Other forms of urticaria

These include the rare vibration induced angioedema, involving deep swellings triggered by vibrations on the skin, contact urticaria involving wheals which exclusively occur after skin contact with certain substances, e.g. food and aquagenic urticaria involving wheals and itching triggered by skin contact with water. Some of these forms are so seldom that many dermatologists never see a patient with such a form of urticaria during their working lives.

Cholinergic urticaria

Sabine Altrichter

Cholinergic urticaria is also one of the inducible forms of urticaria. Cholinergic urticaria is also sometimes called “sweat urticaria“, sometimes the term “heat reflex urticaria” is used. In the case of cholinergic urticaria wheals and itchiness occur by an elevation of the body temperature, e.g. by sweating after sports, but also following emotional stress.

Cholinergic urticaria is not an uncommon disease and is one of the more common forms of urticaria. It affects both sexes, indeed particularly young people between the age of 15 and 25. According to a recent study more than one in ten of the 15 to 25-year olds suffer from cholinergic urticaria. According to a study carried out by the Freie Universität Berlin, over one in ten of the 15 to 35-year-olds suffer from cholinergic urticaria. However, only a few people actually discuss the condition with a doctor because in many cases the symptoms are so slight that quality of life is not significantly impaired. This is also confirmed by the observation that only some 0.2 % of the patients at dermatology practices suffer from cholinergic urticaria. Long-term studies have shown that cholinergic urticaria often lasts a long time, on average about 8 years. Some 30 % of those suffering from cholinergic urticaria spend even more than 10 years struggling against it. Fortunately in most cases the severity of the disease abates over time. Some patients report an improvement of their symptoms in summer, which may be related to heat acclimatisation by the body during the warmer seasons.

Cholinergic urticaria, very seldom does occur clustered within families. Interestingly, almost half of all the cholinergic urticaria patients are also congenitally disposed to developing diseases like hay fever, neurodermatitis (so-called “atopic diseases”). Such a connection is not observed in the other forms of urticaria. Cholinergic urticaria occasionally occurs together with spontaneous chronic urticaria.

Cholinergic urticaria often involves the formation of small pinpoint wheals that are typically surrounded by a larger reddened part of the skin. In most cases the skin changes occur within 2 to 20 minutes after the onset of sweating, generally starting on the neck and the upper part of the body. The patient often first notes itchiness or prickliness or burning of the skin.  Once the body cools down again, the wheals disappear without a trace within minutes or hours. In mild cases only a few wheals appear, particularly on the upper body. In severe cases the entire body may be affected. Fortunately cholinergic urticaria rarely involves serious symptoms like angioedema (= swellings deep down in the skin), breathing difficulties, nausea, headaches or vascular collapse. Heat and cold urticaria, solar urticaria or even spontaneous chronic urticaria are among the diseases with which cholinergic urticaria can easily be confused, particularly when it is induced by stress. Certain common characteristics are shared by cholinergic urticaria and spontaneous chronic urticaria with exercise-induced anaphylaxis. Exercise-induced anaphylaxis is a mast cell dependent reaction which can lead to an allergic shock after ingesting an allergen (often wheat) in combination with physical exertion. Wheals may also appear. Patients do not suffer any symptoms from exertion alone.

Unlike chronic urticaria where the skin changes frequently appear without an external stimulant, cholinergic urticaria symptoms always arise as a result of a trigger. In other words: Cholinergic urticaria patients can bring about an occurrence of the symptoms intentionally. The cholinergic urticaria symptoms are triggered for instance by heat (too thick winter clothing, a hot bath), exertion, eating very spicy food or even by great emotions such as excitement or a scare. Unlike the case of spontaneous chronic urticaria, little is known about the underlying cause of cholinergic urticaria.

Illustration 15: Typical wheals after exertion test in patients with cholinergic urticaria.

The most common test procedure to diagnose a cholinergic urticaria is the exertion test (Ill. 15). It is ideally conducted on a stationary bicycle (bike trainer); however, climbing stairs or running is also a possibility. Recently a 30-minute pulse-controlled exertion test has been developed which, apart from providing a diagnosis also makes it possible to determine the degree of severity. In this test a bike provocation is conducted with an increasing pulse rate, up to 170 beats per minute. The time until wheals appears equals the severity of the disease: The quicker the wheals appear, the severer cholinergic urticaria is.

Another option to test for cholinergic urticaria is to take a hot bath or to sit in a sauna. Wheal formation is triggered by the passive warming up. This method is, however only seldom used today because, unlike the test with a bike ergometer the severity of the disease can only be indicated roughly and conducting such a test is more cumbersome.

