Familial Cold Autoinflammatory Syndrome (FCAS) is a subtype of Cryopyrin-Associated Periodic Syndromes (CAPS). Diagnosis usually occurs shortly after birth.
FCAS is generally caused by mutations in a gene called NLRP3 (nucleotide-binding domain, leucine-rich family [NLR] pyrin domain containing 3). NLRP3 mutations cause increased activity of cryopyrin, a protein that regulates inflammation in the body. Increased cryopyrin activity causes overproduction of a protein called interleukin-1 beta (IL-1β).
Overproduction of IL-1β, in turn, causes recurrent symptoms of inflammation such as
Symptoms may be triggered by exposure to cooling temperatures. In most cases, a rash occurs within a few hours, followed by fever and joint pain. Episodes usually resolve within 24 hours if further exposure to cooling temperatures is avoided.
Patients may try to reduce their symptoms by controlling their environment and limiting their exposure to cold. They may wear multiple layers of clothing, keep warm temperatures in their homes, and stay indoors without air-conditioning.
Diagnosis of FCAS is determined through an evaluation of a patient’s symptoms and medical history. Confirmation of the diagnosis is sometimes achieved through genetic testing and the identification of NLRP3 mutations. Not all patients, however, have a detectable genetic mutation, making accurate symptom evaluation critical.
Some of the common criteria that distinguish FCAS from other hereditary periodic fevers include
There are FDA-approved therapies to treat the symptoms of FCAS.