IgG4 相关性疾病1例报道

2020-07-28 李伊 高洪柳 刘国瑞 临床检验杂志

IgG4相关性疾病( IgG4 related disease) 是一种由 IgG4介 导、累及多器官或组织并伴随血清 IgG4水平升高、组织 IgG4 阳性淋巴细胞浸润及纤维化为特征的慢性自身免疫病

IgG4相关性疾病( IgG4 related disease) 是一种由 IgG4介 导、累及多器官或组织并伴随血清 IgG4水平升高、组织 IgG4 阳性淋巴细胞浸润及纤维化为特征的慢性自身免疫病[1-2]。 该病临床谱非常广泛,包括米库利次病、自身免疫性胰腺炎、 间质性肾炎及腹膜后纤维化等多种疾病,所累及的器官或组 织众多,涉及肝、胆、肺、肾、泪腺、涎腺、淋巴结、纵隔、腹膜 后、甲状腺及前列腺等[3-5]。本文报道 1 例 IgG4相关性疾病 的病例,旨在提高对该病的认识。

1 病例资料

患者男, 23 岁, 2016 年出现眼干,活动后疲乏,胸闷伴有 双腕、双踝关节酸痛症状,无关节活动受限,自觉发热,肤温 增高,但测体温正常,四肢皮肤散在水疱疹,伴有瘙痒,破裂 后呈暗红色硬结,无咳嗽咳痰,无腹痛。2016 年 12 月至当地 医院就诊,血液学检查结果: 红细胞、血红蛋白偏低,血小板 计数、球蛋白持续增高,骨髓穿刺结果: 骨髓象结合他项检 查,考虑浆细胞骨髓瘤( 涂片中见到 6.8%异常浆细胞) ,未予 特殊治疗。随后于 2017 年 7 月至我院血液科就诊,体格检 查显示其平素体健,既往无任何不良病史,否认手术、外伤、 输血、食物药物不耐受史。查血常规: 血红蛋白 102 g/L ( ↓) 、血小板计数 542×109 /L( ↑) 、红细胞计数 4.26×1012 /L ( ↓) 、白细胞计数 9.5×109 /L( ↑) 、 C 反应蛋白( 免疫散射比 浊法) 85.4 mg/L( ↑) ; 血沉>140 mm/h( ↑) ; 血液生化检查 ( 比色法) :球蛋白 90.0 g/L↑、肝功能相关酶学指标( 丙氨酸 氨基转移酶、天门冬氨酸氨基转移酶、碱性磷酸酶、 γ-谷氨酰 转肽酶、乳酸脱氢酶) 正常; 体液免疫学检查( 免疫散射比浊 法) : IgG 62. 800 g/L( ↑) 、 IgG4 9 870. 0 mg/L( ↑) 、 IgA 8.020 g/L( ↑) 、 IgE 755.0 IU/mL( ↑) 、 Igκ 53.40 g/L( ↑) 、 Igλ 11.30 g/L( ↑) 、抗链球菌溶血素 O( ASO) 1 580.0 IU/mL ( ↑) ;自身抗体:抗核抗体( 间接免疫荧光法) 阳性抗体滴度 320( ↑) 、抗核抗体谱( 免疫印迹法) 14 项( 抗 Sm 抗体、抗 U1 核糖核酸蛋白抗体、抗干燥综合征 A( SSA) 抗体、抗干燥综合 征 B( SSB) 抗体、抗 DNA 拓扑异构酶 I 抗体、抗组氨酰tRNA 合成酶抗体、抗核糖体 P 蛋白抗体、抗增殖细胞核抗原抗体、 抗组蛋白抗体、抗 RO52 抗体、抗 PM-Scl 抗体、抗核小体抗 体、抗着丝点 B 蛋白抗体、抗线粒体抗体 2 型抗体) 全阴性、 自身免疫性肝病组合( 免疫印迹法,抗 BPO 复合物三联体抗 体、抗核颗粒蛋白/核点状蛋白 100 抗体、抗早幼粒白血病蛋 白抗体、抗核包膜糖蛋白210 抗体、抗肝肾微粒体-1 抗体、抗 肝细胞溶质抗原-1 抗体、抗可溶性肝抗原/肝胰抗原抗体) 全 阴性;血清蛋白电泳:清蛋白 22.6%( ↓) 、丙种球蛋白 58.2% ( ↑) ;免疫固定电泳图谱:未见单克隆免疫球蛋白;单特异性 游离轻链( free light chain,FLC) 检测( 免疫散射比浊法) : κ/λ 2. 48 ( ↑) 、Igκ FLC 268. 00 mg/L ( ↑) 、Igλ FLC 108.00 mg/L;肿瘤标志物 AFP、 CEA( 化学发光法) 、糖类抗 原 CA-199、 CA-125、 CA-153、 CA-724、 CA24-2、 CA50、 Cyfra21-1 ( 化学发光法) 、乙肝标志物 HBsAg、 HBsAb、 HBeAg、 HBeAb、 HBcAb( ELISA 法) 、 HLA-B27( 流式细胞术) 未见明显异常。 骨髓穿刺: 骨髓象浆细胞占 4. 5%,骨髓免疫分型: P7 占 2.68%,为克隆性浆细胞,胸椎、腰椎、盆骨、胸部、头颅X 片未 见明显异常;上腹部CT:肝脏体积略增大( 图1) ;查体发现腋 窝淋巴结肿大( 图 2) ,行双侧腋窝穿刺活检术,病理诊断为 淋巴细胞增生性病变;免疫组化结果符合 IgG4相关性疾病的 特征( IgG4: >50 个 IgG4 +细胞/高倍视野; IgG4 /IgG>50%) ,故 诊断为“IgG4相关性疾病” ( 图 3) 。 注:脾脏明显增大 ( 红色箭头所示) ,胃腔明显受压减小。

