Urticaria (Cholinergic) from Dermatology / Allergy And Immunology

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Allergy And Immunology

Urticaria (Cholinergic)

Synonyms, Key Words, and Related Terms: heat-induced urticaria, micropapular urticaria, stress-induced urticaria

Author Information | Introduction | Clinical | Differentials | Workup | Treatment | Follow-up | Pictures | Bibliography

AUTHOR INFORMATION

Section 1 of 9

Authored by Jere D Guin, MD, FACP, Professor Emeritus, Department of Dermatology, Baptist Medical Center; St. s; AR Children's; Arkansas Heart Hosp Coauthored by Jim Mark Ingram, MD, Clinical Instructor of Allergy and Immunology, Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Childrens Hospital

Jere D Guin, MD, FACP, is a member of the following medical societies:

American Academy of Dermatology

Edited by Mark Lebwohl, MD, Chair, Professor, Department of Dermatology, Mount Sinai School of Medicine; Vinson, MD, Chief, Department of Dermatology, Beaumont Medical Center;

Christen M Mowad, MD, Assistant Professor, Department of Dermatology, Pennsylvania State College of Medicine, Geisinger Medical Center;

Quirk, MD, Instructor, Department of Dermatology, Brown University;

and Dirk M Elston, MD, Chairman, Department of Dermatology, Army Medical Center, Wilford Hall Medical Center

Author's Email: Jere D Guin, MD, FACP Editor's Email:Mark Lebwohl, MDeMedicine Journal, August 2 2000, Volume 1,

Number 8

INTRODUCTION

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Background: Cholinergic urticaria is one of the physical urticarias, brought on by a physical stimulus. While physical stimulus might be considered to be heat, the actual precipitating cause is sweating.Pathophysiology: Mast cell seems to be critically involved; cholinergic urticaria has been used to study mast cell activity.

Serum histamine, the principal mediator, rises in concentration with experimentally-induced exercise, accompanied by eosinophil and neutrophil chemotactic factors and tryptase.

There is a reduction of alpha 1-antichymotrypsin as seen in some other forms of urticaria, and eruption is improved with danazol. This has prompted some to argue for proteases as a cause of histamine release.

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

Allergic basis is suggested by several factors, including increased incidence of atopic patients; marked sensitivity in some with anaphylactic and anaphylactoid reactions; and demonstration of immediate reactivity in some. One report showed positive immediate sensitivity to sweat with passive transfer. Positive passive transfer has been reported by some investigators, but not others.

Autonomic functions are normal. One patient developed an accentuated response in a positive copper test site, perhaps from vasodilatation or perhaps augmentation of neurologic stimulation. In one study 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.

Treadmill exercise produces a sensation of generalized skin warmth, followed by pruritus, erythema, urticaria, and transient respiratory tract symptoms consisting of shortness of breath or wheezing or both.

Statistically significant falls were observed in 1 second forced expiratory volumes (FEV1), maximal mid expiratory flow rates (MMF) and specific conductance. Rise in residual volume was also detected.Frequency:

In the US: Prevalence of cholinergic urticaria is variable. - and Warin found that about 0.2% of patients in an outpatient dermatology clinic suffered from cholinergic urticaria. However, many published series have found cholinergic urticaria to be very common.

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

Prevalence is higher in atopics (asthma, rhinitis, atopic eczema), but this is by no means exclusive. There is also a rare familial form of the disease.

Mortality/Morbidity: N/A

Race: N/A

Sex: It occurs in both men and women but seems to be more common in males.

Age:

Condition usually begins in people aged 10-30 years, with an average age of onset of 16 years in one study and a mean of 22 years in another. It persists for a number of years. Most patients retain the tendency for many years.

In one series of 22 persons, average duration was 7.5 years with a range of 3-16 years, but in 7 patients on follow up, some retained the tendency for up to 30 years.

In another study, almost 96% were men, with a mean age of 22 years while in another group it was 31 women and 25 men.

CLINICAL

Section 3 of 9

History: Lesions appear rather rapidly, usually within a few minutes after the onset of sweating, and they last for half-hour to an hour or more with a mean duration of about 80 minutes.Symptoms are sufficiently uncomfortable to cause many patients to change their patterns of activity to prevent attacks.Symptoms seem to follow any stimulus to sweat, but crucial point in cholinergic urticaria is not the actual temperature of the skin surface, nor the average skin temperature, nor even the "core" temperature, but a rise or fall in weighted average body temperature.In cholinergic urticaria whether skin lesions were provoked by passive heating of the body at rest (sauna-like conditions) or by active heating at low ambient temperature, it is basically related to the thermoregulatory process.Exercise is the most common precipitating event, but anything causing sweating can bring on an attack in some persons, including elevated environmental temperature, hot food, sauna baths, immersion in hot water, gustatory stimuli, emotional stress, and hemodialysis.Some who report symptoms only during the winter months apparently react only when exposed to heat or heat-producing exercise while unacclimatized to heat.Physical: Often itching, burning, tingling, warmth, or irritation precede the onset of numerous small (1-4 mm) pruritic wheals with very large surrounding flares.Lesions may appear anywhere except on palms or soles, and rarely in the axillae. Sometimes flares are the only presentation.More severely involved may experience systemic symptomatology such as fainting, abdominal cramping, diarrhea, salivation, and headaches.Also reported are hepatocellular injury, angioedema, asthma, anaphylactoid, and even anaphylactic reactions.Those with cardiorespiratory symptoms include patients with increased pulmonary resistance with acetylcholine challenge, which may be a limiting factor in certain occupations such as aerospace.Persistent form is believed to show persistent, individual macules of short duration but with new macules continually appearing at adjacent sites.Exercise and hot baths exacerbate pruritus and provoke lesions in previously unaffected areas.In a reported case, topically applied benzoyl scopolamine blocked the appearance of lesions after challenge.Cholinergic dermographism comprises a localized distribution of typical tiny wheals on stroking the skin of some patients with cholinergic urticaria.There may also be a localized form and a presentation with cold-induced urticarial lesions.Patient with this condition had a generalized reaction to cold ambient air and cold water (but a negative ice-cube test).Cold urticaria and cold-induced cholinergic urticaria may be seen in about 1% of patients with cold urticaria.Other diagnostic considerations

Some reports of chronic urticaria include patients with cholinergic urticaria, but the morphology is very different. However, there are other physical urticarias with similar lesions, such as aquagenic urticaria.

