Muckle-Wells Syndrome (MWS)

What is Muckle-Wells syndrome (MWS)?

Muckle-Wells syndrome (MWS) is a rare autoinflammatory disease characterized by episodes of skin rash, fever, and joint pain. Progressive hearing loss and kidney damage also occur. MWS is the intermediate form of cryopyrin-associated periodic syndrome (CAPS).

What are the symptoms of Muckle-Wells syndrome (MWS)?

The symptoms of MWS include the following:

• Recurrent rashes, usually beginning in infancy or early childhood
• Intermittent fevers
• Joint pain
• Recurrent conjunctivitis
• Progressive hearing loss
• Amyloidosis
• Pigmented skin lesions

Symptoms can flare up seemingly randomly or can also be triggered by cold exposure as well as stress or exercise. Episodes typically last between 24 to 48 hours.

What causes Muckle-Wells syndrome (MWS)?

MWS is usually inherited in an autosomal dominant condition and is caused by a heterozygous mutation in the CIAS1/NLRP3 gene that codes for the protein cryopyrin (NALP3). MWS can be caused by a spontaneous mutation of the NLRP3 gene, but in most cases the genetic mutation is passed along for generations in families. There is a 50% chance that a parent with CAPS will pass the NLRP3 gene mutation onto their child.

How is Muckle-Wells syndrome (MWS) diagnosed?

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.

What are the treatments for Muckle-Wells syndrome (MWS)?

Treatments include:

• Arcalyst (Rilonacept) by Regeneron Pharmaceuticals, an interleukin-1 blocker, was approved by the FDA in 2008 for the treatment of CAPS, including FCAS and MWS, in adults and children 12 and older
• Ilaris (Canakinumab) by Novartis Pharmaceuticals, a monoclonal antibody to interleukin-1 beta, was approved by the FDA in 2009 as a treatment for children and adults with CAPS, including FCAS and MWS
• Kineret (Anakinra) by Biovitrum pharmaceuticals, an IL-1 receptor antagonist, has been used extensively in MWS patients with excellent clinical results. However, it is not currently approved by the FDA for the treatment of MWS or any of the CAPS diseases

Where can I find out more about Muckle-Wells syndrome (MWS)?

• The Autoinflammatory Alliance
• National Organization for Rare Disorders (NORD)
• NIH