Cryopyrin-Associated Periodic Syndromes (CAPS) are a spectrum of rare inherited autoinflammatory disorders linked to gain-of-function mutations in the NLRP3 gene (also known as CIAS1). This gene encodes cryopyrin, a key component of the inflammasome, which regulates the production of interleukin-1β (IL-1β), a major pro-inflammatory cytokine. CAPS is inherited in an autosomal dominant manner, though some cases may result from de novo mutations.
The CAPS spectrum includes three overlapping syndromes of increasing severity:
- FCAS (Familial Cold Autoinflammatory Syndrome): Mild form, triggered by exposure to cold.
- MWS (Muckle-Wells Syndrome): Intermediate form, with hearing loss and risk of amyloidosis.
- NOMID/CINCA (Neonatal-Onset Multisystem Inflammatory Disease): Severe form with neurologic involvement, joint deformities, and chronic urticaria.
These three entities are not completely distinct; rather, they represent a clinical continuum of severity within the same disease spectrum. Symptoms include recurrent fever, urticaria-like rash, joint pain, and fatigue. Neurologic symptoms such as aseptic meningitis and sensorineural hearing loss are common in more severe forms. The mainstay of treatment is IL-1 inhibition, with drugs like anakinra, canakinumab, or rilonacept, which dramatically improve symptoms and quality of life.