Muckle–Wells syndrome

Autosomal dominant - en

Muckle–Wells syndrome (MWS) is a rare autoinflammatory disorder that is part of the spectrum of cryopyrin-associated periodic syndromes (CAPS). It is characterized by recurrent episodes of urticaria, hearing loss, and amyloidosis. The syndrome is named after Thomas J. Muckle and Michael V. Wells, who first described the condition in 1962.

Signs and symptoms

The primary symptoms of Muckle–Wells syndrome include:

• Recurrent episodes of urticaria (hives)
• Progressive sensorineural hearing loss
• Amyloidosis, which can lead to kidney failure
• Recurrent fever
• Arthralgia (joint pain)
• Conjunctivitis (eye inflammation)

Genetics

Muckle–Wells syndrome is caused by mutations in the NLRP3 gene, which encodes the protein cryopyrin. This protein is involved in the regulation of the immune system and inflammation. The condition is inherited in an autosomal dominant manner, meaning that a single copy of the mutated gene can cause the disorder.

Diagnosis

Diagnosis of Muckle–Wells syndrome is based on clinical evaluation and confirmed by genetic testing to identify mutations in the NLRP3 gene. Differential diagnosis includes other autoinflammatory disorders such as Familial Mediterranean fever, Tumor necrosis factor receptor-associated periodic syndrome (TRAPS), and Hyper-IgD syndrome.

Treatment

Treatment for Muckle–Wells syndrome focuses on managing symptoms and preventing complications. Interleukin-1 inhibitors such as Anakinra, Canakinumab, and Rilonacept are commonly used to reduce inflammation and control symptoms. Regular monitoring and supportive care are essential to manage complications such as amyloidosis.

Prognosis

The prognosis for individuals with Muckle–Wells syndrome varies. With appropriate treatment, many patients can manage their symptoms effectively and maintain a good quality of life. However, complications such as amyloidosis can significantly impact health outcomes.

See also

• Cryopyrin-associated periodic syndromes
• Familial Mediterranean fever
• Tumor necrosis factor receptor-associated periodic syndrome
• Hyper-IgD syndrome
• Autoinflammatory disease