November 28, 2021

Uncertainty about the effectiveness of an antihistamine overdose in chronic urticaria

Between 0.5 and 1% of the population suffers from chronic spontaneous urticaria (CSU) which is characterized by recurrent itchy papules and / or angioedema which may persist for up to six weeks.

While the precise cause of UHC remains uncertain, contemporary European guidelines advocate the use of second-generation antihistamines as the first-line treatment for the disease. Although these drugs may be effective, for patients in whom symptom control remains insufficient, the recommendations recommend increasing the dose to four times the recommended dose as a second-line treatment option.

This latter recommendation is based on expert opinion and for this study a team from the Allergology Department, Complexo Hospital, La Coruña, Spain, set out to review the available evidence to support this approach. They included studies published in English or Spanish with patients at least 12 years of age with CCA receiving regular treatment (as opposed to “on demand”) with a second generation antihistamine. Other inclusion criteria were that the study should have a single antihistamine (rather than a combination), a placebo arm, and use the drug at a higher dose than recommended.

Results
In total and after removal of duplicates and exclusions, only 14 articles were analyzed in detail including 20 to 439 patients. Six studies focused on fexofenadine (dose escalation to 720 mg), 2 on cetirizine, levocetirizine, rupatadine, desloratadine and 1 trial on ebastine or bilastine. In addition, only 5 of these trials were placebo-controlled and all of the studies lasted between 2 and 8 weeks except one trial with fexofenadine which lasted 16 weeks. A higher dose of fexofenadine produced a significant dose-dependent response and controlled UHC in the majority of patients. Commenting on their results, the authors noted that of the 14 trials, only 6 were of high quality and the high level of heterogeneity in sample size, design, duration, etc., made comparisons very difficult. . Interestingly, they also note that despite the current guideline recommendations, most studies have not found a significant impact on overdose symptom control.

The authors concluded that while increasing the dose appears to be both effective and safe, there is a lack of evidence to support this approach and requested additional studies to validate the guideline recommendations.

Reference
Iriarte SP T et al. Overdose of antihistamines in chronic spontaneous urticaria: efficacy and tolerance. A systematic review of the literature. J Investig Allergol Clin Immunol 2020 doi: 10.18176 / jiaci.0649


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