CLINICAL QUESTION: Do antihistamines relieve itching in atopic dermatitis?
BACKGROUND: Atopic dermatitis is a common malady characterized by intense pruritus. The itch-scratch cycle exacerbates the problem and is frequently treated with antihistamines, although there is little evidence for their effectiveness. population studied n Three European trials enrolled patients ranging in age from 11 to 67 years who met inclusion criteria for atopic dermatitis.
STUDY DESIGN AND VALIDITY: This was a systematic review in which the authors evaluated randomized controlled trials examining the effect of antihistamines on pruritis in atopic dermatitis. Sixteen studies were initially identified by searching MEDLINE (1966 to 1999), The Cochrane Database of Systematic Reviews, and Best Evidence databases. The authors used a modified version of Sackett’s criteria for clinical evidence to assess quality. Thirteen trials that received a grade of C by the Sackett criteria were excluded because of lack of randomization, placebo control, blinding, or a sample size of less than 20 people. The remaining 3 studies were randomized double-blind placebo-controlled trials. However, all had small sample sizes, and therefore received a grade of B. There were no grade-A studies.
Terfenadine, clemastine fumurate, and cetirizine hydrochloride were evaluated in these 3 studies. All 3 trials permitted the use of emollients and topical steroids. The first 2 studies enrolled fewer than 30 subjects but used a crossover design; this design reduces the needed sample size, since each patient reduces variance by serving as his or her own control. The cetirizine trial enrolled 178 patients who were divided into 4 parallel comparison groups.
The 3 studies suffered from small sample size, which can lead to the possibility of missing a benefit from antihistamines when one existed. Two of the studies excluded dropouts in their analysis, a potential threat to validity. The authors of the systematic review apparently did not contact authors of previous studies to see if additional data were available. Since all 3 of the studies used similar visual analog scales for rating pruritus and had similar patient groups, the data could have been pooled to allow a meta-analysis. Such a meta-analysis would not have been specific for any one of the studied antihistamines but would have helped overcome concerns about sample size.
OUTCOMES MEASURED: All 3 trials used visual analog scores to report the severity of pruritus. Investigator assessments (severity of excoriation or visual analog scores) were used in 2 of the studies. A computerized method of recording symptoms by patients was used in the third.
RESULTS: No improvement in pruritus was found in the 2 smaller crossover trials for terfenadine or clemastine fumurate. In the third trial, the 13 patients taking higher doses (40 mg) of cetirizine and experiencing sedation had an improved mean pruritus score. However, the range of scores overlapped considerably with patients who did not experience sedation, suggesting that the difference may not be significant. Unfortunately, no statistical analysis was done on the effect size.
Although the existing studies are limited in quality and quantity, this systematic review finds no evidence that second generation antihistamines are helpful in relieving pruritus due to atopic dermatitis. Clinical trials of better quality, employing a larger sample size and evaluating both first and second generation antihistamines, would be particularly helpful.