Cold urticaria is a chronic, reactive skin disorder. It is probably the most common form of physical urticaria (hives). Major symptoms may include abnormal reddening of the skin (erythema), hives and itching after exposure of the skin to cold temperatures.
There are two forms of the disorder: essential (acquired) cold urticaria, and familial (hereditary) cold urticaria. The symptoms of the acquired form become obvious in two to five minutes after exposure to the triggering substance or situation, while it takes 24 to 48 hours for symptoms of familial cold urticaria to appear. Also, symptoms tend to last longer with the familial form, typically about 24 hours although they may remain for as long as 48 hours. With the acquired form, symptoms tend to last for one to two hours.
In cold urticaria, the skin has an abnormal reaction to cold. This may, for instance, occur after exposure to cold weather or to swimming in cold water. The skin usually turns red, and develops welts and itching. This may be accompanied by fever, headache, anxiety, tiredness, and, sometimes, even fainting. Some persons may also have palpitations or wheezing.
Symptoms of familial cold urticaria may begin to appear as soon as 30 minutes after exposure to cold. They may persist for up to 48 hours after exposure. The redness and itching of the skin may be accompanied by fever, headache, tiredness, pain in the joints (arthralgia), and the presence of excessive white blood cells (leucocytosis) in the blood.
Essential (acquired) cold urticaria consists, according to some clinicians, of several sub-categories such as primary acquired cold urticaria, delayed cold urticaria, localized cold urticaria, reflex cold urticaria or secondary cold urticaria, which are explained below:
Primary acquired cold urticaria can occur five to 30 minutes after exposure to cold. The reaction may occur in the cold itself, but more often during the rewarming phase. Itching and reddening of the skin may develop first, followed by a burning sensation. Hives appear, usually lasting 30 minutes. The affected person may also experience headache, palpitations, wheezing or fainting.
Delayed cold urticaria may appear several hours after contact with the cold.
Localized cold urticaria has been reported to occur after exposure to cold at the sites of previous ragweed injections for allergies or ladybug bites.
Reflex cold urticaria is characterized by widespread appearance of welts occurring in response to a drop in body temperature after localized exposure to cold applications (e.g. an ice pack).
Secondary cold urticaria can occur in connection with various blood disorders associated with viral infections such as mononucleosis.
Cold urticaria can occur for unknown (idiopathic) reasons, or it may be transmitted as an autosomal dominant trait. Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed “dominating” the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child. The risk is the same for each pregnancy.
The familial form of cold urticaria has been traced to the long arm of chromosome one (1q40). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females.
Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”. Chromosomes are further subdivided into bands that are numbered. For example, chromosome 1q40 refers to band 40 on the long arm of chromosome 1.
Some forms of cold urticaria are also diseases of the autoimmune system. Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons.
Exposure of the skin to cold triggers symptoms of the disorder. Even such commonplace activities as walking in cold weather, swimming in cold water, or even bathing in cool water may trigger an episode.
Cold urticaria affects males and females in equal numbers. Essential cold urticaria makes up about 1% to 3% of all urticaria cases, and occurs most often among young adults. Familial cold urticaria is rare.
Cold urticaria may be diagnosed by placing an ice cube on the skin of the subject's forearm for about four or five minutes. A positive response is indicated by the appearance of a "hive" in the shape of the ice cube, within 10 minutes after the stimulus is removed. This two-step process suggests that exposure to cold is required, but hive formation actually occurs as the skin temperature rises.
A negative response does NOT rule out Familial Cold urticaria. In some cases, cold-air exposure for 20 to 30 minutes is required to bring out the characteristic response.
Treatment consists of patient education, stimulus avoidance and medication. The newer antihistamines (H1 receptor blockers) may be very effective. H2 receptor blockers such as Tegamet may also be effective. The induction of tolerance by repeated regional or generalized cold exposure has had variable results. If attempted at all, such cold exposure should be performed on an in-patient basis and requires a well-motivated patient.
Treatment of cold urticaria may include the use of the drugs epinephrine, diphenhydramine, cyproheptadine, hydrochloride and cetirizine. Symptoms may be prevented with the use of warm clothing during cold weather. The avoidance of cold baths, swimming in cold water, etc., is recommended since loss of consciousness may occur in extreme cases, possibly even resulting in drowning.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
Beers MH, Berkow R, eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:1054-56.
Berkow R, ed. The Merck Manual-Home Edition. Whitehouse Station, NJ: Merck Research Laboratories; 1997:829-30.
Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:2208.
Champion RH, et al., eds. Textbook of Dermatology. 5th ed. Cambridge, MA: Blackwell Scientific Publications; 1992:845-46.
Gumucio DL, Diaz A, Schaner P, et al. Fire and ICE: the role of pyrin domain-containing proteins in inflammation and apoptosis. Clin Exp Rheumatol. 2002;20(4 Suppl 26):S45-53.
Dode C, Le Du N, Cuisset L, et al. New mutations of CIAS1 that are responsible for Muck;le-Wells synrome and familiar cold urticaria: a novel mutation underlies both syndromes. Am J Hum Genet. 2002;70:1498-506.
Ii M, Sayama K, Tohyama M, et al. A case of cold-dependent exercise-induced anaphylaxis. Br J Dermatol. 2002;147:368-70.
Black AK. Unusual urticarias. J Derrmatol. 2001;28:632-34.
Claudy A. Cold Urticaria. J Investig Dermatol Symp Proc. 2001;6:141-42.
Krishnaswamy G, Youngberg G. Acute and chronic urticaria. Postgrad Med. 2001;109:107-08
Hoffman HM, Mueller JL, Broide DH, et al. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet. 2001;29:301-05.
Hoffman HM, Wright FA, Broide DH, et al. Identification of a locus on chromosome 1q44 for familial cold urticaria. Am J Hum Genet. 2000;66:1693-98.
Capulong MC, Tomikawa M, Tahara K, et al. Cold stimulation test and histamine release in primary acquired cold urticaria. Int Arch Allergy Immunol. 1997;114:400-03.
Cooke RA. Essential acquired cold urticaria: stimulated only by systemic as well as local cooling. Occup Med. 1996;46:157-58.
FROM THE INTERNET
Clayton, MH. Cold-Induced Urticaria (HIVES). nd. 1p.
Lanternier ML, Brannon K. Dermatology: Urticaria. In: Virtual Hospital. University of Iowa Family Practice handbook, 4th Edition, Chapter 17. 1/11/2002; 3pp.
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 120100; Last Update: 9/11/2002.
Steinman H. Cold Urticaria. In: Allergy Society of South Africa.
World Allergy Organization. Cold-dependent disorders. nd. 3pp.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100