Article(id=1211269165172781698, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211269157790806494, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2021.04.10, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1609862400000, receivedDateStr=2021-01-06, revisedDate=1614960000000, revisedDateStr=2021-03-06, acceptedDate=null, acceptedDateStr=null, onlineDate=1766718673270, onlineDateStr=2025-12-26, pubDate=1619539200000, pubDateStr=2021-04-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1766718673270, onlineIssueDateStr=2025-12-26, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1766718673270, creator=13701087609, updateTime=1766718673270, updator=13701087609, issue=Issue{id=1211269157790806494, tenantId=1146029695717560320, journalId=1189873630562394117, year='2021', volume='46', issue='4', pageStart='319', pageEnd='424', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1766718671510, creator=13701087609, updateTime=1766718756000, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1211269512217882745, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211269157790806494, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1211269512217882746, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211269157790806494, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=380, endPage=385, ext={EN=ArticleExt(id=1211269166879863451, articleId=1211269165172781698, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Application of rituximab in treating six patients with chronic periaortitis and literature review, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective By literature review to retrospectively study the clinical characteristics, diagnosis and treatment process and prognosis of chronic periaortitis (CP) treated with rituximab (RTX), and to improve the understanding of it. Methods To retrospectively analyze the clinical characteristics, laboratory indicators, changes of imaging findings and adverse reactions before and after RTX treatment of six CP patients admitted in the First Medical Center of Chinese PLA General Hospital from October 2014 to November 2020. The clinical remission was defined as the disappearance of clinical symptoms and hydronephrosis, erythrocyte sedimentation rate (ESR) <15 mm/h and C-reactive protein (CRP) <5 mg/L; complete remission was defined as the clinical remission and the maximum transverse diameter of retroperitoneal mass reduced by 50%. Fifty-eight similar cases were collected by searching the database to investigate the efficacy and safety of RTX in treating patients with CP. Results All the 6 patients were males, aged 49.5 (42.0-62.0) years, with pathogenesis of 60 (30-365) days and mean follow-up time of 25.7 (0.9-66.9)months. Three of the 6 patients had severe cardiovascular disease in the past, one suffered from thoracic aorta involvement. RTX alone was given in 3 patients, and together with prednisone in 3 other patients as induce remission therapy, respectively. Five patients achieved clinical remission, of them one was given small dose of prednisone to maintain long-term remission, the other 4 patients received regular application of RTX to maintain remission. The median remission time was 4.0 (0.5-6.0) months. Three patients got complete remission with the median remission time of 18 months (16-24). No recurrence was observed during follow-up. None of the 6 patients had an infusion-related response. One had pulmonary infection at the 3.5-month after the RTX application. A total of 58 cases were found in literature. Clinical symptoms, laboratory tests and imaging findings were all improved. Five (8.6%) patients were infected, 1 (1.7%) was died and 3 (5.2%) had a recurrence after the treatment of RTX. Conclusion Rituximab is an effective and safe regimen in inducing and maintaining remission for chronic periaortitis patients.

