系统性红斑狼疮

中国医科大学附属一院风湿免疫科张榕系统性红斑狼疮(SLE)SystemicLupusErythematosus

1SystemicLupusErythematosus

ManyDifferentAuto-antibodiesMultipleSystemInvolvement2SLEonsetbysexandage3EtiologyandpathogenesispathologyClinicalfindingsLaboratoryfindingsDiagnosisTreatmentprognosis4EtiologygeneticfactorsenvironmentalfactorsSexhormonalfactors

5PathogenesisExcessive,abnormalproductionof“self〞antibodiesandformationofIC.Autoantibodiesagainstnuclear,cytoplasmicandmembranecomponentsofmultiplecelltypesinmultipleorgans.6EtiologyandpathogenesispathologyClinicalfindingsLaboratoryfindingsDiagnosisTreatmentprognosis7

Pathology光镜:1.结缔组织的纤维蛋白样变性2.基质黏液性水肿3.坏死性血管炎特征性:疣状心内膜炎苏木紫小体“洋葱皮样〞病变临床应用：皮肤狼疮带试验肾活检8EtiologyandpathogenesispathologyClinicalfindingsLaboratoryfindingsDiagnosisTreatmentprognosis910

Systemicfeatures

FeverWeakWeightloss11

skinandmucosa

光敏感photosensitivity脱发alopecia雷诺现象Raynaud’sphenomenon口腔溃疡oralulcer皮疹rash12

skinandmucosa13

skinandmucosa14

skinandmucosa15

skinandmucosa16

skinandmucosa17

skinandmucosa18

MuscleandJoint

arthritis--Jaccoud’sarthropathyMusclepain、myositisfemoralheadnecrosis19

MuscleandJoint20RenallesionProteinuriahematuriacylindruriaNephriticsyndromeRenalinsufficiency21

lupusnephritisClassI

正常ClassII

系膜增殖性mesangialClassIII

局灶增殖性focalproliferativeClassIV

弥漫增殖性diffuseproliferativeClassV

膜性membranousClassVI

肾小球硬化性glomerulosclerosis

22Nervoussystemclinicalmanifestation:-headache、vomiting-psychogenia-epilepsy-convulsion、consciousdisturbance-comapathology-vasculitiscerebrospinalfluid-nospecial(intracranialpressure↑protein↑cellpopulation↑glucose↓)Identifywithothercentralnervoussystemdisease

23Hematologysystemleukopeniathrombocytopeniaanemias:hemolyticanemiasanemiasofchronicdiseaselymphadenectasissplenectasis

24RespiratorysystempleurisyPleuraleffusionPulmonaryinterstitialfibrosisLupuspneumoniaPulmonaryhypertensionRespiratoryfailure25

lung26

Circulatorysystemheart-pericarditis-myocarditis-endocarditisLibman-Sackendocarditis

-cardiacarrhythmias-cardiacfailurevessel-vasculitis27

DigestivesystemClinicalfeatures-anepithymia-nauseaandvomiting-abdominalpain、diarrhea-peritonealeffusion-acuteabdomenpathology-mesenteriumvasculitis28

抗磷脂抗体综合征

(antiphospholipidantibodysyndrome)clinicalmanifestation:-arterousand/orvenousthrombosis-spontaneousabortion-thrombocytopenialaboratoryexamination:-positiveanti-phospholipidantibody29

干燥综合征30%的SLE患者可有继发枯燥综合征患者有临床病症唾液腺ECT可有改变枯燥抗体可为阴性30EtiologyandpathogenesispathologyClinicalfindingsLaboratoryfindingsDiagnosisTreatmentprognosis31一般检查自身抗体补体等狼疮带试验肾活检病理影像学检查血常规尿常规血沉抗核抗体谱抗磷脂抗体抗组织细胞抗体C3C4CH50Igr-G诊断治疗预后MRICT实验室和其他辅助检查SLE50%代表SLE活动性抗核抗体谱抗核抗体ANA抗dsDNA抗体抗ENA抗体Jo-1SmRNPSSBSSA32EtiologyandpathogenesispathologyClinicalfindingsLaboratoryfindingsDiagnosisTreatmentprognosis33

