Long-term reduction in local inflammation by a lipid raft molecule in atopic dermatitis.

Abstract

The complex pathogenesis of atopic dermatitis (AD) is guided by cell surface receptor-mediated signal transduction regulated in lipid rafts. Miltefosine is a raft-modulating molecule targeting cell membranes. With this controlled clinical study, the clinical and immunomodulatory efficacy of miltefosine was investigated in patients with AD in comparison with a topical corticosteroid treatment. Sixteen patients with AD were treated topically with miltefosine and hydrocortisone localized on representative AD target lesions for 3 weeks. To assess the clinical efficacy, the three item severity (TIS) score was evaluated before, during and after treatment as well as after 4-week-follow-up period. To study the anti-inflammatory effect of miltefosine on the cellular T cell pattern, skin biopsies were analysed before and after treatment. The TIS score dropped in both groups significantly after treatment. A carry-over effect was exclusively seen for miltefosine after discontinuing the treatment. These findings were substantiated by thermographic imaging with a significant decrease in the maximum temperature (T(max)) after miltefosine application (P = 0.034, DeltaT(max) = 1.7 degrees C [2.1-3.9]). Immunohistochemically, a reduction in lesional CD4(+)-infiltrating T cells was observed in both treatments. Moreover, increased FoxP3(+) cells were present in the skin after miltefosine treatment (before 5.4% [1.9-9.8], after 6.2% [3.5-9.5]). We demonstrate that miltefosine is locally active in patients with AD and led to a sustained clinical improvement in local skin inflammation. Moreover, the increased frequency of FoxP3(+) cells in the skin of patients with AD suggests its immunomodulatory properties.