title: Muckle-Wells syndrome without mutation in exon 3 of the NLRP3 gene, identified by evidence of excessive monocyte production of functional interleukin 1β and rapid response to anakinra.
abstract: We report a man with lifelong urticaria, night sweats, arthralgia and lethargy. He had high levels of inflammatory markers and serum amyloid A, but no identifiable mutation in exon 3 of the NLRP3 (NOD-like receptor family, pyrin domain-1 containing 3) gene, and no relevant family history. We found marked production of functional interleukin (IL)-1 by the patient's monocytes at baseline and after stimulation with lipopolysaccharide. The patient made an immediate response to treatment with an IL-1β receptor antagonist. We propose that this patient has Muckle-Wells syndrome without deafness, occurring de novo. Functional screening for IL-1 production could aid diagnosis in future similar cases.
authors.affiliation: Department of Dermatology, Royal Hallamshire Hospital, Sheffield, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Sabroe
authors.forename: C A
authors.initials: CA
authors.lastname: Stokes
authors.forename: L C
authors.initials: LC
authors.lastname: Parker
authors.forename: K
authors.initials: K
authors.lastname: Higgins
authors.forename: L R
authors.initials: LR
authors.lastname: Prince
authors.forename: I
authors.initials: I
authors.lastname: Sabroe
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics*; D056587:Cryopyrin-Associated Periodic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005091:Exons / Q000235:genetics; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D002352:Carrier Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human