOMID/CINCA central nervous system inflammation and bone deformities CAPS is caused by single heterozygous germline or somatic gain of function mutations in the NLRP3 gene encoding the protein cryopyrin Cryopyrin nucleates an NLRP3 inflammasome which regulates the activation and cleavage of caspase1 that cleaves the proinflammatory cytokines IL1β and IL18 IL1β plays the key role in the induction of inflammation in CAPS This has been confirmed by the application of IL1 blocking agents which lead not only to a rapid and sustained reversal of daily symptoms but also to some extent of longterm disease sequelae To prevent CAPSinduced organ damage early diagnosis and swift initiation of effective treatment are mandatory

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