Niimoto Takahisa, Todaka Takafumi, Kimura Hirofumi, Suzuki Shotaro, Yoshino Shumpei, Hoashi Kosuke, Yamaguchi Hirotaka
Department of General Internal Medicine, Aso Iizuka Hospital, 3-83, Yoshio-Machi, Iizuka, Fukuoka, 820-8505, Japan.
Department of Intensive Care Medicine, Aso Iizuka Hospital, 3-83, Yoshio-Machi, Iizuka, Fukuoka, 820-8505, Japan.
Int J Emerg Med. 2024 Sep 2;17(1):106. doi: 10.1186/s12245-024-00691-5.
Cytokine release syndrome (CRS) is an acute systemic inflammatory syndrome characterized by fever and multiple organ failure, which is triggered by immunotherapy or certain infections. Immune checkpoint inhibitors rarely cause immune-related adverse event- cytokine release syndrome (irAE-CRS). This article presents a case report of irAE-CRS triggered by coronavirus disease 2019 (COVID-19).
A 60-year-old man with type 2 diabetes received nivolumab treatment for esophagogastric junction carcinoma and experienced two immune-related adverse events: hypothyroidism and skin disorder. Eleven days before his visit to our hospital, he had a fever and was diagnosed with COVID-19. Five days before his visit, he developed a fever again, along with general malaise, water soluble diarrhea, and myalgia of the extremities. On admission, the patient was in a state of multiple organ failure, and although the source of infection was unknown, a tentative diagnosis of septic shock was made. The patient's condition was unstable despite systemic management with antimicrobial agents, high-dose vasopressors, and intravenous fluids. We suspected CRS due to irAE (irAE-CRS) based on his history of nivolumab use. Steroid pulse therapy (methylprednisolone 1 g/day) was started, and the patient temporarily recovered. However, his respiratory condition worsened; consequently, he was placed on a ventilator and tocilizumab was added to the treatment. His muscle strength recovered to the point where he could live at home, and was subsequently discharged.
In patients previously treated with immune checkpoint inhibitors, irAE-CRS should be considered as a differential diagnosis when multiple organ damage is observed in addition to inflammatory findings. It is recommended to start treatment with steroids; if the disease is refractory, other immunosuppressive therapies such as tocilizumab should be introduced as early as possible.
细胞因子释放综合征（CRS）是一种以发热和多器官功能衰竭为特征的急性全身性炎症综合征，由免疫治疗或某些感染引发。免疫检查点抑制剂很少引起免疫相关不良事件——细胞因子释放综合征（irAE-CRS）。本文报告一例由2019冠状病毒病（COVID-19）引发的irAE-CRS病例。
一名60岁2型糖尿病男性因食管胃交界癌接受纳武单抗治疗，出现了两种免疫相关不良事件：甲状腺功能减退和皮肤疾病。在他来我院就诊前11天，出现发热，被诊断为COVID-19。就诊前5天，他再次发热，伴有全身乏力、水溶性腹泻和四肢肌肉疼痛。入院时，患者处于多器官功能衰竭状态，尽管感染源不明，但初步诊断为感染性休克。尽管使用抗菌药物、大剂量血管加压药和静脉输液进行了全身治疗，患者病情仍不稳定。基于他使用纳武单抗的病史，我们怀疑是irAE导致的CRS（irAE-CRS）。开始使用类固醇脉冲疗法（甲泼尼龙1g/天），患者暂时康复。然而，他的呼吸状况恶化；因此，给他使用了呼吸机，并在治疗中加用了托珠单抗。他的肌肉力量恢复到可以居家生活的程度，随后出院。
在先前接受免疫检查点抑制剂治疗的患者中，当除炎症表现外还观察到多器官损害时，应考虑irAE-CRS作为鉴别诊断。建议开始使用类固醇治疗；如果疾病难治，应尽早引入其他免疫抑制疗法，如托珠单抗。
