Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Cholinergic Urticaria

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD  more...
 
Updated: May 24, 2016
 

Background

Cholinergic urticaria is one of the physical urticarias brought on by a physical stimulus. Although this stimulus might be considered to be heat, the actual precipitating cause is sweating. The definition and diagnostic testing of cholinergic urticaria has been the subject of consensus panel recommendations. (See Etiology, Presentation, and Workup.)[1]

Cholinergic urticaria can be divided into the following 4 subtypes[2] :

  • Cholinergic urticaria with poral occlusion
  • Cholinergic urticaria with acquired, generalized hypohidrosis
  • Cholinergic urticaria with sweat allergy
  • Idiopathic cholinergic urticaria

See also the Medscape Reference articles Acute Urticaria; Chronic Urticaria; Contact Urticaria Syndrome; Dermographism Urticaria; Papular Urticaria; Pressure Urticaria; and Solar Urticaria.

Physiology

Autonomic functions are normal in cholinergic urticaria. In one study of cholinergic urticaria, muscarinic receptors were reduced, but binding was normal. Thermography ostensibly shows the areas of involvement.

Elevation of histamine levels can be detected at 5 minutes after exercise, reaching a peak of 25 ng/mL at 30 minutes in persons with cholinergic urticaria. Treadmill exercise produces a sensation of generalized skin warmth, followed by pruritus, erythema, urticaria, and transient respiratory tract symptoms consisting of shortness of breath, wheezing, or both. Statistically significant decreases have been observed in 1 second forced expiratory volumes, maximal midexpiratory flow rates, and specific conductance. An increase in residual volume may also detected. (See Presentation and Workup.)

Patient education

For patient education information, see the Allergies Center and the Skin Conditions and Beauty Center, as well as Hives and Angioedema.

Next

Etiology

Mast cells seem to be critically involved in cholinergic urticaria. In fact, cholinergic urticaria has been used to study mast cell activity.[3] Serum histamine, the principal mediator, rises in concentration with experimentally induced exercise, accompanied by eosinophil and neutrophil chemotactic factors and tryptase. A reduction of the alpha1-antichymotrypsin level, as seen in some other forms of urticaria, is present. The eruption is improved with danazol. These findings have prompted some to argue for proteases as a cause of histamine release.

Although mast cell release seems to be involved in cholinergic urticaria, less eosinophilic major basic protein is present than in many other forms of urticaria.

Possible allergy-based etiology

Several factors, including an increased incidence in patients with atopic dermatitis (AD), a marked sensitivity in some patients with anaphylactic and anaphylactoid reactions, and an immediate reactivity in some patients, suggest an allergic basis for cholinergic urticaria.[4]

One report showed positive immediate sensitivity to sweat with passive transfer.[5] Some investigators, but not others, have documented positive passive transfer. Another group has delineated a follicular pattern of cholinergic urticaria in sweat-sensitized patients, but not in patients without prominent sensitivity.

Patients with atopic dermatitis and those with cholinergic urticaria develop skin reactions and histamine release of basophils in response to autologous sweat.[6, 7] Most patients demonstrate immediate-type skin responses to their own sweat and satellite wheals after acetylcholine injection. The rest have positive autologous serum skin tests.[8] The pathogenesis may involve disordered immune responses to products of skin flora that are soluble in human sweat. Patients with atopic dermatitis and cholinergic urticaria demonstrate elevated immunoglobulin E against the fungal protein MGL1304 produced by Malassezia globosa.[9]

Body temperature

A crucial point in cholinergic urticaria is not the actual temperature of the skin surface, the average skin temperature, or even the core temperature, but an increase or a decrease in the weighted average body temperature. An increase in core body temperature may trigger cholinergic urticaria; some patients appear unaffected by exercise and other activity in the summer.[10]

Seasonal temperature

It has been suggested that 2 conditions are required to provoke seasonal cholinergic urticaria: heat induced by various cholinergic stimuli and a low ambient temperature. Indeed, some persons who report cholinergic urticaria symptoms only during the winter months apparently have a reaction only when exposed to heat or heat-producing exercise while not acclimatized to heat.

In cholinergic urticaria, whether skin lesions are provoked by passive heating of the body at rest (eg, saunalike conditions) or by active heating at a low ambient temperature is basically related to the thermoregulatory process.

Other associated factors

The prevalence of cholinergic urticaria is definitely higher in persons with urticaria; cholinergic urticaria affected 11% of a population with chronic urticaria in one study and 5.1% of persons with urticaria in another.

