Antihistamines represent one of the most widely used drugs and the main character for the treatment of allergic diseases. Therefore, they are not usually suspected as causes of hypersensitivity. However, although rare, there are certain published cases of allergic reactions to these drugs.

We present a 19-year-old female patient with a history of pollens hypersensitivity, who was referred to our Allergy Department due to the appearance of skin lesions 8 to 10 hours after taking cetirizine, loratadine and ebastine, with good tolerance to dexchlorpheniramine. Patch tests with cetirizine were performed with delayed reading at 48 and 96 hours. Oral drug provocation tests to cetirizine and loratadine were carried out.

Patch tests reading 48 and 96 hours later were negative to cetirizine 2.5% and 4.5%. In view of this, the study was continued; performing an oral provocation test with cetirizine. One hour after the second dose (cumulative dose 5mg), she developed erythematous and maculopapular lesions with a whitish center at palms and back of both hands. The test was stopped and lesions disappeared with intramuscular dexchlorpheniramine and methylprednisolone. One month later, an oral provocation test with loratadine was carried out and she started two hours after the last dose (cumulative dose 10mg) with the same skin lesions, resolving with the same treatment as the first time. Since loratadine and ebastine belong to the piperdine chemical group, it was decided not to undergo an oral challenge to Ebastine.

The patient was diagnosed with non-immediate hypersensitivity reaction to antihistamines verified by oral controlled exposure to cetirizine (belonging to the second generation of piperazines) and loratadine (belonging to the second generation of piperidines) with good tolerance to dexchlorpheniramine (first generation of alkylamines).