系统性红斑狼疮课件.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,系统性红斑狼疮,资料仅供参考,不当之处，请联系改正。,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,系统性红斑狼疮,资料仅供参考,不当之处，请联系改正。,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,资料仅供参考,不当之处，请联系改正。,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,资料仅供参考,不当之处，请联系改正。,Systemic Lupus Erythematosus,Many,Different,Auto-,antibodies,Multiple,System,Involvement,SLE onset by sex and age,Etiology and pathogenesis,pathology,Clinical findings,Laboratory findings,Diagnosis,Treatment,prognosis,Etiology,genetic factors,environmental factors,Sex hormonal factors,Pathogenesis,Excessive,abnormal production of“self”antibodies and formation of IC,.,Autoantibodies against nuclear,cytoplasmic and membrane components of multiple cell types in multiple organs,.,Etiology and pathogenesis,pathology,Clinical findings,Laboratory findings,Diagnosis,Treatment,prognosis,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,Etiology and pathogenesis,pathology,Clinical findings,Laboratory findings,Diagnosis,Treatment,prognosis,第一课件网网站,Systemic features,Fever Weak Weight loss,skin and mucosa,光敏感,photosensitivity,脱发,alopecia,雷诺现象,Raynauds phenomenon,口腔溃疡,oral ulcer,皮疹,rash,skin and mucosa,skin and mucosa,skin and mucosa,skin and mucosa,skin and mucosa,skin and mucosa,Muscle and Joint,arthritis-Jaccouds arthropathy,Muscle pain,、,myositis,femoral head necrosis,Muscle and Joint,Renal lesion,Proteinuria,hematuria,cylindruria,Nephritic syndrome,Renal insufficiency,lupus nephritis,Class I,正常,Class II,系膜增殖性,mesangial,Class III,局灶增殖性,focal proliferative,Class IV,弥漫增殖性,diffuse proliferative,Class V,膜性,membranous,Class VI,肾小球硬化性,glomerulosclerosis,Nervous system,clinical manifestation:,-headache,、,vomiting,-psychogenia,-epilepsy,-convulsion,、,conscious disturbance,-coma,pathology-vasculitis,cerebrospinal fluid-no special (intracranial pressureproteincell population glucose),Identify with other central nervous system disease,Hematology system,leukopenia,thrombocytopenia,anemias:hemolytic anemias,anemias of chronic disease,lymphadenectasis,splenectasis,Respiratory system,pleurisy,Pleural effusion,Pulmonary interstitial fibrosis,Lupus pneumonia,Pulmonary hypertension,Respiratory failure,lung,Circulatory system,heart -pericarditis,-myocarditis,-endocarditis,Libman-Sack endocarditis,-cardiac arrhythmias,-cardiac failure,vessel-vasculitis,第一课件网网站,Digestive system,Clinical features,-anepithymia,-nausea and vomiting,-abdominal pain,、,diarrhea,-peritoneal effusion,-acute abdomen,pathology-mesenterium vasculitis,抗磷脂抗体综合征,(,antiphospholipid antibody syndrome),clinical manifestation:,-arterous and/or venous thrombosis,-spontaneous abortion,-thrombocytopenia,laboratory examination:,-positive anti-phospholipid antibody,干 燥 综 合 征,30%,的,SLE,患者可有继发干燥综合征,患者有临床症状,唾液腺,ECT,可有改变,干燥抗体可为阴性,Etiology and pathogenesis,pathology,Clinical findings,Laboratory findings,Diagnosis,Treatment,prognosis,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,C3,C4,CH50,Ig,r-G,诊断,治疗,预后,MRI,CT,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-1,Sm,RNP,SSB,SSA,Etiology and pathogenesis,pathology,Clinical findings,Laboratory findings,Diagnosis,Treatment,prognosis,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.,精神症状,4,项阳性可诊断,SLE,9,.,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-CL and/or LA,11.ANA,CRITERIA FOR THE DIAGNOSIS OF SLE ACCORDING TO THE ACR(1997),1.Butterfly rash,2.Discoid lupus,3.Photosensitivity,4.Oral