Induced tolerance in cold urticaria caused by cold-evoked histamine release

The interrelations between cold sensitivity and release of histamine and other mediators in five patients with cold urticaria undergoing cold tolerance treatment were studied. Tolerance to cold was produced in all patients by repeated cold exposure. In four patients tolerance was maintained by once daily exposures. In the fifth patient 4-hourly exposures were necessary. Cold sensitivity was associated with histamine release in venous blood draining urticated skin. No prostaglandin activity was detected, and low concentrations of kinin activity were found in blood draining the normal and exposed skin of healthy subjects as well as in patients with cold urticaria. After induction of tolerance, no histamine release occurred on challenge by cold. Relapse of sensitivity was associated with reappearance of histamine release on challenge. The conclusion that tolerance is due to depletion of histamine stores in skin after repeated cold exposure was supported by diminished wealing in response to injection of a histamine liberator (compound 48/80) in cold-tolerant skin.