IgG4相关性疾病20例临床特征分析

目的 总结IgG4相关性疾病临床特征及预后,提高认识,做到早期诊断及合理治疗.方法 对在我院住院明确诊断的20例IgG4相关性疾病患者资料进行回顾性分析.结果 20例患者中男性14例,女性6例,平均年龄58岁,胰腺和胆管为最常见受累器官,17例患者(85％)有≥2个器官受累.所有患者血清IgG4均明显升高(＞1350 mg/L).12例患者行组织病理学检查,主要表现为组织弥漫性纤维化,伴有大量淋巴细胞、浆细胞浸润,免疫组织化学可见CD38阳性浆细胞浸润,IgG4阳性浆细胞浸润,IgG4阳性浆细胞占IgG阳性浆细胞比例均＞40％.20例患者中,除1例患者死于急性化脓性胆管炎及1例未治疗,其余患者病情均明显缓解.结论 IgG4相关性疾病临床症状无特异性,血清IgG4可作为疑似病例的首选检查方法,及时应用糖皮质激素可迅速缓解病情.     

IgG4相关性疾病伴肾脏损害病例报告并文献复习

目的:总结IgG4相关性疾病伴肾脏损害的临床特点。方法:回顾性分析4例IgG4相关性疾病伴肾脏损害患者的临床表现、病理特点、实验室检查、治疗及预后情况,并复习相关文献。结果:4例患者均为男性,年龄51~69岁,泌尿系统损害包括不同程度的血尿、蛋白尿、肾功能异常、梗阻性肾病。4例患者均同时存在泌尿系统外的多器官受累。所有患者均存在高球蛋白血症,血清Ig G及IgG4亚型显著升高。影像学表现可分为4类:肾皮质低密度影、肾脏弥漫增大、肾盂和/或输尿管积水、腹膜后纤维化。肾脏病理显示肾间质大量淋巴细胞、IgG4阳性的浆细胞浸润伴纤维化表现。患者对糖皮质激素治疗反应良好,临床症状及肾功能均明显改善。结论:累及泌尿系统的IgG4相关性疾病临床表现复杂多样,糖皮质激素治疗可较快缓解病情。     

IgG4相关性肺疾病二例并文献复习

目的 总结IgG4相关性肺疾病的临床特点及诊治经验,提高临床对该病的认识,减少误诊误治.方法 分析第二军医大学附属长海医院呼吸内科收治的两例IgG4相关性肺疾病的一般情况、临床表现、实验室检查、组织病理学、治疗及预后,并进行相关文献复习.结果 两例患者均为男性,血清IgG4水平均显著升高(2.25 g/L;10 g/L).1例肺部影像学呈实性结节型改变,并有回盲部受累,糖皮质激素治疗有效.另1例肺部影像学呈支气管血管束型改变,对糖皮质激素治疗依赖.文献复习69例IgG4相关性肺疾病,因呼吸道症状就诊者39例(56.5％),伴有肺外受累者41例(59.4％).48例检测了血清IgG4水平,均显著升高(307 ～ 52 500 mg/L).胸部影像学表现实性结节型35例(50.7％).31例(44.9％)患者接受了糖皮质激素治疗,预后良好.结论 IgG4相关性肺疾病是临床少见的免疫性疾病,临床表现缺乏特异性,临床诊断应综合分析其血清免疫学检查、影像学表现及组织病理学结果,糖皮质激素治疗效果良好.     

IgG4相关系统性疾病的肾脏损害

IgG4相关系统性疾病(IgG4-related systemic disease,IgG4-RSD)是一组最近认识的临床综合征,可累及多个器官,胰腺最常受累,主要表现为血清IgG4升高,受累组织弥漫IgG4阳性浆细胞浸润。本文主要介绍IgG4-RSD累及肾脏时的临床表现、影像学、实验室检查、病理特点及治疗情况。     

