How is cryopyrin-associated periodic syndrome (CAPS) diagnosed and treated?

Updated: May 09, 2019
  • Author: Robert O Holmes, Jr, DO; Chief Editor: Herbert S Diamond, MD  more...
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Answer

These disorders are typically associated with heterozygous mutations in the NLRP3 (CIAS1) gene, which encodes the cryopyrin (NALP3) protein, and are inherited in an autosomal dominant manner. [51] The inflammation in CAPS is driven by excessive release of interleukin (IL)–1β. [52] IL-1β release is normally regulated by an intracellular protein complex known as the inflammasome that maps to a gene sequence called NLRP3. Mutations in NLRP3 may cause an aberrant cryopyrin protein inside the inflammasome, leading to the release of too much IL-1β and subsequent multisystem inflammation.

Secondary to increased IL-1β, CAPS patients have chronically elevated levels of acute-phase reactants, especially serum amyloid A (SAA) and high sensitivity C-reactive protein (hsCRP). [53, 54, 55] With elevated SAA coupled with multisystem cytokine dysregulation, multisystem amyloid deposition can be severe, with the most feared complication being renal failure. By blocking the action of IL-1β or down-regulating its production, inflammation and therefore amyloid deposition can be reduced. [56]

In a randomized double-blind CAPS therapy trial, the soluble decoy receptor rilonacept was shown to provide rapid and profound symptom improvement, in addition to improvement in measures of inflammation such as hsCRP and SAA levels. [56] In the second part of the study, continued treatment with rilonacept maintained improvements, where disease activity worsened with discontinuation of the drug. [56]

Canakinumab is a competing human immunoglobulin G (IgG) monoclonal antibody that also targets IL-1β and has shown efficacy in autoinflammatory conditions that, if untreated, are fatal by age 20 years in about 20% of individuals. [28] Both agents have the potential to cause infections, but they are usually mild and treatable.


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