摘要目的：认识韦格纳肉芽肿病的临床病理表现。方法：对北京医科大学第一医院肾内科近3年来经病理检查确诊的6例韦格纳肉芽肿病病例进行临床病理资料的分析和总结。患者血清均行抗中性粒细胞胞浆抗体（antineutrophil cytoplasmic autoantibodies, ANCA）检测，IIF法(indirect immunofluorescence)区分cANCA和pANCA，抗原特异性ELISA以高度纯化的PR3(proteinase 3)和MPO(myeloperoxidase)为靶抗原。结果：6例患者男性2例，女性4例，平均年龄56.8（26～68）岁；pANCA/MPO-ANCA 阳性4例，cANCA/PR3-ANCA阳性2例；6例均经活检病理检查发现肉芽肿性病变，肉芽肿中心多为纤维素样坏死性小血管炎，周围炎性细胞浸润及类上皮样细胞增生，其中4例发现于肾间质，1例于肺结节和1例于鼻粘膜；临床表现为多器官受累，均有肾受累，肾活检除可见肉芽肿性小血管炎外，肾小球均可见毛细血管壁局灶节段性纤维素样坏死伴或不伴新月体形成；所有患者均有肺受累，表现为咳嗽，咯血，胸片可见肺部阴影、结节或空洞；其他器官受累也较常见，包括眼、耳、皮肤、关节肌肉和周围神经病变；实验室检查有白细胞和血小板计数增高、贫血、血沉快和CRP阳性。所有6例患者均有发烧和乏力，4例有体重下降。早期诊断，及时治疗者预后较好，而延误诊断者则进展迅速，达终末期肾功能衰竭。结论：韦格纳肉芽肿病为ANCA相关的原发性小血管炎，上述6例中的主要ANCA靶抗原为MPO和PR3。该病患者以中老年为主，临床可累及多个脏器，病理可见肉芽肿性小血管炎。对怀疑本病者，应尽早行ANCA检查，以期早期诊断，及时治疗。

中国图书资料分类法分类号R759.4

Clinical and pathological manifestations of patients with Wegener's granulomatosis

ZHAO Ming-Hui, LIU Na， ZHANG You-Kang, ZOU Wan-Zhong, LIU Yu-Chun, Jiang Yun, et al

(Department of Nephrology, the First Hospital, Beijing Medical University, Beijing100034)

ABSTRACTObjective: To analyze the clinical and pathological manifestations of patients with Wegener's granulomatosis.Methods: Clinical and pathological data were collected from six patients with pathologically confirmed Wegener's granulomatosis and were further analyzed. Antineutrophil cytoplasmic autoantibodies (ANCA) were detected in all sera, and standard IIF (indirect immunofluorescence) method and antigen specific ELISA, using PR3 (proteinase 3) and MPO (myeloperoxidase) as solid phase ligands, were employed.Results: Of the six patients, four were female and two male with an average age of 56.8 (26－68) years old. Four patients were pANCA/MPO-ANCA positive and two cANCA/PR3-ANCA positive. All six patients were found to have vasculitic granuloma in their biopsy tissues. Four were from renal interstitium, one from lung nodule and one from nosal mucosa. Clinically, all patients had multi-system involvement, especially kidney and lungs. All patients had hematuria and proteinuria, and renal biopsies showed focal segmental necrotizing glomerulonephritis with crescents formation except for granulomatous vasculitis. Patients with lung involvement had cough and cough blood. Chest X-ray showed pulmonary shadows, nodules or cavities. Eye, ear, skin, joints, muscle and peripheral nerve systems were also frequently involved. In laboratory examinations, all patients had anemia with elevated ESR and CRP. WBC and platelet counts were increased. All six patients had fever and fatigue, four of whom had body weight loss. An early diagnosis and appropriate treatment suggested a better prognosis, otherwise, the patients could reach end stage renal failure progressively.Conclusion: Wegener's granulomatosis is an ANCA-related small vessel vasculitis. In this study, the target ANCA antigens were MPO and PR3. The patients were middle to old aged. They all had multi-system involvement clinically and granulomatous vasculitis in pathology. For patients with suspected small vessel vasculitis, an ANCA test should be performed in order to make an early diagnosis and treatment started in time.

