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医药导报  2019, Vol. 38 Issue (6): 803-807    DOI: 10.3870/j.issn.1004-0781.2019.06.027
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丙硫氧嘧啶引起肺部病变明显的ANCA相关性血管炎5例*
罗夏黎1(),宗秋2,齐雪霏2,牟永2,王琪2,熊维宁2,赵建平2,肖宏3(),周敏2()
1.江汉大学医学院,武汉 430056
2.华中科技大学同济医学院附属同济医院呼吸与危重症医学科,武汉 430030
3.武汉大学人民医院,武汉 430060
Clinical Features of 5 Patients with Propylthiouracil-associated ANCA Vasculitis with Serious Pulmonary Involvement
Xiali LUO1(),Qiu ZONG2,Xuefei QI2,Yong MOU2,Qi WANG2,Weining XIONG2,Jianping ZHAO2,Hong XIAO3(),Min ZHOU2()
1.Medical College of Jianghan University, Wuhan 430056,China
2.Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
3.People's Hospital,Wuhan University, Wuhan 430060,China
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摘要 

目的 分析丙硫氧嘧啶(PTU)诱导肺部病变明显的抗中性粒细胞胞浆抗体(ANCA)相关性血管炎患者的临床特征,促进临床医师掌握药物的安全使用,以及对不良反应的处理及治疗方法。方法 采用回顾性调查方法,统计5例由PTU引起的,肺部病变明显的ANCA相关性血管炎的临床特征及后续治疗和转归情况,收集相关信息进行分析。ANCA水平使用免疫荧光(IFT)和酶联免疫吸附测定(ELISA) 法检测。结果 共收集患者5例,男2例,女3例,年龄(52.7±5.4)岁,服用PTU时间3~10年。5例患者血清p-ANCA均阳性,其中4例MPO-ANCA升高,1例MPO-ANCA和PR3-ANCA两项均升高。5例患者均出现发热、咳嗽,2例呼吸困难并出现呼吸衰竭,肺脏受累明显。患者初次就诊均被误诊为肺部感染。5例患者均累及肾脏。所有患者确诊后均立即停药,并使用糖皮质激素治疗,其中2例患者联用环磷酰胺治疗。治疗后5例患者均病情好转出院,随访期间无复发。结论 临床医生须警惕和重视PTU诱导的ANCA相关性血管炎,注意与原发性血管炎相鉴别,尽早停药。对于出现严重脏器损伤时,及时予以糖皮质激素及免疫抑制药治疗,避免病情加重危及生命。

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罗夏黎
宗秋
齐雪霏
牟永
王琪
熊维宁
赵建平
肖宏
周敏
关键词 丙硫氧嘧啶抗中性粒细胞胞浆抗体血管炎ANCA相关性甲状腺功能亢进    
Abstract

Objective To retrospectively investigate the clinical features of patients with pulmonary involvement in propylthiouracil (PTU)-associated antineutrophil cytoplasmic autoantibody vasculitis (AAV).The aim of our study was to summarize these data of the reasonable medication and the follow-up treatment for clinician physicians. Methods Clinical features and outcomes of 5 patients developed AAV with pulmonary involvement after treatment with PTU were collected and analyzed.ANCA was detected by both immunofluorescence (IFT) and enzyme linked immunosorbent assay (ELISA). Results Five patients, male 2,female 3, average age(52.7±5.4) years, PTU for 3-10 years, received when PTU-AAV was diagnosed.All patients had positive serum p-ANCA, 4 of them were MPO-ANCA, 1 of them was MPO and PR3-ANCA double positive.All patients present with fever and cough.Two patients of them suffered from dyspnea and developed respiratory failure.Initial diagnosis of all patients was misdiagnosed as pulmonary infection.All patients got renal involvement presented with hematuria and/or proteinuria.All patients withdrew PTU and received steroid therapy,2 of them were treated with cyclophosphamidesimultaneously.All patients got clinical remission with no recurrence during the follow-up period. Conclusion It is important to comprehend PTU-induced AAV and distinguish it from primary vasculitis for clinicians.PTU should be discontinued immediately after diagnosis.Corticosteroids and immunosuppressive agents may be promptly used in patients with vital organ involvements.