美国风湿病学会(ACR)1997年SLE诊断标准1.蝶形红斑2.盘状红斑3.光过敏4.口腔溃疡5.关节炎6.浆膜炎(胸膜炎/心包炎)7.肾病变a.蛋白尿>0.5g/day b.细胞管型8.神经系统病变a.癫痫发作 b.精神病症≥4项阳性可诊断SLE9.血液系统异常

a.溶血性贫血

b.白细胞减少

c.淋巴细胞绝对值减少

d.血小板减少10.免疫学异常

a.anti-dsDNA b.anti-Sm c.anti-CLand/orLA11.ANA34

CRITERIAFORTHEDIAGNOSISOFSLEACCORDINGTOTHEACR(1997)1.Butterflyrash2.Discoidlupus3.Photosensitivity4.Oralulceration5.Polyarthritis6.Nephritis teinuriaover0.5g/day b.cellularcasts7.Pleuritis/pericarditis8.Neuropsychiatricsymptoms a.convulsions b.psychosis4ormoresymptomsarerequiredforthediagnosis

9.Haematologicalalterations a.haemolyticanaemia b.leucopenia(4.0G/l) c.lymphopenia(1.5G/l) d.thrombocytopenia(100G/l)10.Immunologicalterations a.anti-dsDNA b.anti-Sm c.anti-CLand/orLA11.ANA35SLE-DAI狼疮性头痛精神病症器质性脑病视觉障碍颅神经病变脑血管意外血管炎癫痫发作发热1分血小板减少白细胞减少关节炎肌炎管型尿血尿蛋白尿脓尿新出皮疹黏膜溃疡高效价dsDNA低补体血症心包炎胸膜炎脱发2分8分4分

总积分为105分，10分以上为活动,20以上者提示很明显的活动36提示SLE活动性的指证病症体征:乏力、体重下降发热新出现的皮肤黏膜改变关节炎浆膜炎尿少、浮肿头痛、癜痫辅助检查：血细胞减少蛋白尿、血尿、管型尿、非感染性白细胞尿补体下降DNA抗体滴度升高37SLE病情轻重的评估1.轻型SLE：无系统受累2.重型SLE：有系统受累3.狼疮危象(lupuscrisis)：危及生命的重型SLE，包括：急进性狼疮肾炎，严重的中枢神经系统损害，严重的溶血性贫血，血小板减少性紫癜，粒细胞缺乏症，严重心脏损害，严重狼疮肺炎，严重狼疮肝炎，严重血管炎等。SLE的诊断思路(3个是否):

是否狼疮-是否活动-是否严重38EtiologyandpathogenesispathologyClinicalfindingsLaboratoryfindingsDiagnosisTreatmentprognosis39

治疗层次

基因

发病机制诱因感染药物光照激素等SLE病症发热关节皮肤肾脏心血管等

彻底治愈祛除诱发因素对症处理致病基因位点纠正免疫异常40generaltreatmentdrugtreatmentplasmapheresishaemopoieticstemcelltransplantation

41

Generaltreatment心理治疗急性活动期卧床休息，防止过劳及早发现和治疗感染防止使用可能诱发狼疮的药物防止阳光暴晒和紫外线照射(SPFofatleast25)缓解期才可作防疫注射定期随访42MedicationstreatmentNSAIDSAntimalarialsCorticosteroidsImmunosuppressantBiologicaltherapy43

轻型SLE的治疗1.非甾体抗炎药-关节炎2.抗疟药-皮疹3.小剂量激素强的松0.5mg/kg口服6-8周后减量4.酌情应用免疫抑制剂44非甾体抗炎药(NSAIDS)主要作用-抗炎止痛和退热

-对症治疗、无免疫抑制作用用于治疗-发热

-关节痛

-肌肉痛

-轻度的浆膜炎代表药物-阿斯匹林、消炎痛

-布洛芬、双氯酚酸、舒林酸、洛索洛芬

-塞来昔布、罗非昔布副作用-胃肠道

45

抗疟药(Antimalarials)

主要作用-抗炎、免疫抑制用于治疗-皮疹

-口腔溃疡

-肌肉痛

-关节痛

-浆膜腔积液

-SLE的维持治疗用药代表药物-硫酸羟氯喹副作用-眼毒性(服药期间每3-6月查眼底)-皮疹

-胃肠道

-心肌病变

46重型SLE的治疗诱导缓解:激素和免疫抑制剂常规：强的松1mg/kg口服6-8周后减量冲击：甲基强的松龙500mg-1g/d，连3天冲击指证:严重的肾脏受累狼疮脑病严重的血液系统改变重症血管炎环磷酰胺冲击疗法：0.5-1g/m2体外表积,每月1次持续时间：6月-1年维持治疗:强的松7.5-20mg/d和硫唑嘌呤50mg/d持续时间:局部终身47狼疮危象(lupuscrisis)的治疗1.甲基强的松龙冲击:500mg-1g/d，连3天2.丙种球蛋白治疗:0.4g/kg/天,4-5天3.对症治疗

