噬血细胞淋巴组织细胞增生症(HLH),一种罕见但可能致命的免疫过度激活综合征,可能是未被识别的免疫相关不良事件(irAE)。与其他iRAE不同,由免疫检查点阻断引发的HLH没有很好的描述;不存在特定的诊断指南和治疗方案。HLH-2004标准仍然是常见的诊断指南。对于HLH的治疗,化疗的各种组合,使用免疫抑制剂和糖皮质激素。
我们报告了一例58岁转移性黑色素瘤患者的HLH病例,该患者正在接受pembrolizumab免疫检查点阻断,程序性细胞死亡-1(PD-1)受体抑制剂。病人出现发烧,正常大小的脾脏,贫血,血小板减少症,高甘油三酯血症,高铁蛋白血症,NK细胞活性降低,sCD163水平升高,符合组织细胞协会HLH-2004诊断标准。我们的患者成功口服泼尼松(1毫克/千克/天),提示来自免疫检查点抑制剂的HLH可能仅对类固醇有反应.
HLH的早期诊断和治疗对于避免进行性组织损伤至关重要。器官衰竭,可能死亡。HLH应在发热的临床表现中被怀疑,血细胞减少和高炎症标志物。在免疫检查点阻断的情况下,HLH只能用类固醇治疗,但需要进一步的证据。
Hemophagocytic Lymphohistiocytosis (HLH), a rare but potentially fatal syndrome of immune hyperactivation, may be an under-recognized immune-related adverse event (irAE). Unlike other irAEs, HLH triggered by immune checkpoint blockade is not well described; no particular diagnostic guidelines and treatment regimens exist. The HLH-2004 criteria remain as the common diagnostic guide. For the treatment of HLH, various combinations of chemotherapeutic, immunosuppressive and glucocorticoid agents are used.
We report a
case of HLH in a 58-year-old metastatic melanoma patient who was undergoing immune checkpoint blockade with pembrolizumab, a programmed cell death-1 (PD-1) receptor inhibitor. The patient presented with fever, upper normal sized spleen, anemia, thrombocytopenia, hypertriglyceridemia, hyperferritinemia, reduced NK cell activity and elevated sCD163 levels, fulfilling the Histiocyte Society HLH-2004 diagnostic criteria. Our patient was successfully treated with oral prednisone (1 mg/kilogram/day), suggesting that HLH from immune checkpoint inhibitors may respond to steroids alone.
Early diagnosis and treatment of HLH are critical to avoid progressive tissue damage, organ failure and possibly death. HLH should be suspected in clinical presentations with fever, cytopenias and hyperinflammatory markers. HLH in the setting of immune checkpoint blockade may be treated with steroids only but further evidence is required.