Rebound Pruritus and Urticaria After Discontinuation of Chronic Antihistamine Use-A Scoping Review

Rebound pruritus and urticaria have been increasingly reported following discontinuation of chronic antihistamines, particularly with cetirizine and levocetirizine, prompting the United States Food and Drug Administration to issue a recent safety warning for these two medications. Currently, there are significant gaps regarding the risk factors, course and optimal management of rebound pruritus and urticaria after discontinuation of chronic antihistamine use, and if this represents a class-specific adverse effect. This review aimed to map the literature related to rebound pruritus and urticaria after discontinuation of chronic antihistamine use.

A scoping review was conducted across four major literature databases (PubMed, Embase, Web of Science and Cochrane database) and grey literature (GreySource, OpenGrey, Google Scholar) from inception to December 2025. Articles describing rebound pruritus following discontinuation of chronic antihistamine use in paediatric or adult populations were included. Antihistamines evaluated included all first- and second-generation histamine-1 antagonists. Non-English articles were excluded. A narrative synthesis was conducted to summarise the reported risk factors, clinical course and potential management strategies for rebound pruritus following antihistamine discontinuation.

Of the 17,346 records retrieved, two retrospective studies, one case series and one case report were included in the review. The studies were conducted in the United States (n = 2), the Netherlands (n = 1) and Singapore (n = 1). The main antihistamines implicated in after discontinuation rebound pruritus were cetirizine (n = 327), levocetirizine (n = 39) and, both cetirizine and levocetirizine (n = 2). Among these patients, 85 patients experienced concomitant urticaria after discontinuation of chronic antihistamines. No report was noted for other antihistamines. The patients' age ranged from 6 to 71 years, with a female predominance (76.1%). Antihistamine use ranged from months to years, with pruritus developing between 1 to 5 days after discontinuation. Among the common treatment strategies adopted, cetirizine or levocetirizine re-initiation was the most effective (n = 136 of 137, 99.2%), while antihistamine tapering had the lowest rate of symptoms resolution (n = 11 of 33, 33.3%).

Rebound pruritus following discontinuation of chronic cetirizine or levocetirizine use represents a clinically relevant adverse effect that warrants careful monitoring and management. Future research is required to identify the optimal treatment strategy and if the discontinuation of other antihistamines could also lead to rebound pruritus.