Paradoxical exacerbation of chronic urticaria by H1-antihistamines and montelukast.

Histamine is the main mediator of urticaria and H1-receptor antagonists represent the treatment of choice in all patients with chronic urticaria. Leukotriene receptor antagonists as montelukast have also been used in patients with chronic urticaria unresponsive to H1-antihistamines alone. We report a patient with chronic urticaria whose disease was paradoxically exacerbated by H1-antihistamines and montelukast, and controlled by immunosuppressive drugs as ciclosporin and azathioprine. Urticaria exacerbations were caused by different molecules including either piperidine (fexofenadine, desloratadine, ebastine, rupatadine) or piperazine (hydroxyzine, cetirizine) derivatives as well as by montelukast suggesting that an IgE-mediated mechanism was not involved. A possible explanation of the observed urticaria exacerbation is that H1-antihistamines and montelukast may shift the H1 histamine receptor and the leukotriene receptor to the active conformation instead of the inactive state. The beneficial effects of ciclosporin and azathioprine confirm that immunosuppressive drugs have an important role in the treatment of refractory chronic urticaria and back the hypothesis that an autoimmune/autoreactive mechanism often underlies the disease.