Dr. Robert Schmaling: Antihistamines have limited efficacy in treating eczema

Dr. Wala’a Hafez: Approximately half of eczema patients in the United States use oral antihistamines to alleviate accompanying symptoms, primarily itching and sleep disturbances. However, a recent review suggests that these medications offer minimal benefit for treating eczema itself, with some potentially linked to side effects, particularly concerning cognitive function. These findings are significant given the widespread use of antihistamines among eczema patients, despite the fact that disease-related itching is not solely caused by histamine release but involves a complex interplay of inflammatory and neural pathways. Consequently, antihistamine-targeted drugs may not be as effective as expected in controlling atopic dermatitis-related itching.

What did the review entail?

The review, published in the British Medical Journal (BMJ) and led by Dr. Robert Shmerling, former Chief Clinical Officer of Rheumatology and current faculty member at Harvard Medical School, analyzed 47 clinical trials involving over 6,200 children and adults aged one to 43 years, most of whom suffered from moderate to severe atopic dermatitis. Researchers evaluated the efficacy of oral antihistamines, alongside several other medications, in alleviating a range of eczema-related symptoms, including skin symptom severity, itching, and sleep disturbances. They also assessed the safety of these drugs and monitored potential side effects. This review is important because it does not focus solely on whether a drug produces statistically significant improvement, but also on whether that improvement is substantial enough for patients to perceive it in their daily lives.

Limited Improvement

The results indicated that while antihistamines may lead to some improvement in eczema symptoms, the extent of this improvement was minimal—so much so that it is unlikely to be noticeably perceived by patients. According to physician assessments, both first-generation antihistamines, such as diphenhydramine (Benadryl), and newer, non-drowsy second-generation antihistamines, such as loratadine (Claritin), resulted in an average reduction of 1.87 points in eczema symptom severity on an 83-point scale. Although this numerical decrease might appear positive, it does not reach the threshold for clinically significant improvement. The threshold for patient-perceived improvement was estimated at approximately 8.2 points, meaning the difference created by antihistamines was far below the level at which patients would feel a clear improvement in their condition.

The impact was not limited to skin symptom severity; the effect of these drugs on itching was also limited. Itching scores, as reported by patients or caregivers, decreased by less than one point on a 10-point scale, whereas an improvement of approximately 3 points is considered clinically significant for the patient. Furthermore, antihistamines did not show a significant effect in reducing the frequency of eczema flare-ups, suggesting that their use does not treat the underlying mechanism of the disease nor necessarily prevent future episodes.

First-Generation Drugs and Cognitive Impact

If the benefit is limited, another question concerns the safety of these drugs, where greater concerns arise, particularly with first-generation antihistamines. The use of these medications was associated with approximately 66 additional cases of cognitive impairment per 1,000 patients, including mental confusion and memory problems, alongside higher rates of treatment discontinuation due to side effects. This is partly because first-generation antihistamines can cross the blood-brain barrier and affect the central nervous system, potentially leading to drowsiness and reduced alertness, as well as cognitive effects in some individuals. These effects may be more significant in certain groups, such as children and the elderly, or in individuals who require a high degree of concentration and attention during their daily activities.

Second-Generation Drugs

In contrast, second-generation antihistamines, designed to cause less drowsiness compared to older drugs, yielded mixed results from one drug to another. For example, loratadine was not associated with an increased risk of cognitive impairment, whereas both cetirizine and levocetirizine (Xyzal) were linked to a slight increase in cognitive risks, according to the review findings. This variation among drugs underscores that antihistamines should not be treated as a uniform group regarding efficacy and safety. Even drugs belonging to the same generation may differ in their effects on the nervous system and their likelihood of causing drowsiness or other side effects.

Should Use Be Discontinued?

These results do not necessarily mean that all eczema patients should stop taking antihistamines; rather, they suggest that routine use of antihistamines solely for treating eczema may not be justified in most cases. Researchers recommended against the routine use of antihistamines for treating atopic dermatitis, as their benefit in alleviating symptoms appears limited, while some types may carry unnecessary risks and side effects. Regular skin care, primarily the use of moisturizers and topical anti-inflammatory agents, remains a fundamental option for controlling eczema, according to a treatment plan determined by a physician. Some patients may require other treatments depending on disease severity and response to therapy.

Conversely, antihistamines may remain a suitable option when a patient also suffers from other allergic conditions responsive to these drugs, such as hives or hay fever. In such cases, their use may be justified for managing allergy symptoms rather than treating atopic dermatitis itself.

Overall, the review results indicate that oral antihistamines often do not provide significant improvement in eczema symptoms, particularly itching, and do not appear to reduce the frequency of disease flare-ups. Therefore, the decision to use them should be based on the patient’s condition and accompanying symptoms, weighing potential benefits against side effects, rather than using them routinely simply due to the presence of eczema.