In urticaria centres skin tests are made in addition. Patients with cholinergic urticaria develop a wheal in the upper skin layer where pricked by the injection when so-called cholinergic substances (e.g. metacholine, acetylcholine or pilocarpine) are injected. Unfortunately the test is frequently falsely negative, this means no wheal arises even though the patient suffers from cholinergic urticaria. This skin test can therefore only be used to confirm a diagnosis. Furthermore, an autologous test sweat-skin-test can be done for which a little inherent sweat of different dilutions is injected in the skin as for an allergy test. It leads to the development of wheals in some patients. This indicates that there is an allergy to an (auto) allergy against inherent sweat.

Are all the tests are negative, although you can be sure you are suffering from cholinergic urticaria? In such a case possibly the tests were carried out in the so-called “refractory time” of the skin. The refractory time is the time after a severe bout of urticaria. The mast cells of the skin are not able to release histamine again in this time. They first have to “recover” to be able to react to stimuli again. It is still not exactly known whether histamine or a yet unknown trigger for mast cell activation (e.g. a neuropeptide or an allergen) is missing in this time. Therefore the exertion tests should not be carried out before at least 24 hours have lapsed since the last bout of cholinergic urticaria.

Unfortunately due to the lack of knowledge about the underlying causes of most cases of cholinergic urticaria there is rarely an approach for a causal therapy and thus for a cure. In most cases of cholinergic urticaria recourse to a treatment of the symptoms (symptomatic therapy) has to be made: antihistamines. Modern histamine therapy tops the list for cholinergic urticaria; it prevents histamine from fully effectively triggering the wheal effect. Various preparations have proven to be effective. If a certain antihistamine does not lead to a satisfactory protection, a test may be made as to which of the many other substances available alleviate the symptoms best.

Many patients take antihistamines daily or preventatively before doing sports or other activities which, as experience has shown, produce wheals. Usually one tablet is enough to completely suppress the symptoms. As a whole the therapy of cholinergic urticaria is oriented along the lines of the therapy recommendations in the guidelines for spontaneous chronic urticaria. However cholinergic urticaria has some particularities, which in particular cases also allow variations from therapy recommendations to be successful:  