, correspAuthors=Jian Zhu, authorNote=null, correspAuthorsNote=
*E-mail:
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目的 报道6例经利妥昔单抗(RTX)治疗的慢性主动脉周围炎(CP)患者的临床特点、诊治经过及预后并进行文献复习,以提高对该病的认识。方法 回顾性分析解放军总医院第一医学中心2014年10月—2020年11月收治的6例CP患者应用RTX治疗前后的临床症状、实验室指标、影像学表现变化及不良反应。临床缓解定义为临床症状消失、肾盂积水消失、红细胞沉降率<15 mm/h、C反应蛋白<5 mg/L;完全缓解定义为临床缓解及影像学提示腹膜后包块最大横径缩小50%。检索相关数据库,结合文献报道的58例患者,总结RTX治疗CP的有效性及安全性。结果 6例患者均为男性,年龄49.5(42.0~62.0)岁,病程60(30~365) d,随访时间25.7(0.9~66.9)个月。其中3例既往合并严重心血管疾病、1例合并胸主动脉受累。3例应用泼尼松0.25~0.5 mg/(kg·d)联合RTX作为诱导缓解方案,其余3例单用RTX诱导缓解。5例达到临床缓解,其中4例规律应用RTX维持缓解,1例应用小剂量泼尼松维持,中位缓解时间为4.0(0.5~6.0)个月;3例达到完全缓解,中位缓解时间为18(16~24)个月;6例均未出现疾病复发。6例患者未出现输注反应,1例在应用RTX后的第3.5个月出现肺部感染。国内外报道RTX治疗CP共58例,治疗后患者临床症状、实验室指标及影像学表现均有改善,应用RTX后仅5例(8.6%)出现感染,1例(1.7%)死亡,3例(5.2%)复发。结论 应用RTX作为诱导缓解及维持缓解方案治疗CP临床效果好,且安全性较高。

, correspAuthors=朱剑, authorNote=null, correspAuthorsNote=
朱剑,E-mail:
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廖思敏,博士研究生,主要从事腹膜后纤维化与IgG4相关性疾病方面的研究

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廖思敏,博士研究生,主要从事腹膜后纤维化与IgG4相关性疾病方面的研究

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廖思敏,博士研究生,主要从事腹膜后纤维化与IgG4相关性疾病方面的研究

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CT. 电子计算机断层扫描;MIP. CT最大密度投影;PET-CT. 正电子发射计算机断层成像;箭头示周围有软组织代谢伴摄取增高。

, figureFileSmall=E9h3Wg93IF+uIEU6aRlcYg==, figureFileBig=P3TGUfbKdCaD2LAKOVsiyQ==, tableContent=null), ArticleFig(id=1211269172965798851, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269165172781698, language=EN, label=Tab.1, caption=

Baseline demographic data and clinical features of the six CP patients

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患者编号性别年龄(岁)病程(d)随访时间(月)既往疾病临床症状肾盂积水血清IgG4(mg/dl)病理受累部位
14221041.6高血压病、风湿性心脏病、房颤、心功能不全腹痛、腰痛、背痛149未做腹主动脉旁、两侧髂总动脉旁
2516022.8高血压病腰痛、睾丸疼痛89.7非IgG4相关性CP腹主动脉旁
362400.9冠心病、陈旧性心肌梗死、2型糖尿病腹痛、腰痛、发热158未做腹主动脉旁、右侧髂总动脉旁
4556066.9陈旧性肺结核45.2IgG4-CP腹主动脉旁、左侧肾门
548301.2高血压病、冠心病腹痛274IgG4-CP腹主动脉旁
64236528.7背痛、发热57.7未做胸主动脉旁、腹主动脉旁
), ArticleFig(id=1211269173049684934, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269165172781698, language=CN, label=表1, caption=

6例慢性主动脉周围炎患者基线期一般资料

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患者编号性别年龄(岁)病程(d)随访时间(月)既往疾病临床症状肾盂积水血清IgG4(mg/dl)病理受累部位
14221041.6高血压病、风湿性心脏病、房颤、心功能不全腹痛、腰痛、背痛149未做腹主动脉旁、两侧髂总动脉旁
2516022.8高血压病腰痛、睾丸疼痛89.7非IgG4相关性CP腹主动脉旁
362400.9冠心病、陈旧性心肌梗死、2型糖尿病腹痛、腰痛、发热158未做腹主动脉旁、右侧髂总动脉旁
4556066.9陈旧性肺结核45.2IgG4-CP腹主动脉旁、左侧肾门
548301.2高血压病、冠心病腹痛274IgG4-CP腹主动脉旁
64236528.7背痛、发热57.7未做胸主动脉旁、腹主动脉旁
), ArticleFig(id=1211269173120988106, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269165172781698, language=EN, label=Tab.2, caption=

