系統(tǒng)性紅斑狼瘡

中國醫(yī)科大學(xué)附屬一院風(fēng)濕免疫科張榕系統(tǒng)性紅斑狼瘡(SLE)SystemicLupusErythematosus

1SystemicLupusErythematosus

ManyDifferentAuto-antibodiesMultipleSystemInvolvement2SLEonsetbysexandage3EtiologyandpathogenesispathologyClinicalfindingsLaboratoryfindingsDiagnosisTreatmentprognosis4EtiologygeneticfactorsenvironmentalfactorsSexhormonalfactors

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

Pathology光鏡:1.結(jié)締組織的纖維蛋白樣變性2.基質(zhì)黏液性水腫3.壞死性血管炎特征性:疣狀心內(nèi)膜炎蘇木紫小體“洋蔥皮樣〞病變臨床應(yīng)用：皮膚狼瘡帶試驗(yàn)?zāi)I活檢8EtiologyandpathogenesispathologyClinicalfindingsLaboratoryfindingsDiagnosisTreatmentprognosis910

Systemicfeatures

FeverWeakWeightloss11

skinandmucosa

光敏感photosensitivity脫發(fā)alopecia雷諾現(xiàn)象Raynaud’sphenomenon口腔潰瘍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

彌漫增殖性diffuseproliferativeClassV

膜性membranousClassVI

腎小球硬化性glomerulosclerosis

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

23Hematologysystemleukopeniathrombocytopeniaanemias:hemolyticanemiasanemiasofchronicdiseaselymphadenectasissplenectasis

24RespiratorysystempleurisyPleuraleffusionPulmonaryinterstitialfibrosisLupuspneumoniaPulmonaryhypertensionRespiratoryfailure25

lung26

Circulatorysystemheart-pericarditis-myocarditis-endocarditisLibman-Sackendocarditis

-cardiacarrhythmias-cardiacfailurevessel-vasculitis27

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

抗磷脂抗體綜合征

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

干燥綜合征30%的SLE患者可有繼發(fā)枯燥綜合征患者有臨床病癥唾液腺ECT可有改變枯燥抗體可為陰性30EtiologyandpathogenesispathologyClinicalfindingsLaboratoryfindingsDiagnosisTreatmentprognosis31一般檢查自身抗體補(bǔ)體等狼瘡帶試驗(yàn)?zāi)I活檢病理影像學(xué)檢查血常規(guī)尿常規(guī)血沉抗核抗體譜抗磷脂抗體抗組織細(xì)胞抗體C3C4CH50Igr-G診斷治療預(yù)后MRICT實(shí)驗(yàn)室和其他輔助檢查SLE50%代表SLE活動性抗核抗體譜抗核抗體ANA抗dsDNA抗體抗ENA抗體Jo-1SmRNPSSBSSA32EtiologyandpathogenesispathologyClinicalfindingsLaboratoryfindingsDiagnosisTreatmentprognosis33

美國風(fēng)濕病學(xué)會(ACR)1997年SLE診斷標(biāo)準(zhǔn)1.蝶形紅斑2.盤狀紅斑3.光過敏4.口腔潰瘍5.關(guān)節(jié)炎6.漿膜炎(胸膜炎/心包炎)7.腎病變a.蛋白尿>0.5g/day b.細(xì)胞管型8.神經(jīng)系統(tǒng)病變a.癲癇發(fā)作 b.精神病癥≥4項(xiàng)陽性可診斷SLE9.血液系統(tǒng)異常

a.溶血性貧血

b.白細(xì)胞減少

c.淋巴細(xì)胞絕對值減少

d.血小板減少10.免疫學(xué)異常

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狼瘡性頭痛精神病癥器質(zhì)性腦病視覺障礙顱神經(jīng)病變腦血管意外血管炎癲癇發(fā)作發(fā)熱1分血小板減少白細(xì)胞減少關(guān)節(jié)炎肌炎管型尿血尿蛋白尿膿尿新出皮疹黏膜潰瘍高效價dsDNA低補(bǔ)體血癥心包炎胸膜炎脫發(fā)2分8分4分

