D3.381 - The paradox of treatment: H1-antihistamines-induced urticaria in a patient with chronic spontaneous urticaria

Background: Hypersensitivity reactions to H1-antihistamines are very rare; however, paradoxical urticaria (PU) caused by antihistamines has been reported in the literature. While the exact mechanism of this phenomenon remains unclear, several pathogenic hypotheses have been proposed: mast cell degranulation via the complement pathway, disruption of the arachidonic acid pathway and shifting the H1 histamine receptor to the active conformation. Diagnosing antihistamine-induced urticaria presents a significant challenge, particularly in patients with chronic spontaneous urticaria (CSU).

Case report:  A 41-year-old female patient with an atopic constitution was diagnosed with CSU. She was also suffering from allergic rhinitis due to the pollen allergy and had a history of hypersensitivity cutaneous reaction to ibuprofen. After years of good tolerance to antihistamines, she recently reported the onset of urticaria flares occurring within one hour of antihistamine intake. Urticaria exacerbations were caused by multiple antihistamines, including piperidine (rupatadine) and piperazine (cetirizine and levocetirizine) derivatives. Suspecting PU, the incriminated antihistamines were stopped, and the patient underwent an oral provocation test (OPT) with an antihistamine from the alternative class, bilastine. Following a negative OPT, she continued to use bilastine without any adverse effects.

Conclusion: Although uncommon, antihistamine-induced urticaria in CSU patients may occur and must not be underestimated. Considering the proposed pathogenic hypotheses, patients with an atopic background and a history of cross-reactivity to nonsteroidal anti-inflammatory drugs may be at an increased risk.