The treatment and outcomes of six CP patients

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患者编号既往治疗RTX治疗临床缓解/完全缓解
1/激素+RTX(第0周、第2周)完全缓解
2激素+CTX+HCQRTX(第0周、第2周)临床缓解
3/RTX(第0周、第2周、第6个月)临床缓解
4手术+MMF+HCQRTX(第0周、第2周、第6个月、第12个月、第18个月、第24个月、第30个月、第36个月、第42个月、第54个月)完全缓解
5/激素+RTX(第0周、第2周)
6/激素+RTX(第0周、第2周、第6个月、第12个月、第24个月)完全缓解
), ArticleFig(id=1211269173179708365, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269165172781698, language=CN, label=表2, caption=

6例慢性主动脉周围炎患者治疗及缓解情况

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患者编号既往治疗RTX治疗临床缓解/完全缓解
1/激素+RTX(第0周、第2周)完全缓解
2激素+CTX+HCQRTX(第0周、第2周)临床缓解
3/RTX(第0周、第2周、第6个月)临床缓解
4手术+MMF+HCQRTX(第0周、第2周、第6个月、第12个月、第18个月、第24个月、第30个月、第36个月、第42个月、第54个月)完全缓解
5/激素+RTX(第0周、第2周)
6/激素+RTX(第0周、第2周、第6个月、第12个月、第24个月)完全缓解
), ArticleFig(id=1211269173242622930, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269165172781698, language=EN, label=Tab.3, caption=

Rituximab for treatment of chronic periaortitis reported in previous literature

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发表文献例数男/女(例)平均年龄(岁)随访时间(月)受累部位治疗方案预后
Dedinská等[9]11/045/腹主动脉旁375 mg/(m2·周)RTX×4周,激素联合吗替麦考酚酯维持肌酐由180 μmol/L降至110 μmol/L,肿物缩小
Almeqdadi等[10]10/1645.25腹主动脉旁40 mg/d泼尼松×4周,第5周起375 mg/(m2·周)RTX×4周21周达临床缓解
Urban等[17]20//17-61主动脉旁、髂动脉旁4例单用RTX[1 g/2周或375 mg/(m2·周)×4周]治疗,16例泼尼松联合RTX(方案如上)75%(15/20)达临床缓解;3例复发;1例死亡;1例并发慢性淋巴细胞白血病
Boyeva等[18]108/258.5//RTX 1 g/2周×2次肌酐、C反应蛋白下降;2例感染
Wallwork等[19]2622/4552.8-4.2主动脉旁、髂动脉旁19例单用RTX 1 g/2周×2次;7例泼尼松联合RTX(方案如上)88%(22/25)影像学肿块缩小10%;100%(19/19)症状消失;25%(4/16)红细胞沉降率降至正常;20%(2/10)C反应蛋白降至正常;3例感染
), ArticleFig(id=1211269173326509012, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269165172781698, language=CN, label=表3, caption=