  • Ketotifen: Ketotifen is both an antihistamine and also a mast cell stabiliser. In some cases it revealed a good effect in connection with cholinergic urticaria, even in patients who do not respond to other antihistamines. Due to the sedative effect ketotifen is, however, a second option drug and should only be administered in exceptional cases.
  • Anticholinergics: Clidinium bromide and butylscopolamine bromide were successfully used for cholinergic urticaria. These drugs lead to reduced sweat production, flares, bloating, disturbed vision, palpitation (tachycardia) and a dry mouth may occur as unwanted side effects. Long-term surveys or studies with a greater number of patients are not available for this drug.
  • Other drugs: In individual cases successful therapy was described using propranolol (Beta-Blocker), maprotiline (tetracyclic antidepressant with antihistaminic effect) and chlordiazepoxide (benzodiazepine). However, studies with a greater number of patients would have to be carried out to evaluate the therapeutic benefit of these.
  • Hardening – Making use of the refractory time: a further option to get the cholinergic urticaria symptoms under control is to exploit the refraction time, i.e. the time in which the mast cells cannot release histamine. Some patients take advantage of this condition by triggering a controlled bout of urticaria (e.g. by physical exercise) to then be wheal-free for 24 hours. Regular and underlying physical exertion (i.e. without giving rise to symptoms) is better. Therefore if this form of therapy is carried out like a small daily fitness program; the occurrence of severe bouts of wheals can be prevented.
  1. Adachi J, Aoki T, Yamatodani A. Demonstration of sweat allergy in cholinergic urticaria. J Dermatol Sci 7 (2): 142-9., 1994.
  2. Berth-Jones J, Graham-Brown RA. Cholinergic pruritus, erythema and urticaria: a disease spectrum responding to danazol. Br J Dermatol 121 (2): 235-7., 1989.
  3. Casale TB, Keahey TM, Kaliner M. Exercise-induced anaphylactic syndromes. Insights into diagnostic and pathophysiologic features. Jama 255 (15): 2049-53., 1986.
  4. Czarnetzki BM. Ketotifen in cholinergic urticaria. J Allergy Clin Immunol 86 (1): 138-9., 1990.
  5. Eftekhari N, Ward AM, Allen R, Greaves MW. Protease inhibitor profiles in urticaria and angio-oedema. Br J Dermatol 103 (1): 33-9., 1980.
  6. Haustein UF, Schliebs R, Schaller J. Changes in muscarinic acetylcholine receptor binding in skin slices of cholinergic urticaria. Acta Derm Venereol 70 (3): 208-11., 1990.
  7. Hirschmann JV, Lawlor F, English JS, Louback JB, Winkelmann RK, Greaves MW. Cholinergic urticaria. A clinical and histologic study. Arch Dermatol 123 (4): 462-7., 1987.
  8. Itakura E, Urabe K, Yasumoto S, Nakayama J, Furue M. Cholinergic urticaria associated with acquired generalized hypohidrosis: report of a case and review of the literature. Br J Dermatol 143 (5): 1064-6., 2000.
  9. Kaplan AP, Beaven MA. In vivo studies of the pathogenesis of cold urticaria, cholinergic urticaria, and vibration-induced swelling. J Invest Dermatol 67 (3): 327-32., 1976.
  10. Lawlor F, Greaves MW. [The development of recent strategies in the treatment of urticaria as a result of clinically oriented research]. Z Hautkr 65 (1): 17-27., 1990.
  11. Lawrence CM, Jorizzo JL, Kobza-Black A, Coutts A, Greaves MW. Cholinergic urticaria with associated angio-oedema. Br J Dermatol 105 (5): 543-50., 1981.
  12. McClean SP, Arreaza EE, Lett-Brown MA, Grant JA. Refractory cholinergic urticaria successfully treated with ketotifen. J Allergy Clin Immunol 83 (4): 738-41., 1989.
  13. Moore-Robinson M, Warin RP. Some clinical aspects of cholinergic urticaria. Br J Dermatol 80 (12): 794-9., 1968.
  14. Murphy GM, Greaves MW, Zollman PE, Winkelmann RK. Cholinergic urticaria, passive transfer experiments from human to monkey. Dermatologica 177 (6): 338-40., 1988.
  15. Onn A, Levo Y, Kivity S. Familial cholinergic urticaria. J Allergy Clin Immunol 98 (4): 847-9., 1996.
  16. Shoenfeld Y, Harari Z, Sheonfeld Y, Keren G. Cholinergic urticaria. A seasonal disease. Arch Intern Med 141 (8): 1029-30., 1981.
  17. Wong E, Eftekhari N, Greaves MW, Ward AM. Beneficial effects of danazol on symptoms and laboratory changes in cholinergic urticaria. Br J Dermatol 116 (4): 553-6., 1987.
  18. Zuberbier T, Althaus C, Chantraine-Hess S, Czarnetzki BM. Prevalence of cholinergic urticaria in young adults. J Am Acad Dermatol 31 (6): 978-81., 1994.
  19. Zuberbier T, Munzberger C, Haustein U, Trippas E, Burtin B, Mariz SD, Henz BM. Double-blind crossover study of high-dose cetirizine in cholinergic urticaria. Dermatology 193 (4): 324-7., 1996.


Machen Sie mit bei der Online-Umfrage zu MEDI-DIGITAL (anonym, max. 15 min). Medizinische Beschwerden vom Erstauftreten bis zur fachärztlichen Versorgung im Kontext digitaler Medien und der Arzt-Patienten-Beziehung

Read more

Das Allergie-Centrum-Charité führt eine Befragung von Patient:innen mit chronischer spontaner und/der chronischer induzierbarer Urtikaria durch. Wir würden uns freuen, wenn sie als Betroffene:r  teilnehmen würden. Bitte...

Read more

Der Welt Urtikaria Tag (UDAY) findet jedes Jahr am 01. Oktober statt. Nun schon in seinem 8. Jahr, ist erein Tag, an dem Urtikaria-Patient:innenim Mittelpunkt der Aufmerksamkeit stehen. Am UDAY soll das Bewusstsein für...

Read more

Berlin, 21.09.2021 (GA2LEN UCARE Network). Brennen, Jucken, Schmerzen – allein in Deutschland leiden etwa eine Million Menschen unter chronischer Urtikaria (Nesselsucht) und die Zahl wächst. Leider erhält die Krankheit...

Read more

Zoom-Meeting am Dienstag, 21. September 2021 - 17:30 –18:30 Uhr, Online-Publikumveranstaltung für Patienten/Betroffene zum Thema Urtikaria

Read more

Verfolgen Sie die Expertendiskussion zwischen Dr. Martin Metz und Dr. Ana Maria Giménez-Arnau über die neuesten Daten zu Therapieformen für die chronische spontane Urtikaria, die sich aktuell noch in der Entwicklung...

Read more