Cholinergic Urticaria

Updated: Apr 04, 2017
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD  more...
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Overview

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 four subtypes [2] :

  • Cholinergic urticaria with poral occlusion
  • Cholinergic urticaria with acquired, generalized hypohidrosis with idiopathic pure sudomotor failure and localized hypohidrosis showing sweat gland eosinophilic infiltration [3]
  • Cholinergic urticaria with sweat allergy
  • Idiopathic cholinergic urticaria

See also the Medscape Drugs & Diseases 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.

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Etiology

Mast cells seem to be critically involved in cholinergic urticaria. In fact, cholinergic urticaria has been used to study mast cell activity. [4] 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. [5]

One report showed positive immediate sensitivity to sweat with passive transfer. [6] 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. [7, 8] 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. [9] 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. [10]

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. [11]

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. [12] Superficial obstruction of the acrosyringium has sometimes been associated with acquired generalized hypohidrosis. [13]

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

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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. [14] 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%. [15]

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.

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