Key wordsPropylthiouracil    Antineutrophil cytoplasmic autoantibody    ANCA-associated vasculitis    Hyperthyroidism
收稿日期: 2018-08-09      出版日期: 2019-06-11
基金资助:*国家自然科学基金资助项目(81700032)
引用本文:   
罗夏黎,宗秋,齐雪霏,牟永,王琪,熊维宁,赵建平,肖宏,周敏. 丙硫氧嘧啶引起肺部病变明显的ANCA相关性血管炎5例*[J]. 医药导报, 2019, 38(6): 803-807.
Xiali LUO,Qiu ZONG,Xuefei QI,Yong MOU,Qi WANG,Weining XIONG,Jianping ZHAO,Hong XIAO,Min ZHOU. Clinical Features of 5 Patients with Propylthiouracil-associated ANCA Vasculitis with Serious Pulmonary Involvement. Herald of Medicine, 2019, 38(6): 803-807.
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http://www.yydbzz.com/CN/10.3870/j.issn.1004-0781.2019.06.027      或      http://www.yydbzz.com/CN/Y2019/V38/I6/803
患者 性别 年龄/
PTU治疗
时间/个月
肺部受
累时间
全身症状 肺部症状 肺肾外表现 p-ANCA MPO-ANCA/
(RU·mL-1)
例1 60 72 5个月 发热、乏力 咳嗽、咯血、呼吸困难 阳性 197.3
例2 55 36 1个月 发热 咳嗽 阳性 150.9
例3 54 96 20余天 发热、纳差、乏力 咳嗽、咯痰 阳性 >200
例4 45 60 1个月 发热、关节痛、乏力 胸痛 鼻塞、右眼结膜炎 阳性 >200
例5 51 120 6个月 发热 咳嗽、呼吸困难 双下肢及足底烧灼感 阳性 124.7
患者 c-ANCA PR3-ANCA/
(RU·mL-1)
尿常规 肾功能/
(μmol·L-1)
ESR/
(mm·h-1)
肺部CT 动脉血气
例1 阴性 <2 RBC 3+,Pro 3+ 217 51 双肺片状密度影,部分呈软 PaO2 6.65 kPa,Ⅰ型呼吸衰
组织影,右肺为甚,部分呈
网格状,双侧胸腔积。
例2 阴性 9.46 RBC 1+,Pro - 78 99 右肺见淡薄斑片影,右侧少 PaO2 10.64 kPa,PaCO2
量胸腔积液 4.655 kPa
例3 阴性 <2 RBC 3+,Pro 2+ 89 104 双肺散在斑片影 PaO2 11.97 kPa,PaCO2
4.256 kPa
例4 阴性 5.4 RBC 3+,Pro - 41 97 左上叶、左舌叶见斑片状模 未查
糊影
例5 弱阳性 41.3 RBC 2+,Pro - 191 51 双肺见多发斑片影,以左肺 PaO27.049 kPa。PaCO2
为著,双肺下叶胸膜下小 5.120 kPa,Ⅰ型呼吸衰
叶间隔增厚呈网格状改
变,双侧胸腔积液。
患者 治疗激素用量 环磷酰胺 转归 随访
例1 静脉滴注甲泼尼龙40 mg·d-1,逐渐减量 累积剂量1.2 g 好转出院 口服泼尼松逐渐减量5 mg·d-1维持,6个月后复诊无
复发,后失访。
例2 口服泼尼松20 mg·d-1,然后逐渐减量 好转出院 1个月后泼尼松减量至5 mg·d-1维持,2个月后停用,
无复发。
例3 静脉滴注地塞米松3 mg·d-1,后改为口服泼尼松 好转出院 3个月后泼尼松减量至停用,无复发,后失访。
20 mg·d-1,逐渐减量
例4 口服甲泼尼龙30 mg·d-1,逐渐减量 好转出院 失访。
例5 静脉滴注甲基泼尼松龙40 mg·d-1,逐渐减量 累积剂量1.0 g 好转出院 口服泼尼松逐渐减量,12个月后减至2.5 mg·d-1
持,无复发,后失访。
表1  丙硫氧嘧啶诱导肺部病变明显的ANCA相关性血管炎患者临床资料
图1  病例1肺部CT的典型影像
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