192例成人噬血细胞淋巴组织细胞增生症患者的临床分析

Clinical characteristics of 192 adult hemophagocytic lymphohistiocytosis

目的 分析噬血细胞淋巴组织细胞增生症（HLH）的临床表现、实验室特点、治疗及预后.方法 对2003至2013年北京友谊医院收治并确诊的192例资料完整的成人HLH患者的临床表现、实验室检查、诊断、治疗方案及临床转归等资料进行回顾性综合分析.结果 192例患者中肿瘤相关HLH 70例,感染相关HLH 64例,位居前列.HLH-2004诊断标准中各指标的符合率分别为：发热98.96％,铁蛋白升高94.27％,可溶性IL-2受体（sCD25）升高94.79％,NK细胞活性减低94.27％,两系或三系血细胞减少80.73％,脾大80.21％,噬血现象74.48％,低纤维蛋白原血症50.52％,高甘油三脂血症37.50％.此外,94.27％的患者存在肝功能异常,96.35％的患者存在轻度或重度感染,75.52％的患者存在凝血功能异常.出现中枢神经系统症状、皮疹的患者分别占19.27％、20.31％.比较肿瘤、感染、风湿免疫相关HLH三组患者初诊时各实验室指标,WBC、PLT、sCD25表达、ALT、AST、总胆红素、球蛋白（GLO）水平差异有统计学意义（P＜ 0.05）.比较存活组和死亡组初诊时各实验室指标,WBC、PLT、白蛋白（ALB）、GLO、脑尿钠肽、肌酐、尿素氮水平两组差异有统计学意义（P＜0.05）.结论 继发性HLH与多种潜在疾病有关,成人以恶性肿瘤,尤其是T细胞淋巴瘤为主要诱因,其次是EB病毒感染.在HLH-2004的8条诊断标准中,发热、铁蛋白升高、NK细胞活性降低或缺如、sCD25升高灵敏性较高.风湿免疫相关的HLH患者其血细胞在初期可能不减低.WBC、PLT、ALB、GLO以及是否出现心功能不全、肾功能不全、凝血功能障碍可能是影响预后的指标.

Objective To analyze the clinical manifestations,laboratory data,therapy,and prognosis in patients with hemophagocytic lymphohistiocytosis （HLH）.Methods A retrospective study was carried out in 192 adult patients with HLH between 2003 and 2013.Results Of the 192 cases,70 cases were secondary to cancer and 64 cases secondary to infection.According to HLH-2004 criteria,the coincidence rate of indices were：fever （98.96％）,high level of serum ferritin （94.27％）,increased level of soluble interleukin-2 receptor （sCD25） （94.79％）,decreased or absent activity of NK cells （94.27％）,cytopenias （80.73％）,splenomegaly （80.21％）,hemophagocytosis in bone marrow,spleen or lymph nodes （74.48％）,hypofibrinogenemia （50.52％）,hypertriglyceridemia （37.50％）.In addition,94.27％ of patients were presented with liver dysfunction,96.35％ with infections,and 75.52％ with coagulopathy.Incidences of central nervous system symptoms and rash were 19.27％ and 20.31％,respectively.Among cancer,infection and rheumatic group,there were statistically differences on white blood cells （WBC）,platelet （PLT）,sCD25,alanine aminotransferase,aspartate aminotransferase,total bilirubin and globulin （GLO） （P＜0.05）.The differences of WBC,PLT,albumin （ALB）,GLO,brain natriuretic peptide,creatinine,urea nitrogen between survival group and death group had statistical significance.Conclusions The secondary HLH occurs from various underlined diseases.Cancer,especially T-cell lymphoma,is the main cause,Secondly,it is EB virus infection.The diagnostic sensitive indicators are Persistent fever,higher level of serum ferritin,low or absent NK-cell activity,and increased sCD25 were the most valuable parameters for diagnosis.Cytopenias were not common in early phase of HLH secondary to rheumatic diseases.WBC,PLT,ALB,GLO could be used as the preliminary parameters for diagnosis.Cardiac insufficiency,renal insufficiency and coagulation dysfunction play important roles in prognosis.