IgG4相关性疾病9例临床特征分析

目的总结IgG4相关性疾病的临床特点以提高临床医师对该病的认知,做到早期诊断、规范治疗。方法选取2016年至2018年承德医学院附属医院收治的9例诊断为IgG4相关性疾病的患者为研究对象,观察其临床特点,分析其各项实验室检验结果、影像与病理学资料、治疗及预后。结果 9例IgG4相关性疾病患者中男性5例,女性4例,男女比例为1.25∶1。年龄35～68岁,平均54.89±10.03岁。其临床表现各异,可累及胰腺、胆囊、肺、肾、淋巴结、颌下腺、泪腺、关节、皮肤等多种组织器官。血清学表现为IgG4的升高及补体水平的降低,影像学表现为受累器官的肿大或占位。病理学表现为组织器官淋巴细胞、浆细胞浸润,IgG4及浆细胞增多。对糖皮质激素治疗反应良好,预后较好。结论 IgG4相关性疾病是一种系统性疾病,可累及多种组织器官,临床表现各异,需要结合临床表现、实验室检查、病理学检查及激素治疗效果等进行综合诊断     

血清IgG4检测在IgG4相关性疾病诊治中的作用

IgG4相关性疾病(IgG4-related disease,IgG4-RD)是一种新发现的以IgG4阳性淋巴细胞-浆细胞浸润为特点的累及多器官的系统性纤维炎症性病变.IgG4-RD受累器官广泛,临床表现多样,具有独特的病理学及血清学表现.但病理学检查存在诸多缺点:标本不易获取,尤其涉及到特定组织(如腹膜后组织、纵膈)、器官(如垂体、胰腺);为有创检查,患者不易接受等,使其在临床实施过程中受到一定限制.血清IgG4浓度升高作为IgG4-RD的诊断标准之一,其检测在临床应用方面有许多优点:方便、快捷、具有较高的敏感度和特异度,在疾病的诊治过程有一定的价值.     

IgG4相关性硬化性胆管炎100例临床特征分析

目的 由于临床和影像学表现的相似及临床医生认知不足,IgG4相关性硬化性胆管炎(IgG4-SC)常被误诊为原发性硬化性胆管炎(PSC)或胆管癌(CC)等胆汁淤积性疾病,而采取了不必要的手术治疗,因此对IgG4-SC的准确认识非常重要。目前,对IgG4-SC的临床研究比较缺乏,文献多为零星的临床病例报道,缺乏系统总结。我们通过汇总分析国内报道的病例,探讨了IgG4-SC患者的临床特点和误诊原因,以提高对该病的认识和诊断水平。方法 以“IgG4相关性硬化性胆管炎”为关键词在中国知网数据库、万方数据库和维普数据库检索2019年9月前公开发表的文献,并提取相关病例的一般资料、临床表现、实验室检查、影像学表现、病理学特征、误诊情况、治疗和预后等信息进行汇总分析。结果 纳入25篇文献,包括100例患者,男女比例为4∶1,平均发病年龄为(58.8±12.3)岁;最常见的临床表现为黄疸(85%)和腹痛(53%); 94.2%(81/86)患者血清IgG4水平增高,33%患者血清CA19-9升高;影像学表现为胆总管下段狭窄57例,肝门区胆管狭窄伴肝内胆管扩张15例;34例肝组织检查发现胆囊壁/胆管壁纤维组织增生伴大量淋巴细胞和浆细胞浸润,可见闭塞性静脉炎或席纹状硬化;免疫组化检测,15例显示IgG4⁺浆细胞>10/HPF;在100例中,12例因误诊为胆管癌而实施手术治疗,61例应用糖皮质激素治疗,58例(95%)病情缓解。结论 IgG4-SC患者多以梗阻性黄疸和腹痛为主要表现,在临床和影像学表现上与原发性硬化性胆管炎和胆管癌十分相似,需注意鉴别诊断。     

IgG4相关疾病误诊为多中心型Castleman病3例并文献回顾

目的通过病例资料分析IgG4相关疾病特点,总结IgG4相关疾病被误诊为多中心型Castleman病的原因,提高对此类疾病的诊断准确性。方法回顾性分析2008年1月至2012年12月北京协和医院诊治的3例IgG4相关疾病患者误诊为多中心型Castleman病的临床资料。结果 3例患者均为男性,年龄为53～57岁,均有全身广泛的淋巴结肿大及多系统受累,均曾行1次以上淋巴结活检。经病理检查,2例确诊、1例疑诊为多中心型Castleman病。筛查3例患者血清IgG4水平均明显升高,均大于1350mg/L;正电子发射计算机断层显像仪-CT(positron-emission tomography/computed tomography,PET-CT)显示全身广泛淋巴结及多脏器摄取增高;2例患者病理免疫组化证实IgG4阳性淋巴细胞占淋巴细胞50%以上。3例患者最终被确诊为IgG4相关疾病。经足量糖皮质激素及环磷酰胺治疗后3例患者的临床、血清学及影像学异常均迅速显著缓解。结论 IgG4相关疾病易被误诊为多中心型Castleman病,对临床表现、血清IgG4水平、PET-CT检查及病理免疫组化的综合分析有助于IgG4相关疾病的诊断。     