ulceration,5.Polyarthritis,6.Nephritis,a.proteinuria over 0.5g/day,b.cellular casts,7.Pleuritis/pericarditis,8.Neuropsychiatric symptoms,a.convulsions,b.psychosis,4 or more symptoms are required for the diagnosis,9,.Haematological alterations,a.haemolytic anaemia,b.leucopenia(4.0 G/l),c.lymphopenia(1.5G/l),d.thrombocytopenia(100G/l),10.Immunologic alterations,a.anti-dsDNA,b.anti-Sm,c.,anti-CL and/or LA,11.ANA,SLE-DAI,狼疮性头痛,精神症状,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,提示,SLE,活动性的指证,症状体征,:,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,SLE,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,(lupus crisis),：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,Etiology and pathogenesis,pathology,Clinical findings,Laboratory findings,Diagnosis,Treatment,prognosis,治疗层次,基因,发病,机制,诱因,感染 药物 光照 激素等,SLE,症状,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,general treatment,drug treatment,plasmapheresis,haemopoietic stem,cell transplantation,General treatment,心理治疗,急性活动期卧床休息，避免过劳,及早发现和治疗感染,避免使用可能诱发狼疮的药物,避免阳光暴晒和紫外线照射,(SPF of at least 25),缓解期才可作防疫注射,定期随访,Medications,treatment,NSAIDS,Antimalarials,Corticosteroids,Immunosuppressant,Biological therapy,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,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,第一课件网网站,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,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,体表面积,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,50,mg/d,持续时间,:,部分终身,狼疮危象,(lupus crisis),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,:,0.4 g/kg/,天,4-5,天,3.,对症治疗,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,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,Hydrocortisone,20,8-12h,1,+,cortisone,25,8-12h,0.8,+,Prednisone,5,12-36h,4,+,Prednisolone,5,12-36h,4,+,methylprednisolone,4,12-36h,5,0,Triamcinalone,4,12-36h,5,0,Betamethasone,0.6,36-54h,20-30,0,Dexamethasone,0.75,36-54h,20-30,+,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,神经精神症状,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,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）,注意事项,-,冲击前验血常规,-,冲击中水化疗法,-,同时给予止吐药,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,胃肠道反应,脱发,肝肾损害,诱发肿瘤,免疫抑制剂,(,Immunosuppressant),环磷酰胺（,CTX,）,硫唑嘌呤,(,依木兰,Imuran),环孢素,(cyclosporin A),麦考酚吗乙酯,(,骁悉,CellCept),甲氨碟呤,(MTX),爱若华（,Leflunomide,）,雷公藤多甙,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,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,2-3 mg/kg/day,口服,-,维持剂量,1-3 mg/kg /day,口服,副作用,-,骨髓抑制,-,肝损害,-,胃肠道反应,环孢素,(cyclosporin A),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,-,胃肠道症状,-,皮疹,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：,1.5-2.0g/d,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,甲氨碟呤,(MTX),用于治疗症状轻,内脏损害不重而关节症状明显或皮疹较重的,SLE,患者,还可用于鞘内注射,剂量,:7.5-25 mg/,周,口服或静脉注射,副作用,-,胃肠道反应,-,口腔溃疡,-,肝功能损害,-,骨髓抑制,-,脱发,爱若华（,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,-,胃肠道反应,-,肝功能损害,-,皮疹,-,脱发,-,高血压,雷公藤多甙,用法,:20mg,tid p.o.,病情控制后可减量或间歇疗法,对本病有一定疗效,不良反应较大,性腺的抑制,肝损害,胃肠道反应,白细胞减少,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,:0.4 g/kg/,天,4-5,天,费用昂贵,第一课件网网站,血浆置换,将血液中异常成分,(CIC,自身抗体,),去除,从而达到血液净化的作用,多用于重症狼疮,连做,4,次,费用昂贵,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,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,Etiology and pathogenesis,pathology,Clinical findings,Laboratory findings,Diagnosis,Treatment,prognosis,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,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,THE END,