48糖皮质激素(Corticosteroids)

主要作用-小剂量起抗炎作用

-大剂量起免疫抑制作用代表药物-强的松

-美卓乐

-甲基强的松龙

-地塞米松49糖皮质激素类药物的比较药物等效剂量半衰期抗炎效力水钠潴留Hydrocortisone208-12h1++cortisone258-12h0.8++Prednisone512-36h4+Prednisolone512-36h4+methylprednisolone412-36h50Triamcinalone412-36h50Betamethasone0.636-54h20-300Dexamethasone0.7536-54h20-30++50糖皮质激素(Corticosteroids)副作用水钠储留：水肿，高血压肥胖：满月脸，水牛背，紫纹神经精神病症易感染消化系统溃疡高血糖激素性肌无力眼：青光眼，白内障骨质疏松51环磷酰胺

〔Cyclophosphamide,CTX〕用法-每日口服-隔日静点-静脉冲击〔1g/次，每2-4周1次，4-6次后间期逐渐延长〕本卷须知-冲击前验血常规-冲击中水化疗法-同时给予止吐药52环磷酰胺〔CTX〕副作用感染出血性膀胱炎

生殖系统影响血液系统影响胃肠道反响脱发肝肾损害诱发肿瘤53免疫抑制剂(Immunosuppressant)

环磷酰胺〔CTX〕硫唑嘌呤(依木兰Imuran)环孢素(cyclosporinA)麦考酚吗乙酯(骁悉CellCept)甲氨碟呤(MTX)爱假设华〔Leflunomide〕雷公藤多甙54免疫抑制剂主要用于：活动程度较严重的狼疮减少激素用量55硫唑嘌呤(Imuran)较CTX作用弱但副作用小经常作为CTX的续贯治疗用法-起始剂量2-3mg/kg/day口服-维持剂量1-3mg/kg/day口服副作用-骨髓抑制-肝损害-胃肠道反响56环孢素(cyclosporinA)一般不作为首选，当其它免疫抑制剂无效时应用起始剂量：3～5mg/kg/d维持剂量：2～3mg/kg/d副作用-肝肾损害-胃肠道病症-皮疹57

麦考酚吗乙酯(CellCept)作用与CTX相似,但副作用小,价钱昂贵起始剂量：口服维持剂量:1g/d口服副作用-骨髓抑制少见

-无明显的肝肾毒性58甲氨碟呤(MTX)

用于治疗病症轻,内脏损害不重而关节病症明显或皮疹较重的SLE患者还可用于鞘内注射剂量:7.5-25mg/周,口服或静脉注射副作用-胃肠道反响-口腔溃疡-肝功能损害-骨髓抑制-脱发59爱假设华〔Leflunomide〕为一种新型的免疫抑制剂主要用于RA的治疗,对SLE的治疗作用尚需进一步临床试验的评价用法:10-20mg/d口服副作用-胃肠道反响-肝功能损害-皮疹-脱发-高血压

60雷公藤多甙用法:20mg,tidp.o.病情控制后可减量或间歇疗法对本病有一定疗效不良反响较大性腺的抑制肝损害胃肠道反响白细胞减少61生物制剂-丙种球蛋白用于重症SLE-严重血液系统受累

-严重的感染

-狼疮脑病

-免疫球蛋白降低者主要作用为中和血清中的抗体用法:0.4g/kg/天,4-5天费用昂贵62

血浆置换将血液中异常成分(CIC,自身抗体)去除,从而到达血液净化的作用多用于重症狼疮连做4次费用昂贵63

造血干细胞移植免疫系统中所有的细胞都来源于造血干细胞，SLE患者异常的细胞到底是由于干细胞异常还是子代细胞受损还不清楚。近年来有学者提出“自身免疫病是造血干细胞病〞学说，并认为干细胞异常是原发性缺陷.至2003年5月全世界报告有106例SLE行HSCT治疗，我国进行了71例自体移植。随访时间最长达65个月。虽有复发,但总体疗效令人满意

64

狼疮与妊娠允许妊娠-病情稳定1年以上

-仅用小剂量激素或停用

-停用免疫抑制剂6月以上SSA抗体阳性母亲,其新生儿易患新生儿狼疮或心脏传导阻滞分娩当天及产后第二天激素加量65EtiologyandpathogenesispathologyClinicalfindingsLaboratoryfindingsDiagnosisTreatmentprognosis66

预后1963年Jessar等报道SLE的五年生存率仅20％1973年Dubois等报道10年的生存率为57％1990年Reville等及1993年陈顺乐等分别报道的10年生存率皆达84％说明近2O年来本病的预后有了显著改善67