重视IgG4相关性疾病的诊治刘朝君 辛星 董培源 孙汉英

IgG4相关性疾病(IgG4-Related Disease)是一种与IgG4阳性淋巴细胞-浆细胞密切相关的慢性、系统性、进行性的自身免疫性疾病,其主要特征有：IgG4阳性浆细胞浸润多种器官及组织；受累器官肿胀、纤维化、硬化；闭塞性脉管炎；伴或不伴有血清IgG4升高。由于IgG4-RD临床谱广泛,临床表现多样,目前尚无统一的诊断标准,患者可能因不同临床表现而于不同的专科就诊,故常误诊、漏诊。本文就近年来IgG4-RD的流行病学、发病机制、临床表现、诊断、治疗等方面的研究进展进行综述,以加深临床医生对该病的重视。     

IgG4相关性疾病临床特点分析

目的总结Ig G4相关性疾病在中国患者的临床特点、诊断及治疗,提高对该病的认识和临床诊治。方法对解放军总医院2012年1月至2014年9月期间诊断为Ig G4相关性疾病的患者的临床资料进行回顾性分析。结果 54例患者被诊断为Ig G4相关性疾病,其中男40例(74.1%),女14例;平均年龄为(58.6±1.6)岁(35~82岁);31例(57.4%)出现多器官受累,中位受累器官为2个(2~5个),受累组织包括胰腺(51.9%)、颌面部腺体(48.1%)、淋巴结(20.4%)、胆管(18.5%)等。94%(51/54)的患者伴有血清Ig G4[6.9 g/L(1.4~59.5 g/L)]、Ig G、Ig E等升高为主的高球蛋白血症,97.4%(37/38)患者糖皮质激素治疗后症状有所缓解或恢复正常。结论 Ig G4相关性疾病多见于中老年男性,可累及身体多个部位或组织,以胰腺、颌面部腺体受累最为多见,糖皮质激素治疗有较高疗效。     

