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Urticaria, Cholinergic

Synonyms of Urticaria, Cholinergic

  • Physical Urticaria, Cholinergic Type

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Cholinergic urticaria is a relatively common disorder of the immune system characterized by an immediate skin reaction (hypersensitivity) to heat, emotional stress, and/or exercise. Symptoms of the disorder include the appearance of distinctive small skin eruptions (hives) with well-defined borders and pale centers, surrounded by patches of red skin (wheal-and-flare reaction). These red areas are typically intensely itchy (pruritus). Occasionally, cholinergic urticaria may be associated with systemic symptoms such as fever and/or difficulty breathing.

The symptoms of cholinergic urticaria may develop due to the reaction of specific immune system antibodies (IgE) to certain antigens, leading to a hypersensitivity response (Type I) and the wheal-and-flare reaction that is typical of cholinergic urticaria.


The symptoms of cholinergic urticaria occur in association with exercise, hot showers, sweating, and/or anxiety. Symptoms include the appearance of extremely itchy, small circular hives (pruritic urticaria) that have well-defined borders and pale (blanched) centers. Areas around these skin lesions become intensely red (wheal-and-flare reaction). Small hives occur most frequently on the upper back, upper arms, and/or neck and may last for minutes or up to an hour. Urticarial lesions may come together (coalesce) to form larger red areas, giving the skin a "blushed" appearance.

Some individuals with cholinergic urticaria may have swelling (angioedema) of the eyelids, lips, hands, and/or feet. A small number of people with cholinergic urticaria may also experience a variety of systemic symptoms including abdominal cramps, flushing, diarrhea, faintness, general weakness, asthma, and/or excessive sweating (hyperhidrosis).


Cholinergic urticaria is a disorder of the immune system characterized by a hypersensitivity reaction (IgE-mediated) to environmental factors that raise skin temperature and cause sweating. These include hot baths, warm rooms, exercise, and/or direct exposure to the sun. Other irritants in some cosmetics or drugs may also contribute to this hypersensitivity reaction. Eating hot foods, over-excitement, stress, and/or anxiety may also cause an episode of symptoms. Some scientists believe that some affected individuals may be hypersensitive to abnormally elevated levels of a substance in the body that transmits nerve impulses (the neurotransmitter acetylcholine).

The symptoms of cholinergic urticaria may develop due to the reaction of specific immune system antibodies (IgE) to certain antigens. This reaction causes the release of chemicals (i.e., Substance P or other neuropeptides), leading to the hypersensitivity response (Type I) and wheal-and-flare reaction that is typical of cholinergic urticaria.

Affected Populations

Cholinergic urticaria is an immunological disorder that affects males and females in equal numbers. This disorder is fairly common; urticaria and angioedema affect about 20 percent of the general population at some time. Of these people, about 4 to 5 percent are believed to have cholinergic urticaria.

The symptoms of cholinergic urticaria begin most frequently between the ages of 20 and 39 years. Recurrent episodes of symptoms usually last for less than 6 weeks. However, when symptoms last for more than 6 weeks, they are considered chronic. Repeated episodes of hives may persist for months or years and then tend to improve on their own (spontaneously).

Related Disorders

Symptoms of the following disorders can be similar to those of cholinergic urticaria. Comparisons may be useful for a differential diagnosis:

Physical urticaria is a term used to describe a group of common immunological conditions characterized by red (erythematous) allergic skin eruptions and itching (pruritus). Symptoms occur when a susceptible individual is exposed to cold temperatures (cold urticaria), hot temperatures leading to sweating (cholinergic), water (aquagenic), or mild trauma. Cholinergic urticaria is a specific form of physical urticaria. The most common symptoms of physical urticaria are itching (pruritus) and hives (wheals). Sensitivity to cold is usually accompanied by swelling of the soft tissues (angioedema) of the neck, lips, face, hands, and/or feet. In severe cases, contraction of the muscles around the airway (bronchospasm) and shock (histamine-mediated) may also occur. (For more information on this disorder, choose "Physical Urticaria" as your search term in the Rare Disease Database.)

Cold urticaria, a distinct form of physical urticaria, is a chronic disorder of the immune system characterized by the development of hives (urticaria) upon exposure to cold. The skin becomes intensely itchy (pruritis), and in some cases, swelling develops in the soft tissues (angioedema) of the hands, face, and/or neck. Systemic symptoms may include fever, headache, anxiety, fatigue, and, occasionally, loss of consciousness (syncope). The familial form of cold urticaria is characterized by the development of hives about 30 minutes after exposure to a cold environment. (For more information on this disorder, choose "Cold Urticaria" as your search term in the Rare Disease Database.)

Papular urticaria, generally known as common hives, is characterized by local elevated ridges (wheals) and redness (erythema) of the skin. This condition is usually triggered by allergic reactions to drugs, insect bites, food, or other environmental triggers. The first symptom of papular urticaria is usually itching (pruritus). This is followed by the appearance of wheals (hives) that may remain small or may become large. The larger wheals tend to be clear in the center, and may be noticed first as large rings of red skin (erythema) with localized swelling (edema). (For more information on this disorder, choose "Papular Urticaria" as your search term in the Rare Disease Database.)

