Nghiem Paul, Pearson Greg, Langley Richard G
Cutaneous Oncology Unit, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
J Am Acad Dermatol. 2002 Feb;46(2):228-41. doi: 10.1067/mjd.2002.120942.
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.
他克莫司软膏是一种磷酸酶钙调神经磷酸酶的局部抑制剂，最近在美国被批准用于治疗特应性皮炎。它是第一种非氢化可的松衍生物的局部免疫抑制剂，而氢化可的松衍生物在近50年里一直是皮肤科的重要帮手。尽管他克莫司穿透厚皮肤的能力不如糖皮质激素，但它不会引起皮肤萎缩，这是相对于氢化可的松类药物的一个重要优势。吡美莫司（ASM 981）是一种与他克莫司密切相关的新型钙调神经磷酸酶抑制剂，也正在开发用于特应性皮炎的治疗。吡美莫司具有不同的皮肤渗透特性，但与他克莫司有相同的作用机制。在这篇综述中，我们记录了钙调神经磷酸酶抑制剂的发现、它们作为细菌对抗真菌的“智能炸弹”的假定进化作用、在免疫系统中的分子和细胞作用机制、全身和局部副作用、在特应性皮炎中的疗效以及在皮肤科专业领域的未来应用。特别关注他克莫司的全身吸收问题、吸收可能成为问题的情况、相对于糖皮质激素的疗效以及成人和儿童使用0.03%或0.1%他克莫司软膏的选择。