既往文献报道的利妥昔单抗(RTX)治疗慢性主动脉周围炎的情况

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发表文献例数男/女(例)平均年龄(岁)随访时间(月)受累部位治疗方案预后
Dedinská等[9]11/045/腹主动脉旁375 mg/(m2·周)RTX×4周,激素联合吗替麦考酚酯维持肌酐由180 μmol/L降至110 μmol/L,肿物缩小
Almeqdadi等[10]10/1645.25腹主动脉旁40 mg/d泼尼松×4周,第5周起375 mg/(m2·周)RTX×4周21周达临床缓解
Urban等[17]20//17-61主动脉旁、髂动脉旁4例单用RTX[1 g/2周或375 mg/(m2·周)×4周]治疗,16例泼尼松联合RTX(方案如上)75%(15/20)达临床缓解;3例复发;1例死亡;1例并发慢性淋巴细胞白血病
Boyeva等[18]108/258.5//RTX 1 g/2周×2次肌酐、C反应蛋白下降;2例感染
Wallwork等[19]2622/4552.8-4.2主动脉旁、髂动脉旁19例单用RTX 1 g/2周×2次;7例泼尼松联合RTX(方案如上)88%(22/25)影像学肿块缩小10%;100%(19/19)症状消失;25%(4/16)红细胞沉降率降至正常;20%(2/10)C反应蛋白降至正常;3例感染
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利妥昔单抗治疗慢性主动脉周围炎:6例及文献复习
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廖思敏 , 赵玉荣 , 张洁 , 李坤鹏 , 邓小虎 , 王炎焱 , 张江林 , 黄烽 , 朱剑 *
解放军医学杂志 | 临床研究 2021,46(4): 380-385
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解放军医学杂志 | 临床研究 2021, 46(4): 380-385
利妥昔单抗治疗慢性主动脉周围炎:6例及文献复习
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廖思敏, 赵玉荣, 张洁, 李坤鹏, 邓小虎, 王炎焱, 张江林, 黄烽, 朱剑*
作者信息
  • 解放军总医院第一医学中心风湿免疫科,北京 100853
  • 廖思敏,博士研究生,主要从事腹膜后纤维化与IgG4相关性疾病方面的研究

通讯作者:

朱剑,E-mail:
Application of rituximab in treating six patients with chronic periaortitis and literature review
Si-Min Liao, Yu-Rong Zhao, Jie Zhang, Kun-Peng Li, Xiao-Hu Deng, Yan-Yan Wang, Jiang-Lin Zhang, Feng Huang, Jian Zhu*
Affiliations
  • Department of Rheumatology and Immunology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
出版时间: 2021-04-28 doi: 10.11855/j.issn.0577-7402.2021.04.10
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目的 报道6例经利妥昔单抗(RTX)治疗的慢性主动脉周围炎(CP)患者的临床特点、诊治经过及预后并进行文献复习,以提高对该病的认识。方法 回顾性分析解放军总医院第一医学中心2014年10月—2020年11月收治的6例CP患者应用RTX治疗前后的临床症状、实验室指标、影像学表现变化及不良反应。临床缓解定义为临床症状消失、肾盂积水消失、红细胞沉降率<15 mm/h、C反应蛋白<5 mg/L;完全缓解定义为临床缓解及影像学提示腹膜后包块最大横径缩小50%。检索相关数据库,结合文献报道的58例患者,总结RTX治疗CP的有效性及安全性。结果 6例患者均为男性,年龄49.5(42.0~62.0)岁,病程60(30~365) d,随访时间25.7(0.9~66.9)个月。其中3例既往合并严重心血管疾病、1例合并胸主动脉受累。3例应用泼尼松0.25~0.5 mg/(kg·d)联合RTX作为诱导缓解方案,其余3例单用RTX诱导缓解。5例达到临床缓解,其中4例规律应用RTX维持缓解,1例应用小剂量泼尼松维持,中位缓解时间为4.0(0.5~6.0)个月;3例达到完全缓解,中位缓解时间为18(16~24)个月;6例均未出现疾病复发。6例患者未出现输注反应,1例在应用RTX后的第3.5个月出现肺部感染。国内外报道RTX治疗CP共58例,治疗后患者临床症状、实验室指标及影像学表现均有改善,应用RTX后仅5例(8.6%)出现感染,1例(1.7%)死亡,3例(5.2%)复发。结论 应用RTX作为诱导缓解及维持缓解方案治疗CP临床效果好,且安全性较高。

