Objective: To explore the clinical characteristics and outcomes of patients with non-Epstein-Barr virus (EBV) infection-associated hemophagocytic lymphohistiocytosis (IAHLH) . Methods: Clinical data of 48 patients diagnosed with non-EBV IAHLH in Beijing Friendship Hospital from January 2015 to March 2021 were collected, and the clinical characteristics, treatment, curative effect and prognosis of the patients were analyzed retrospectively. Results: This study included 48 patients, 28 males and 20 females, with a median (range) age of 34.5 (2-74) years. Pathogens that cause IAHLH were as follows: virus (16 cases, 33.3%) , bacteria (17 cases, 35.4%) , parasitic agents (13 cases, 27.1%) , and fungi (2 cases, 4.2%) . The median time from onset to diagnosis of hemophagocytic syndrome (HLH) was 40 (10-160) days. The median (range) time duration from prodrome to the definite diagnosis of IAHLH was 67 (23-270) days. The clinical characteristics were fever (48 cases, 100%) , splenomegaly (34 cases, 70.8%) , cytopenia (38 cases, 79.1%) , elevated ferritin (45 cases, 93.8%) , elevated fasting triglyceride levels (7 cases, 14.6%) , hypofibrinogenemia (17 cases, 35.4%) , decrease natural killer cell activity (26 in 44 cases, 59.1%) , and elevated sCD25 (35 cases, 74.5%) . Twenty-five patients (52.1%) had adenopathy. Once a certain pathogen was identified as the causative factor of hemophagocytic lymphohistiocytosis (HLH) , cytotoxic agents and glucocorticoids were withdrawn, and specific pathogen-directed treatment was initiated. After treatment, 36 cases (75.0%) achieved complete response, and 14 of 15 patients (93.3%) with parasitic and fungal HLH got a response; however, the response rate of patient with bacterial and viral HLH was only 66.7% (22 of 33 patients) . The estimated 5-year overall survival rate was 72.3% (95%CI 50.3%-69.8%) . The adverse prognostic factors were total bilirubin over the upper limit of normal (OR=20.0, 95%CI 1.1-378.3, P=0.046) and pathogenic infection not fully controlled (OR=19.9, 95%CI 2.9-134.5, P=0.002) . Conclusion: Non-EBV IAHLH has a good prognosis. When diagnosed, cytotoxic agents and glucocorticoids should be tapered off, and pathogen-targeted therapy should be critically administered to clear the triggering infection.
目的： 探讨非EB病毒病原体所致感染相关噬血细胞综合征（IAHLH）患者的临床特征及预后。 方法： 收集2015年1月至2021年3月首都医科大学附属北京友谊医院确诊的48例非EB病毒病原体所致IAHLH患者的临床资料，对患者的临床特征、治疗、疗效及预后进行回顾性分析。 结果： 共纳入48例患者，男28例，女20例，中位年龄34.5（2.0~74.0）岁，导致IAHLH的病原体中，病毒16例（33.3%），细菌17例（35.4%），寄生虫13例（27.1%），真菌2例（4.2%），患者发病至确诊噬血细胞综合征（HLH）的中位时间为40（10~160）d，发病至确诊为IAHLH的中位时间为67（23~270）d。患者起病时临床表现如下：发热48例（100%），脾大34例（70.8%），血细胞减低38例（79.1%），铁蛋白升高45例（93.8%），甘油三酯升高7例（14.6%），纤维蛋白原降低17例（35.4%），NK细胞活性减低26例（59.1%），可溶性CD25升高35例（74.5%）。25例（52.1%）患者起病时伴淋巴结肿大。明确导致HLH的病原体后尽快减停细胞毒药物及激素并应用有效的抗感染治疗，36例（75.0%）患者获得完全缓解，93.3%（14/15）的寄生虫及真菌所致IAHLH患者获得了病情缓解，细菌及病毒相关IAHLH仅有66.7%（22/33）的缓解率。患者5年预期总生存（OS）率为72.3%（95%CI 50.3%~69.8%），多因素分析显示，总胆红素大于2倍正常上限（OR=20.0，95%CI 1.1~378.3，P=0.046）及诱发HLH的病原体感染未控制（OR=19.9，95%CI 2.9~134.5，P=0.002）为预后不良因素。 结论： 非EB病毒病原体所致IAHLH预后较好，诊断后应尽快减停细胞毒药物及激素，有效控制病原体感染为关键性治疗。.
Keywords: Clinical characteristics; Hemophagocytic lymphohistiocytosis; Infection; Outcome.