APPRAISAL OF THE VALIDITY OF HISTAMINE-INDUCED WHEAL AND FLARE TO PREDICT THE CLINICAL EFFICACY OF ANTIHISTAMINES

Antihistaminic drugs have been used successfully for many years in the treatment of allergic diseases. Second-generation antihistamines have fewer sedating side effects than first-generation agents, and the num ber of newer drugs available for clinical use is growing. Various meth ods have been used to assess antihistaminic activity, the most popular of which is the epicutaneous histamine-induced wheal and flare. This test relies on the ability of epicutaneously injected histamine to bri ng about the wheal and flare, a neurovascular response that involves r eflex vasodilation (flare) and local swelling caused by plasma extrava sation (wheal). Antihistamines have been compared on the basis of thei r ability to block the histamine-induced wheal and flare in the skin. Results of these trials have been applied to predict the global antial lergic efficacy of various antihistamines. This review has examined th e reliability of suppression of the histamine wheal and flare reaction in the skin to predict an antihistamine's clinical efficacy in two co mmon allergic diseases, seasonal allergic rhinitis and chronic idiopat hic urticaria. Although histamine is one mediator in the allergic resp onse in the skin and nasal mucosa, many other agents are important mod ulators of the allergic response. In addition, the major structural an d functional differences that exist between the nasal mucosa and the s kin affect the type of local response. These manifest themselves as di fferences between the responses to antigen and histamine challenge in the skin and the nose. The allergic responses in these tissues are not simply the consequence of one chemical but are the result of a cascad e of interactions among various cells and mediators. The clinical mani festations of these complex interactions obviously cannot be fully rep licated by injection of one chemical mediator, histamine, into the out er layer of the skin. Studies with antihistamines have shown that cert ain drugs, such as cetirizine, are more suppressive than others (lorat adine, terfenadine) in controlling the histamine-induced wheal and fla re reaction in the skin. When the clinical efficacy of these medicatio ns is compared in clinical trials in seasonal allergic rhinitis and ch ronic idiopathic urticaria, all are equally efficacious in controlling symptoms. Although the histamine-induced wheal and flare reaction can serve as a useful clinical pharmacologic test to assess dose-response relations for antihistamine, its lack of correlation with clinical re sponses among antihistamines indicates that this model should not be u sed to predict or compare clinical efficacies of antihistamines in sea sonal allergic rhinitis and chronic idiopathic urticaria.