Evidence that water acts as a carrier for an epidermal antigen in aquagenic urticaria

Two female patients with aquagenic urticaria were studied in order to better clarify the pathogenesis of urticarial reactions to water. One patient suffered also from atopy and from cholinergic and chronic urticaria, and two of her sisters had noted aquagenic urticaria since puberty. The second patient had had aquagenic urticaria for only 2 years. Local applications of ethyl alcohol (96%) to the patients' skin did not elicit any lesions, and pretreatment of the skin with topically applied atropine did not inhibit whealing in response to water. Intracutaneous injections of aqueous extracts of human callus resulted in reproducible burning sensations in the patients' skin but not in control skin. Injections of buffer alone or of supernatants of stimulated epidermal cell suspension induced no abnormal reactions in patients' skin or control skin. Callus extracts also caused in vitro basophil histamine release from patients' peripheral blood basophils but not from cells of a healthy volunteer. These data suggest that patients with aquagenic urticaria react to a water-soluble antigen in the epidermal horny layer that diffuses into the dermis to cause histamine release from sensitized dermal mast cells.