Aquagenic urticaria responds to water at both cold and hot temperatures and demonstrates lesions resembling cholinergic urticaria to an application of room temperature tap water.

In adrenergic urticaria, wheals are surrounded by vasoconstriction and there is a positive response to epinephrine and norepinephrine.

Commonly patients with one physical urticaria tend to have another physical urticaria as well, sometimes precipitated by the same stimulus.

Cholinergic urticaria may be accompanied by cold urticaria, pressure urticaria, and even aquagenic urticaria. Causes: N/A

DIFFERENTIALS

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Urticaria (Chronic) Other Problems to be Considered: Adrenergic urticaria

Aquagenic urticaria

Pressure urticaria

WORKUP

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Lab Studies:

Most reliable way to reproduce the disease is probably to have the patient sweat from some stimulus such as a treadmill or another form of exercise.Traditionally intradermal injection of 0.05 ml carbamoylcholine chloride (carbachol) 0.002% or of 0.05 ml of 0.02% (0.01 mg) of methacholine has been used to produce a flare containing characteristic wheals (often with satellites). This occurs in about 51% of patients. One may see the same flare in normals, but it is usually smaller and without whealing.Nicotinic acid has also been employed at a dilution of 1:500,000 or 1:100,000 and is preferred by some.Lesions of cholinergic urticaria have even been reproduced by curare derivatives, eg, D-tubocurarine.Cholinergic dermographism also can be reproduced by stroking the skin, methyl acetylcholine, or other stimuli causing sweating.Persistent form is said to show persistent, individual macules of short duration but with new macules continually appearing at adjacent sites.Exercise and hot baths exacerbate pruritus and provoke lesions in previously unaffected areas.Topically applied benzoyl scopolamine blocked the appearance of lesions after challenge in the case reported.Cholinergic dermographism comprises a localized distribution of typical tiny wheals on stroking the skin of some patients with cholinergic urticaria.There may also be a localized form and presentation with cold-induced urticarial lesions.Patient with this condition had a generalized reaction to cold ambient air and cold water, but a negative ice-cube test.Cold urticaria and cold-induced cholinergic urticaria may be seen in about 1% of patients with cold urticaria.Imaging Studies:

N/AOther Tests:

N/AProcedures:

N/AHistologic Findings: N/AStaging: N/A

TREATMENT

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Medical Care: Sometimes an attack can be aborted by rapid cooling.Antihistamines including cetirizine are helpful.Response to cetirizine is important, as some of the antihistaminic effect has been attributed to antimuscarinic activity.UV light has been beneficial in some, but one must be circumspect about contraindications to UV light.Diet may be helpful, as attacks can sometimes result from hot foods and beverages, highly spiced foods, and alcohol.Aspirin also aggravated 52% of patients with cholinergic urticaria, which is similar to other forms of urticaria.

For patients with both cold and cholinergic urticaria, ketotifen where available may be helpful.

About 62% experience a reduction in whealing and 68% report reduced itching.

Cardiorespiratory symptoms also reportedly respond to ketotifen.

Danazol can be beneficial ostensibly because it elevates antichymotrypsin levels.

Beta blockers such as propranolol, have been reported to be useful.

In evaluating any response to therapy, one must always consider that the condition can clear spontaneously.

Surgical Care: N/AConsultations: N/ADiet: N/AActivity: N/A

FOLLOW-UP

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Further Inpatient Care:

N/AFurther Outpatient Care:

N/AIn/Out Patient Meds:

N/ATransfer:

N/ADeterrence/Prevention:

N/AComplications:

N/APrognosis:

N/APatient Education:

N/A

PICTURES

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Caption: Picture 1. Close up showing small urticarial wheals within large erythematous flares.View Full Size Image

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Picture Type: Photo

BIBLIOGRAPHY

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

Czubalski K, Rudzki E: Neuropsychic factors in physical urticaria. Dermatologica 1977; 154(1): 1-4[Medline].

Hirschmann JV, Lawlor F, English JS: Cholinergic urticaria. A clinical and histologic study. Arch Dermatol 1987 Apr; 123(4): 462-7[Medline].

Jorizzo JL: Cholinergic urticaria. Arch Dermatol 1987 Apr; 123(4): 455-7[Medline].

Kierland R: Physical allergies. Arch Dermatol Syphilol 1953; 68: 61-68.

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

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

Tupker RA, Doeglas HM: Water vapour loss threshold and induction of cholinergic urticaria. Dermatologica 1990; 181(1): 23-5[Medline].

Warin R, Champion R: Urticaria. Philadephia: WB Saunders 1974; 136-144.

NOTE:

Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. FULL DISCLAIMER

eMedicine Journal, August 2 2000, Volume 1,

Number 8

© Copyright 2001, eMedicine.com, Inc.

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Author Information | Introduction | Clinical | Differentials | Workup | Treatment | Follow-up | Pictures | Bibliography