TOPLINE

Oral antihistamines added to standard atopic dermatitis treatment likely result in statistically detectable but clinically unimportant reductions in eczema severity and itch. First-generation antihistamines likely increase cognitive impairment and may increase treatment discontinuation because of adverse events, while second-generation agents show varying cognitive impairment risks.

METHODOLOGY

• Researchers conducted a systematic review and network meta-analysis of 47 randomized controlled trials involving 6230 children and adults with moderate to severe atopic dermatitis from database inception to May 5, 2025.
• Investigators evaluated add-on oral H1 antihistamines (first and second generation), H2 blockers, and mast cell stabilizers compared with placebo or with each other, with most trials (77%) reporting concomitant background treatments such as moisturizers or topical corticosteroids.
• Primary outcomes included clinician-reported atopic dermatitis severity using objective scoring atopic dermatitis (oSCORAD, 0-83 scale; minimally important difference 8.2), itch severity (numerical rating scale, 0-10; minimally important difference 3), sleep disturbance, quality of life, and adverse events including cognitive impairment.
• Analysis used Bayesian random effects network meta-analysis with Markov chain Monte Carlo approaches, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for network meta-analysis.
• Studies were conducted internationally and included participants with a median reported mean age of 20 years (range 1-43), with 57% of trials including pediatric participants and 66% being placebo controlled.

TAKEAWAY

• Second-generation H1 antihistamines likely resulted in a statistically detectable but not clinically important reduction in atopic dermatitis severity (mean difference, -1.87; 95% credible interval, -3.47 to -0.27; moderate certainty) and itch severity (mean difference, -0.89; 95% credible interval, -1.41 to -0.37; moderate certainty), with effect sizes falling well below minimally important differences.
• First-generation H1 antihistamines likely increase cognitive impairment (odds ratio [OR], 3.24; 95% credible interval, 0.99 to 10.64; risk difference, 66 more per 1000; 95% credible interval, 0 to 231 more; moderate certainty) and may increase treatment discontinuation because of adverse events (OR, 4.61; 95% credible interval, 1.10 to 19.21; risk difference, 29 more per 1000; 95% credible interval, 1 to 131 more; low certainty).
• Among second-generation H1 antihistamines, loratadine does not increase cognitive impairment risk (0 more per 1000; 95% credible interval, 6 fewer to 7 more; high certainty), while cetirizine (17 more per 1000; 95% credible interval, 12 to 21 more; high certainty) and levocetirizine (16 more per 1000; 95% credible interval, 5 to 30 more; moderate certainty) increase cognitive impairment.
• According to the authors, all antihistamines investigated may not importantly differ from placebo in improving sleep disturbance (low certainty) or reducing atopic dermatitis exacerbations, with no antihistamines increasing serious adverse events (high certainty for first- and second-generation H1 antihistamines).

IN PRACTICE

"Among patients with atopic dermatitis, adding H1 antihistamines probably results in a clinically unimportant reduction in atopic dermatitis severity and itch severity, and may not reduce sleep disturbance or atopic dermatitis exacerbations. First generation agents increase cognitive impairment and may increase treatment discontinuation because of adverse events. Cognitive impairment risk differs among second generation agents. These findings provide evidence against routine antihistamine use in atopic dermatitis management and will inform updated clinical guidelines," wrote the authors of the study.

SOURCE

The study was led by Alexandro W.L. Chu, McMaster University in Hamilton, Ontario, Canada, and Derek K. Chu, MD, PhD, McMaster University in Hamilton, Ontario, Canada. It was published online in BMJ.

LIMITATIONS

Trial populations differed in baseline atopic dermatitis severity, though researchers addressed this through analyzing changes from baseline and conducting structured assessments, finding consistent lack of effects across the spectrum of baseline severities. Some crossover trials reported results over the entire trial duration rather than by crossover period, introducing potential crossover effects, though risk of bias assessments evaluated these effects and subgroup analyses comparing parallel versus crossover trials yielded consistent results. The review includes nearly 60 years of trials during which atopic dermatitis assessment and management has evolved, though the oral H1 antihistamines evaluated are longstanding agents with stable pharmacology and similar dosing in current practice. Subgroup analyses, while providing limited statistical support for clinically important effect modification, may be constrained by low sample sizes for subgroups, potentially limiting the ability to detect true effect modifications.

DISCLOSURES

This study received support from the American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma and Immunology through the Joint Task Force on Practice Parameters for Atopic Dermatitis. The funder contributed to defining the scope of the review but had no role in study design, data collection, data synthesis, or data interpretation. Julie Wang disclosed receiving research support paid to their institution from the National Institute of Allergy and Infectious Diseases, DBV Technologies, and Siolta, and consultancy fees from DBV Technologies and Novartis, outside of the submitted work. Derek K. Chu holds an EJ Moran Campbell Career Award, Canadian Institutes of Health Research Inclusive Excellence Prize, and Canadian Institutes of Health Research Implementation Science Chair in Human Development, Child, and Youth Health. All other authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.