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.,
Muckle-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 Muckle-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 nonsteroidal antiinflammatory drugs, steroids,
and gold. Some patients have also been treated with interleukin-1 antagonists and stanozolol.