慢性主动脉周围炎  /  腹膜后纤维化  /  利妥昔单抗

Objective By literature review to retrospectively study the clinical characteristics, diagnosis and treatment process and prognosis of chronic periaortitis (CP) treated with rituximab (RTX), and to improve the understanding of it. Methods To retrospectively analyze the clinical characteristics, laboratory indicators, changes of imaging findings and adverse reactions before and after RTX treatment of six CP patients admitted in the First Medical Center of Chinese PLA General Hospital from October 2014 to November 2020. The clinical remission was defined as the disappearance of clinical symptoms and hydronephrosis, erythrocyte sedimentation rate (ESR) <15 mm/h and C-reactive protein (CRP) <5 mg/L; complete remission was defined as the clinical remission and the maximum transverse diameter of retroperitoneal mass reduced by 50%. Fifty-eight similar cases were collected by searching the database to investigate the efficacy and safety of RTX in treating patients with CP. Results All the 6 patients were males, aged 49.5 (42.0-62.0) years, with pathogenesis of 60 (30-365) days and mean follow-up time of 25.7 (0.9-66.9)months. Three of the 6 patients had severe cardiovascular disease in the past, one suffered from thoracic aorta involvement. RTX alone was given in 3 patients, and together with prednisone in 3 other patients as induce remission therapy, respectively. Five patients achieved clinical remission, of them one was given small dose of prednisone to maintain long-term remission, the other 4 patients received regular application of RTX to maintain remission. The median remission time was 4.0 (0.5-6.0) months. Three patients got complete remission with the median remission time of 18 months (16-24). No recurrence was observed during follow-up. None of the 6 patients had an infusion-related response. One had pulmonary infection at the 3.5-month after the RTX application. A total of 58 cases were found in literature. Clinical symptoms, laboratory tests and imaging findings were all improved. Five (8.6%) patients were infected, 1 (1.7%) was died and 3 (5.2%) had a recurrence after the treatment of RTX. Conclusion Rituximab is an effective and safe regimen in inducing and maintaining remission for chronic periaortitis patients.

