COLD URTICARIA

 

There are both acquired and inherited forms of cold urticaria/angioedema; however, the familial form is rare. Idiopathic or primary acquired cold urticaria may be associated with headache, hypotension, syncope, wheezing, shortness of breath, palpitations, nausea, vomiting, and diarrhea. Attacks occur within minutes after exposures that include changes in ambient temperature and direct contact with cold objects. The elicitation of a wheal after the application of ice has been called a diagnostic cold contact test . If the entire body is cooled, as in swimming, hypotension and syncope, which are potentially lethal events (causing drowning), may occur. In rare instances, acquired cold urticaria has been associated with circulating cryoglobulins, cryofi-brinogens, cold agglutinins, and cold hemolysins, especially in children with infectious mononucleosis.

Passive transfer of cold urticaria by intracutaneous injection of serum or IgE to the skin of normal recipients has been documented. Histamine, chemotactic factors for eosinophils and neutrophils, PGD₂, cysteinyl leukotrienes, platelet-activating factor, and TNF-α have been released into the circulation after experimental challenge. Histamine, SP, and VIP, but not calcitonin gene-related peptide, have been detected in experimental suction-blister aspirates. Histamine has been released in vitro from chilled skin biopsy specimens that have been re-warmed. Neutrophils harvested from the blood of an experimentally cold-challenged arm manifested an impaired chemotactic response suggesting in vivo desensitization. Whereas complement has no role in primary acquired cold urticaria, cold challenge of patients with cold urticaria who have circulating immune complexes (such as cryoglobulins) can provoke a cutaneous necrotizing venulitis with complement activation.

Rare forms of acquired cold urticaria that have been described mainly in case reports include systemic cold urticaria, localized cold urticaria, cold-induced cholinergic urticaria, cold-dependent dermographism, and localized cold reflex urticaria. Two forms of dominantly inherited cold urticaria have been described. Familial cold urticaria has been termed familial cold autoinflammatory syndrome and is considered a type of periodic fever. It is a disorder showing an autosomal dominant pattern of inheritance with a genetic linkage to chromosome band 1q44. The responsible gene has been identified as CIASI, which codes for a protein involved in regulation of inflammation and apoptosis. The eruption occurs as erythematous macules and infrequent wheals and is associated with burning or pruritus. Fever, headaches, conjunctivitis, arthralgias, and a neutrophilic leukocytosis are features of attacks. The delay between cold exposure and onset of symptoms is 2.5 hours, and the average duration of an episode is 12 hours. Renal disease with amyloidosis occurs infrequently. Skin biopsy specimens show mast cell degranulation and an infiltrate of neutrophils. Results of the cold contact test and passive transfer with serum have been negative. Serum levels of IL-6 and granulocyte colony-stimulating factor were elevated in one patient. Other studies suggest a pathogenic role for IL-1. Delayed cold urticaria occurs as erythematous, edematous, deep swellings that appears 9 to 18 hours after cold challenge. Lesional biopsy specimens show edema with minimal numbers of mononuclear cells; mast cells are not degranulated; and neither complement proteins nor immunoglobulins are detected. Cold immersion does not release histamine, and the condition cannot be passively transferred.