系统性小血管炎诊治及进展.pptx
系统性血管炎是指以血管壁坏死性炎症和/或纤维素样坏死为主要病理特征的一类自身免疫性疾病病变血管局限于微小动脉、静脉和毛细血管时为小血管炎系统性小血管炎第1页/共30页原发性系统性小血管炎显微镜下型多血管炎（MPA）韦格纳肉芽肿病（WG）变应性肉芽肿性血管炎（CSS）过敏性紫癜原发性冷球蛋白血症性血管炎皮肤白细胞碎裂性血管炎Jennette et al.Arthritis Rheum 1994;37:187-192ANCA相关性血管炎（AAV）1994年ChapelHill会议命名第2页/共30页201115thInternationalvasculitis&ANCAworkshoEuropeanLeagueAgainstRheumatism(EULAR)EuropeanVasculitisStudyGroup(EUVAS)第3页/共30页Microscopic polyangiitis(MPA)(MPA)Granulomatosis with polyangiitis(GPA)(GPA)Eosinophilic Granulomatosis with Polyangiitis（CSSCSS）ANCA-associated Vasculitis（AAV）2012 Chapel Hill Consensus Conference Vasculitis Nomenclature第4页/共30页ANCAANCA阴性不能排除血管炎诊断阴性不能排除血管炎诊断原发性系统性小血管炎原发性系统性小血管炎第5页/共30页临床表现-小血管炎肾损害常见，7090%血尿（100%）、蛋白尿、RPGN可隐袭起病多为非少尿性，易误诊为CRF免疫荧光寡免疫复合物沉积光镜局灶节段坏死性GN伴/不伴新月体形成肾间质、小球病变不平行第6页/共30页临床表现-肺受累的表现5090%肺受累50%肺出血咳嗽、咯血、呼吸困难胸片阴影、结节和空洞易误诊为感染、肿瘤和结核弥漫性肺泡毛细血管炎易误诊为感染、肺水肿老年人可以肺间质纤维化首发，且全身小血管炎无明显活动老年人可以肺间质纤维化首发，且全身小血管炎无明显活动MPA主要为肺部浸润影、肺间质纤维化、弥漫性肺泡出血WG肺结节性病变第7页/共30页临床表现-头颈部受累多数病人可分别受累，问诊眼:“红眼病”、畏光流泪、视力下降耳：33%首发中耳受累多，中耳炎，耳鸣，听力下降（传导性、感音神经性）很少外耳受累鼻:鼻窦炎，鼻息肉，鼻甲肥大咽喉:咽鼓管炎，声门下狭窄第8页/共30页临床表现-其他脏器受累外周神经系统：约50%多发性单神经炎感觉过敏、迟钝关节肌肉痛皮肤-皮疹，溃疡，坏疽，结节，网状青斑消化道-约2/3受累。食道炎，溃疡，出血心血管系统：心绞痛、心包炎、心衰血液系统前列腺炎，睾丸炎第9页/共30页MPA 临床表现好发年龄为4060岁，男女11.8:1大多数起病急，进展快，部分起病隐匿同时或相继出现多系统受累表现，肺肾综合征肾脏几乎100%受累，以RPGN为特点，少尿、血尿、肾功能不全半数累及肺脏，弥漫性肺泡出血和肺间质纤维化，咯血、贫血和呼吸困难可有发热、关节痛、肌痛、紫癜、肢体麻木和无力、眼炎和ENT受累表现第10页/共30页GPA 临床表现（WG）特征：反复发作的上、下呼吸道坏死性肉芽肿和肾小球肾炎及其他系统性小血管炎性损害典型WG三联症：上呼吸道症状，肺病变，肾病变另有患者以眼部病变首发，眼球突出最具特征性第11页/共30页eGPA 临床表现(CSS)典型病程为三期：前驱期:多种过敏性疾病表现，如：变应性鼻炎、鼻息肉、哮喘（可持续10年左右）；血管炎期：全身不适、腓肠肌痛，可急性发作，急剧恶化血管炎后期：重症哮喘及系统性血管炎继发改变，如高血压、慢性心功能不全、外周神经损伤等各期可见外周血嗜酸粒细胞增多及其在肺、胃肠道、心脏组织浸润。84%累及肾脏，多数轻度损害，少数发生肾梗死、高血压第12页/共30页实验室检查一般指标ESR多大于100mm/h，CRP升高Hb低(与出血不相称)，WBC和PLT高球蛋白升高C3正常或偏低RF可阳性血尿、蛋白尿、Cr、BUN升高特异性指标-ANCA诊断，指导治疗，判断复发，滴度与活动相关 第13页/共30页ANCAP-ANCA 核周型（MPA）MPO(髓过氧化物酶）ANCAANCA滴度与病情活动相关滴度与病情活动相关 C-ANCA 胞浆型（WG）PR3（丝氨酸蛋白酶3）第14页/共30页临床表现（症状体征）不明原因的发热、难以解释的全身症状多系统损害进展迅速的脏器功能衰竭（肺肾综合征）肾脏损害（特别是活动性肾小球肾炎）肺部病变（浸润、出血、呼衰）肌肉和关节疼痛皮肤紫癜及结节性坏死性皮疹突发神经系统病变，尤其是多发性单神经炎实验室检查ESR、CRP、与肾功能下降不平行的贫血ANCA病理学证据：金标准如何诊断ANCA相关小血管炎？第15页/共30页诊断流程一元论一元论多系统性损害，尤其肺、肾损害详细的病史及查体血清学检查：ANCA、ESR、CRP、自身抗体、RF、补体、蛋白电泳治疗确诊血管炎 组织活检心、肺、肾、神经系统检查，明确系统损害的范围和程度 金标准第16页/共30页如何判断病情活动？临床病理表现BVAS积分高滴度的ANCA其它指标ESR，CRP（+）第17页/共30页BVAS（伯明翰血管炎评分系统）分为9大类或系统（63）全身非特异性表现（3）皮肤（6）粘膜（6）耳鼻喉（6）肺（6）心血管（6）胃肠道（9）肾脏（12）神经系统（9）耳鼻喉无0鼻分泌物/鼻堵2鼻窦炎2鼻出血4鼻痂4外耳道溢液4中耳炎4新发听力下降/耳聋6声嘶/喉炎2声门下受累 6BVAS达到达到25即为高危即为高危第18页/共30页ANCA相关小血管炎的治疗策略诱导缓解治疗长期保护肾功能减少复发维持治疗尽快控制炎症争取完全缓解治疗目标提高生存率、保存靶器官功能、减少副作用复发治疗尽快控制炎症争取完全缓解第19页/共30页l13.1:13.1:13.1:13.1:Initial treatment Initial treatment Initial treatment Initial treatment of pauci-immune focal and of pauci-immune focal and of pauci-immune focal and of pauci-immune focal and segmental necrotizing GNsegmental necrotizing GNsegmental necrotizing GNsegmental necrotizing GN13.1.1:We recommend that cyclophosphamide and corticosteroids be used as initial treatment.(1A)13.1.2:We recommend that rituximab and corticosteroids be used as an alternative initial treatment in patients without severe disease or in whom cyclophosphamide is contraindicated.