A Systematic Review of Aquagenic Urticaria-Subgroups and Treatment Options

Aquagenic urticaria (AquaU) is a rare variant of chronic inducible urticaria where wheals occur after skin contact with water. Information on clinical manifestations and treatment outcomes is limited, which makes the management of AquaU challenging.To systematically review disease features and relevant triggers of AquaU and patients' response to treatment.Related articles were searched by use of the terms "aquagenic urticaria" and "aquagenic angioedema" until June 2021 and reviewed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations.A total of 77 patients with AquaU were investigated in 59 studies including 47 case reports and 12 case series. AquaU predominantly presented in women (47 patients, 61%), and the mean age of onset of the disease was 19.6 ± 10.8 years (range: 0-54 years). Wheals commonly occurred in localized areas and regardless of the water temperature. Based on the reviewed evidence, AquaU can be classified as familial AquaU (FAquaU, 18.2%) and acquired AquaU (AAquaU, 81.8%). Although many treatments were used in both subtypes of AquaU, the use of second-generation HAquaU is proposed to be classified into 2 subtypes, FAquaU and the more common AAquaU. Treatment with a 2