Antihistamines were introduced in France by Halpern in 1942 and in the United States at the end of World War II; they had been investigated extensively during the war for therapy of motion sickness. By the late 1940s, a mass of information on the structure activity relationship had accumulated and most major drug manufacturens had introduced antihistamines into the market for oral, parenteral, and topical administration. Topical use was efficacious in acute dermatitis because the local anesthetic activity of the drugs diminished pruritus.
The first reports of sensitization to the topical antihistamines, which began to appear in 1947, incriminated tnipelennamine (Pyribenzamine), diphenhydramine (Benadryl), antazoline (Antistine), and pheniramine (Trimeton).1-4 In the ensuing 25 years, though thousands of instances of antihistamine contact dermatitis have occurred, many topical antihistamines remain on the market. The Committee is concerned about the use of topical antihistamines which are sold over the counter for use in such conditions as chickenpox and poison ivy. Table I lists most of the preparations currently available for topical use.
CLASSES OF ANTIHISTAMINES
The antihistamines are classified according to their chemical structure into five primary groups as shown in Table II. Each drug carries its own index of sensitization and other adverse effects when employed topically. The ethylenediamine derivatives include the following: antazoline phosphate (Antistine), promethazine hydrochloride (Phenergan*), and tripelennamine (Pyribenzamine). They are particularly active in inducing contact dermatitis and were responsible for the cases first reported.5,6 Ethylenediamine, because of its dibasic structure, is widely used in various organic syntheses for the preparation of dyes, inhibitors, rubber accelerators, fungicides, synthetic waxes, resins, insecticides, and asphalt-wetting agents.