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.
MeSH terms
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Adult
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Anti-Inflammatory Agents / therapeutic use*
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Carrier Proteins / genetics
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Cryopyrin-Associated Periodic Syndromes / complications
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Cryopyrin-Associated Periodic Syndromes / diagnosis
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Cryopyrin-Associated Periodic Syndromes / drug therapy*
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Cryopyrin-Associated Periodic Syndromes / genetics
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Cryopyrin-Associated Periodic Syndromes / immunology*
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Cryopyrin-Associated Periodic Syndromes / physiopathology
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DNA Mutational Analysis / methods
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Female
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Fertility / drug effects
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Genetic Predisposition to Disease
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Humans
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Infertility, Female / drug therapy
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Infertility, Female / genetics
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Infertility, Female / immunology
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Infertility, Female / physiopathology
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Inflammation Mediators / antagonists & inhibitors*
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Inflammation Mediators / metabolism
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Interleukin 1 Receptor Antagonist Protein / therapeutic use*
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Interleukin-1 / antagonists & inhibitors*
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Interleukin-1 / metabolism
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Male
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Mutation
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NLR Family, Pyrin Domain-Containing 3 Protein
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Pedigree
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Phenotype
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Polymerase Chain Reaction
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Time Factors
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Treatment Outcome
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Up-Regulation
Substances
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Anti-Inflammatory Agents
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Carrier Proteins
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Inflammation Mediators
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1
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NLR Family, Pyrin Domain-Containing 3 Protein
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NLRP3 protein, human