系统性硬化症患者血清IgG亚类特点

目的探讨血清IgG亚类与系统性硬化症(systemic sclerosis,SSc)的关系,分析IgG亚类在SSc中的分布特点以及在SSc中血清IgG4是否显著升高。方法利用免疫散射比浊法检测102例SSc患者及40例健康对照者(healthy controls,HC)血清IgG1-4浓度,比较分析SSc组血清IgG亚类水平与HC组有无差异,并结合SSc患者临床资料,分析具有不同临床特征的SSc患者IgG亚类分布特点及其相关性。结果与HC组相比,SSc组血清IgG1(IgG1IgG)[IgG1:(8 085.00±1 565.68)mgL vs.(9 236.67±3 258.62)mgL;IgG1IgG:(56.83±8.16)%vs.(63.66±9.68)%]、IgG3(IgG3IgG)[IgG3:(394.60±232.79)mgL vs.(703.69±509.57)mgL;IgG3IgG:(2.72±1.46)%vs.(4.74±2.92)%]水平显著升高,而IgG2(IgG2IgG)[IgG2:(5406.25±2150.77)mgL vs.(4117.56±1668.37)mgL;IgG2IgG:(36.57±7.84)%vs.(28.46±8.47)%]、IgG4(IgG4IgG)[IgG4:485.50(53.62,1454.00)mgL vs.289.00(91.26,1529.50)mgL;IgG4IgG:3.20(0.52,10.17)%vs.2.04(0.65,8.83)%]水平显著降低;IgG正常的SSc组患者与HC组比较,其血清IgG3(IgG3IgG)[IgG3:(617.68±435.42)mgL vs.(368.24±220.54)mgL;IgG3IgG:(4.69±2.90)%vs.(2.73±1.50)%]、IgG1IgG[IgG1IgG:(63.16±9.50)%vs.(58.41±6.72)%]水平显著升高,IgG2(IgG2IgG)[IgG2:(3745.14±1489.10)mgL vs.(4 677.58±1 240.16)mgL;IgG2IgG:(29.06±8.45)%vs.(34.73±5.66)%]、IgG4(IgG4IgG)[IgG4:250.00(91.01,1365.50)mgL vs.511.00(50.71,1644.00)mgL;IgG4IgG:2.03(0.65,8.73)%vs.3.54(0.47,11.11)%]水平显著降低,差异均有统计学意义(均P0.05)。SSc组中IgG41 350 mgL者占6.86%,HC组中1 350 mgL者占5.00%,两组比较差异无统计学意义(P=0.978)。与抗Scl-70阴性SSc患者比较,抗Scl-70阳性SSc患者血清IgG2(IgG2IgG)[IgG2:3 460.00(1 346.95,8 352.00)mgL vs.4 280.00(1 568.00,7 612.00)mgL;IgG2IgG:25.44(8.09,46.94)%vs.30.94(15.39,41.92)%]水平显著升高,血清IgG1IgG[68.26(45.95,88.07)%vs.62.33(48.04,76.41)%]水平显著下降;合并肺动脉高压(pulmonary arterial hypertension,PAH)的SSc患者血清IgG1(IgG1IgG)[IgG1:7 850.00(5250.00,17 300.00)mgL vs.9 170.00(7 461.00,16 470.00)mgL;IgG1IgG:64.04(46.64,74.89)%vs.67.45(51.25,84.91)%]水平显著高于未合并PAH者,血清IgG2IgG[28.72(17.19,42.89)%vs.24.77(10.29,42.39)],IgG4IgG[2.21(0.65,8.80)%vs.1.94(0.42,7.40)%]水平显著低于未合并PAH者,差异均有统计学意义(P0.05)。SSc患者从出现雷诺现象到SSc发病的时间与血清IgG2呈现低度相关(r=0.353,P=0.001)。结论血清IgG亚类在SSc患者中的分布明显不同于健康人群,即使是IgG正常的SSc患者其IgG亚类分布也不同于健康人群,SSc患者中血清IgG4(IgG4IgG)水平明显低于健康人群,血清IgG亚类在具有不同临床特点的SSc患者中的分布存在显著差异。     

自身免疫性肝病患者血清IgG4水平分析

探讨不同自身免疫性肝病患者血清免疫球蛋白G4（immunoglobulin G4,IgG4）水平差异,并分析不同血清IgG4水平的自身免疫性肝病患者临床特点的差异。方法收集自身免疫性肝病患者65例,其中自身免疫性肝炎（AIH）11例、原发性胆汁性肝硬化（primary biliary cirrhosis,PBC）47例及AIH与PBC重叠综合征7例。采用免疫散射比浊法检测三组患者血清IgG4水平,并分析三组之间血清IgG4水平的差异。根据血清IgG4水平的不同进行分组,分析不同血清IgG4水平的自身免疫性肝病患者临床特点的差异。对组间正态分布的计量资料的比较应用独立样本t检验,对非正态分布者采用Mann-Whitney U检验。计数资料的比较采用Fisher’s确切概率法。结果 AIH患者血清 IgG4水平为642.2 mg/L （97.7 mg/L~1687.0 mg/L）,高于 PBC 患者[153.9 mg/L（78.9 mg/L~400.3 mg/L）,P=0.076]及重叠综合征患者[229.9 mg/L（154.9 mg/L~417.9 mg/L）,P=0.388],无统计学差异。其中3例AIH患者血清IgG4水平异常升高（≥1350 mg/L）,与血清IgG4水平较低的8例AIH患者比,IgG4水平和IgG4/IgG比值较高,差异具有统计学意义（P〈0.05）;3例血清IgG4水平≥1350 mg/L的AIH患者均合并2型糖尿病,其中1例合并类风湿性关节炎,而其他8例AIH患者未合并其他自身免疫性或代谢性疾病;血清IgG4水平较高（IgG4水平≥200 mg/L）的14例PBC患者与IgG4水平较低的33例PBC患者比,血清总胆红素水平较高[（45.09±74.85）μmol/L 对（26.38±23.03）μmol/L,P=0.05]。结论与PBC及PBC与AIH 重叠综合征患者比,AIH患者血清IgG4水平较高。血清IgG4水平较高的AIH患者可能较易合并其他自身免疫性或代谢性疾病。     