MeSHWegener's granulomatosis/patholWegener's granulomatosis/diag

韦格纳肉芽肿病（Wegener's granulomatosis, WG）是一种系统性小血管炎，临床上典型的表现为三联征，即上呼吸道、下呼吸道炎症和肾小球肾炎，病理特点为肉芽肿性小血管炎^［1］。近年发现抗中性粒细胞胞浆抗体（antineutrophil cytoplasmic autoantibodies, ANCA）为其重要的血清学诊断工具，应用间接免疫荧光法（indirect immunofluorescence, IIF）可有两种荧光形态：胞浆型染色为cANCA, 环核型染色为pANCA, 其特异性靶抗原分别为蛋白酶3（proteinase 3, PR3）和髓过氧化物酶（myeloperoxidase, MPO）^［2］。国外研究发现WG病人多为cANCA/抗PR3抗体阳性，也有少数病人为pANCA/抗MPO抗体阳性。本病在白种人中发病率较高，我国报道较少, 可能与该病的临床表现复杂多样，缺乏较为敏感和特异的血清免疫学指标有关，同时也与对其病理改变认识不足，有时易与其它疾病混淆等原因相关^［3～5］。本研究通过对近3年来我科可疑住院病人系统地进行ANCA监测及肾、肺和鼻粘膜活检证实了6例WG。本文对该6例WG进行了临床病理分析，以期提高对该病的认识。

1资料与方法

6例患者均系我院近3年来临床病理资料完整的住院病人，WG的确诊依据为病理检查发现肉芽肿性小血管炎及典型的临床表现。全部患者均行ANCA检测，以标准的IIF法区分cANCA和pANCA^［2］，抗原特异性ELISA以高度纯化的PR3和MPO为靶抗原, 方法同前报道^［6］。

2结果

2.1一般情况

6例患者中：男性2例，女性4例，平均年龄56.8（26～68）岁；病程20 d～3个月。首发症状均以上呼吸道症状为主，全部均有发烧和乏力，4例有明显的体重下降。

2.2多系统受累表现

4例患者有上呼吸道受累，如鼻炎和副鼻窦炎，表现为反复鼻塞、流涕、头痛和鼻出血。6例均有下呼吸道受累，表现为肺部阴影（4/6）、结节（3/6）和薄壁空洞（1/6），确诊前均被误诊为肺部感染、肿瘤或结核，2(2/6)例有胸腔积液。所有患者均有肾受累，均有镜下血尿和少量蛋白尿（＜3.5 g/d），1例病人就诊时表现为急进性肾炎综合征，伴少尿/无尿，肾功能达到尿毒症水平。

除上述的三联征外，其他脏器受累也较多见。4例有反复发作的眼结膜炎；2例耳受累，表现为耳异物感、中耳炎和听力下降；3例关节肌肉疼痛；3例有皮疹；2例外周神经炎，表现为痛觉过敏或麻木感；1例腹痛、腹泻；1例心包积液。

2.3病理表现

5例病人进行了肾活检。免疫荧光检查均为阴性或少量免疫复合物沉积。光镜下均为局灶节段坏死性肾小球肾炎伴或不伴细胞新月体形成，表现为典型的肾小球毛细血管襻纤维素样坏死，其中1例已发展至新月体性肾炎。5例肾活检病人中，4例在肾间质发现以小血管为中心的肉芽肿形成，小血管可以有节段性纤维素样坏死，周围淋巴、单核细胞浸润伴有上皮样细胞增生，有时亦可见多形核白细胞浸润(图1)；并均有多寡不一的肾小球坏死和新月体形成。2例患者分别行肥大的鼻甲活检和肺部结节活检证实肉芽肿形成。1例肾活检证实为WG的患者还作了皮疹处皮肤活检，证实为皮肤白细胞碎裂性血管炎。

2.4实验室检查

6例ANCA均阳性，4例为pANCA/MPO-ANCA阳性，2例为cANCA/PR3-ANCA阳性。全部患者均有外周血白细胞升高［（10.3～19.6）×10⁹L^－1］；5（5/6）例血小板计数增高［（37.4～66.6）×10⁹ L^－1］；6例均有贫血，Hb平均为83g·L^－1（54～102g·L^－1）；全部患者红细胞沉降率增快，其中4例在100 mm/1 hr以上；病情活动期CRP和类风湿因子均为阳性。6例患者中，1例就诊时肾功能已达尿毒症水平（血清肌酐1470 μmol·L^－1），1例为氮质血症期（血清肌酐158 μmol·L^－1）, 其余4例就诊时肾功能正常。所有患者抗核抗体（anti-nuclear antibocly, ANA）为阴性。

图1肾小叶间动脉纤维素样变性坏死，

周围肉芽肿样结构形成PASM×100

Figure 1Fibrinoid necrosis of renal interlobular artery,

granulomatous inflammatory cells infiltration around

the vasculit