Disease Directory Cryopyrin-Associated Periodic Syndromes
Immune

Cryopyrin-Associated Periodic Syndromes

Also known as: CAPS, TRAPS, Muckle-Wells syndrome, NOMID, FCAS, NLRP3 mutation

Prevalence

CAPS: 1-2 in 1,000,000; TRAPS: 1 in 1,000,000

Onset

Infancy to early childhood for CAPS; any age for TRAPS

Type

Autoinflammatory periodic fever syndrome (inflammasomopathy)

Gene

NLRP3, TNFRSF1A

About Cryopyrin-Associated Periodic Syndromes

Cryopyrin-Associated Periodic Syndromes represent a spectrum of autoinflammatory disorders caused by gain-of-function mutations in NLRP3 encoding cryopyrin, an inflammasome component that drives pathological IL-1 beta overproduction, ranging in severity from the mild cold-triggered urticaria of FCAS to the chronic devastating multisystem inflammation of NOMID/CINCA syndrome. TNF Receptor-Associated Periodic Syndrome (TRAPS) is caused by TNFRSF1A mutations and is included in this grouping as a related periodic fever syndrome with overlapping phenotypic features. IL-1 inhibition with anakinra, canakinumab, or rilonacept has transformed outcomes in CAPS, while TRAPS is primarily managed with IL-1 or TNF blockade.

Common Clinical Features

Recurrent urticarial rash (non-pruritic, cold-triggered in FCAS) Fever and systemic inflammation during attacks Sensorineural hearing loss (Muckle-Wells, NOMID) Chronic meningitis and elevated intracranial pressure (NOMID) Joint deformities and epiphyseal overgrowth (NOMID) Uveitis and papilledema AA amyloidosis with renal involvement in untreated disease

Clinical Trial Eligibility Tips

What to know before applying to Cryopyrin-Associated Periodic Syndromes trials.

Molecular confirmation of NLRP3 or TNFRSF1A pathogenic variant is required for most trials; somatic mosaic mutations may be present and require sensitive sequencing methods if standard testing is negative

Anakinra and canakinumab trials for CAPS typically require minimum C-reactive protein or SAA elevation at screening; ensure assessments are performed off anti-IL-1 therapy during washout

Pediatric and adult arms are often separate; confirm age cutoffs and weight thresholds (especially for somatic NOMID patients with growth delay)

Patient Resources

Patient Organization

CAPS Network / Autoinflammatory Alliance

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Natural History Registry

Eurofever Registry

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Orphanet

European reference resource for rare diseases (ORPHA:425)

View on Orphanet ↗

NORD

National Organization for Rare Disorders

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Find recruiting Cryopyrin-Associated Periodic Syndromes trials

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