肺吸虫特异性IgG4快速检测方法的建立与应用

目的创建简易、快速、准确的肺吸虫病免疫诊断方法。方法用卫氏并殖吸虫成虫粗提液为抗原,以胶体金标记抗人IgG4单抗为检测探针,采用自行设计的垂直流渗滤装置,创建快速检测人血清肺吸虫特异性IgG4方法(P-IgG4-DIGFA),平行检测IgG作比较分析;以经典ELISA为对照,评价其诊断价值,应用P-IgG4-DIGFA检测有效治疗后病人血清,评价其疗效考核价值。结果P-IgG4-DIGFA检测人血清中肺吸虫特异性IgG4的敏感性和特异性分别为95.2%(40/42)、100%(50/50),与血吸虫病患者血清的交叉反应率仅为2%(1/50),未发现与华支睾吸虫病有交叉反应。P-IgG4-DIGFA的敏感性和特异性略高于经典ELISA,差异无统计学意义(χ2=0.25,P>0.05);应用P-IgG4-DIGFA检测有效治疗后3个月、6个月和12个月病人血清特异性IgG4,阴转率分别为0%、16.7%(1/6)和100%。结论金标渗滤法快速检测肺吸虫特异性IgG4,不仅操作简便、快速,而且敏感性高、特异性强,适用于临床检验和现场查病,对治疗后1年病人具有疗效考核价值,有待进一步开发应用。     

Utility of Serum IgG4 Levels in a Multiethnic Population

Background

IgG4-related disease (IgG4-RD) is a recently recognized condition defined by characteristic histopathologic findings in affected organs. Serum IgG4 concentration is often but not always elevated. The sensitivity and specificity of serum IgG4 vary greatly across studies and has been anecdotally associated to ethnicity. Our study was conducted to investigate the difference in serum IgG4 levels between Asian and non-Asian patients with IgG4-RD.

Enfermedad relacionada con IgG4: ¿es el rituximab la mejor estrategia terapéutica en los casos refractarios a terapia convencional? Resultados de una revisión sistemática

IntroductionIgG4 related disease is a fibroinflammatory condition characterised by lymphoplasmocytic infiltration with predominance of IgG4+ plasma cells, fibrosis, and in most cases elevated IgG4 serum levels. It can affect any organ and result in varying clinical manifestations. Steroids are the cornerstone of treatment, however there is a high percentage of relapse. Recent studies have demonstrated favourable effects with rituximab.ObjectiveTo evaluate effectiveness related to the response to treatment with rituximab in patients with IgG4 related disease refractory to steroids and other immunosuppressant therapies.Materials and methodsWe undertook a systematic search of the specialist databases EMBASE, LILACS, PUBMED and OVID-Cochrane for publications up until December 2017.ResultsAfter the quality analysis, we selected 27 articles (264 patients in total) for the final review, of which 23 were case reports and case series (105 patients), 3 were observational follow-up cohort studies (129 patients), and there was one clinical trial (30 patients). IgG4 related disease presents predominantly in male patients aged between 50 and 70 years on average. Multiple organs are compromised with an average of 3.5 compromised organs. Orbital, glandular and lymph-node compromise is most frequent. Patients in the different studies we included had received various treatments prior to starting rituximab, including glucocorticoids and disease-modifying anti-rheumatic drugs. There was 90.7% response in the cases where rituximab was used as second line therapy; rituximab was used as first line treatment for 10% of the patients with a 100% response rate.ConclusionThe use of rituximab for patients refractory to first-line treatments was associated with a high response percentage and less dependence on glucocorticoids.     

