以噬血细胞综合征为首发表现的肝炎相关性再生障碍性贫血五例分析

Analysis of five cases of hepatitis associated aplastic anemia presenting with hemophagocytic lymphohistiocytosis at onset

目的探讨以噬血细胞综合征(HLH)为首发表现的肝炎相关性再生障碍性贫血(HAAA)的临床特点及诊治要点。方法回顾性分析2017年1月至2019年5月于首都医科大学附属北京儿童医院住院治疗的5例以HLH为首发表现的HAAA患儿的临床病例资料。结果5例患儿中男4例、女1例,发病年龄6.0(2.7~12.7)岁。所有患儿在发病初期均表现为不明原因的高热、肝肿大、入院前血生化提示肝功能损伤[天冬氨酸转氨酶1716(1409~2570)U/L、丙氨酸转氨酶1699(937~2540)U/L],入院后查血细胞减少[白细胞计数1.2(0.6~6.7)×109/L、血红蛋白94(65~111)g/L、血小板计数29(10~41)×109/L]、纤维蛋白原降低[1.3(1.1~2.5)g/L],甘油三酯[4.0(2.8~5.1)mmol/L]、铁蛋白[1766(399~5253)μg/L]、可溶性CD25[27457(9625~44000 ng/L)]明显升高,患儿骨髓涂片中都可见吞噬现象,故急性肝炎、HLH诊断明确。在HLH治疗过程中,患儿血细胞持续减低不缓解,完善骨髓(髂骨)活检提示骨髓增生低下,在除外先天骨髓衰竭性疾病及其他全血细胞减少性疾病后,HAAA诊断成立。HAAA确诊后,1例患儿在北京儿童医院行抗人胸腺免疫球蛋白(ATG)和环孢素治疗,1例外院行造血干细胞移植,2例明确诊断后外院行ATG治疗,1例患儿死亡。结论HAAA可以HLH为首发表现,临床表现以高热、肝功能损伤、血细胞减少、铁蛋白升高及骨髓吞噬现象为主。若经免疫抑制治疗,HLH以及肝炎相关指标均好转而血常规持续不恢复应考虑HAAA可能。当HAAA符合重型再生障碍性贫血诊断标准或依赖输注时,应尽快行ATG或者造血干细胞移植治疗。

Objective To discuss the clinical characteristics and management approaches to hepatitis associated aplastic anemia(HAAA)presenting as hemophagocytic lymphohistiocytosis(HLH)at onset.Methods The clinical data and laboratory results of hospitalized 5 HAAA patients presenting as HLH at onset in Beijing Children′s Hospital from January 2017 to May 2019 were analyzed retrospectively.Results Among 5 cases,there were 4 males and 1 female.The age of onset was 6.0(2.7-12.7)years.All patients presented with high fever,hepatomegaly,hepatic dysfunction(aspartate aminotransferase 1716(1409-2570)U/L,alanine aminotransferase 1699(937-2540)U/L)at onset.After admission,the laboratory results showed pancytopenia(white blood cell 1.2(0.6-6.7)×109/L,haemoglobin 94(65-111)g/L,blood platelet 29(10-41)×109/L),decreased fibrinogen(1.3(1.1-2.5)g/L),significantly elevated triglyceride(4.0(2.8-5.1)mmol/L),ferritin(1766(399-5253)μg/L)and soluble CD25(27457(9625-44000)ng/L).Hemophagocytosis was found in the bone marrow smears of all 5 patients.The diagnosis of acute hepatitis and HLH was confirmed.During the treatment of HLH,the blood cells remain below normal level and the further biopsy of bone marrow(iliac bone)indicated low myeloproliferation.After exclusion of congenital bone marrow failure syndromes and other pancytopenic diseases,HAAA was confirmed.After the diagnosis of HAAA,1 patient received antithymocyte globulin(ATG)and cyclosporin treatment in our hospital,1 patient received allogeneic stem cell transplantation(HSCT)in other hospital,2 patients received ATG in other hospitals.Only 1 patient died of severe infection.Conclusions HAAA can present as HLH at onset.It is mainly manifested by high fever,acute severe hepatitis,pancytopenia,elevated ferritin and hemophagocytosis in the bone marrow.The diagnosis of HAAA should be considered whenever cytopenia could not completely corrected while apparent improvement of HLH and hepatitis related complications were improved after immunosuppressive therapy.ATG or HSCT treatment should be performed as soon as the diagnosis of severe or transfusion dependent aplastic anemia is confirmed.