Muckle Wells Syndrome

Muckle-Wells syndrome [Also known by the names of  UDA (Urticaria Deafness Amyloidosis) syndrome   is a rare autosomal dominant disease which results in

• Sensorineural deafness
• Recurrent hives
• Amyloidosis – A disease where abnormal deposition of amyloid occurs in various organs.
• Fevers
• Painful joints (arthritis)

Muckle-Wells syndrome was first described in 1962 by Thomas James Muckle and Michael Vernon Wells. It is rare disorder and exact incidence is not known.

Pathophysiology of Muckle Wells Syndrome

Protein cryopyrin is partly responsible for the body’s response to damage or infection leading to release of interleukin 1[Produced by an immune cell known as a macrophage] to produce symptoms of inflammation such as fever, arthritis, and malaise.

In Muckle-Wells syndrome, a mutation in the CIAS1 gene on chromosome 1q44 leads to the increased activity of cryopyrin leads to an increase in interleukin 1?. This leads to inflammation all throughout the body with the associated symptoms.

People with Muckle-Wells syndrome have recurrent “flare-ups” that begin during infancy or early childhood. These episodes may appear to arise spontaneously or be triggered by cold, heat, fatigue, or other stresses. Affected individuals typically develop a non-itchy rash, mild to moderate fever, painful and swollen joints, and in some cases redness in the whites of the eyes (conjunctivitis).

Hearing loss caused by progressive nerve damage (sensorineural deafness) typically becomes apparent during the teenage years. Abnormal deposits of a protein called amyloid (amyloidosis) cause progressive kidney damage in about one-third of people with Muckle-Wells syndrome; these deposits may also damage other organs. In addition, pigmented skin lesions may occur in affected individuals.

Diagnosis of Muckle-Wells Syndrome

History and clinical examination usually clinch the diagnosis. A genetic test would confirm the diagnosis

Treatment

Following drugs have been found useful in this syndrome

Anakinra

Anakinra is an interleukin 1 receptor antagonist and has been found to lead to an improvement in the hearing loss. A recent study has also funded it useful in treating musculoskeletal manifestation.

Rilonacept

It is a dimeric fusion protein used for the treatment of cryopyrin-associated periodic syndromes (CAPS) and also found effective in Muckle-Wells syndrome.

Canakinumab

It is a monoclonal antibody against interleukin-1, in CAPS and Muckle-Wells.