chronic periaortitis  /  retroperitoneal fibrosis  /  rituximab
廖思敏, 赵玉荣, 张洁, 李坤鹏, 邓小虎, 王炎焱, 张江林, 黄烽, 朱剑. 利妥昔单抗治疗慢性主动脉周围炎:6例及文献复习. 解放军医学杂志, 2021 , 46 (4) : 380 -385 . DOI: 10.11855/j.issn.0577-7402.2021.04.10
Si-Min Liao, Yu-Rong Zhao, Jie Zhang, Kun-Peng Li, Xiao-Hu Deng, Yan-Yan Wang, Jiang-Lin Zhang, Feng Huang, Jian Zhu. Application of rituximab in treating six patients with chronic periaortitis and literature review[J]. Medical Journal of Chinese People’s Liberation Army, 2021 , 46 (4) : 380 -385 . DOI: 10.11855/j.issn.0577-7402.2021.04.10
慢性主动脉周围炎(chronic periaortitis,CP)是以纤维炎症组织包绕腹主动脉、髂动脉周围为主要特点的一类自身免疫性疾病,部分患者主动脉起始部及胸主动脉亦可受累[1]。20%~50%的CP与IgG4相关性疾病(IgG4-related disease,IgG4-RD)有关[2]。糖皮质激素(简称激素)是CP的一线治疗药物,国际推荐以0.75~1.0 mg/(kg·d)泼尼松作为初始剂量,并在6~9个月内逐渐减至5.0~7.5 mg/d[3]。40%的患者在激素减量的第1年易出现复发[4],而联合应用免疫抑制剂可有效预防其复发[5-6]。复发的CP患者越来越多地选择生物制剂如利妥昔单抗(rituximab,RTX)进行治疗,但文献报道较少,且以个案报道居多。本研究对在解放军总医院第一医学中心应用RTX治疗的6例CP患者的临床特点及疗效进行总结,并复习总结国内外关于RTX治疗CP的文献,以帮助临床医师提高对该病的认识,现报道如下。
收集2014年10月—2020年11月解放军总医院第一医学中心收治的6例应用RTX治疗的CP患者的临床资料。IgG4相关性慢性主动脉周围炎(IgG4-CP)根据病理进行确诊[1]。本研究获得解放军总医院第一医学中心伦理委员会审批。6例患者均为男性,年龄49.5(42.0~62.0)岁,病程60(30~365) d,随访时间25.7(0.9~66.9)个月,详细的临床资料见表1。6例中有3例行病理检查,其中2例诊断为IgG4-CP,1例诊断为非IgG4相关性CP;1例为胸主动脉联合腹主动脉受累(图1),其余5例为单纯腹主动脉受累。
2例既往接受过治疗,患者2接受泼尼松200、500、500 mg冲击治疗后改为40 mg/d,联合环磷酰胺0.6 g/2周及羟氯喹0.2 g,2次/d治疗,泼尼松逐渐减量至停用,在随访的第22个月出现复发,后改为RTX治疗。患者4经手术切除左肾+腹膜后肿物后,联合吗替麦考酚酯0.5 g,2次/d及羟氯喹0.2 g,2次/d治疗,在随访的第12个月出现复发,后改为RTX治疗。其余4例患者既往未接受过激素、免疫抑制剂治疗。
按375 mg/m2静脉滴注RTX,于首次给药后的第2周再次给药1次,随后根据病情每隔半年给药1次。RTX输注时口服马来酸氯苯那敏片8 mg、肌内注射盐酸异丙嗪注射液12.5 mg抗过敏。RTX治疗后激素逐渐减量,视病情决定是否停用。患者1因合并风湿性心脏病、二尖瓣重度狭窄伴关闭不全、房颤、心功能Ⅱ级,确诊后按0.25 mg/kg泼尼松及RTX(第0周、第2周)治疗,在随访的第3个月泼尼松减至5 mg/d,后维持。患者3因合并陈旧性心肌梗死、2型糖尿病,确诊后单用RTX(第0周、第2周、第6个月)治疗;患者5因合并陈旧性心肌梗死,确诊后按0.5 mg/kg泼尼松口服及RTX(第0周、第2周)治疗。患者6为胸、腹主动脉均受累,在确诊后按0.5 mg/kg泼尼松及RTX(第0周、第2周、第6个月、第12个月、第24个月)治疗,在随访的第3个月泼尼松减至5 mg/d,后维持。2例为复发性CP,患者2复发后单用RTX(第0周、第2周)治疗;患者4复发后单用RTX(第0周、第2周、第6个月、第12个月、第18个月、第24个月、第30个月、第36个月、第42个月、第54个月)治疗。详细情况见表2
