H1-antihistamines are commonly used drugs, and probably the most frequently used for allergic diseases.
They are pharmacologic inverse agonists of histamine at H1 receptor sites and try to shift the equilibrium of this receptor toward the inactive state, preventing H1 response. A wide variety of adverse effects have been attributed to antihistamines, and they can exceptionally induce skin reactions.
We report the case of a patient with several episodes of urticaria induced by different families of antihistamines - piperazines and piperidines.
We performed skin prick tests (SPT), patch tests and oral challenges to different antihistamines. We found positive SPT to some antihistamines, and positive oral challenge in others with negative SPT. The route of sensitization remained unclear, and our patient could not finally tolerate any antihistamine after the oral challenges we performed.
We support the hypothesis that antihistamines may shift the H1 histamine receptor to the active conformation instead of the inactive conformation, prompting adverse reactions after dosing.
This is the first report of urticaria induced by different antihistamines in the same patient with positive SPT to several others.

Key words: Antihistamines, H1 inverse agonist, H1 receptor, urticaria.