Urasaki Tetsuya, Ono Makiko, Mochizuki Toshiaki, Takeda Koichi, Nishizawa Aya, Fukagawa Eri, Fujiwara Motohiro, Komai Yoshinobu, Kitano Shigehisa, Yuasa Takeshi, Yonese Junji, Takahashi Shunji
Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Department of Emergency Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Front Oncol. 2021 Apr 30;11:681997. doi: 10.3389/fonc.2021.681997. eCollection 2021.
Currently, only a few reports exist on the cytokine release syndrome (CRS) as one of the severe immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs). Notably, it is very rare that grade 4 CRS related to ICI therapy overlaps with the drug-induced hypersensitivity syndrome (DiHS). A 46-year old woman with metastatic kidney cancer had grade 3 interstitial pneumonitis induced by four cycles of combination therapy of anti-programmed death-1 and anti-cytotoxic T lymphocyte-4 antibodies after right cytoreductive nephrectomy. Prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) was started concomitantly with prednisolone therapy to treat the interstitial pneumonitis. She developed hypotensive shock when reducing the dosage of prednisolone, and required intubation and ventilation using vasopressors at the intensive care unit. She subsequently exhibited prominent leukocytosis and an increased level of C-reactive protein, suggesting markedly increased cytokine levels. Interestingly, facial edema and erythema increased in association with pyrexia, leukocytosis, liver dysfunction, and renal failure, suggesting that she developed DiHS. She received hemodialysis three times, a plasma exchange, and anti-interleukin-6 therapy to treat severe renal dysfunction, a thrombotic thrombocytopenic purpura-suspected condition, and possible grade 4 CRS, respectively. Although these therapies did not elicit sufficient effects, high-dose administration of intravenous immunoglobulin was successful. With steroid mini-pulse therapy and the subsequent administration of prednisolone, she recovered successfully. To the best of our knowledge, this is the first report that ICIs and TMP/SMX can induce hypotensive shock accompanied with CRS and DiHS during immunosuppressive therapy for an irAE. Importantly, the prophylactic administration of TMP/SMX should be performed cautiously to avoid severe drug reactions such as CRS or DiHS.
目前，关于细胞因子释放综合征（CRS）作为免疫检查点抑制剂（ICI）诱导的严重免疫相关不良事件（irAE）之一的报道较少。值得注意的是，与ICI治疗相关的4级CRS与药物性超敏反应综合征（DiHS）重叠的情况非常罕见。一名46岁的转移性肾癌女性患者在右肾肿瘤减瘤切除术后接受了四个周期的抗程序性死亡-1和抗细胞毒性T淋巴细胞-4抗体联合治疗，引发了3级间质性肺炎。在使用泼尼松龙治疗间质性肺炎的同时，开始预防性给予甲氧苄啶/磺胺甲恶唑（TMP/SMX）。在减少泼尼松龙剂量时，她出现了低血压休克，在重症监护病房需要插管并使用血管升压药进行通气。随后，她出现了明显的白细胞增多和C反应蛋白水平升高，提示细胞因子水平显著升高。有趣的是，面部水肿和红斑随着发热、白细胞增多、肝功能障碍和肾衰竭而加重，提示她发生了DiHS。她分别接受了三次血液透析、一次血浆置换和抗白细胞介素-6治疗，以治疗严重肾功能不全、疑似血栓性血小板减少性紫癜的病症以及可能的4级CRS。尽管这些治疗没有产生足够的效果，但大剂量静脉注射免疫球蛋白取得了成功。通过类固醇小剂量脉冲疗法及随后给予泼尼松龙，她成功康复。据我们所知，这是首例关于ICI和TMP/SMX在免疫抑制治疗irAE期间可诱发伴有CRS和DiHS的低血压休克的报道。重要的是，应谨慎进行TMP/SMX的预防性给药，以避免发生CRS或DiHS等严重药物反应。
