Abstract

Muckle–Wells syndrome (MWS), also known as urticaria-deafness-amyloidosis syndrome (UDA), is a rare autosomal dominant disease which causes sensorineural deafness and 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).

Causes

MWS occurs when a mutation in the "CIAS1" gene, encoding for NLRP3, 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 cytokine called interleukin 1β is produced by an innate immune cell known as a macrophage. This cytokine 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.

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.

History

MWS was first described in 1962 by Thomas James Muckle (1938-2014) and Michael Vernon Wells (born 1932).

Society and culture

The CBC Radio One program, "White Coat, Black Art", hosted by Dr. Brian Goldman, presents a real-life study of the self-diagnosis by and successful treatment of a father and daughter with Muckle–Wells syndrome: 24 September 2016 episode

In the episode of popular "TV series House", the main patient of the Season 7 episode Recession Proof is ultimately diagnosed with this condition.In an episode of TV series "Cake Boss", Buddy Valastro works with a girl with this condition through Make-A-Wish Foundation.