Cryopyrin associated periodic syndromes (CAPS)

What are cryopyrin associated periodic syndromes (CAPS) and what causes them?

  • • Autoinflammatory syndrome caused by autosomal dominant, gain-of-function mutations in gene for cryopyrin (NLRP3; formerly denoted CIAS1).
  • • Cryopyrin mutations result in constitutive activation of the inflammasome and subsequent increase in proinflammatory cytokines, including IL-1β.
  • • CAPS includes three clinically distinguishable syndromes, although there is symptom overlap.

Three major phenotypes of CAPS

Neonatal onset multisystem inflammatory disease (NOMID):

  • • Most severe monogenetic autoinflammatory syndrome.
  • • Symptoms begin at birth or early infancy; classic triad of rash (commonly urticaria), arthropathy, and chronic aseptic meningitis. Sensorineural hearing loss. Daily fever and other multisystem abnormalities are common.
  • • Lymphadenopathy and hepatosplenomegaly may occur in some patients.
  • • Growth restriction and abnormal facies (frontal bossing, “saddle-shaped” nose, protruding eyes) may occur.
  • • Focal epiphyseal overgrowth may be substantial in some patients and confused with malignancy.
  • • Renal AA can occur.
  • • Mortality rate ∼20% before adulthood.
  • Muckle Wells syndrome:
  • • Intermediate in severity among CAPS presentations.
  • • Fever, headache, urticarial rash, limb pain, conjunctivitis, arthralgias > arthritis, sensorineural hearing loss.
  • • Symptoms commonly develop in adolescence.
  • • Renal AA can occur.
  • • Variable duration/frequency of flares: attacks on average last 2 to 3 days, but duration can be irregular or even continuous in some patients.
  • Familial cold autoinflammatory syndrome (FCAS):
  • • Mildest form of CAPS.
  • • Self-limited episodes of urticarial rash, fever, arthralgia, conjunctivitis, headache, malaise, and diaphoresis following cold exposure (or even a relative drop in temperature).
  • • Begins in infancy (95% of patients); can decrease in severity over time.
  • • Average time to symptom onset following exposure ∼6 hours.
  • • Flare duration: hours to 2 to 3 days (commonly <24 hours).
  • • Rash: ubiquitous among patients; urticaria, erythematous macules and petechiae have been described; often begin on extremities.
  • • Renal AA is rare.
  • • Ice cube test (observing for immediate appearance of skin changes after contact) is negative. This helps distinguish FCAS from acquired cold urticaria, which is a nongenetic condition that does not present in infancy and lacks systemic features.
  • • Absence of deafness, periorbital edema, lymphadenopathy, and serositis.

Sign up to receive the trending updates and tons of Health Tips

Join SeekhealthZ and never miss the latest health information

Scroll to Top