预后有下述者预后差:-肾功衰竭

-中枢神经系统损害

-心肌损害伴心功能不全

-高血压常见死亡原因:-肾功衰竭

-心力衰竭

-脑损害

-感染68

THEEND695JdSm!v0E9NhWq*z4IcRl#u+D7MgVp&y2HbQkZt)C6LfUo%x1GaPjYs(B5KeTn!w0F9OiWr*A4JdRm#v+E8MhVq&z3IcQlZu-D7LgUp%y2GbPkYt)B6KfTo$w1FaOjXs(A5JeSn!v0E9NiWq*z4IdRl#u+D8MgVp&y3HbQkZt-C7LfUo%x2GaPjYs)B5KeTn$w0F9OiXr*A4JdSm!v+E8NhWq&z3IcRlZu-D7MdRm#v+D8MhVq&y3HcQlZt-C7LgUo%x2GbPjYs)B6KfTn$w1FaOiXr(A5JdSm!v0E8NhWq*z3IcRl#u-D7MgVp&y2HbQkZt)C6LfUo$x1GaPjXs(B5KeSn!w0F9NiWr*A4JdRm#v+E8MhVq&z3HcQlZu-C7LgUp%x2GbPkYt)B6KfTo$w1FaOjXr(A5JeSm!v0E9NhWq*z4IcRl#u+D8MgVp&y3HbQkZt-C6LfUo%x1GaPjYs(B5KeTn$w0F9OiXr*A4JdSm#v+E8NhVq&z3IcQlZu-D7LgUp%y2HbPkYt)C6KfTo$x1FaOjXs(A5JeSn!v0E9NiWr*z4IdRm#u+D8MhVp&y3HcQkZt-C7LfUo%x2GaPjYs)B6KeTn$w1F9OiXr(A4JdSm!v+E8NhWq&z3IcRlZu-D7MgVp%y2HbQkYt)C6LfTo$x1GaOjXs(B5JeSn!w0F9NiWr*A4IdRm#v+D8MhVq&y3HcQlZt-C7LgUo%x2GbPkYs)B6KfTn$w1FaOiXr(A5JdSm!v0E8NhWq*z4IcRl#u+D7MgVp&y2HbQkZt)C6LfUo$x1GaPjXs(B5KeTn!w0F9OiWr*A4JdRm#v+E8MhVq&z3HcQlZu-C7LgUp%y2GbPkYt)B6KfToZt-C7LfUo%x2GaPjYs)B5KeTn$w0F9OiXr*A4JdSm!v+E8NhWq&z3IcRlZu-D7MgUp%y2HbPkYt)C6KfTo$x1GaOjXs(B5JeSn!w0E9NiWr*z4IdRm#u+D8MhVp&y3HcQlZt-C7LgUo%x2GbPjYs)B6KeTn$w1F9OiXr(A5JdSm!v0E8NhWq*z3IcRl#u-D7MgVp%y2HbQkYt)C6LfUo$x1GaPjXs(B5KeSn!w0F9NiWr*A4IdRm#v+E8MhVq&z3HcQlZu-C7LgUp%x2GbPkYs)B6KfTn$w1FaOjXr(A5JeSm!v0E9NhWq*z4IcRl#u+D7MgVp&y2HbQkZt-C6LfUo%x1GaPjYs(B5KeTn!w0F9OiWr*A4JdSm#v+E8NhVq&z3IcQlZu-D7LgUp%y2GbPkYt)B6KfTo$x1FaOjXs(A5JeSn!v0E9NiWq*z4IdRl#u+D8MhVp&y3HcQkZt-C7LfUo%x2GaPjYs)B5KeTn$w0F9OiXr(A4JdSm!v+E8NhWq&z3IcRlZu-D7MgUp%y2HbQkYt)C6LfTo$x1GaOjXs(B5JeSn!w0E9NiWr*z4IdRm#v+D8MhVq&y3HcQlZt-C7LgUo%x2GbPjYs)B6KeTn$w1FaOiXr(A5JdSm!v0E8KeTn!w0F9OiWr*A4JdRm#v+E8MhVq&z3HcQlZu-D7LgUp%y2GbPkYt)B6KfTo$w1FaOjXr(A5JeSm!v0E9NiWq*z4IdRl#u+D8MgVp&y3HbQkZt-C6LfUo%x1GaPjYs)B5KeTn$w0F9OiXr*A4JdSm#v+E8NhVq&z3IcRlZu-D7MgUp%y2HbPkYt)C6KfTo$x1FaOjXs(A5JeSn!w0E