系統(tǒng)性小血管炎診治及進(jìn)展(2016-4-26)

1、系統(tǒng)性小血管炎診治及進(jìn)展(2016-4-26)系統(tǒng)性血管炎是指以血管壁壞死性炎癥和/或纖維素樣壞死為主要病理特征的一類自身免疫性疾病病變血管局限于微小動(dòng)脈、靜脈和毛細(xì)血管時(shí)為小血管炎系統(tǒng)性小血管炎原發(fā)性系統(tǒng)性小血管炎顯微鏡下型多血管炎（MPA）韋格納肉芽腫?。╓G）變應(yīng)性肉芽腫性血管炎（CSS）過敏性紫癜原發(fā)性冷球蛋白血癥性血管炎皮膚白細(xì)胞碎裂性血管炎Jennette et al. Arthritis Rheum 1994;37:187-192ANCA相關(guān)性血管炎（AAV）1994年Chapel Hill 會(huì)議命名2011 15th International vasculitis &ANCA

2、 worksho European League Against Rheumatism(EULAR) EuropeanVasculitis Study Group (EUVAS)Microscopic polyangiitis (MPA)Granulomatosis with polyangiitis (GPA)Eosinophilic Granulomatosis with Polyangiitis（CSS）ANCA-associated Vasculitis （AAV）2012 Chapel Hill Consensus Conference Vasculitis Nomenclature

3、ANCA陰性不能排除血管炎診斷原發(fā)性系統(tǒng)性小血管炎臨床表現(xiàn)-小血管炎腎損害常見，7090%血尿（100%）、蛋白尿、RPGN可隱襲起病多為非少尿性，易誤診為CRF免疫熒光寡免疫復(fù)合物沉積光鏡局灶節(jié)段壞死性GN伴/不伴新月體形成腎間質(zhì)、小球病變不平行臨床表現(xiàn)-肺受累的表現(xiàn)5090%肺受累50%肺出血咳嗽、咯血、呼吸困難胸片陰影、結(jié)節(jié)和空洞易誤診為感染、腫瘤和結(jié)核彌漫性肺泡毛細(xì)血管炎易誤診為感染、肺水腫老年人可以肺間質(zhì)纖維化首發(fā)，且全身小血管炎無明顯活動(dòng)MPA主要為肺部浸潤影、肺間質(zhì)纖維化、彌漫性肺泡出血WG肺結(jié)節(jié)性病變臨床表現(xiàn)-頭頸部受累多數(shù)病人可分別受累，問診眼:“紅眼病”、畏光流淚、視力下降

4、耳：33%首發(fā)中耳受累多，中耳炎，耳鳴，聽力下降（傳導(dǎo)性、感音神經(jīng)性）很少外耳受累鼻: 鼻竇炎，鼻息肉，鼻甲肥大咽喉: 咽鼓管炎，聲門下狹窄臨床表現(xiàn)-其他臟器受累外周神經(jīng)系統(tǒng)：約50%多發(fā)性單神經(jīng)炎感覺過敏、遲鈍關(guān)節(jié)肌肉痛皮膚-皮疹，潰瘍，壞疽，結(jié)節(jié)，網(wǎng)狀青斑消化道-約2/3受累。食道炎，潰瘍，出血心血管系統(tǒng)：心絞痛、心包炎、心衰血液系統(tǒng)前列腺炎，睪丸炎MPA 臨床表現(xiàn)好發(fā)年齡為4060歲，男女11.8:1大多數(shù)起病急，進(jìn)展快，部分起病隱匿同時(shí)或相繼出現(xiàn)多系統(tǒng)受累表現(xiàn)，肺腎綜合征腎臟幾乎100%受累，以RPGN為特點(diǎn)，少尿、血尿、腎功能不全半數(shù)累及肺臟，彌漫性肺泡出血和肺間質(zhì)纖維化，咯血、貧血

5、和呼吸困難可有發(fā)熱、關(guān)節(jié)痛、肌痛、紫癜、肢體麻木和無力、眼炎和ENT受累表現(xiàn)GPA 臨床表現(xiàn)（WG）特征：反復(fù)發(fā)作的上、下呼吸道壞死性肉芽腫和腎小球腎炎及其他系統(tǒng)性小血管炎性損害典型WG三聯(lián)癥：上呼吸道癥狀，肺病變，腎病變另有患者以眼部病變首發(fā)，眼球突出最具特征性eGPA 臨床表現(xiàn)(CSS)典型病程為三期：前驅(qū)期:多種過敏性疾病表現(xiàn)，如：變應(yīng)性鼻炎、鼻息肉、哮喘（可持續(xù)10年左右）；血管炎期：全身不適、腓腸肌痛，可急性發(fā)作，急劇惡化血管炎后期：重癥哮喘及系統(tǒng)性血管炎繼發(fā)改變，如高血壓、慢性心功能不全、外周神經(jīng)損傷等各期可見外周血嗜酸粒細(xì)胞增多及其在肺、胃腸道、心臟組織浸潤。84%累及腎臟，多數(shù)

