**3. Aquagenic urticaria (AU)**

Aquagenic urticaria (AU) is a rare form PU which is characterized by wheals following cuta‐ neous exposure to water, including tears and sweat. Mostly, 1–3 mm follicular wheals and 1–3 cm erythematous flares surrounding them are present. The lesions develop 20–30 min after exposure to water. Lesions usually resolve in 30–60 min after the cessation of contact to water [4]. Most of the patients are peri‐pubertal females. Trunk and proximal arms are the most commonly affected sites, sparing palms and soles [5]. Wheezing and dyspnea can accompany the lesions. When there is such a systemic symptom, large lesions rather than 1–3 mm punctate lesions are present [24].

Most of the AU cases are sporadic. However, there are some reports of familial cases. No spe‐ cific gene locus has been identified so far [5]. There are few cases showing the association of AU and HIV infection and papillary thyroid gland carcinoma [25, 26].

The pathogenesis of AU is not clear yet. In 1981, Tkach hypothesized that sudden changes in osmotic pressure around hair follicles, leading to passive diffusion of water caused whealing [27]. A recent proposal involves existence of water‐soluble antigens in the epidermis which later migrate to dermis and cause histamine release [10]. The lack of a proper etiologic mecha‐ nism makes AU difficult to treat.

Water challenge test is necessary for the proper diagnosis. For this, water at room temperature is applied to a cloth, and this cloth is applied to patient's skin for 20 min. In case of an urticar‐ ial lesion, the provocation test is considered as positive. Water should be at room temperature. Because, if the temperature is higher or lower, the test could give arise to other forms of PU (cold or heat urticaria) [28]. Bayle et al. reported a case with AU, dermatographism and cho‐ linergic urticaria at the same time [29]. It is possible to induce AU, heat urticaria, cold urticaria and cholinergic urticaria with applying water at different temperatures [30]. So, one should be very careful to differentiate among these conditions.

Management of AU is difficult. Avoidance is almost impossible. The first‐line therapy is H1 antihistamines [11]. Long acting newer antihistamines with fewer side effects are usually pre‐ ferred. H2 receptors are thought to be not operating in the pathogenesis of PU. Yet there is a case report that claims that H2 antihistamines reduce wheal response [31].

Topical barrier therapies show promising results in AU. They are also safer. Application of oil‐in‐water emulsions before bathing can reduce wheals. Such physical barriers must be used in the pediatric patients before everything else to prevent the potential side effects of the anti‐ histamines [29].

Phototherapy, both PUVA and narrow‐band UVB, has been reported to be effective in AU treatment. Possible action of mechanism is the reduction of mast cell activity and thickening of the skin, mostly epidermis, leading to decreased water penetration [32].

Stanozolol which is used in the treatment of hereditary angioedema was shown to be effective in one male patient at a dose of 10 mg daily [25].
