非EB病毒病原体所致感染相关噬血细胞综合征的临床特征及预后

Characteristic and prognosis of patients with non-EBV infection-associated hemophagocytic lymphohistiocytosis

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。

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identified as the causative factor of hemophagocytic lymphohistiocytosis(HLH),cytotoxic agents and glucocorticoids were withdrawn,and specific pathogen-directed treatment was initiated.After treatment,36 cases(75.0%)achieved complete response,and 14 of 15 patients(93.3%)with parasitic and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.