施打免疫檢查點抑制劑 (immune checkpoint inhibitors, ICIs) 引起的免疫相關不良反應 (immune-related adverse events, irAEs) 大多屬第1–2 級輕微的副作用，常見如疲倦、皮疹以及腹瀉等；引發嚴重甚至危及生命的神經系統急症如腦炎、腦病變的案例相對罕見。本案例為一名診斷晚期肝細胞癌48 歲男性，因接受首次atezolizumab 合併標靶bevacizumab 組合治療後第12 天出現發燒、畏寒的情形收治住院觀察，在入院第3 天併發失語、頸部僵硬與癲癇發作的情形。經腦部電腦斷層與腦脊髓液檢查排除腦出血、細菌及病毒感染後，懷疑為施打atezolizumab 導致的無菌性腦膜炎，因此立即給予methylprednisolone 1000 mg/day 之脈衝治療 (pulse therapy)，個案意識於用藥隔天迅速恢復，3 天脈衝療程後，醫師將類固醇轉換為口服並逐漸降低劑量。因病況穩定，個案於第14 天出院並安排於門診追蹤，後續轉換口服標靶藥物lenvatinib 持續癌症治療至今。藉由此案例突顯及時診斷神經免疫相關不良反應與早期類固醇介入的重要性，提醒臨床醫療人員注意此少見的副作用，以改善病患預後及接續癌症治療。

 

Most immune-related adverse events (irAEs) are grade 1–2 and usually manageable, like fatigue, rash and diarrhea; Severe or life-threatening neurological emergencies, such as encephalitis and encephalopathy are relatively rare in clinical practice. In present case, a 48-year-old man with chronic hepatitis B virus infection, hypertension and advanced hepatocellular carcinoma, was admitted due to fever and chills episode on the 12th day after receiving the first cycle of atezolizumab plus bevacizumab. On the third day of hospitalization, the patient developed aphasia and neck stiffness with seizure attacked. While brain computed tomography and lumbar cerebrospinal fluid (CSF) analysis were nearly normal, atezolizumab associated aseptic meningitis was in high suspicion, and methylprednisolone 1000 mg (pulse therapy) was administered immediately. The patient was completely recovered on the next day after pulse therapy. Based on stable condition, he was discharged on the 14th day of hospitalization, and shifted immune checkpoint inhibitor regimen to targeted therapy with lenvatinib. This case highlights the importance of early diagnosis of neurological irAEs and preemptive steroid intervention. All the medical professionals should be aware of this rare neurological irAE so as to improve the prognosis of these patients.

 

 

Submitted for publication: 2021.12.5; Accepted for publication: 2023.8.9