The prevalence is also higher in persons with atopic conditions (eg, asthma, rhinitis, atopic eczema), but this is by no means exclusive. A rare, familial form of cholinergic urticaria has also been reported.

Cholinergic urticaria may also occur in the setting of acquired forms of generalized absence or decrease in sweating. Some patients with acquired idiopathic generalized hypohidrosis are theorized to have a defect in the nerve-sweat gland junction.[11] Superficial obstruction of the acrosyringium has sometimes been associated with acquired generalized hypohidrosis.[12]

Aspirin aggravated the urticaria in 52% of patients with cholinergic urticaria, which is similar to other forms of urticaria.

Previous
Next

Epidemiology

The prevalence of cholinergic urticaria is variable. Moore-Robinson and Warin found that about 0.2% of patients in an outpatient dermatologic clinic had cholinergic urticaria.[13] However, many published series have found cholinergic urticaria to be common. The prevalence of cholinergic urticaria is definitely higher in persons with urticaria.

The overall prevalence of cholinergic urticaria in one survey of 600 medical and engineering students in western India was 4%.[14]

Although the disorder occurs in both sexes, it seems to be more common in males than in females. In one study, almost 96% of patients with cholinergic urticaria were men.

Cholinergic urticaria usually first develops in people aged 10-30 years, with an average age at onset of 16 years in one study and a mean age of 22 years in another survey.

Previous
 
 
Contributor Information and Disclosures
Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

Jerri Hoskyn, MD Private Practice, River City Dermatology

Disclosure: Nothing to disclose.

Mark G Lebwohl, MD Chairman, Department of Dermatology, Mount Sinai School of Medicine

Mark G Lebwohl, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Amgen/Pfizer Honoraria Consulting; GlaxoSmithKline Honoraria Consulting; Novartis Honoraria Consulting; Ranbaxy Honoraria Lectures; Pfizer Honoraria Consulting; BioLineRX, Ltd. Honoraria Consulting; Celgene Corporation Consulting; Clinuvel None Investigator; Eli Lilly & Co. None Investigator; Genentech Honoraria Consulting

Christen M Mowad, MD Associate Professor, Department of Dermatology, Geisinger Medical Center

Christen M Mowad, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

References
  1. Magerl M, Borzova E, Gimenez-Arnau A, et al. The definition and diagnostic testing of physical and cholinergic urticarias--EAACI/GA2LEN/EDF/UNEV consensus panel recommendations. Allergy. 2009 Dec. 64(12):1715-21. [Medline].

  2. Nakamizo S, Egawa G, Miyachi Y, Kabashima K. Cholinergic urticaria: pathogenesis-based categorization and its treatment options. J Eur Acad Dermatol Venereol. 2012 Jan. 26(1):114-6. [Medline].

  3. Soter NA, Wasserman SI. Physical urticaria/angioedema: an experimental model of mast cell activation in humans. J Allergy Clin Immunol. 1980 Nov. 66(5):358-65. [Medline].

  4. Montgomery SL. Cholinergic urticaria and exercise-induced anaphylaxis. Curr Sports Med Rep. 2015 Jan. 14(1):61-3. [Medline].

  5. Nakazato Y, Tamura N, Ohkuma A, Yoshimaru K, Shimazu K. Idiopathic pure sudomotor failure: anhidrosis due to deficits in cholinergic transmission. Neurology. 2004 Oct 26. 63(8):1476-80. [Medline].

  6. Takahagi S, Tanaka T, Ishii K, et al. Sweat antigen induces histamine release from basophils of patients with cholinergic urticaria associated with atopic diathesis. Br J Dermatol. 2009 Feb. 160(2):426-8. [Medline].

  7. Fukunaga A, Bito T, Tsuru K, et al. Responsiveness to autologous sweat and serum in cholinergic urticaria classifies its clinical subtypes. J Allergy Clin Immunol. 2005 Aug. 116(2):397-402. [Medline].

  8. Horikawa T, Fukunaga A, Nishigori C. New concepts of hive formation in cholinergic urticaria. Curr Allergy Asthma Rep. 2009 Jul. 9(4):273-9. [Medline].

  9. Hiragun M, Hiragun T, Ishii K, et al. Elevated serum IgE against MGL_1304 in patients with atopic dermatitis and cholinergic urticaria. Allergol Int. 2014 Mar. 63(1):83-93. [Medline].

  10. Ramam M, Pahwa P. Is cholinergic urticaria a seasonal disorder in some patients?. Indian J Dermatol Venereol Leprol. 2012 Mar. 78(2):190-1. [Medline].

