This site is intended for healthcare professionals

Go to /sign-in page

You can view 5 more pages before signing in

Cryopyrin-associated periodic syndromes (CAPS)

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

Cryopyrin-associated periodic syndromes (CAPS)

  • represent a spectrum of CIAS1 gene-mediated autoinflammatory diseases characterized by recurrent systemic inflammation (1) - caused by missense mutations in the cold-induced autoinflammatory syndrome-1-gene (CIAS1), also referred to as NLRP3 or NALP3
  • CAPS results from a gain-of-function mutation of the NLRP3 gene coding for cryopyrin, which forms intracellular protein complexes known as inflammasomes (2)
    • defects of the inflammasomes lead to overproduction of interleukin-1, resulting in inflammatory symptoms seen in CAPS.
  • clinical spectrum of CAPS varies from mild to severe and includes the syndromes historically described as familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID)
  • in all three phenotypes of CAPS, there is a gain-of-function mutation of the NLRP3 gene (also known as CIAS1), which is located on chromosome 1q44 and codes for cryopyrin
    • note though that as many as 40% of patients with clinical NOMID do not show mutations on this gene, implicating the involvement of other autoinflammatory genes or the involvement of genetic mosaicism (2)
  • clinical manifestations of CAPS are a continuum of disease severity with overlapping phenotypic features, but can be separated on the basis of their organ manifestations and the disease triggers
    • FCAS
      • is of the mildest phenotype and was first reported in 1940 (2)
      • characterized by recurrent urticaria, arthralgia, and fever after general exposure to cold, not necessarily by touch
        • mildest form of CAPS, is characterized by recurrent and short-lived episodes of rash, fever, arthralgias, and conjunctivitis that are triggered by exposure to cold
      • symptoms occur early and in many patients within the first 6 months of life
      • most patients have a normal life span, and the development of complications from chronic inflammation such as amyloidosis and hearing loss (HL) is rare
    • MWS
      • MWS is of the intermediate phenotype and was first described in 1962 (2)
      • present with recurrent attacks of rash, fever, arthralgias, and conjunctivitis
      • disease is typically not triggered by exposure to cold
      • develop more severe ocular and central nervous system (CNS) symptoms including uveitis, episcleritis, and headaches
      • hearing loss is described in many patients in their second and third decades of life, and the development of amyloidosis has been reported in up to 30% of patients (1)
    • NOMID
      • the most severe form of CAPS and has the worst prognosis
      • hallmark of NOMID is neonatal onset of cutaneous symptoms along with end-organ damage
        • these include the "triad" of arthropathy, chronic urticaria, and central nervous system (CNS) involvement (2)
      • symptoms typically occur at birth or in early infancy and include rash, fever, and joint inflammation
        • joint manifestations vary in severity, ranging from arthralgias with swelling and effusion to debilitating arthropathy resulting from excessive bony overgrowth occurring in one-third of the patients (1)
        • ocular manifestations are severe and include uveitis, optic atrophy, and blindness
        • CNS involvementcan present as chronic headaches, papilledema, aseptic meningitis, seizures, and cerebral atrophy
  • treatment with IL-1 blocking agents such as anakinra, a recombinant IL-1 receptor antagonist, has been very effective in these patients
    • a study assessed the clinical characteristics of patients with cryopyrin-associated periodic syndrome (CAPS) in Japan and evaluated the real-world efficacy and safety of interleukin (IL)-1 inhibitors, primarily canakinumab (3):
      • concluded that:
        • initiation of anti-IL-1 treatment with canakinumab is beneficial for improving disease prognosis, some patients do not achieve remission despite a high serum concentration of canakinumab
        • inflammatory bowel disease (IBD) may develop in CAPS following canakinumab treatment


  • Ahmadi N, Brewer CC, Zalewski C, King KA, Butman JA, Plass N, Henderson C, Goldbach-Mansky R, Kim HJ. Cryopyrin-associated periodic syndromes: otolaryngologic and audiologic manifestations. Otolaryngol Head Neck Surg. 2011 Aug;145(2):295-302.
  • Yu JR, Leslie KS. Cryopyrin-associated periodic syndrome: an update on diagnosis and treatment response. Curr Allergy Asthma Rep. 2011 Feb;11(1):12-20. doi: 10.1007/s11882-010-0160-9.
  • Miyamoto, T. et a.l. Clinical characteristics of cryopyrin-associated periodic syndrome and long-term real-world efficacy and tolerability of canakinumab in Japan: results of a nationwide survey. Arthritis Rheumatol. January 25th 2024.

Create an account to add page annotations

Annotations allow you to add information to this page that would be handy to have on hand during a consultation. E.g. a website or number. This information will always show when you visit this page.