26例IgG4相关性腹膜后纤维化的系统评价

目的 探讨IgG4相关性腹膜后纤维化的临床病理特点、治疗及预后情况.方法 联机检索中国期刊全文数据库、维普中文科技期刊数据库、Medlme/Pubmed及OVID全文数据库,检索截止至2013年11月,结合南京大学医学院附属鼓楼医院消化科诊治的1例患者,进行系统评价.结果 15篇文献进入本系统综述,共纳入26例诊断明确的病例.系统评价结果显示（1）该病好发于69岁左右男性,临床表现以腰背痛、腹痛及肾盂积水为主;（2）血清IgG4升高多见;CT或MRI提示腹膜后肿块;（3）组织病理学检查显示软组织纤维化和IgG4＋浆细胞聚集;（4）目前无标准化方案,糖皮质激素仍是治疗IgG4相关性腹膜后纤维化的首选方案.结论 IgG4相关性腹膜后纤维化是一新的疾病亚型,临床症状缺乏特异性,极易误诊,需进一步研究以提高对该病的认识.     

Hypothyroidism in patients with autoimmune pancreatitis

AIM To examine thyroid function and clinical features of hypothyroidism in autoimmune pancreatitis(AIP) patients.METHODS We examined thyroid function in 77 patients with type 1 AIP(50 males, 27 females; median age 68 years, range 33-85) diagnosed according to the Japanese diagnostic criteria for AIP 2011. We compared clinical and serological findings between patients with and without various categories of hypothyroidism. The change in hypothyroidism after steroid therapy was also examined. RESULTS Eight patients(10%) had hypothyroidism of 6 patients had subclinical hypothyroidism with a normal serum free thyroxine(FT4) and high thyroid stimulating hormone(TSH) level, and 2 patients had central hypothyroidism with low serum free triiodothyronine(FT3), FT4 and TSH levels. A significant goiter of the thyroid was not observed in any patient. There were no significant differences in age; male to female ratio; serum concentrations of IgG and IgG 4-related disease(IgG4-RD); presence of antithyroglobulin antibody, antinuclear antigen or rheumatoid factor; or presence of extrapancreatic lesions between the 6 patients with subclinical hypothyroidism and patients with euthyroidism. After steroid therapy, both subclinical and central hypothyroidism improved with improvement of the AIP.CONCLUSION Hypothyroidism was observed in 8(10%) of 77 AIP patients and was subclinical in 6 patients and central in 2 patients. Further studies are necessary to clarify whether this subclinical hypothyroidism is another manifestation of IgG4-RD.     

918例布鲁氏菌病病人血清IgG、IgM的检测及其临床意义

目的探讨布病病人血清IgG、IgM的水平及对诊断的临床意义。方法对2 394例门诊就诊者,以RBPT和SAT（WS269―2007）结合临床症状诊断布病病人918例和非布病病人1 476例,用酶联免疫吸附试验（ELISA）方法检测IgG、IgM水平并比较分析其在诊断中的意义。结果布病病人血清IgG、IgM高于非布病病人,对判断布病感染有一定意义。结论血清IgM、IgG检测对布病早期（急性期）和亚急性期及慢性病人诊断有一定的参考价值。     

Establishment of a serum IgG4 cut-off value for the differential diagnosis of IgG4-related disease in Chinese population

Objective: This study was performed to better know diagnosis associated with serum IgG4 concentration, and to explore the possibility for development of a serum IgG4 for IgG4-related disease (IgG4-RD) in Chinese populations.

Methods: We studied retrospectively 497 IgG4 serum subclass measurements from Peking Union Medical College Hospital during the four-year period, including 242 IgG4-RD, 130 other diseases and 125 healthy individuals.

Results: Serum IgG4 concentrations were significantly higher in IgG4-RD than in other pathologies (1662.9?±?3760.9?mg/L, p?<?0.001) and healthy individuals (538.2?±?458.6?mg/L, p?<?0.001). There were no significant differences in serum IgG4 level between other pathologies group and healthy individuals (p?=?0.075). Among the 242 IgG4-RD patients analyzed, serum IgG4 concentrations were normal in 46 patients (19.0%). We found 32 patients (24.6%) with elevated serum IgG4 levels among the 130 patients who suffered from other pathologies. There were seven (5.6%) with serum IgG4 over 1350?mg/L in healthy individuals. The ROC curve analysis revealed that the optimal sensitivity and specificity were 80.0% and 88.2%, respectively, at the concentration of 1575?mg/L for Chinese patients.

Conclusions: Our study demonstrated that serum IgG4 elevation was not specific of IgG4-RD. Further studies are needed to define the sensibility and specificity of IgG4 values for the diagnosis of IgG4-RD.