A familial form of urticaria with systemic reactions that
occurs as a result of cold exposure.
Familial Cold Urticaria; Familial Cold-Induced
Autoinflammatory Syndrome; Familial Cold Autoinflammatory Syndrome; Familial
Polymorphous Cold Eruption Syndrome.
Approximately 1:1,000,000 of the
general population is affected. Autosomal dominant inheritance, although
sporadic cases (de novo mutations) have also been described. 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.,
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.
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.