[New horizons in the treatment of atopic dermatitis]

Nearly fifty years after their introduction, corticoids continue to be one of the main pillars of dermatological therapy in general and in atopic dermatitis in particular. However, their use is limited by local and systemic adverse effects.There is enormous demand for anti-inflammatory agents not belonging to the corticoid group that would be useful in the different inflammatory dermatoses.In the last few years the therapeutic arsenal for atopic dermatitis has increased with two distinct groups of drugs: topical immunomodulators and leukotriene inhibitors. Both groups of drugs are new and new compounds belonging to these types of drugs will probably appear in the next few years.Among the alternatives to corticoids are the immunomodulators and the most promising of these are macrolide antibiotics. Tacrolimus (FK 506) and pimecrolimus (ASM 981) belong to this group of substances with a high capacity to inhibit T lymphocyte activation. Although they also act on other cells playing a role in atopic dermatitis (mastocytes, Langerhans' cells, B lymphocytes) their action on T lymphocytes seems to be the most important. In T lymphocytes, these drugs act by inhibiting the action of calmodulin, a vital enzyme in the activation chain of these cells that ends in the production of interleukin 2 and other proinflammatory cytokines.The accumulated evidence of the various publications seems to indicate that tacrolimus is a safe and effective treatment of atopic dermatitis in patients aged 2 years or more. The drug was approved for clinical use 3 years ago in Japan and more than 1 year ago in the United States. The number of randomized clinical trials comparing this drug with placebo or various corticoids demonstrate that its action is overwhelming. Its anti-inflammatory action is similar to that of high-potency topical corticoids. Two doses daily are required and the drug has been tested in patients with moderate-to-severe atopic dermatitis. Published data from more than 10,000 patients guarantee its safety. The most frequent short-term adverse effect is a burning sensation in the site of application lasting a few minutes.Pimecrolimus has not yet been commercialized in any country and is currently undergoing phase III clinical investigations. It has been tested in three clinical trials in patients aged more than 3 months old with mild-moderate atopic dermatitis. Its safety profile is good and similar to that of tacrolimus.The number and quality of the data provided by studies of treatment with leukotriene inhibitors (zafirlukast, montelukast and zileuton) is much lower but these substances seem to warrant further investigation. Only five small series undergoing treatment with these products have been published.