title: Muckle-Wells cryopyrinopathy: complex phenotyping and response to therapy in a new multiplex kindred.
abstract: Muckle-Wells syndrome (MWS) is a member of the cryopyrin-associated periodic syndrome family of auto-inflammatory diseases, originally described as a triad of urticaria, sensorineural deafness and amyloidosis. IL-1 blockade is a proven therapy for MWS. The clinical, laboratory and genotypic characteristics of a novel kindred of five individuals with Muckle-Wells syndrome are described. Response to IL-1 blockade therapy in the proband was evaluated. All five affected family members experienced symptoms of multi-organ inflammation. Lead time between symptom onset and diagnosis was approximately 30 years in the proband. Fever was not a universal feature in all affected family members. Anti-IL-1 therapy in the proband resulted in improvements in patient-reported symptoms, inflammatory markers, auditory acuity and reversal of her infertility. Muckle-Wells syndrome is a rare, multisystem, auto-inflammatory syndrome. Delay in diagnosis prevents effective treatment. We propose reversal of infertility to be among the potential benefits of IL-1 inhibition in this disease.
authors.affiliation: Department of Immunology, Concord Hospital, Hospital Rd, Concord, NSW 2139, Australia.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Headley
authors.forename: Frank
authors.initials: F
authors.lastname: Cordingley
authors.forename: Phillip N
authors.initials: PN
authors.lastname: Hawkins
authors.forename: D Sean
authors.initials: DS
authors.lastname: Riminton
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics; D056587:Cryopyrin-Associated Periodic Syndromes / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005298:Fertility / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D002352:Carrier Proteins; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human