Primary (idiopathic) cold urticaria and cholinergic urticariaFrom the Ronald O. Perelman Department of Dermatology, New York University
Gene Kim MD
Dermatology Online Journal 10 (3): 13
A 76-year-old man with a longstanding history of cold sensitivity developed wheals after the application of an ice cube. Cold urticaria is a type of physical urticaria that is characterized urticaria and angiodema after exposure to cold. It may be idiopathic or secondary to hematologic or infectious diseases. Treatment of primary cold urticaria includes antihistamines; however, ketotifen, doxantrazole, zafirlukast, cyclosporine, and cold-tolerance induction may be tried in refractory cases.
History.—The patient is an otherwise healthy man, who is being followed at the Department of Veterans Affairs New York Harbor Healthcare System Dermatology Service. He describes a 12-year history of cold sensitivity, which is characterized by the development of pruritic wheals after exposure to cold air or cold objects. He described similar but less severe symptoms after exercise. He denied headaches, dizziness, palpitations, wheezing, nausea, vomiting, abdominal pain, or diarrhea. He experienced a near syncopal episode after swimming in a cold swimming pool. He has taken many antihistamines with partial improvement of his symptoms. Current medications include cyproheptadine and loratadine.
Physical Examination.— After application of an ice-cube, erythematous, edematous plaques developed in the area restricted to the cold-stimulation test.
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Laboratory Data.— A complete blood count, comprehensive metabolic profile, cryoglobulins, hepatitis B antigen and hepatitis C antibody, an antinuclear antibody test, and a bone-marrow biopsy specimen were normal or negative
Diagnosis.—Primary (idiopathic) cold urticaria and cholinergic urticaria
Cold urticaria is a form of physical urticaria that may be primary (idiopathic) or secondary to underlying hematologic or infectious diseases. Associations between cold urticaria and cryoglobulinemia, chronic lymphocytic leukemia, lymphosarcoma, syphilis, rubeola, varicella, hepatitis, infectious mononucleosis, and mycoplasma have been reported. 
The pathogenesis of cold urticaria is not completely understood. The activation of mast cells and subsequent release of histamine and other inflammatory mediators is thought to play a central role.  However, the mechanism by which the cold stimulus is transformed into a signal for molecular and cellular activation has not been elucidated. Anti-IgE antibodies may play a role. [1,3]
Patients with cold urticaria typically develop pruritic wheals and angioedema that may be localized or generalized after cold exposure. Other organ systems that may be involved include the respiratory tract (hoarseness, dyspnea, and wheezing), gastrointestinal system (duodenal ulcers and abdominal pain), and the cardiovascular system (hypotension, tachycardia, and arrythmia.). Shocklike symptoms have been reported after aquatic exposures. [1,4]
The diagnosis is dependent on a complete history and physical examination as well as a positive cold-stimulation test. The cold stimulation test is considered positive if a wheal develops after the skin is rewarmed after application of an ice cube to the skin. In addition to laboratory studies suggested by the history and physical examination, cryoglobulins and cold agglutinins should be obtained.
Treatment consists primarily of antihistamines.  Variable results have been obtained with other pharmacologic agents that include ketotifen, doxantrazole, zafirlukast, and cyclosporine. Cold tolerance induction may also be tried. [6,7]
References1. Wanderer AA. Cold urticaria syndromes: historical background, diagnostic classification, clinical and laboratory characteristics, pathogenesis and management. J Allergy Clin Immunol 1990; 85:965.
2. Grabbe J. Pathomechanisms in physical urticaria. J Invest Dermatol Symp Proc 2001; 6:135.
3. Claudy A. Cold urticaria. J Invest Dermatol Symp Proc 2001; 6:141.
4. Mathelier-Fusade P, et al. Clinical predictive factors of severity in cold urticaria. Arch Dermatol 1998; 134:106.
5. Zuberbier T, et al. Management of urticaria: a consensus report. J Invest Dermatol Symp Proc 2001; 6:128.
6. Bonadonna P, et al. Treatment of acquired cold urticaria with cetirizine and zafirlukast in combination. J Am Acad Dermatol 2003; 49:714.
7. Marsland AM, Beck MH. Cold urticaria responding to systemic ciclosporin. Br J Dermatol 2003; 149:214.
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