  11. Kobayashi H, Aiba S, Yamagishi T, et al. Cholinergic urticaria, a new pathogenic concept: hypohidrosis due to interference with the delivery of sweat to the skin surface. Dermatology. 2002. 204(3):173-8. [Medline].

  12. 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. 2000 Nov. 143(5):1064-6. [Medline].

  13. Moore-Robinson M, Warin RP. Some clinical aspects of cholinergic urticaria. Br J Dermatol. 1968 Dec. 80(12):794-9. [Medline].

  14. Godse K, Farooqui S, Nadkarni N, Patil S. Prevalence of cholinergic urticaria in Indian adults. Indian Dermatol Online J. 2013 Jan. 4(1):62-3. [Medline]. [Full Text].

  15. Confino-Cohen R, Goldberg A, Magen E, Mekori YA. Hemodialysis-induced rash: a unique case of cholinergic urticaria. J Allergy Clin Immunol. 1995 Dec. 96(6 Pt 1):1002-4. [Medline].

  16. Sheraz A, Halpern S. Cholinergic Urticaria Responding to Botulinum Toxin injection for Axillary Hyperhidrosis. Br J Dermatol. 2013 Jan 10. [Medline].

  17. Silpa-Archa N, Kulthanan K, Pinkaew S. Physical urticaria: prevalence, type and natural course in a tropical country. J Eur Acad Dermatol Venereol. 2010 Dec 22. [Medline].

  18. Vadas P, Sinilaite A, Chaim M. Cholinergic Urticaria with Anaphylaxis: An Underrecognized Clinical Entity. J Allergy Clin Immunol Pract. 2016 Mar-Apr. 4 (2):284-91. [Medline].

  19. Torabi B, Ben-Shoshan M. The association of cholinergic and cold-induced urticaria: diagnosis and management. BMJ Case Rep. 2015 Feb 18. 2015:[Medline].

  20. Abajian M, Schoepke N, Altrichter S, Zuberbier HC, Maurer M. Physical urticarias and cholinergic urticaria. Immunol Allergy Clin North Am. 2014 Feb. 34(1):73-88. [Medline].

  21. Mihara S, Hide M. Adrenergic urticaria in a patient with cholinergic urticaria. Br J Dermatol. 2008 Mar. 158(3):629-31. [Medline].

  22. Otto HF, Calabria CW. A case of severe refractory chronic urticaria: a novel method for evaluation and treatment. Allergy Asthma Proc. 2009 May-Jun. 30(3):333-7. [Medline].

  23. Magerl M, Altrichter S, Borzova E, Giménez-Arnau A, Grattan CE, Lawlor F, et al. The definition, diagnostic testing, and management of chronic inducible urticarias - The EAACI/GA(2) LEN/EDF/UNEV consensus recommendations 2016 update and revision. Allergy. 2016 Jun. 71 (6):780-802. [Medline].

  24. Kozaru T, Fukunaga A, Taguchi K, Ogura K, Nagano T, Oka M, et al. Rapid desensitization with autologous sweat in cholinergic urticaria. Allergol Int. 2011 Sep. 60(3):277-81. [Medline].

  25. Alsamarai AM, Hasan AA, Alobaidi AH. Evaluation of different combined regimens in the treatment of cholinergic urticaria. World Allergy Organ J. 2012 Aug. 5(8):88-93. [Medline]. [Full Text].

  26. Altrichter S, Wosny K, Maurer M. Successful treatment of cholinergic urticaria with methantheliniumbromide. J Dermatol. 2015 Jan 9. [Medline].

  27. Ammann P, Surber E, Bertel O. Beta blocker therapy in cholinergic urticaria. Am J Med. 1999 Aug. 107(2):191. [Medline].

  28. Tsunemi Y, Ihn H, Saeki H, Tamaki K. Cholinergic urticaria successfully treated with scopolamine butylbromide. Int J Dermatol. 2003 Oct. 42(10):850. [Medline].

  29. Feinberg JH, Toner CB. Successful treatment of disabling cholinergic urticaria. Mil Med. 2008 Feb. 173(2):217-20. [Medline].

  30. Metz M, Bergmann P, Zuberbier T, Maurer M. Successful treatment of cholinergic urticaria with anti-immunoglobulin E therapy. Allergy. 2008 Feb. 63(2):247-9. [Medline].

 
Previous
Next
 
Close-up view shows small urticarial wheals within large erythematous flares.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.