Approximately 20% of patients with cold urticaria lack an immediate response to cold stimulus with an ice cube; these patients have so-called atypical acquired cold urticaria syndromes1,12 (eg, cold-dependant dermatographism, delayed cold urticaria, systemic cold urticaria). Other forms of cold stimulus testing that can be considered include partially immersing a limb of the patient's in cold water3 or placing the patient in a cold room15; however, these forms of cold stimulus may put the patient at increased risk for a systemic reaction. Finally, scratching the skin prior to cooling or during cooling also may be of diagnostic value in cases of cold-dependant dermatographism.9,15
Additional testing should be guided by a patient's history. To determine if a secondary cause is responsible for the clinical presentation of cold urticaria, laboratory studies could include complete blood count, erythrocyte sedimentation rate, antinuclear antibodies titer, infectious mononucleosis serology, syphilis serology, rheumatoid factor, total complement, cold agglutinins, cold hemolysin, cryofibrinogen, and cryoglobulin.12 Of note, approximately 4% of patients with cold urticaria have been observed to have cryoglobulinemia. Thus, testing for cryoglobulinemia is the most likely laboratory study to yield positive results.1,16 Beyond evaluation for cryoprecipitates, however, an extensive search for etiology is not indicated unless additional clinical findings warrant investigation.16
Treatment of patients with cold urticaria can be difficult. Patients and their families should be counseled on the risks of aquatic activities and should be instructed on the proper use of an epinephrine autoinjector. In severe cases, patients may elect to move to warmer climates. Antihistamines sometimes provide benefit, especially at high doses and/or with the more potent formulations, such as doxepin. Cyproheptadine has been shown to be more effective than chlorpheniramine.17 Second-generation antihistamines also may be considered to minimize sedation. Cetirizine, loratadine, and desloratadine have been shown to be effective and well-tolerated options for treatment.18,19 Additionally, leukotriene receptor antagonists may have a role in treatment.5 Bonadonna et al6 demonstrated that cetirizine and zafirlukast in combination are more effective than either drug alone. Adjusting the level of medication so that the patient requires more than 3 minutes of cold stimulus testing before having a wheal response is a recommended goal of therapy that is aimed at minimizing the patient's risk of having a hypotensive reaction.12
Cold urticaria is an uncommon disorder that can put patients at significant risk. Taking a thorough history and confirming the condition through the use of cold stimulation tests can lead to a diagnosis in most cases. Although most forms of cold urticaria are idiopathic and acquired, familial and secondary forms also must be kept in mind when considering this diagnosis. In addition to antihistamine therapy, an epinephrine autoinjector and preventive measures play an important role in treating patients with cold urticaria.