Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Mod Rheumatol Case Rep. 2021 Jul;5(2):425-430. doi: 10.1080/24725625.2021.1899444. Epub 2021 Apr 6.
Immune checkpoint inhibitors (ICIs) such as nivolumab and ipilimumab are emerging agents for the treatment of cancers including melanoma. ICIs are known to cause immune-related adverse events (irAEs), including the development of enterocolitis, dermatitis, and nephritis. However, ICI-induced pancreatitis has seldom been reported, and its pathophysiology and clinical importance remain largely unknown. We describe a 76-year-old man with melanoma who developed acute pancreatitis without abdominal pain after immunotherapy with nivolumab and ipilimumab. The patient was referred due to 2-week-long general fatigue, anorexia, and dermatitis after his second immunotherapy. Laboratory examinations in serum showed high inflammation and renal dysfunction. Plain computed tomography (CT) on admission showed no new lesions including colitis or pancreatitis. On the 4th day of hospitalisation, serum pancreatic enzymes were extremely elevated. Amylase was increased to 683 U/L (normal range: 44-132) and lipase was increased to 1520 U/L (13-55), but he had no abdominal tenderness. Contrast-enhanced CT showed enlarged pancreatic parenchyma and magnetic resonance cholangiopancreatography showed peripancreatic fat stranding, suggesting pancreatitis. Blood culture tests and empirical antibiotic therapy with ceftriaxone indicated no active infectious diseases. We diagnosed ICI-induced pancreatitis and treated him with 0.5 mg/kg/day of prednisolone, which improved his general fatigue, anorexia, dermatitis, and pancreatitis. The potential significance of asymptomatic elevations of pancreatic enzymes has been unclear; however, this case suggested that ICI-induced pancreatitis without abdominal tenderness could be clinically significant. Clinicians should pay attention to the development of latent pancreatitis in patients receiving ICIs, even those without abdominal pain.
免疫检查点抑制剂（ICIs），如纳武单抗和伊匹单抗，是治疗癌症（包括黑色素瘤）的新兴药物。ICIs 已知会引起免疫相关的不良反应（irAEs），包括肠炎、皮炎和肾炎的发生。然而，ICI 诱导的胰腺炎很少被报道，其病理生理学和临床意义在很大程度上仍不清楚。我们描述了一名 76 岁男性黑色素瘤患者，在接受纳武单抗和伊匹单抗免疫治疗后出现无腹痛的急性胰腺炎。该患者因第二次免疫治疗后出现 2 周的全身疲劳、食欲不振和皮炎而被转介。血清实验室检查显示炎症和肾功能障碍严重。入院时的平扫 CT 未见新病变，包括结肠炎或胰腺炎。入院第 4 天，血清胰腺酶显著升高。淀粉酶升高至 683 U/L（正常范围：44-132），脂肪酶升高至 1520 U/L（13-55），但无腹痛。增强 CT 显示胰腺实质增大，磁共振胰胆管造影显示胰周脂肪线，提示胰腺炎。血培养试验和头孢曲松的经验性抗生素治疗提示无活动性传染病。我们诊断为 ICI 诱导的胰腺炎，并给予他 0.5mg/kg/天的泼尼松龙治疗，改善了他的全身疲劳、食欲不振、皮炎和胰腺炎。无症状性胰腺酶升高的潜在意义尚不清楚；然而，本例提示无腹痛的 ICI 诱导性胰腺炎可能具有临床意义。临床医生应注意接受 ICIs 治疗的患者中潜在胰腺炎的发生，即使他们没有腹痛。
