Clinical Features of Muckle-Wells Syndrome

 

Inheritance: typically autosomal dominant, rarely de novo (sporadic)

 

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 involve recurrent episodes with:

(1) urticarial skin rash

(2) fever (variable)

(3) arthralgias and/or arthritis

(4) conjunctivitis and/or uveitis and/or episcleritis

 

Episodes are not precipitated by exposure to a trigger like cold. Symptoms may be worse in the evening. Some patients may have continuous symptoms.

 

Laboratory findings:

(1) leukocytosis

(2) increase in acute phase reactants

 

Complications:

(1) deafness (may appear during childhood)

(2) renal amyloidosis

(3) joint destruction