**2. Cholinergic urticaria (CU)**

Physical urticaria (PU) is a subgroup of acquired, chronic inducible urticaria which is associ‐ ated with a known physical trigger [5]. In PU, the symptoms are induced by exogenous physi‐ cal triggers such as friction, pressure, vibration, cold, heat or solar radiation. All the PUs may manifest with both wheals and angioedema at the sites of the triggers with the exceptions that urticaria factitia (symptomatic dermographism) presents with wheals only and pressure urticaria presents with angioedema only [6, 7]. **Table 1** summarizes the types and subtypes of

Cholinergic urticaria is another subtype of inducible urticaria. Because of the fact that the symptoms are not triggered by exogenous physical exposure, cholinergic urticaria is not con‐

Almost 0.5% of the population suffers from chronic inducible urticaria that makes nearly 15–25% of all chronic urticarias [7]. All forms of urticaria do not only cause impaired quality of

Delayed pressure urticaria Vertical pressure

Solar urticaria UV or visible light Symptomatic dermographism Mechanical stroking

Exercise‐induced anaphylaxis Physical exercise

Vibratory urticaria Vibration

*Other inducible urticarias* Aquagenic urticaria Water at any temperature

Heat urticaria Hot contact (air, water and solid)

Contact urticaria (Non)immunological contactant Cholinergic urticaria Increment of body temperature

sidered as PU. Rather, it is induced by an increase in the body core temperature [8].

*Physical urticarias* Cold urticaria Cold contact (air, water and solid)

chronic inducible urticaria and the triggering agents.

28 A Comprehensive Review of Urticaria and Angioedema

**Table 1.** Classification of chronic inducible urticaria.

**Type Subtypes Trigger**

**Figure 1.** Classification of urticaria, according to EAACI/GA2LEN/WAO 2013 guideline.

Cholinergic urticaria, simply, is a type of chronic urticaria which is triggered by elevated body temperature. Physical exercise, strong emotions, hot or spicy food and hot showers seem to be the most common causes [13]. CU accounts for 5% of all chronic urticaria cases [7]. Generalized flushing, itching and wheals surrounded by macular erythema make the clini‐ cal picture in CU. The lesions spread from the trunk and neck to the extremities. Some of the CU cases are complicated with systemic symptoms such as hypotension, angioedema and bronchospasm [14]. CU due to exercise starts 5–10 min after the beginning of the exercise and maximizes after 12–25 min [15].

The pathophysiology in CU is thought to be related to the elevation of histamine in the serum. Adachi et al. proposed that CU occurs after a type 1 allergic reaction to the patient's own sweat. They reported that the patients underwent autologous sweat testing and demonstrated an immediate skin reaction [8].

In case of a suspicion, confirmatory testing should be conducted. Appearance of whealing after the intradermal injection of 0.01 mg methacholine in 0.1 ml saline is diagnostic. Assuming that only one‐third of the patients demonstrate positive testing CU cannot be ruled out with a negative provocation test [9]. Specific provocative challenges such as exercise, hot showers or spicy food trials can also be tried. The best way to provoke is to increase the individual's body temperature by submerging the patient in a hot water bath at 40°C. Developing of general‐ ized hives confirms the diagnosis [6]. Unfortunately, this testing can have interference with aquagenic urticaria (AU) or heat urticaria.

Best treatment of CU is the avoidance of the offending stimulus in cases where possible. First‐ line medical therapy is the oral antihistamines. Hydroxyzine is believed to be more effec‐ tive than the others [16]. Oral anticholinergics have been tried with failure mostly. Use of pre‐exercise propranolol 80 mg daily has been found effective in controlling the symptoms of CU [17]. These data have not been supported by further studies because of the fact that beta‐blockers, themselves, cause allergic reactions.

The prognosis of CU is mostly pleasing. About 70% of the patients heal within 10 years of the diagnosis. Sibbald et al. estimated the duration of CU to be 3–16 years with an average of 7.5 years [2].

Cholinergic urticaria must be distinguished from exercise‐induced anaphylaxis (EIA). The main symptoms of EIA include laryngospasm, bronchospasm, vascular collapse, fatique, vocal changes, gastrointestinal upset, flushing and hives [18]. In contrast to CU, the urticarial plaques are larger, up to 10–15 mm. All types of exercise including walking can be the trigger. In EIA, although the anaphylaxis symptoms are at the forefront, only a few cases of death have been reported [19].

EIA is treated like any other forms of anaphylaxis. Epinephrine is the life‐saving treatment. Diphenhydramine 25–50 mg is helpful. Systemic steroids are used to prevent delayed bipha‐ sic reactions [20]. Any individual with the diagnosis of EIA should carry an epinephrine auto‐ injector [21]. Cetirizine and montelukast combination also has been reported to be useful in preventing symptoms of EIA [22].

CU can be differentiated from EIA with the size of the whealings. Also, in CU, the hives are in the front, whereas the edema and the anaphylaxis are in the front in case of EIA. In addition, passive warming test in a bath and methacholine injection tests are positive in CU [23].