Contact dermatitis is a common inflammatory reaction of the skin in response to irritants and allergy producing substances (allergens). This disorder may be acute or chronic. Primary irritant contact dermatitis affects those who have a reaction even the first time they are exposed to an irritating substance. Allergic contact dermatitis affects only those individuals who have a reaction to an irritating substance to which they have already been sensitized and to which they have developed a delayed hypersensitivity reaction. The symptoms of contact dermatitis include red, inflamed skin and possible blisters at the site of contact with the offending agent. During an acute episode, the area may be very red, crusty, and scaly. Burning pain and itching are usually present. (For more information on this disorder, choose "Contact Dermatitis" as your search term in the Rare Disease Database.)

Standard Therapies

The diagnosis of cholinergic urticaria may be confirmed by a thorough clinical evaluation including specialized tests that induce the development of hives (urticarial wheals). About 30 percent of people with this disease develop hives when a cholinergic drug such as nicotine or acetylcholine is injected directly into the skin (intradermal). A heat challenge, such as immersing an arm in warm water or exercising while wearing warm clothing, may also help to confirm the diagnosis of cholinergic urticaria. During a systemic attack of cholinergic urticaria, the level of histamine may be elevated in the fluid surrounding the skin lesion (plasma histamine).

Hydroxyzine hydrochloride (Atarax) is the drug of choice for the treatment of cholinergic urticaria. The drug ketotifen, an H1 histamine- receptor antagonist, has been used to treat people with severe cases of cholinergic urticaria. Anticholinergic drugs are not usually effective at tolerable doses. Other common antihistamines such as benadryl may reduce skin redness and itching in some affected individuals. The application of benzoyl scopolamine cream to the skin (topical) may prevent the appearance of new skin lesions during an attack.

Some people with cholinergic urticaria may avoid episodes of symptoms by wearing protective clothing (e.g., a hat or long-sleeved shirt), applying sunscreens to exposed areas of skin, avoiding direct sunlight, and staying in a cool well-ventilated environment to minimize sweating. Repeated episodes of hives may persist for months or years and then tend to improve spontaneously. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at 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

For information about clinical trials sponsored by private sources, contact:

Second generation investigational antihistamines are also being studied for the treatment of cholinergic urticaria. Drugs such as cetirizine and acrivastine may help to decrease the severity of symptoms and to improve breathing difficulties that may occur in some rare cases. More studies regarding safety and long-term effectiveness are needed before these drugs may be recommended as a standard therapy for cholinergic urticaria.

Urticaria, Cholinergic Resources



Berkow R, ed. The Merck Manual-Home Edition. Whitehouse Station, NJ: Merck Research Laboratories; 1997:829-31.

Larson DE, ed. Mayo Clinic Family Health Book. New York, NY: William Morrow and Company, Inc; 1996:1038-39.

Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. W.B. Saunders Co., Philadelphia, PA; 1996:2208.

Frank MM, Austen KF, Claman HN, et al., eds. Samter's Immunological Diseases. 5th ed. Little Brown and Company, Boston, MA; 1995:1336-37.

Champion RH, Burton JL, Ebling FJG, eds. Textbook of Dermatology. 5th ed. Blackwell Scientific Publications. London, UK; 1992:1875-76.

Kobayashi H, Tohyama M, Hashimoto K. Cholinergic urticaria, a new pathogenic concept: Hypohydrosis due to interference with the delivery of sweat to the skin surface. Dermatology. 2002;204:173-78.

Black AK. Unusual urticarias. J Dermatol. 2001;28:632-34.

Nair B. Final report on the safety of Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate. Int J Toxicol. 2001;20 Suppl 3:23-50.

Lee EE, Maibach HI. Treatment of urticaria. An evidence-based evaluation of the antihistamines. Am J Clin Dermatol. 2001;2:27-32.

Hosey RG, Carek PJ, Goo A. Exercise-induced anaphylaxis and urticaria. Am Fam Physician. 2001;64:1367-72.

Ring J, Hein R, Gauger A, et al. Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled study. Int J Dermatol. 2001;40:72-76.

Ammann P, Spurber E, Bertel O. Beta blocker therapy in cholinergic urticaria. Am J Med. 1999;107:191.

Guin JD, Ingram JM. Urticaria, Cholinergic. EMedicine. Last Updated: April 30,2002. 8pp.

Cholinergic Urticaria. About Dermatology. nd. 3pp.

Urticaria (hives, nettlerash). Asthma & Allergy Information & Research. Updated: Dec 2002. 14pp.

Hosey RG. Carek PJ, Goo A. Exercise-Induced Anaphylaxis and Urticaria. J Am Fam Physician. 2001. 8pp.

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Report last updated: 2008/02/05 00:00:00 GMT+0

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