總積分為105分，10分以上為活動,20以上者提示很明顯的活動36提示SLE活動性的指證病癥體征:乏力、體重下降發(fā)熱新出現(xiàn)的皮膚黏膜改變關(guān)節(jié)炎漿膜炎尿少、浮腫頭痛、癜癇輔助檢查：血細(xì)胞減少蛋白尿、血尿、管型尿、非感染性白細(xì)胞尿補(bǔ)體下降DNA抗體滴度升高37SLE病情輕重的評估1.輕型SLE：無系統(tǒng)受累2.重型SLE：有系統(tǒng)受累3.狼瘡危象(lupuscrisis)：危及生命的重型SLE，包括：急進(jìn)性狼瘡腎炎，嚴(yán)重的中樞神經(jīng)系統(tǒng)損害，嚴(yán)重的溶血性貧血，血小板減少性紫癜，粒細(xì)胞缺乏癥，嚴(yán)重心臟損害，嚴(yán)重狼瘡肺炎，嚴(yán)重狼瘡肝炎，嚴(yán)重血管炎等。SLE的診斷思路(3個是否):

是否狼瘡-是否活動-是否嚴(yán)重38EtiologyandpathogenesispathologyClinicalfindingsLaboratoryfindingsDiagnosisTreatmentprognosis39

治療層次

基因

發(fā)病機(jī)制誘因感染藥物光照激素等SLE病癥發(fā)熱關(guān)節(jié)皮膚腎臟心血管等

徹底治愈祛除誘發(fā)因素對癥處理致病基因位點(diǎn)糾正免疫異常40generaltreatmentdrugtreatmentplasmapheresishaemopoieticstemcelltransplantation

41

Generaltreatment心理治療急性活動期臥床休息，防止過勞及早發(fā)現(xiàn)和治療感染防止使用可能誘發(fā)狼瘡的藥物防止陽光暴曬和紫外線照射(SPFofatleast25)緩解期才可作防疫注射定期隨訪42MedicationstreatmentNSAIDSAntimalarialsCorticosteroidsImmunosuppressantBiologicaltherapy43

輕型SLE的治療1.非甾體抗炎藥-關(guān)節(jié)炎2.抗瘧藥-皮疹3.小劑量激素強(qiáng)的松0.5mg/kg口服6-8周后減量4.酌情應(yīng)用免疫抑制劑44非甾體抗炎藥(NSAIDS)主要作用-抗炎止痛和退熱

-對癥治療、無免疫抑制作用用于治療-發(fā)熱

-關(guān)節(jié)痛

-肌肉痛

-輕度的漿膜炎代表藥物-阿斯匹林、消炎痛

-布洛芬、雙氯酚酸、舒林酸、洛索洛芬

-塞來昔布、羅非昔布副作用-胃腸道

45

抗瘧藥(Antimalarials)

主要作用-抗炎、免疫抑制用于治療-皮疹

-口腔潰瘍

-肌肉痛

-關(guān)節(jié)痛

-漿膜腔積液

-SLE的維持治療用藥代表藥物-硫酸羥氯喹副作用-眼毒性(服藥期間每3-6月查眼底)-皮疹

-胃腸道

-心肌病變

46重型SLE的治療誘導(dǎo)緩解:激素和免疫抑制劑常規(guī)：強(qiáng)的松1mg/kg口服6-8周后減量沖擊：甲基強(qiáng)的松龍500mg-1g/d，連3天沖擊指證:嚴(yán)重的腎臟受累狼瘡腦病嚴(yán)重的血液系統(tǒng)改變重癥血管炎環(huán)磷酰胺沖擊療法：0.5-1g/m2體外表積,每月1次持續(xù)時間：6月-1年維持治療:強(qiáng)的松7.5-20mg/d和硫唑嘌呤50mg/d持續(xù)時間:局部終身47狼瘡危象(lupuscrisis)的治療1.甲基強(qiáng)的松龍沖擊:500mg-1g/d，連3天2.丙種球蛋白治療:0.4g/kg/天,4-5天3.對癥治療

48糖皮質(zhì)激素(Corticosteroids)

主要作用-小劑量起抗炎作用

-大劑量起免疫抑制作用代表藥物-強(qiáng)的松

-美卓樂

-甲基強(qiáng)的松龍

-地塞米松49糖皮質(zhì)激素類藥物的比較藥物等效劑量半衰期抗炎效力水鈉潴留Hydrocortisone208-12h1++cortisone258-12h0.8++Prednisone512-36h4+Prednisolone512-36h4+methylprednisolone412-36h50Triamcinalone412-36h50Betamethasone0.636-54h20-300Dexamethasone0.7536-54h20-30++50糖皮質(zhì)激素(Corticosteroids)副作用水鈉儲留：水腫，高血壓肥胖：滿月臉，水牛背，紫紋神經(jīng)精神病癥易感染消化系統(tǒng)潰瘍高血糖激素性肌無力眼：青光眼，白內(nèi)障骨質(zhì)疏松51環(huán)磷酰胺

