银屑病治疗研究的一些进展_张长宋

10M izushima Y,Amano Y,Kitagaw a H,et al.Oral admini stration of leflunom ide(HWA486)res ults i n prominent suppression of im-munoglobulin E formation in a rat type1allergy model.J Pharmacol Exp Ther,1999,288(2):849-857.

11Coblyn JS,Shadick N,Helfgott S.Leflunom i de-associated wei ght loss in rheumatoid arthritis.Arthritis Rheum,2001,44(5):1048-1051.

12Brent RL.T eratogen update:reproductive risks of leflunomide(Ar-ava);a pyri midine synthesi s inhibitor:counseling w om en taking leflunom ide before or during pregnancy and men taking leflunomide w ho are contemplating fathering a child.T eratology,2001,63(2): 106-112.

13W einblatt M E,Dixon JA,Falchuk KR.S erious liver disease in a pa-tient receivi ng methotrexate and leflunomide.Arthritis Rheum, 2000,43(11):2609-2611.

14Schiff M H,W helton A.Renal tox icity as sociated with disease-mod-i fying antirheumatic drugs used for the treatment of rh eumatoid arthriti s.Sem i n Arthriti s Rh eum,2000,30(3):196-208.

15Auer J,Hinterreiter M,Allinger S,et al.S evere pancytopenia after leflunomide in rheumatoid arthri tis.Acta M ed Austriaca,2000,27

(4):131-132.

16W einblatt M E,Kremer JM,Coblyn JS,et al.Pharmacokinetics, safety,and efficacy of combination treatment w ith methotrexate and leflunom i de in patients w ith active rheumatoi d arthritis.Arthri tis Rheum,1999,42(7):1322-1328.17Remer CF,W eisman M H,Wallace DJ.Benefits of leflunomide i n systemic lupus erythematosus:a pilot observational study.Lupus, 2001,10(7):480-483.

18M irmohammadsadegh A,H omey B,Abts H F,et al.Differential modulation of pro-and ant-i inflammatory cytokine receptors by N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxy-crotonic acid amide(A771726),the physiologically active metabolite of the novel immunomodulator leflunomide.Biochem Pharmacol,1998,55

(9):1523-1529.

19W aldman W J,Knight DA,Bli nder L,et al.Inh i bition of cy-tomegalovirus in vitro and in vivo by the experimental immunosup-pressive agent leflunomide.Intervirology,1999,42(5-6):412-418.

20Knight DA,H ejmanowski AQ,Dierksheide JE,et al.Inhibi tion of herpes simplex virus type1by the experimental i mm unosuppressive agent leflunomide.Transplantation,2001,71(1):170-174.

21Cohen T ervaert JW,Stegeman CA,Kallenberg CG.Novel therapies for ant-i neutrophil cytoplasmic antibody-associated vasculitis.Curr Opin Nephrol Hypertens,2001,10(2):211-217.

22S cott DL,Smolen JS,Kalden JR,et al.T reatment of active rh eumatoid arthritis with leflunomide:tw o year follow up of a double blind,placebo controlled tri al versus s ulfasalazi n e.Ann Rheum Dis, 2001,60(10):913-923.

(收稿日期:2002-02-01)

#综述#

银屑病治疗研究的一些进展

张长宋陈树民

摘要银屑病病因和发病机制仍不明确,但在过去的20年里,对银屑病的认识日渐加深。从遗传学、免疫学、新型免疫抑制剂、血管生成和生长因子、核受体靶击疗法、心理干预、物理疗法等角度对银屑病的病因、发病机制和治疗方法进行论述。在此基础上,展望未来对银屑病的治疗方法。

关键词基因免疫银屑病

近15年来,对银屑病发病机制及其治疗研究都有较大进展。免疫机制在银屑病发病中的探讨为新治疗方法提供了策略。同样,分子基因学的进展使得确认银屑病易感性致病基因位点成为可能。现详述银屑病研究的进展、并对未来银屑病治疗措施的展望进行综述。

一、遗传学

临床实践已证明,银屑病有遗传倾向。现阶段最为迫切的工作是发现易感性致病基因对银屑病作用的证据。据报道银屑病患者第一代亲属发病率大

作者单位:250022济南,山东省皮肤病性病防治研究所约为1/3。同卵双生子同时患病概率为70%,双卵双生子为25%[1];还发现多种类型的人类白细胞抗原(H LA)与银屑病有关,尤其是早发型(I型)银屑病患者的HLA-Cw6抗原。对银屑病多个发病家族及其同胞广泛基因组调查,发现4个主要易感位点与银屑病有关,称为银1,2,3和4,分别位于染色体6p,17q,4q和1q上[2]。其它少见的位点见于染色体的16q和20p。这些资料提示,银屑病是一种在强烈的环境刺激下发病的多基因遗传性疾病。近来,其它位于染色体6p上的银屑病相关易感位点已在中国人群中鉴定出来,它是一种与Ñ类主要组织相容性复合体(MHC)分子相关的基因(M ICA)[3]。