Antihistamines Panned for Eczema

— Network meta-analysis finds no meaningful benefit across the board and some harms

Antihistamines hold only a slight benefit for atopic dermatitis (eczema) and shouldn’t be routinely used in management, a network meta-analysis concluded.

For moderate to severe atopic dermatitis, adding a first-generation H1 antihistamine had no significant impact on severity of the condition or itch severity compared with placebo, found Derek K. Chu, MD, PhD, of McMaster University in Hamilton, Ontario, and colleagues.

Adding second-generation H1 antihistamines yielded reductions in atopic dermatitis severity (mean difference -1.87 on the 0-83 oSCORAD scale, 95% credible interval [CrI] -3.47 to -0.27) and itch severity (-0.89 on a 0-10 point numerical rating scale, 95% CrI -1.41 to -0.37) that were “well below established minimal important differences,” Chu’s group reported in The BMJ.

First-generation agents also had moderate certainty evidence for increased cognitive impairment (risk difference 66 more per 1,000, 95% CrI 0 to 231), while the second-generation agents ranged in risk of cognitive impairment from no more risk than placebo with loratadine to a statistically significant 16-17 more cases per 1,000 patients for levocetirizine and cetirizine.

“The findings support moving away from routine antihistamine use in atopic dermatitis care and toward treatments that are more effective, less likely to cause harm, and are more certain to control eczema inflammation. This may also help keep eczema control as simple and straightforward as possible, with patients focusing on high-value treatments,” Chu said in a statement.

Despite widespread use based in reasoning that histamine inhibition and sedation might reduce the frequent itch and sleep disturbance common in eczema, clinical practice and guidelines vary in recommending for or against adding oral antihistamines for atopic dermatitis, or stating no recommendation is possible owing to lack of evidence, the researchers noted.

“Our review’s moderate and high certainty findings of harms and no clinically important benefit of oral antihistamines added to placebo with or without background topical treatments can support stronger, more consistent recommendations in updated evidence-based clinical practice guidelines,” Chu and colleagues wrote.

Indeed, almost all moderate to severe eczema patients should have antihistamines deprescribed in favor of sticking with the more effective topical anti-inflammatory treatments, biological agents, and small molecule drugs, they argued.

“The main scenario in which antihistamines may still have a role is in patients with associated allergic conditions that respond to antihistamines (e.g., urticaria or rhinoconjunctivitis),” Chu’s group suggested. “Those wishing to take advantage of sedating effects, in the absence of proven sleep-directed treatments, may also favor continuing first-generation antihistamines; however, no data were reported on their effects in improving sleep disturbance.”

The network meta-analysis encompassed 47 randomized trials with a total of 6,230 children and adults who had mainly moderate to severe atopic dermatitis.

The only small trial to look at atopic dermatitis-related quality of life found little to no difference between levocetirizine and placebo (mean difference 0.22, 95% CrI -3.05 to 3.49). While four trials looked at impact on sleep disturbance, none showed an important difference between an antihistamine and placebo for this measure. None of the 13 trials that looked at eczema exacerbations showed an impact of antihistamines either.

Treatment discontinuation because of adverse events was 4.61-fold more likely with a first-generation H1 antihistamine than placebo (risk difference 29 more per 1,000, 95% CrI 1-131 more; low certainty) but not more likely with second-generation H1 antihistamines or H2 blockers. Serious adverse events didn’t appear elevated across antihistamines.