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CAPS — pathogenesis, presentation and treatment of an autoinflammatory disease

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Abstract

The cryopyrin-associated periodic syndrome (CAPS) is a severity spectrum of rare diseases. CAPS comprises the three conditions previously described as familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset 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 cold-induced 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 caspase-1 that cleaves the pro-inflammatory cytokines, IL-1β and IL-18. IL-1β plays the key role in the induction of inflammation in CAPS. This has been confirmed by the application of IL-1 blocking agents, which lead not only to a rapid and sustained reversal of daily symptoms but also to some extent of long-term disease sequelae. To prevent CAPS-induced organ damage, early diagnosis and swift initiation of effective treatment are mandatory.

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Conflict of interest statement

Dr. Kuemmerle-Deschner is consultant/speaker for Novartis and Sobi pharmaceuticals. She has received grant support from Sobi and Novartis.

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  1. Division of Pediatric Rheumatology, Department of Pediatrics, University Children’s Hospital Tuebingen, Hoppe-Seyler-Strasse 1, 72076, Tuebingen, Germany

    Jasmin B. Kuemmerle-Deschner

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Correspondence to Jasmin B. Kuemmerle-Deschner.

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This article is a contribution to the Special Issue on The Inflammasome and Autoinflammatory Diseases - Guest Editors: Seth L. Masters, Tilmann Kallinich and Seza Ozen

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Kuemmerle-Deschner, J.B. CAPS — pathogenesis, presentation and treatment of an autoinflammatory disease. Semin Immunopathol 37, 377–385 (2015). https://doi.org/10.1007/s00281-015-0491-7

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