Approximately 1:1,000,000 of the general population is affected. The responsible gene (CAS1) has been mapped to 1q44 and encodes for cryopyrin, a protein that is expressed on peripheral leukocytes and chondrocytes and appears to be involved in apoptosis and caspase-1 activation.
The diagnosis is based on the clinical findings and the family history and is confirmed by sequencing analysis of the CAS1 gene (although CAS1 mutations also occur in other syndromes, e.g., Mackle-Wells Syndrome). Usually the onset of symptoms occurs hours after birth or as soon as the baby is exposed to a cold environment.
Delayed presentation is possible, but the maximal age at onset is believed to be less than 6 months. Urticarial eruptions are triggered by exposure to cold, damp air, and/or wind (air conditioning), generally occur 1 to 2 hours after exposure, and initially present as macules and papules on exposed skin areas, which then spread to covered sites.
The distinctive lesions have a purple cyanotic color and are surrounded by a white halo, causing a burning pain rather than itch. Intense cold exposure not only is associated with eruptions lasting for up to 48 hours, but potentially also with a systemic reaction of fever, sweating, arthralgia, myalgia, headache, conjunctivitis, and leukocytosis, which usually follow 4 to 6 hours after exposure.
Systemic amyloidosis has been suspected in some cases, but the diagnosis in these cases was questioned and reevaluation found the diagnosis of Mackle-Wells syndrome more likely. Nevertheless, a small percentage of patients with cold hypersensitivity syndrome suffers from renal amyloidosis. Although the disorder is a lifelong issue, it does not affect life expectancy. Treatment is primarily preventive. Medications used to treat the disease are no steroidal antiinflammatory drugs, steroids, and gold. Some patients have also been treated with interleukin-1 antagonists and stanozolol.
Avoid cold exposure. Arterial hypotension and cardiovascular collapse may occur. Increasing the temperature in the operating room and warming the operating room table before patients are brought into the room are recommended. The use of warming mattresses or better forced-air convective warming devices and warmed infusions should be considered.
Hypothermic cardiopulmonary bypass and cold cardioplegia should be avoided although they have been used successfully in one patient with prebypass and on-bypass antiinflammatory treatment. Because some patients are on gold therapy, a complete blood count (to rule out thrombocytopenia, leukopenia, agranulocytosis, or aplastic anemia) should be obtained, and renal function (because of possible renal amyloidosis; creatinine, blood urea nitrogen) and hepatic function (transaminases, bilirubin, coagulation profile, serum albumin) should be assessed.
Patients may be on steroid therapy and, depending on the procedure, perioperative steroid stress coverage may be required.