Muckle-Wells syndrome

Muckle-Wells syndrome (MWS), also known as Urticaria-deafness-amyloidosis (UDA)^[1], 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.

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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.^[2] 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.

MWS was first described in 1962 by Thomas James Muckle and Michael Vernon Wells.^[3] Treatment of MWS with anakinra, an interleukin 1 receptor antagonist, can lead to an improvement in the hearing loss.^[4]

References

1. ^ http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=575
2. ^ Mariathasan S, Weiss DS, Newton K, McBride J, O'Rourke K, Roose-Girma M, Lee WP, Weinrauch Y, Monack DM, Dixit VM. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature. 2006 Mar 9;440(7081):228-32. Epub 2006 Jan 11. PMID 16407890
3. ^ Muckle TJ, Wells M. Urticaria, deafness, and amyloidosis: a new heredo-familial syndrome. Q J Med. 1962 Apr;31:235-48. PMID 14476827
4. ^ Rynne M, Maclean C, Bybee A, McDermott MF, Emery P. Hearing improvement in a patient with variant Muckle-Wells syndrome in response to interleukin 1 receptor antagonism. Ann Rheum Dis. 2006 Apr;65(4):533-4. PMID 16531551