Acute pancreatitis without abdominal pain induced by administration of nivolumab and ipilimumab
Acute pancreatitis without abdominal pain induced by administration of nivolumab and ipilimumab
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DOI：
10.1080/24725625.2021.1899444
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发表时间：
2021-04-03
影响因子：
0.8
通讯作者：
Otsuka, Fumio
中科院分区：
文献类型：
--
作者：
Yamamoto, Koichiro;Oka, Kosuke;Otsuka, Fumio
免疫检查点抑制剂(ICIS)，如nivolumab和ipilimumab，是治疗包括黑色素瘤在内的癌症的新兴药物。已知ICIS可引起免疫相关不良事件(IrAEs)，包括发展为小肠结肠炎、皮炎和肾炎。然而，ICI诱发的胰腺炎很少被报道，其病理生理学和临床重要性仍很不清楚。我们描述一位76岁的男性黑色素瘤患者，在接受尼伏路单抗和伊普利单抗免疫治疗后，发展为急性胰腺炎，无腹痛。患者在第二次免疫治疗后，由于持续两周的全身疲劳、食欲不振和皮炎而转诊。实验室检查显示高炎症和肾功能不全。入院时的计算机断层扫描(CT)显示没有新的病变，包括结肠炎或胰腺炎。入院第4天，血清胰酶极显著升高。淀粉酶升高至683U/L(正常范围44~132U)，脂肪酶升高至1520U/L(13~55岁)，但无腹部压痛。增强CT显示胰腺实质增大，磁共振胆胰管成像显示胰腺周围脂肪滞留，提示为胰腺炎。血培养测试和头孢曲松的经验性抗生素治疗表明，没有活动性传染病。我们诊断了ICI诱发的胰腺炎，并给予他每天0.5 mg/kg的强的松龙治疗，这改善了他的全身疲倦、厌食、皮炎和胰腺炎。无症状的胰酶升高的潜在意义尚不清楚；然而，该病例提示无腹部压痛的ICI诱发的胰腺炎可能具有临床意义。临床医生应该注意ICIS患者的潜伏性胰腺炎的发展，即使是那些没有腹痛的患者。
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.