按以下标准评估患者应用RTX后的疗效。(1)临床缓解[7]:临床症状消失、肾盂积水消失、红细胞沉降率<15 mm/h、C反应蛋白<5 mg/L;(2)完全缓解[8]:临床缓解及影像学提示腹膜后包块最大横径缩小50%;(3)复发[8]:肌酐较正常值上限升高30%、肾盂积水复发或新出现、影像学提示腹膜后包块最大横径较前增大20%。6例患者在首次使用RTX后C反应蛋白由25.4(1.0~154.6) g/L降至2.6(0.5~6.4) g/L,红细胞沉降率由33(10~58) mm/h降至7(2~15) mm/h,肌酐由120.6(66.0~227.2) μmol/L降至92.1(53.8~122.5) μmol/L。患者3、5因随访时间短,暂未行影像学复查,其余4例患者经RTX治疗后,影像学复查结果显示,腹膜后肿块最大横径由4.05(2.0~6.3) cm缩小至0.73(0.5~1.3) cm。随访过程中,5例达到临床缓解,中位缓解时间4.0(0.5~6.0)个月,另1例因随访时间不足1个月,仍有轻度肾盂积水而未能满足临床缓解标准。合并肾盂积水者中位缓解时间较无肾盂积水者长4.6个月。3例达到完全缓解,中位缓解时间为18(16~24)个月。随访过程中6例均无复发。
6例患者均无输注反应。患者1在使用RTX后的第3.5个月出现肺部感染,经抗生素治疗2周后好转出院。
以中文“慢性主动脉周围炎”“腹膜后纤维化”“利妥昔单抗”;英文“chronic periaortitis”“retroperitoneal fibrosis”“rituximab”为关键词,在中国知网、万方数据知识服务平台、PubMed-NCBI等数据库检索出中文文献1篇(未明确腹膜后纤维化是否经利妥昔单抗治疗)、英文文献48篇。经获取全文后,筛选出论著4篇,个案报道2篇,其中2篇论著为意大利报道的同系列研究(2例、20例),美国报道26例,英国报道10例(表3)。病例总数共58例,其中20例未明确性别,其余38例中男性患者31例、女性患者7例。58例患者平均年龄55.6岁,随访时间2.8~61.0个月。RTX治疗有方案两种,分别为375 mg/(m2.周)共4次、1 g/2周共2次。34例(58.6%)患者单用RTX诱导及维持缓解,其余24例(41.4%)患者联合激素及RTX治疗。经治疗患者症状、实验室指标及影像学表现均有好转。个案报道中,Dedinská等[9]报道了1例腹膜后纤维化合并膜性肾病应用激素联合RTX治疗的病例,375 mg/(m2.周)RTX规律治疗4周后,泼尼松由60 mg/d减至20 mg/d,影像学检查提示肾盂积水缓解且腹膜后包块体积缩小。Almeqdadi等[10]报道了1例经病理确诊的IgG4-CP患者经外科手术及泼尼松40 mg/d治疗后出现复发,而接受1个疗程RTX治疗后,炎症指标降至正常,21周后达到临床缓解。58例患者应用RTX后仅5例(8.6%)出现感染,1例(1.7%)死亡,3例(5.2%)复发。
CP最常见的受累部位为腹主动脉及髂血管,严重者累及主动脉起始部、冠状动脉可出现心肌缺血样表现,甚至可发生心肌梗死;累及输尿管时,可出现肾盂积水及肾功能不全的表现。部分CP病理可见大量IgG4+浆细胞浸润、席纹状纤维化、嗜酸性粒细胞浸润,与IgG4-RD的病理表现重叠[1-2]。CP可表现为腹膜后纤维化、炎性腹主动脉瘤、腹主动脉瘤旁纤维化[1],影像学结果显示为异常信号影的纤维炎症组织包块。尽早药物干预可延缓甚至逆转炎症过程,缩小炎症包块的体积,缓解其对周围组织的压迫,从而达到缓解临床症状和(或)保护肾功能的目的。CP发病机制复杂且为多因素参与,其中,遗传因素方面现已发现HLA-DRB1*03可能为易感基因[11];环境因素中石棉、烟草被证实为明确的诱因[12-14]。在遗传因素的背景下,抗原提呈细胞接受可疑的环境刺激后,将抗原递呈给动脉壁或主动脉旁炎性组织中的CD4+ T细胞,CD4+ T细胞活化后可分泌白细胞介素(IL)-4、IL-6、IL-10、IL-13[15],从而诱导B细胞及纤维母细胞活化。B细胞活化后可分化成分泌IgG4的浆细胞,亦可持续刺激产生效应CD4+记忆T细胞[16],在CP发病及纤维化过程中起重要作用。故B细胞清除治疗是针对CP发病机制的重要靶点通路之一。
