Pathogenesis: mutation in NLRP3 (previously termed CIAS1) = nucleotide-binding oligomerization domain, leucine-rich repeat family, pyrin domain containing 3
Product: NALP3 (aka NACHT or cryopyrin)
Clinical features:
(1) autosomal dominant inheritance
(2) recurrent bouts triggered by cold exposure with symptoms appearing in 1-4 hours:
(2a) low grade fever
(2b) urticarial skin rash, which may appear in areas not exposed to cold
(2c) polyarthralgia
(2d) conjunctivitis
(3) chronic signs of inflammation, typically peaking in the evening with:
(3a) headaches
(3b) myalgias
(3c) fatigue
Cold exposure may include:
(1) air-conditioning
(2) cool breeze
(3) winter weather
Both the white blood cell count and serum interleukin-6 increase 4-8 hours after cold exposure.
The response to cold exposure can be blocked by pre-exposure therapy with an antagonist to the interleukin-1 receptor (IL-1Ra).
Differential diagnosis:
(1) nonfamilial cold-induced urticaria