〔Cyclophosphamide,CTX〕用法-每日口服-隔日靜點(diǎn)-靜脈沖擊〔1g/次，每2-4周1次，4-6次后間期逐漸延長〕本卷須知-沖擊前驗(yàn)血常規(guī)-沖擊中水化療法-同時給予止吐藥52環(huán)磷酰胺〔CTX〕副作用感染出血性膀胱炎

生殖系統(tǒng)影響血液系統(tǒng)影響胃腸道反響脫發(fā)肝腎損害誘發(fā)腫瘤53免疫抑制劑(Immunosuppressant)

環(huán)磷酰胺〔CTX〕硫唑嘌呤(依木蘭Imuran)環(huán)孢素(cyclosporinA)麥考酚嗎乙酯(驍悉CellCept)甲氨碟呤(MTX)愛假設(shè)華〔Leflunomide〕雷公藤多甙54免疫抑制劑主要用于：活動程度較嚴(yán)重的狼瘡減少激素用量55硫唑嘌呤(Imuran)較CTX作用弱但副作用小經(jīng)常作為CTX的續(xù)貫治療用法-起始劑量2-3mg/kg/day口服-維持劑量1-3mg/kg/day口服副作用-骨髓抑制-肝損害-胃腸道反響56環(huán)孢素(cyclosporinA)一般不作為首選，當(dāng)其它免疫抑制劑無效時應(yīng)用起始劑量：3～5mg/kg/d維持劑量：2～3mg/kg/d副作用-肝腎損害-胃腸道病癥-皮疹57

麥考酚嗎乙酯(CellCept)作用與CTX相似,但副作用小,價錢昂貴起始劑量：口服維持劑量:1g/d口服副作用-骨髓抑制少見

-無明顯的肝腎毒性58甲氨碟呤(MTX)

用于治療病癥輕,內(nèi)臟損害不重而關(guān)節(jié)病癥明顯或皮疹較重的SLE患者還可用于鞘內(nèi)注射劑量:7.5-25mg/周,口服或靜脈注射副作用-胃腸道反響-口腔潰瘍-肝功能損害-骨髓抑制-脫發(fā)59愛假設(shè)華〔Leflunomide〕為一種新型的免疫抑制劑主要用于RA的治療,對SLE的治療作用尚需進(jìn)一步臨床試驗(yàn)的評價用法:10-20mg/d口服副作用-胃腸道反響-肝功能損害-皮疹-脫發(fā)-高血壓

60雷公藤多甙用法:20mg,tidp.o.病情控制后可減量或間歇療法對本病有一定療效不良反響較大性腺的抑制肝損害胃腸道反響白細(xì)胞減少61生物制劑-丙種球蛋白用于重癥SLE-嚴(yán)重血液系統(tǒng)受累

-嚴(yán)重的感染

-狼瘡腦病

-免疫球蛋白降低者主要作用為中和血清中的抗體用法:0.4g/kg/天,4-5天費(fèi)用昂貴62

血漿置換將血液中異常成分(CIC,自身抗體)去除,從而到達(dá)血液凈化的作用多用于重癥狼瘡連做4次費(fèi)用昂貴63

造血干細(xì)胞移植免疫系統(tǒng)中所有的細(xì)胞都來源于造血干細(xì)胞，SLE患者異常的細(xì)胞到底是由于干細(xì)胞異常還是子代細(xì)胞受損還不清楚。近年來有學(xué)者提出“自身免疫病是造血干細(xì)胞病〞學(xué)說，并認(rèn)為干細(xì)胞異常是原發(fā)性缺陷.至2003年5月全世界報告有106例SLE行HSCT治療，我國進(jìn)行了71例自體移植。隨訪時間最長達(dá)65個月。雖有復(fù)發(fā),但總體療效令人滿意

64

狼瘡與妊娠允許妊娠-病情穩(wěn)定1年以上

-僅用小劑量激素或停用

-停用免疫抑制劑6月以上SSA抗體陽性母親,其新生兒易患新生兒狼瘡或心臟傳導(dǎo)阻滯分娩當(dāng)天及產(chǎn)后第二天激素加量65EtiologyandpathogenesispathologyClinicalfindingsLaboratoryfindingsDiagnosisTreatmentprognosis66

預(yù)后1963年Jessar等報道SLE的五年生存率僅20％1973年Dubois等報道10年的生存率為57％1990年Reville等及1993年陳順樂等分別報道的10年生存率皆達(dá)84％說明近2O年來本病的預(yù)后有了顯著改善67

預(yù)后有下述者預(yù)后差:-腎功衰竭

-中樞神經(jīng)系統(tǒng)損害

-心肌損害伴心功能不全

-高血壓常見死亡原因:-腎功衰竭

-心力衰竭

-腦損害

-感染68

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