Muckle-Wells cryopyrinopathy: complex phenotyping and response to therapy in a new multiplex kindred

Inflammation. 2014 Apr;37(2):396-401. doi: 10.1007/s10753-013-9752-6.

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.

Publication types

  • Case Reports

MeSH terms

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

Substances

  • Anti-Inflammatory Agents
  • Carrier Proteins
  • Inflammation Mediators
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human