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Brief communication

Regional expression of cold urticaria

Arthur S. Kurtz, MD, and Allen P. Kaplan, MD Stony Brook, N.Y.

Idiopathic cold urticaria is associated with pruritus, erythema, and swelling after exposure to a cold stim- ulus. In the typical case it is confined to portions of the body that have contacted the cold, such as when cold objects are touched, exposed to the wind, or in swimming. Any part of the body can react, given a suitable stimulus. In this article, we report an unusual patient with cold urticaria in which cold exposure causes hives in a localized region of the body and the ice-cube test is positive only in that area.

CASE REPORT

A 47-year-old white man presented with a 2-year history of local urticaria when he was exposed to the cold. For example, a windy, rainy day would typically cause facial redness, pruritus, and hive formation. He could not recall a similar reaction on any other part of his body. Oral mu- cocutaneous swelling could not be elicited by ingestion of iced beverages, and he could swim in cold water as long as he kept his head out of the water. The patient's urticaria was never generalized, he had never experienced any other form of urticaria, and there was no past history of atopy. Physical examination revealed no abnormalities. When an ice-cube test was applied to the forehead, a typical wheal was observed in 3 to 6 minutes (Fig. 1). This could be reproduced any place on his forehead, face, or on the lower neck, and no response could be elicited on the chest, back, arms, legs, or shoulders. The face, neck, and upper ex- tremities were minimally tanned. Laboratory examination revealed no evidence of cryoglobulins or cold agglutinins, and the sedimentation rate, antinuclear antibodies, blood count, urinalysis, serology, and complement levels were normal. Treatment with cyproheptadine hydrochloride, at 16 mg/day in divided doses, elicited a striking decrease in his symptoms within 72 hours and markedly diminished his ice-cube test. Sixteen months after initial evaluation, the patient reported a significant diminution of symptoms while he was taking cyproheptadine. When he stopped the med- ication for a short duration, a return of the urticaria in its original distribution and magnitude was noted.

From the Division of Allergy, Rheumatology, and Clinical Im- munology, The Department of Medicine, State University of New Yorkat Stony Brook Health Sciences Center, Stony Brook, N.Y. Reprint requests: Allen P. Kaplan, MD, Department of Medicine, SUNY at Stony Brook Health Sciences Center, Stony Brook, NY 11794.

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FIG. 1. Positive ice-cube test applied to the forehead of the patient. The test was positive at any site on his face, equivocal on the neck, and negative elsewhere.

DISCUSSION

The pathogenesis of cold urticaria is not understood in detail, although some of the requirements for hive development have been determined. Cold urticaria has been associated with the release of mediators from cutaneous mast cells during the warming phase after a region has been chilled in both in vitro~and in vivo2 models. These include histamine, neutrophil chemo- tactic factor, eosinophilotactic peptides, prostaglandin D2, platelet factor 4, and platelet-activating factor. In some patients, an antibody-mediated mechanism has been demonstrated. Passive transfer studies have con- firmed that most of these cases are IgE dependent3 and, less commonly, IgM mediated.4. ~However, it is not yet known how IgE or IgM can confer cold sen- sitivity on an otherwise normal mast cell. A variety of cold-induced syndromes that are vari-

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ants of cold urticaria have been reported. Although the syndrome is most commonly idiopathic (implying no obviously abnormal circulating proteins), an oc- casional case may be associated with cryoproteins, such as cryoglobulins, cold agglutinins, cryofibro- gens, and the Donath-Landsteiner antibody, as ob- served in paroxysomal cold hemoglubinuria. Isolated cryogtobulin has demonstrated the ability to transfer the sensitivity,6 although the mechanism remains un- clear. Variants of cold urticaria have been described in which the ice-cube test is typically negative. For ex- ample, a patient with cold-induced cholinergic urti- caria develops lesions resembling cholinergic urticaria after exercise in the cold. 7 In contrast to typical cho- linergic urticaria, exercise in a warm environment does not cause hive formation, and the ice-cube test is normal. Delayed cold urticaria, in which swelling appears 9 to 18 hours after cold exposure, and sys- temic cold urticaria, which is immediate and anaphy- lactoid in severity but requires chilling of the whole body, have also been described, s" 9 The ice-cube test is negative in both of these conditions. Cold- dependent dermographism is a related disorder 1~ in which scratching the skin will yield a mildly positive dermatographic response, but scratching the chilled skin of patients causes a marked accentuation of the response. No urticaria is observed after ice-cube or systemic cold challenge. Localized cold urticaria has been reported after pre- disposing conditions, such as cold injury, ragweed immunotherapy,11 insect bites,12 and intracutaneous allergen injections. 13 These may be confined to a small area of skin. The patient we describe had no identi- fiable antecedent or associated event, and his disorder was more generalized; that is, it affected an entire part of the body. Cases of localized cold urticaria, such as the patient we describe, argue against a circulating factor and speak in favor of a local abnormality of mast cells. We have not, however, performed passive transfer studies, and thus do not know whether a cir- culating factor is involved.

Regional expression of cold urticaria

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This case illustrates the varied clinical spectrum of patients who are observed with cold sensitivity. A detailed history that addresses the sites and circum- stances in which hives are induced plus an ice-cube test at multiple sites can distinguish many of the types, including regional cold sensitivity. In certain cases systemic cold challenge or exercise at different tem- perature conditions are also indicated.

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