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Mild-to-Moderate Psoriasis - part 5

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Các chất ức chế calcineurin được phát triển như là một thay thế cho glucocorticoid dùng tại chỗ và hệ thống cho điều trị ức chế miễn dịch. Họ chủ yếu được sử dụng cho công tác phòng chống thải ghép cơ quan. | __9__ Topical Calcineurin Inhibitors Patricia Tinio and Mark G. Lebwohl Department of Dermatology Mount Sinai School of Medicine New York New York U.S.A. The calcineurin inhibitors were developed as an alternative to topical and systemic glucocorticoids for immunosuppressive therapy. They were primarily used for the prevention of organ transplant rejection. These drugs include cyclosporin and the macrolides tacrolimus FK 506 and most recently pimecrolimus SDZ ASM 981 which are known to modify immune function by inhibition of calcineurin-dependent reactions critical in the production of inflammatory cytokines 1 . Cyclosporin is effective in and approved for the treatment of inflammatory dermatoses including psoriasis but is limited by systemic side effects such as renal toxicity and hypertension and topical cyclosporin has almost negligible skin penetration 2 3 . Tacrolimus and pimecrolimus have smaller molecular weights giving them the advantage of better skin penetration which led to the development of topical formulations. Both topical tacrolimus and pimecrolimus do not cause skin atrophy mainly because calcineurin is not needed for collagen synthesis 1 4 . This is in contrast to topical corticosteroids which are associated with telangiectasia Fig. 1 atrophogenicity striae Fig. 2 and other local cutaneous adverse effects when used over a long period of time 5 6 . Both tacrolimus and pimecrolimus belong to the group of macrolide immunosuppressants which are xenobiotics possessing a complex structure. They are derived from several strains of Streptomyces. The first macrolide to be developed was tacrolimus which is produced by Streptomyces 105 106 Tinio and Lebwohl Figure 1 See color insert Telangectasia ear. tsukubaensis 1 . Several controlled trials have shown systemic tacrolimus to be effective in the treatment of psoriasis 7 8 . Pimecrolimus is an ascomycin derivative which is produced by another strain of .