Muckle-Wells syndrome

Synonyms

2

Overview

Muckle–Wells syndrome (MWS, also known as UDA), is a rare autosomal dominant disease which causes sensorineural deafness, recurrent hives, and can lead to amyloidosis. Individuals with MWS often have episodic fever, chills, and joint pain. As a result, MWS is considered a type of periodic fever syndrome. MWS is caused by a defect in the CIAS1 gene which creates the protein cryopyrin. MWS is closely related to two other syndromes, familial cold urticaria and neonatal onset multisystem inflammatory disease—in fact, all three are related to mutations in the same gene and subsumed under the term cryopyrin-associated periodic syndromes (CAPS).

Symptoms

  • Sensorineural deafness
  • Recurrent urticaria (hives)
  • Fevers
  • Chills
  • Arthralgia (painful joints)

Causes

MWS occurs when a mutation in the CIAS1 gene leads to increased activity of the protein cryopyrin. This protein is partly responsible for the body's response to damage or infection. During these states, a chemical called interleukin 1β is produced by an immune cell known as a macrophage. This chemical interacts with a receptor on the surface of other immune cells to produce symptoms of inflammation such as fever, arthritis, and malaise. In MWS, the increased activity of cryopyrin leads to an increase in interleukin 1β. This leads to inflammation all throughout the body with the associated symptoms.

Diagnosis

Diagnosis of MWS is determined through an evaluation of a patient's symptoms. Confirmation of the diagnosis is achieved through genetic testing and the identification of a CIAS1/NLRP3 mutation, although not all MWS patients possess a mutation in this gene.

Prognosis

The chronic inflammation present in MWS over time can lead to deafness. In addition, the prolonged inflammation can lead to deposition of proteins in the kidney, a condition known as amyloidosis.

Treatment

  • Treatment with anakinra, an interleukin 1 receptor antagonist, can lead to an improvement in the hearing loss.
  • Rilonacept (Arcalyst) a dimeric fusion protein for the treatment of CAPS.
  • Canakinumab, a monoclonal antibody against interleukin-1β