Muckle-Wells syndrome

Abstract

Muckle-Wells syndrome (MWS) is a rare autosomal dominant hereditary autoinflammatory condition, with a mutation found in the NLRP3/CIAS1 gene in 50[%] of the patients. This gene codes for cryopyrine, a protein that plays a supporting role in the proteincomplex called inflammasome, which is involved in the regulation of interleukin (IL)-1beta. Mutations in the NLRP3/CIAS1 gene lead to dysregulated inflammation. However, patients without a detectable mutation are indistinguishable from patients with the mutation in clinical presentation and treatment response. MWS, along with the Familial Cold Autoinflammatory Syndrome (FCAS) and Chronic Infantile Neurologic Cutaneous Articular Syndrome (CINCA-syndrome), belongs to the group of Cryopyrin Associated Periodic Syndromes (CAPS). The disease is characterized by episodes of fever with urticaria, arthralgias, progressive sensorineural hearing loss, papilledema, uveitis or conjunctivitis and secondary amyloidosis. Systemic IL-1 blocking medication (anakinra and canakinumab) is highly effective. Early recognition of the disorder is important in order to initiate effective treatment and to prevent potentially serious long-term complications such as amyloidosis. In children with an atypical presentation of urticaria who do not respond to antihistamines, and with unexplained systemic symptoms, the diagnosis MWS should be considered.