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Tacrolimus and pimecrolimus: from clever prokaryotes to inhibiting calcineurin and treating atopic dermatitis.

Abstract

Tacrolimus ointment, a topical inhibitor of the phosphatase calcineurin, has recently been approved in the United States for use in the treatment of atopic dermatitis. It is the first topical immune suppressant that is not one of the hydrocortisone derivatives, important allies in dermatology for nearly 50 years. Although tacrolimus is less able to penetrate thick skin than glucocorticoids, it does not cause dermal atrophy, an important advantage over the hydrocortisone class. Pimecrolimus (ASM 981), a newer calcineurin inhibitor closely related to tacrolimus, is also being developed for atopic dermatitis therapy. Pimecrolimus has an altered skin penetration profile but the same mechanism of action as tacrolimus. In this review we chronicle the discovery of the calcineurin inhibitors, their presumed evolutionary role as a bacterial "smart bomb" against fungi, molecular and cellular mechanisms of action in the immune system, systemic and topical side effects, efficacy in atopic dermatitis, and future applications within the specialty of dermatology. Particular attention is given to the issues of systemic absorption of tacrolimus, the conditions in which absorption can become a concern, efficacy relative to glucocorticoids, and the choice of 0.03% or 0.1% tacrolimus ointment for use in adults and children.

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  • Publisher Full Text
  • Authors

    Nghiem P, Pearson G, Langley RG

    Institution

    Cutaneous Oncology Unit, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. pnghiem@partners.org

    Source

    Journal of the American Academy of Dermatology 46:2 2002 Feb pg 228-41

    MeSH

    Administration, Topical
    Adult
    Calcineurin
    Child
    Child, Preschool
    Clinical Trials as Topic
    Dermatitis, Atopic
    Female
    Follow-Up Studies
    Humans
    Immunosuppressive Agents
    Male
    Middle Aged
    Risk Assessment
    Tacrolimus

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Review

    Language

    eng

    PubMed ID

    11807435