Suppression of histamine- and allergen-induced skin reactions: comparison of first- and second-generation antihistamines

Nonsedating antihistamines (nsAHs) are recommended as first-line therapeutics for the treatment of mast cell-driven disorders, including allergic rhinitis and urticaria. However, their superiority over first-generation AHs (fgAHs) has recently been called into question, mainly because of the lack of supporting head-to-head therapeutic studies.

To compare the effects of 3 modem nsAHs with those of the fgAH hydroxyzine on histamine- and allergen-induced skin reactions in a controlled, double-blind, clinical trial.

Skin prick tests with histamine and Dermatophagoides pteronyssinus extract were performed before and 4 hours after treatment with hydroxyzine, 25 mg; desloratadine, 5 mg; epinastine, 20 mg; fexofenadine, 120 mg; or placebo. Wheal and erythema development was evaluated by digital photography and planimetric analyses.

The nsAHs prevented the development of positive reactions to histamine in only 10% to 20% of all individuals tested (n = 75). In contrast, more than 50% of all hydroxyzine-treated individuals showed negative test reactions to histamine (ie, wheals <7 mm2 in area or <3 mm in diameter). Similar differences, although less pronounced, were detected when comparing the effects of nsAHs with hydroxyzine on D pteronyssinus prick testing in a limited number of D pteronyssinus-sensitized individuals.

These results indicate that hydroxyzine is more effective than nsAHs when given as recommended in suppressing histamine-induced or allergic skin reactions. Our results suggest that higher doses of nsAHs than those currently recommended are required for the treatment of skin responses to obtain antihistaminic and antiallergic effects that are equivalent to those of fgAHs.