国外研究显示,RTX治疗CP在诱导缓解阶段效果甚佳,但因研究间的异质性,未能提供详细缓解时间。本研究报道了6例经RTX治疗的CP,结果显示RTX诱导缓解疗效良好,5例达到临床缓解,其中3例为完全缓解。6例患者中3例既往存在严重的心脏疾病,对于此类患者若以0.75~1.0 mg/kg剂量的泼尼松作为诱导缓解方案,血脂代谢异常及水钠潴留等相关不良反应突出,再次发生恶性心血管事件的风险较高。因此,本研究中2例合并严重心脏疾病CP患者以0.25~0.50 mg/kg剂量的泼尼松联合RTX诱导缓解,在治疗后的第2周患者临床症状消失,且泼尼松在3个月内可逐渐减至5 mg/d,随访过程中患者未出现心肌梗死、恶性高血压等事件。本研究中3例联合激素及RTX诱导缓解,3例单用RTX诱导缓解,联合组临床缓解时间为2.5(1.0~4.0)个月,单用组临床缓解时间为6.0(0.5~6.0)个月。该结果提示在诱导缓解阶段联合应用激素及RTX能更早达到临床缓解,尤其是对于合并心血管疾病者,但由于本研究病例数少,仍需大规模前瞻性对照研究进一步证实。
虽然RTX在CP诱导缓解中疗效较好,但停用RTX后仍较易复发。Urban等[17]报道了20例特发性CP应用RTX治疗的患者,中位随访时间为38个月,其中4例仅接受RTX[1 g/2周或375 mg/(m2.周)×4周]治疗,16例接受RTX(方案如上)联合泼尼松治疗,结果显示15例(75%)患者达到临床缓解,但有3例患者分别在第4个月、第47个月、第59个月出现复发。本研究中6例患者在随访过程中无复发。6例患者中5例达到临床缓解,其中1例因经济问题单用激素维持缓解,其余4例则为规律应用RTX维持缓解。本研究中RTX维持缓解方案为每隔半年给药1次。随访时间最长的病例为患者4,随访时间5.5年,为手术联合免疫抑制剂治疗后复发的CP,经3次RTX(第0周、第2周、第6个月)治疗后达到临床缓解,然后规律地每半年输注1次RTX共6次维持缓解,随访期间无复发,根据患者情况延长输注间隔时间至1年输注1次RTX共1次,截至2020年11月未见复发。上述结果表明规律应用RTX作为维持缓解方案在控制病情方面有较好效果。
RTX治疗过程中的输注反应已相继文献有报道。Boyeva等[18]应用RTX治疗10例特发性腹膜后纤维化患者时,1例在输注过程中出现严重荨麻疹,给予抗过敏治疗后症状消失。本研究中所有患者在输注RTX时均同时接受了抗过敏治疗,无一例出现输注不良反应。RTX最常见的不良反应为感染,其他的不良反应有白细胞减少、中性粒细胞减少、IgG降低等。Wallwork等[19]发现,26例腹膜后纤维化患者接受RTX(1g/2周×2次)或联合激素治疗后,半年内3例出现严重感染。本研究中1例在RTX应用后的第3.5个月出现肺部感染,其余患者未观察到不良反应事件。1例患者(患者4)合并陈旧性肺结核,在单用RTX诱导缓解及维持治疗过程中,定期检测外周血T细胞抗原刺激试验(T-Spot)并行预防性抗结核治疗,未出现活动性肺结核表现。
本研究为单中心回顾性研究,病例数仅6例,随访时间不等,最短随访时间仅1个月,最长随访时间为5.5年。部分患者在疾病缓解后,单用RTX维持治疗,均表现出良好的疗效,但仍需进一步通过大样本前瞻性研究来证实RTX对CP的疗效。此外,本研究6例中仅3例有病理结果,还需通过进一步研究探讨RTX对IgG4-CP及特发性CP的疗效是否存在差异。
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2021年第46卷第4期
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doi: 10.11855/j.issn.0577-7402.2021.04.10
  • 接收时间:2021-01-06
  • 首发时间:2025-12-26
  • 出版时间:2021-04-28
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  • 收稿日期:2021-01-06
  • 修回日期:2021-03-06
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    解放军总医院第一医学中心风湿免疫科,北京 100853

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朱剑,E-mail:
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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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