6、輕度損害，少數(shù)發(fā)生腎梗死、高血壓實(shí)驗(yàn)室檢查一般指標(biāo)ESR多大于100mm/h，CRP升高Hb低(與出血不相稱)，WBC和PLT高球蛋白升高C3正常或偏低RF可陽性血尿、蛋白尿、Cr、BUN升高特異性指標(biāo)-ANCA診斷，指導(dǎo)治療，判斷復(fù)發(fā) ，滴度與活動(dòng)相關(guān) ANCAP-ANCA 核周型（MPA） MPO (髓過氧化物酶）ANCA滴度與病情活動(dòng)相關(guān) C-ANCA 胞漿型 （WG） PR3（絲氨酸蛋白酶3）臨床表現(xiàn)（癥狀體征）不明原因的發(fā)熱、難以解釋的全身癥狀多系統(tǒng)損害進(jìn)展迅速的臟器功能衰竭（肺腎綜合征）腎臟損害（特別是活動(dòng)性腎小球腎炎）肺部病變（浸潤、出血、呼衰）肌肉和關(guān)節(jié)疼痛皮膚紫癜及結(jié)節(jié)性壞死

7、性皮疹突發(fā)神經(jīng)系統(tǒng)病變，尤其是多發(fā)性單神經(jīng)炎實(shí)驗(yàn)室檢查ESR、CRP、與腎功能下降不平行的貧血ANCA病理學(xué)證據(jù)：金標(biāo)準(zhǔn)如何診斷ANCA相關(guān)小血管炎？診斷流程一元論多系統(tǒng)性損害，尤其肺、腎損害詳細(xì)的病史及查體血清學(xué)檢查： ANCA、ESR、CRP、自身抗體、RF、補(bǔ)體、蛋白電泳治療確診血管炎 組織活檢心、肺、腎、神經(jīng)系統(tǒng)檢查，明確系統(tǒng)損害的范圍和程度 金標(biāo)準(zhǔn)如何判斷病情活動(dòng)？臨床病理表現(xiàn)BVAS積分高滴度的ANCA其它指標(biāo)ESR，CRP（+）BVAS（伯明翰血管炎評分系統(tǒng)）分為9大類或系統(tǒng)（63）全身非特異性表現(xiàn)（3）皮膚（6）粘膜（6）耳鼻喉（6）肺（6）心血管（6）胃腸道（9）腎臟（12）

8、神經(jīng)系統(tǒng)（9）耳鼻喉無0鼻分泌物/鼻堵2鼻竇炎2鼻出血4鼻痂4外耳道溢液4中耳炎4新發(fā)聽力下降/耳聾6聲嘶/喉炎2聲門下受累 6BVAS達(dá)到25即為高危ANCA相關(guān)小血管炎的治療策略誘導(dǎo)緩解治療長期保護(hù)腎功能減少復(fù)發(fā)維持治療盡快控制炎癥爭取完全緩解治療目標(biāo)提高生存率、保存靶器官功能、減少副作用復(fù)發(fā)治療盡快控制炎癥爭取完全緩解13.1: Initial treatment of pauci-immune focal and segmental necrotizing GN13.1.1: We recommend that cyclophosphamide and corticosteroids

9、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治療指南-113.3: Maintenance therapy13.3.1: We recommend maintenance therap

10、y 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 diseas

11、e. (1C)KDIGO-AAV治療指南-213.4: Choice of agent for maintenance therapy13.4.1: We recommend 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)

12、13.4.3: We suggest 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 25 mg/wk) for maintenance therapy in patients intolerant of azathioprine and MMF, but not if GF

13、R is 60 ml/min per 1.73m2. (1C)13.4.5: We recommend not using etanercept as adjunctive therapy. (1A)KDIGO-AAV治療指南-313.5: Treatment 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

14、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 M

15、MF. (2C)13.6: Treatment 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 . immunoglobulin (2C) or plasmapheresis (2D) as alternatives.KDIGO-AAV治療指南-413.7: Monitoring13.7.1: We sug

16、gest not changing immunosuppression based on changes in ANCA titer alone. (2D)13.8: Transplantation13.8.1: 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治療指南-5建議聯(lián)合用CTX（靜脈或口服）和糖皮質(zhì)激素進(jìn)行誘導(dǎo)緩解治療；建議對無危及生命或器官的AAV患者聯(lián)合甲