Losurdo Giuseppe, Angelillo Daniele, Favia Nicolas, Sergi Maria Chiara, Di Leo Alfredo, Triggiano Giacomo, Tucci Marco
Section of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari "Aldo Moro", 70124 Bari, Italy.
Medical Oncology Unit, Azienda Ospedaliero Universitaria Policlinico di Bari, 70124 Bari, Italy.
Biomedicines. 2023 May 22;11(5):1496. doi: 10.3390/biomedicines11051496.
Immunotherapy with immune checkpoint inhibitors (ICIs) nowadays has indications for several solid tumors. The current targets for ICIs are CTLA-4, PD-1, and PD-L1 receptors. Despite the clinical advantages derived from ICIs, a variety of side effects are linked to overstimulation of the immune system. Among these, ICI-related colitis is one of the most common, with a disabling impact on the patient. Diarrhea, abdominal pain, abdominal distension, cramping, and hematochezia are the most common ICI enterocolitis presenting symptoms. The most frequently used grading system for assessment of the severity of ICI enterocolitis is called the Common Terminology Criteria for Adverse Events (CTCAE) grading. With regard to the histological picture, there is no specific feature; however, microscopic damage can be classified into five types: (1) acute active colitis, (2) chronic active colitis, (3) microscopic colitis-like, (4) graft-versus-host disease-like, and (5) other types. Supportive therapy (oral hydration, a bland diet without lactose or caffeine, and anti-diarrheal agents) is indicated in mild colitis. Symptomatic treatment alone or with loperamide, a low-fiber diet, and spasmolytics are recommended for low-grade diarrhea. In more severe cases, corticosteroid treatment is mandatory. In refractory cases, off-label use of biological therapies (infliximab or vedolizumab) was proposed.
如今,免疫检查点抑制剂(ICI)免疫疗法已被用于多种实体瘤的治疗。ICI目前的作用靶点是细胞毒性T淋巴细胞相关抗原4(CTLA-4)、程序性死亡受体1(PD-1)和程序性死亡受体配体1(PD-L1)受体。尽管ICI具有临床优势,但免疫系统的过度刺激会引发多种副作用。其中,ICI相关结肠炎是最常见的副作用之一,会对患者造成严重影响。腹泻、腹痛、腹胀、绞痛和便血是ICI相关小肠结肠炎最常见的症状。评估ICI相关小肠结肠炎严重程度最常用的分级系统称为不良事件通用术语标准(CTCAE)分级。关于组织学表现,没有特定特征;然而,微观损伤可分为五种类型:(1)急性活动性结肠炎,(2)慢性活动性结肠炎,(3)微观结肠炎样,(4)移植物抗宿主病样,(5)其他类型。轻度结肠炎患者建议采取支持性治疗(口服补液、不含乳糖或咖啡因的清淡饮食以及止泻药)。对于轻度腹泻,建议单独进行对症治疗或联合使用洛哌丁胺、低纤维饮食和解痉药。在更严重的情况下,必须进行皮质类固醇治疗。对于难治性病例,有人建议使用生物疗法(英夫利昔单抗或维多珠单抗)进行超说明书用药治疗。