Topical corticosteroids are now the first-line treatment for atopic dermatitis. Short-term use of corticosteroids is beneficial; however, long-term usage is linked to connective tissue suppression, which manifests as skin atrophy or therapeutic resistance. For atopic dermatitis, two topical noncorticosteroid immunomodulators, tacrolimus (FK506) and pimecrolimus (SDZ ASM 981) are currently being developed or are already on the market in some countries. The structural similarities between these two molecules are striking. They attach to the same biological receptor in T lymphocytes, the FK-binding protein (FKBP) or macrophilia-12. When compared to pimecrolimus, tacrolimus has a 3-fold higher affinity for FKBP. The tacrolimus/pimecrolimus-FKBP complex also binds to calcineurin, an enzyme that is required for T cell activation early on. The absence of activation of both T helper cell types 1 and 2 is a result of calcineurin binding. Other inflammatory cells, such as Langerhans cells and mast cells/basophils, have been proposed to be affected by these chemicals. In contrast to corticosteroids, connective tissue cells have not been shown to be suppressed. When inflammation is treated holistically, the skin’s barrier function is restored. When compared to systemic usage, this results in lower medication bioavailability.

Both tacrolimus (at 0.03 and 0.1%) and pimecrolimus have been demonstrated to be effective in placebo-controlled trials (at 0.6 and 1%). The most common side effects in these investigations were a burning feeling and increased pruritus at the application site.