Cholinergic Urticaria 

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

CU may be divided into 4 subtypes: CU with poral occlusion, CU with acquired generalized hypohidrosis, CU with sweat allergy, and idiopathic CU.^{[2, 3]}

Additional Medscape Reference articles on urticaria include Urticaria, Acute;Urticaria, Chronic;Urticaria, Contact Syndrome;Urticaria, Dermographism;Urticaria, Papular;Urticaria, Pressure; and Urticaria, Solar.

Mast cells seem to be critically involved in cholinergic urticaria; 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 alpha 1-antichymotrypsin level, as seen in some other forms of urticaria, is present, and 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.

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

Autonomic functions are normal in cholinergic urticaria. One patient with cholinergic urticaria developed an accentuated response in a positive copper test site, perhaps from either vasodilatation or augmentation of neurologic stimulation. 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 were observed in 1 second forced expiratory volumes, maximal midexpiratory flow rates, and specific conductance. An increase in residual volume was also detected.

Frequency

United States

The prevalence of cholinergic urticaria is variable. Moore-Robinson and Warin^[9] found that about 0.2% of patients in an outpatient dermatologic clinic had cholinergic urticaria. However, many published series have found cholinergic urticaria to be common. 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 study. The prevalence is 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 is also reported.

Sex

Cholinergic urticaria occurs in both men and women, but it seems to be more common in men than in women.

Age

Cholinergic urticaria usually begins 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 study. Cholinergic urticaria persists for a number of years. Most patients retain the tendency for many years.

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

In another study, almost 96% of patients with cholinergic urticaria were men, with a mean age of 22 years, whereas in another group, 31 women and 25 men had cholinergic urticaria.