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使用伊匹单抗治疗后发生的自身免疫性结肠炎及随后的巨细胞病毒诱导性肝炎

Autoimmune Colitis and Subsequent CMV-induced Hepatitis After Treatment With Ipilimumab.

作者信息

Uslu Ugur, Agaimy Abbas, Hundorfean Gheorghe, Harrer Thomas, Schuler Gerold, Heinzerling Lucie

机构信息

Departments of *Dermatology ‡Internal Medicine I §Internal Medicine III †Institute of Pathology, University Hospital of Erlangen, Erlangen, Germany.

出版信息

J Immunother. 2015 Jun;38(5):212-5. doi: 10.1097/CJI.0000000000000081.

Abstract

Ipilimumab, a humanized CTLA-4 antibody, improves overall survival in patients with metastatic melanoma. However, immune-related adverse effects occur in about 65% of ipilimumab-treated patients and have to be adequately managed. A 55-year-old patient developed grade 3 autoimmune colitis 7 weeks after initiation of ipilimumab treatment and subsequently hepatitis with grade 3 elevation of transaminases and γ-glutamyl transferase. Colitis manifested with up to 18 watery and bloody stools per day and severe attacks of abdominal pain. After exclusion of infectious causes, immunosuppression with corticosteroids was initiated. Because of recurrent abdominal pain, spontaneous perforation of the colon had to be excluded. Elevated liver function tests (grade 3 CTCAE) occurred and differential diagnosis included immune-mediated, toxic, and viral hepatitis. It is interesting to note that, not an immune-mediated but a cytomegalovirus-induced hepatitis was diagnosed by serum blood tests and liver biopsy and was subsequently successfully treated. Careful elaboration of the patient under immunotherapy was essential as further immunosuppression mandatory for autoimmune hepatitis would have worsened the viral hepatitis. In conclusion, cytomegalovirus reactivation should be included in the differential in patients under immunotherapy with checkpoint inhibitors and has to be considered as a cause for morbidity.

摘要

伊匹单抗是一种人源化的细胞毒性T淋巴细胞相关抗原4(CTLA-4)抗体,可提高转移性黑色素瘤患者的总生存率。然而,约65%接受伊匹单抗治疗的患者会出现免疫相关不良反应,必须进行适当处理。一名55岁患者在开始伊匹单抗治疗7周后出现3级自身免疫性结肠炎,随后出现肝炎,转氨酶和γ-谷氨酰转移酶升高至3级。结肠炎表现为每天多达18次水样便和血便,并伴有严重腹痛发作。排除感染原因后,开始使用皮质类固醇进行免疫抑制治疗。由于反复出现腹痛,必须排除结肠自发性穿孔。出现肝功能检查结果升高(3级美国国立癌症研究所常见不良反应事件评价标准),鉴别诊断包括免疫介导性、中毒性和病毒性肝炎。值得注意 的是,血清学检查和肝活检诊断为巨细胞病毒诱导的肝炎,而非免疫介导性肝炎,随后成功治愈。对接受免疫治疗的患者进行仔细评估至关重要,因为自身免疫性肝炎所需的进一步免疫抑制会使病毒性肝炎恶化。总之,在接受检查点抑制剂免疫治疗的患者中,鉴别诊断应包括巨细胞病毒再激活,且必须将其视为发病原因。

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