muckle [muhk-uhl]

Muckle-Wells syndrome

Muckle-Wells syndrome (MWS), also known as Urticaria-deafness-amyloidosis (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 painful joints. 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.

Sign and Symptoms

Sensorineural deafness
Recurrent urticaria (hives)
Fevers
Chills
Arthritis - Painful joints

Possible Causes

MWS occurs when a mutation in the CIAS1 gene leads to increased activity of the cryopyrin protein. 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.

History

MWS was first described in 1962 by Thomas James Muckle and Michael Vernon Wells.

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 Cryopyrin-Associated Periodic Syndromes (CAPS).

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.