(1B)KDIGO-AAV治疗指南-1第20页/共30页l13.3:13.3:13.3:13.3:Maintenance therapyMaintenance therapyMaintenance therapyMaintenance therapy13.3.1:We recommend maintenance therapy in patients who have achieved remission.(1B)13.3.2:We suggest continuing maintenance therapy for at least 18 months in patients who remain in complete remission.(2D)13.3.3:We recommend no maintenance therapy in patients who are dialysis-dependent and have no extrarenal manifestations of disease.(1C)KDIGO-AAV治疗指南-2第21页/共30页l13.4:13.4:13.4:13.4:Choice of agent for maintenance therapyChoice of agent for maintenance therapyChoice of agent for maintenance therapyChoice of agent for maintenance therapy13.4.1:We recommend azathioprine 12 mg/kg/d azathioprine 12 mg/kg/d orally as maintenance therapy.(1B)13.4.2:We suggest that MMF,up to 1 g twice daily,be used for maintenance therapy in patients who are allergic to,or intolerant of,azathioprine.(2C)13.4.3:We suggest trimethoprim-sulfamethoxazol trimethoprim-sulfamethoxazole as an adjunct to maintenance therapy in patients with upper respiratory tract disease.(2B)13.4.4:We suggest methotrexate(initially 0.3 mg/kg/wk,maximum methotrexate(initially 0.3 mg/kg/wk,maximum 25 mg/wk)25 mg/wk)for maintenance therapy in patients intolerant of azathioprine and MMF,but not if GFR is 60 ml/min per 1.73m2.(1C)13.4.5:We recommend not using etanercept not using etanercept as adjunctive therapy.(1A)KDIGO-AAV治疗指南-3第22页/共30页l13.5:13.5:13.5:13.5:Treatment of relapseTreatment of relapseTreatment of relapseTreatment of relapse13.5.1:We recommend treating patients with severe relapse of ANCA vasculitis(life-or organ-threatening)according to the same guidelines as for the initial therapy(see Section 13.1).(1C)13.5.2:We suggest treating other relapses of ANCA vasculitis by reinstituting immunosuppressive therapy or increasing its intensity with agents other than cyclophosphamide,including instituting or increasing dose of corticosteroids,with or without azathioprine or MMF.(2C)13.6:13.6:13.6:13.6:Treatment of resistant diseaseTreatment of resistant diseaseTreatment of resistant diseaseTreatment of resistant disease13.6.1:In ANCA GN resistant to induction therapy with cyclophosphamide and corticosteroids,we recommend the addition of rituximab(1C),and suggest i.v.immunoglobulin(2C)or plasmapheresis(2D)as alternatives.KDIGO-AAV治疗指南-4第23页/共30页l13.7:13.7:MonitoringMonitoring13.7.1:We suggest not changing immunosuppression based on changes in ANCA titer alone.(2D)l13.8:13.8:TransplantationTransplantation13.8.1:We recommend delaying transplantation until patients are in complete extrarenal remission for 12 months.(1C)13.8.2:We recommend not delaying transplantation for patients who are in complete remission but are still ANCA-positive.(1C)KDIGO-AAV治疗指南-5第24页/共30页建议联合用CTX（静脉或口服）和糖皮质激素进行诱导缓解治疗；建议对无危及生命或器官的AAV患者联合甲氨蝶呤和糖皮质激素替代CTX作为诱导缓解治疗；建议对快速进展或重度肾损害者，加用血浆置换治疗（1B级证据，A级推荐）；建议小剂量激素联合硫唑嘌呤或来氟米特或甲氨蝶呤作为维持缓解治疗。EUVAS治疗建议第25页/共30页预 后影响因素年龄就诊时肌酐水平有无肺出血激素联合免疫抑制剂治疗后1年生存率可达80100%；5年生存率较未治疗的10%提高到7080%第26页/共30页预预 后后第27页/共30页思 考误漏诊多，如何解决？提高认识，综合诊断思维临床和病理表现熟悉诊断标准规范化ANCA检测（IF、ELISA）第28页/共30页THANKS FOR YOUR ATTENTION！第29页/共30页感谢您的观看！第30页/共30页
