Nassri Ammar B, Muenyi Valery, AlKhasawneh Ahmad, Ribeiro Bruno De Souza, Scolapio James S, Malespin Miguel, de Melo Silvio W
Division of Gastroenterology and Hepatology, Department of Medicine, University of Florida at Jacksonville, Jacksonville, FL 32207, United States.
Department of Pathology and Laboratory Medicine, University of Florida at Jacksonville, Jacksonville, FL 32209, United States.
World J Gastrointest Pharmacol Ther. 2019 Jan 21;10(1):29-34. doi: 10.4292/wjgpt.v10.i1.29.
A variety of immune-modulating drugs are becoming increasingly used for various cancers. Despite increasing indications and improved efficacy, they are often associated with a wide variety of immune mediated adverse events including colitis that may be refractory to conventional therapy. Although these drugs are being more commonly used by Hematologists and Oncologists, there are still many gastroenterologists who are not familiar with the incidence and natural history of gastrointestinal immune-mediated side effects, as well as the role of infliximab in the management of this condition.
We report a case of a 63-year-old male with a history of metastatic renal cell carcinoma who presented to our hospital with severe diarrhea. The patient had received his third combination infusion of the anti-CTLA-4 monoclonal antibody Ipilimumab and the immune checkpoint inhibitor Nivolumab and developed severe watery non-bloody diarrhea the same day. He presented to the hospital where he was found to be severely dehydrated and in acute renal failure. An extensive workup was negative for infectious etiologies and he was initiated on high dose intravenous steroids. However, he continued to worsen. A colonoscopy was performed and revealed no endoscopic evidence of inflammation. Random biopsies for histology were obtained which showed mild colitis, and were negative for Cytomegalovirus and Herpes Simplex Virus. He was diagnosed with severe steroid-refractory colitis induced by Ipilimumab and Nivolumab and was initiated on Infliximab. He responded promptly to it and his diarrhea resolved the next day with progressive resolution of his renal impairment. On follow up his gastrointestinal side symptoms did not recur.
Given the increasing use of immune therapy in a variety of cancers, it is important for gastroenterologists to be familiar with their gastrointestinal side effects and comfortable with their management, including prescribing infliximab.
多种免疫调节药物越来越多地用于治疗各种癌症。尽管适应症不断增加且疗效有所提高,但它们常常与多种免疫介导的不良事件相关,包括可能对传统治疗无效的结肠炎。尽管血液科医生和肿瘤科医生越来越普遍地使用这些药物,但仍有许多胃肠病学家不熟悉胃肠道免疫介导的副作用的发生率和自然病程,以及英夫利昔单抗在治疗这种疾病中的作用。
我们报告一例63岁男性,有转移性肾细胞癌病史,因严重腹泻入院。该患者接受了第三次抗CTLA-4单克隆抗体伊匹单抗和免疫检查点抑制剂纳武单抗的联合输注,并于同日出现严重的水样非血性腹泻。他到医院就诊时被发现严重脱水并伴有急性肾衰竭。广泛检查未发现感染病因,遂开始给予高剂量静脉类固醇治疗。然而,他的病情继续恶化。进行了结肠镜检查,未发现炎症的内镜证据。获取随机组织活检标本,显示轻度结肠炎,巨细胞病毒和单纯疱疹病毒检测均为阴性。他被诊断为伊匹单抗和纳武单抗诱导的严重类固醇难治性结肠炎,并开始使用英夫利昔单抗治疗。他对此迅速产生反应,腹泻于次日缓解,肾功能损害也逐渐好转。随访时,他的胃肠道副作用未复发。
鉴于免疫疗法在各种癌症中的应用日益增加,胃肠病学家熟悉其胃肠道副作用并能熟练管理,包括开具英夫利昔单抗的处方,非常重要。