9NiWr*z4IdRm#u+D8MhVp&y3HcQkZt-C7LgUo%x2GbPjYs)B6KeTn$w1F9OiXr(A4JdSm!v+E8NhWq*z3IcRl#u-D7MgVp%y2HbQkYt)C6LfTo$x1GaOjXs(B5KeSn!w0F9NiWr*A4IdRm#v+D8MhVq&y3HcQlZu-C7LgUp%x2GbPkYs)B6KfTn$w1FaOiXr(A5JdSm!v0E9NhWq*z4IcRl#u+D7MgVp&y2HbQkZt)C6LfUo%x1GaPjYs(B5GbPkYt)B6KfTo$x1FaOjXs(A5JeSn!v0E9NiWq*z4IdRl#u+D8MhVp&y3HcQkZt-C7LfUo%x2GaPjYs)B5KeTn$w0F9OiXr(A4JdSm!v+E8NhWq&z3IcRlZu-D7MgUp%y2HbQkYt)C6LfTo$x1GaOjXs(B5JeSn!w0E9NiWr*z4IdRm#v+D8MhVq&y3HcQlZt-C4IcRl#u+D7MgVp&y2HbQkZt)C6LfUo$x1GaPjXs(B5KeTn!w0F9OiWr*A4JdRm#v+E8MhVq&z3HcQlZu-D7LgUp%y2GbPkYt)B6KfTo$w1FaOjXr(A5JeSm!v0E9NiWq*z4IdRl#u+D8MgVp&y3HbQkZt-C6LfUo%x1GaPjYs)B5KeTn$w0F9OiXr*A4JdSm#v+E8NhVq&z3IcRlZu-D7MgUp%y2HbPkYt)C6KfTo$x1FaOjXs(A5JeSn!w0E9NiWr*z4IdRm#u+D8MhVp&y3HcQkZt-C7LgUo%x2GbPjYs)y2HbQkYt)C6LfUo$x1GaPjXs(B5KeSn!w0F9NiWr*A4IdRm#v+E8MhVq&z3HcQlZu-C7LgUp%x2GbPkYs)B6KfTn$w1FaOjXr(A5JeSm!v0E9NhWq*z4IcRl#u+D7MgVp&y3HbQkZt-C6LfUo%x1GaPjYs(B5KeTn!w0F9OiWr*A4JdSm#v+E8NhVq&z3IcQlZu-D7LgUp%y2GbPkYt)B6KfTo$x1FaOjXs(A5JeSn!v0E9NiWq*z4IdRl#u+D8MhVp&y3HcQkZt-C7LfUo#u-D7MgVp%y2HbQkYt)C6LfTo$x1GaOjXs(B5JeSn!w0F9NiWr*A4IdRm#v+D8MhVq&y3HcQlZt-C7LgUo%x2GbPkYs)B6KfTn$w1FaOiXr(A5JdSm!v0E8NhWq*z4IcRl#u+D7MgVp&y2HbQkZt)C6LfUo$x1GaPjXs(B5KeTn!w0F9OiWr*A4JdRm#v+E8MhVq&z3HcQlZu-D7LgUp%y2GbPkYt)B6KfTo$w1FaOjXr(A5JeSm!v0E9NiWq*z4IdRl#u+D8MgVp&v+E8NhWq&z3IcRlZu-D7MgUp%y2HbPkYt)C6KfTo$x1GaOjXs(B5JeSn!w0E9NiWr*z4IdRm#u+D8MhVq&y3HcQlZt-C7LgUo%x2GbPjYs)B6KeTn$w1F9OiXr(A5JdSm!v0E8NhWq*z3IcRl#u-D7MgVp%y2HbQkYt)C6LfUo$x1GaPjXs(B5KeSn!w0F9NiWr*A4IdRm#v+E8MhVq&z3HcQlZu-C7LgUp%x2GbPkYs)B6KfTn$w1FaOjXr(A5JaPjYs(B5KeTn$w0F9OiXr*A4JdSm#v+E8NhVq&z3IcQlZu-D7LgUp%y2HbPkYt)C6KfTo$x1FaOjXs(A5JeSn!v0E9NiWr*z4IdRm#u+D8MhVp&y3HcQkZt-C7LfUo%x2GaPjYs)B6KeTn$w1F9OiXr(A4JdSm!v+E8NhWq&z3IcRl#u-D7MgVp%y2HbQkYt)C6LfTo$x1GaOjXs(B5JeSn!w0F9NiWr*A4IdRm#v+D8MhVq&y3HcQlZt-C7LgU