益赛普联合泼尼松龙治疗类风湿关节炎合并自身免疫性肝炎肝硬化1例

2017-11-07 佚名 临床肝胆病杂志

患者女性,55岁,因“反复四肢多关节肿痛12年”于2015年4月入院。

【一般资料】

患者女性,55岁,

【主诉】

因“反复四肢多关节肿痛12年”于2015年4月入院。

【现病史】

2003年曾于外院诊断“类风湿关节炎”,予强的松、甲氨蝶呤、氯喹治疗2年余,效果欠佳,后自行停口服药物,长期予针灸及外用膏药对症处理。2011年1月因反复肝功能异常,行肝穿刺病理检查,提示:内见约6~7个肝小叶结构,穿刺边缘小叶结构较紊乱。肝细胞轻度肿胀变性;小叶内见散在炎性细胞浸润;少数汇管区扩大,肝细胞呈单个或小簇状碎屑样坏死,炎性细胞向小叶内延伸形成桥接坏死。未见以“肝腺泡Ⅲ带为主的融合灶”为特点的药物性肝损伤病理表现,故排除药物性肝损伤。上腹部CT增强示:肝硬化,脾肿大;门静脉高压,胃底及食管下段静脉曲张。诊断为“自身免疫性肝炎后肝硬化”。

【既往史】

追问病史,该患者使用强的松、甲氨蝶呤、氯喹药物治疗期间未发现肝功能异常,自行停用药物多年平素体检也未发现肝功能异常。予熊去氧胆酸、谷胱甘肽等治疗,不规则服用强的松,关节肿痛反复,逐渐出现关节畸形。

【体格检查】

双手第三近端指间关节、腕关节、双膝关节肿痛,双肘关节屈伸不利。查体:肝掌阳性,腹软,无压痛及反跳痛,肝脾肋下未及,肝区叩击痛阴性,移动性浊音阴性,双下肢无浮肿。双手第三近端指间关节S+T+,双膝关节S+T+,双肘关节S-T+,双肘关节成角畸形。否认饮酒、血吸虫感染、病毒性肝炎史。

【辅助检查】

类风湿因子1370.00IU/ml(<20IU/ml),抗环瓜氨酸肽802.9RU/ml(<20RU/ml),T-spot阴性。肝功能检查示:ALT79U/L,AST54U/L,ALP240U/L,GGT142U/L,TBil20.0μmol/L,DBil4.9μmol/L,IBil15.1μmol/L;Glo40.4g/L。CRP5.9mg/L(0~8mg/L),红细胞沉降率49mm/h(0~20mm/h)。抗核抗体:颗粒型阳性(1∶100)。抗可溶性抗原(包括抗U1RNP、抗Sm、抗SSA、抗SSB、抗Scl-70、PM-SCL、抗Jo-1、着丝粒蛋白、增殖细胞核抗原、双链DNA、核小体、组蛋白、核糖P蛋白)、抗中性粒细胞胞浆抗体、肝病自身抗体(包括抗线粒体抗体M2亚型,肝细胞溶质抗原、肝肾微粒体抗体、可溶性/肝胰抗原)、人类白细胞抗原B27、肿瘤标志物、病毒性肝炎标志物(包括甲型肝炎抗体、乙型肝炎血清学标志物、丙型肝炎抗体、戊型肝炎抗体IgG及IgM、丁型肝炎抗体)均阴性。X片示:左侧尺、桡骨远端和前排腕骨及钩骨、第5掌管远端信号改变,左腕关节间隙狭窄伴信号异常,

【初步诊断】

考虑类风湿关节炎表现。

【病例分析】

本病例符合2009年美国风湿病学会制订的类风湿关节炎诊断标准,以及国际自身免疫性肝炎学术组1993年的自身免疫性肝炎诊断标准。诊断:(1)类风湿关节炎;(2)自身免疫性肝炎后肝硬化。因患者上腹部CT增强已提示存在肝硬化、胃底及食管下段静脉曲张,故根据《自身免疫性肝炎诊断和治疗共识(2015)》,并与患者沟通,签署治疗知情同意书。起始治疗给予小剂量泼尼松龙4mg,1次/d,抗TNF拮抗剂(益赛普)25mg,皮内注射,2次/周(从第16周开始,根据类风湿关节炎疾病活动度的减轻,每天注射25mg至观察结束),熊去氧胆酸(因上述肝功能示胆红素正常,但ALP、GGT升高,提示有一定肝内胆汁淤积情况,故加用以利胆)、谷胱甘肽等保肝药物,随访1年,观察患者类风湿关节炎活动性指标[CRP、类风湿关节炎疾病活动度评价(DAS28)]及肝功能指标(ALT、AST、GGT、ALP、Glo)。在使用益赛普前,患者DAS28评分达5.9,处于高疾病活动度,肝功能ALT、AST、ALP、GGT、Glo水平均升高。在获得患者知情同意后,予泼尼松龙及益赛普作为起始治疗方案。在第12周时,患者四肢关节肿痛明显减轻,DAS28评分为3.2,并一直处于低疾病活动度。从第16周开始,患者DAS28评分为3.0。根据2013年欧洲风湿病防治联合会建议,所有类风湿关节炎患者的治疗应以达到缓解或低疾病活动度为目标,该患者已处于低疾病活动度,故已达标,且患者目前疼痛减轻,生活质量已得到改善。肝功能ALT(40U/L)、AST(42U/L)、ALP(159U/L)、GGT(70U/L)均较前得到有效改善,其中ALT、AST、ALP水平基本处于正常水平,并从第30周起,DAS28评分为3.2,类风湿关节炎尚处于低疾病活动度,患者泼尼松龙的剂量逐渐开始减量至停药。近1年治疗过程中,未发生感染情况。由此可见,该方案有效控制了类风湿关节炎的疾病活动度,并具有一定的安全性。同时,在治疗自身免疫性肝炎方面,患者肝功能得到有效改善,处于稳定水平,但Glo水平未见明显变化。

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    2017-11-09 lmm397
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    2017-11-07 orangesking

    0

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