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 stimulus. In the typical case it is confined to portions o f the body that have contacted the cold, such as when cold objects are touched, exposed to the wind, or in swimming. Any part o f 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 mucocutaneous 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 extremities 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 medication 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 Immunology, The Department of Medicine, State University of New York at 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. 111122299

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 o f mediators from cutaneous mast cells during the warming phase after a region has been chilled in both in vitro ~ and in vivo 2 models. These include histamine, neutrophil chemotactic 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 confirmed that most o f these cases are IgE dependent 3 and, less commonly, IgM mediated.4. ~ However, it is not yet known how IgE or IgM can confer cold sensitivity on an otherwise normal mast cell. A variety o f cold-induced syndromes that are vari-

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Regional expression of cold urticaria

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ants o f cold urticaria have been reported. Although the syndrome is most c o m m o n l y idiopathic (implying no obviously abnormal circulating proteins), an occasional case may be associated with cryoproteins, such as cryoglobulins, cold agglutinins, cryofibrogens, and the Donath-Landsteiner antibody, as observed in paroxysomal cold hemoglubinuria. Isolated cryogtobulin has demonstrated the ability to transfer the sensitivity, 6 although the mechanism remains unclear. Variants o f cold urticaria have been described in which the ice-cube test is typically negative. For example, a patient with cold-induced cholinergic urticaria develops lesions resembling cholinergic urticaria after exercise in the cold. 7 In contrast to typical cholinergic 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 systemic cold urticaria, which is immediate and anaphylactoid 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. Colddependent dermographism is a related disorder 1~ in which scratching the skin will yield a mildly positive dermatographic response, but scratching the chilled skin o f 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 predisposing conditions, such as cold injury, ragweed immunotherapy,11 insect bites,12 and intracutaneous allergen injections. 13These may be confined to a small area o f skin. The patient we describe had no identifiable antecedent or associated event, and his disorder was more generalized; that is, it affected an entire part of the body. Cases o f localized cold urticaria, such as the patient we describe, argue against a circulating factor and speak in favor o f a local abnormality of mast cells. We have not, however, performed passive transfer studies, and thus do not know whether a circulating factor is involved.

This case illustrates the varied clinical spectrum o f patients who are o b s e r v e d with cold sensitivity. A detailed history that addresses the sites and circumstances in which hives are induced plus an ice-cube test at multiple sites can distinguish many o f the types, including regional cold sensitivity. In certain cases systemic cold challenge or exercise at different temperature conditions are also indicated.
REFERENCES

1. Kaplan AP, Garofalo J, Sigler R, Hauber T. Idiopathic cold urticaria: in vitro demonstration of histamine release upon challenge of skin biopsies. N Engl J Med 1981;305:1074. 2. Kaplan AP, Gray L, Shaft RE, et al. In vivo studies of medicator release in cold urticaria and cholinergic urticaria. J ALLERGYCLIN 1MMONOL1975;55:394. 3. Kaplan AP, Gray L, Shaft RE, et al. In vivo studies of mediator release in cold urticaria and cholinergic urticaria. I ALLERGY CLIN IMMlmOL1975;55:394. 4. Inoue S, Teshimo H, Ago Y, Nagata S. Cold urticaria associated with immunoglobulin M serum factor. J ALLERGY CLIN IMMUNOL1980;66:299. 5. Wanderer AA, Maselli R, Ellis EF, Ishizaka K. Immunologic characterization of serum factors responsible for cold urticaria.
J ALLERGYCLIN IMMUNOL1971;48:13.

6. Costanzi JJ, Coltman CA Jr. Kappa chain precipitable immunoglobulinG (IgG) associated with cold urticaria. I. Clinical observations. Clin Exp Immunol 1967;2:167. 7. Kaplan AP, Garofalo J. Identification of a new physically induced urticaria: cold-induced cholinergic urticaria. J ALLERGY CLIN IMMUNOL1981;68:438. 8. Soter WA, Joski NP, Twarog FJ, et al. Delayed cold-induced urticaria: a dominantly inherited disorder. J ALLERGYCLIN IMMtmOL1977;54:294. 9. Kaplan AP. New cold-induced disorders: cold-dependent dermatographism and systemic cold urticaria. J ALLERGYCLIN IMMUNOL1984;73:453. 10. Kaplan AP. Unusual cold-induced disorders: cold-dependent dermatographism and systemic cold urticaria. J ALLERGY CLIN IMMtmOL1984;73:453. 11. Solomon LM, Strauss H, Leznoff A. Localized "secondary" cold urticaria. Arch Dermatol 1966;94:156. 12. Jytte RP. l_x~alizedcold urticaria. Contact Dermatitis 1978; 4:59. 13. Gerhard HI, Schopf E. Klinische und Therapeutische Kurzberichte. Uber ein Kobnerpharomen bei sog. Kaltwasser-bzw. Kalfluft-Urticaria. Der Hautarzt 1974;25:197.