 

2 住院治疗及随访

为进一步治疗,患者被收治于我院中西医结合科。治疗 方案:先后予以强的松( 15 mg/d) 、来氟米特免疫抑制、白芍 总苷胶囊免疫调疫以及参麦注射剂益气扶正等药物。治疗 效果:患者病情稳定,胸闷、发热、多关节酸痛等症状缓解,无 明显不适。出院前检查: C 反应蛋白 36.8 mg/L( ↑) 、血小板 计数 468×109 /L( ↑) 、白细胞计数 12.2×109 /L( ↑) 、血红蛋 白 104 g/L( ↓) ;血沉 83 mm/h( ↑) ; 球蛋白 86.0 g/L( ↑) ; IgG4 9 060.0 mg/L( ↑) 。 出院后,患者遵循医嘱每日口服强的松片并且先后 4 次 来我院复查,目前患者一般情况稳定,生命体征平稳。最近 一次复查结果: 血红蛋白 124 g/L( ↓) ,球蛋白 42.9 g/L ( ↑) , IgG46 310.0 mg/L( ↑) 。 3 讨论 目前对于 IgG4相关性疾病的诊断主要参考以下标准[7]: ( 1) 临床上一个或多个器官出现局限性/弥漫性肿胀或肿块 的症状;( 2) 血清中丙种球蛋白( 特别是 IgG 和 IgG4) 异常增 高,存在自身抗体;( 3) 组织病理学表现为显著的淋巴细胞、 浆细胞浸润和纤维化; IgG4阳性浆细胞浸润( IgG4 /IgG>40%, 且 IgG4阳性浆细胞>10 个/高倍视野) 。以上 3 条全部符合 者为确定诊断,符合第 1 和第 3 条者为疑似诊断,符合第 1 和第 2 条者为可能诊断。 此外,判断该疾病的发生还需排除以下几种可能:( 1) 淋 巴瘤:患者临床可表现为进行性淋巴结肿大,常伴有发热、体重减轻等表现;乳酸脱氢酶水平多升高; 淋巴活检可见大量 异型细胞,核分裂,呈破坏、浸润性生长,存在异常免疫表型; ( 2) 干燥综合征:患者临床表现为外分泌腺受到大量淋巴细 胞浸润;抗 SSA、 SSB 抗体阳性;( 3) 淋巴结反应性增生: 一种 常见的淋巴结良性增生,一般发生在炎症的引流淋巴结,肉 眼可见一般为轻度增大,病理活检可协助诊断。而在此病例 中,患者骨髓象未见异常,血清中各类免疫球蛋白( 特别是 IgG 和 IgG4) 均不同程度的升高,抗 SSA、 SSB 抗体阴性, IgG4 阳性浆细胞浸润率>50%,故可与以上几种疾病相区别。 由此可见,对于 IgG4相关性疾病的诊断不能依靠某个单 一的指标,而应综合患者全面的临床表现、包括 IgG 和 IgG4 在内的血清学检查、影像学检查以及组织病理学检查结果作 出判断。此病例中患者的治疗依然采用糖皮质激素类药物, 在药物治疗剂量区间内可以取得良好的疗效,然而长期使用 激素类药物会引发一系列严重的不良反应,此外当剂量减少 时,病情又会反复,因此临床上如何有效的减轻激素治疗的 依赖性将是今后提升疗效的研究重点。

参考文献略。

原始出处:

李伊,高洪柳,刘国瑞,蒋卫军等,IgG4 相关性疾病 1 例报道[J],临床检验杂志 2020,38(4)。

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    2021-03-08 18925378

    骨穿没有问题吗?前后不一致

    0

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    2020-12-08 笔记陈丹丹

    学习打卡

    0

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    2020-08-12 两百斤的胖子

    为什么不用环磷酰胺

    0

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    2020-08-07 146a390fm17暂无昵称

    学习了

    0

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    2020-07-28 GWsz

    免疫病好像越来越多:)

    0