Kraskovsky Valeri, Harhay Jason, Mador Martin Jeffery
Pulmonary, Critical Care and Sleep Medicine, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, USA
Internal Medicine, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, USA.
BMJ Case Rep. 2021 Mar 31;14(3):e241222. doi: 10.1136/bcr-2020-241222.
Haemophagocytic lymphohistiocytosis (HLH) is a rare diagnosis that carries a high degree of mortality. We present this case of a previously healthy 22-year-old woman, who was admitted acutely ill to the hospital. One week prior, she had been seen by her primary care physician for fatigue and malaise. At that time, she was noted to have anterior and posterior cervical lymphadenopathy. She was referred to the emergency room and was diagnosed with acute Epstein-Barr virus (EBV) mononucleosis based on her clinical symptoms and positive heterophile antibody test. She was discharged after an uneventful 48-hour stay on the wards. She represented 7 days after discharge with cough, fatigue, nausea, vomiting, epigastric abdominal pain, diarrhoea, weight loss and subjective fevers. She had also reported haematemesis, epistaxis and melaena. Vital signs included temperature 36.9°C, blood pressure 90/50 mm Hg, heart rate 130 beats per minute and respiratory rate 32 breaths per minute. Physical examination was notable for an acutely ill appearing woman with scleral icterus, hepatosplenomegaly and palpable cervical and axillary lymphadenopathy. Complete blood count showed pancytopaenia with haemoglobin 59 g/L (normal 120-160 g/L), white blood cell count 2.7×10/L (normal 4-10.5×10/L) and platelet count 50×10/L (normal 150-450×10/L). The white blood cell count differential included 58% neutrophils (normal 38%-77%) with immature neutrophils in band form elevated at 45% (normal <14%), 16% lymphocytes (normal 20%-48%), 7% monocytes (normal <12%) and no eosinophils (normal <6%). Blood smear revealed anisocytosis, poikilocytosis and hypochromia. Coagulation panel showed elevated levels of d-dimer level at 1.39 µg/mL (normal <0.45 µg/mL), prolonged prothrombin time at 34.4 s (normal 11-15 s), prolonged activated partial thromboplastin time of 55.6 s (normal 25-34 s), prolonged international normalised ratio at 3.31 (normal <1.1) and low fibrinogen 60 mg/dL (normal >200 mg/dL). Lipid panel showed cholesterol at 114 mg/dL (normal 125-200 mg/dL), triglycerides 207 mg/dL (normal 30-150 mg/dL), high-density lipoprotein cholesterol 10 mg/dL (normal 40-60 mg/dL) and low-density lipoprotein cholesterol 63 mg/dL (normal <100 mg/dL). Other lab abnormalities included elevated ferritin of 6513 ng/mL (normal 10-150 ng/mL) and elevated lactate dehydrogenase of 1071 unit/L (normal 95-240 unit/L). Soluble interleukin-2 receptor alpha level was elevated at 60 727 units/mL (normal 223-710 units/mL). Fluorodeoxyglucose-positron emission tomography (FDG-PET) scan showed abnormal tracer localisation within the paratracheal, hilar, pelvic, abdominal and subcarinal lymph nodes, along with FDG-PET positive hepatosplenomegaly. A bone marrow biopsy showed hypercellular marrow (95% cellularity) with trilineage haematopoiesis, haemophagocytic cells, polytypic plasmacytosis and T-cell lymphocytosis, along with positive latent membrane protein-1 immunohistochemical staining for EBV. EBV quantitative DNA PCR showed >1 million copies. These findings were consistent with a diagnosis of HLH secondary to EBV infection. Despite intense therapy with the HLH-94 protocol, the patient expired from her illness after a prolonged hospital course.
噬血细胞性淋巴组织细胞增生症（HLH）是一种罕见的诊断，死亡率很高。我们报告了一名此前健康的22岁女性病例，她因重病急症入院。一周前，她因疲劳和不适就诊于初级保健医生。当时，发现她有颈部前后淋巴结肿大。她被转诊至急诊室，根据临床症状和嗜异性抗体试验阳性，被诊断为急性爱泼斯坦-巴尔病毒（EBV）单核细胞增多症。在病房平稳度过48小时后她出院了。出院7天后，她因咳嗽、疲劳、恶心、呕吐、上腹部腹痛、腹泻、体重减轻和自觉发热前来就诊。她还报告有呕血、鼻出血和黑便。生命体征包括体温36.9°C、血压90/50 mmHg、心率130次/分钟和呼吸频率32次/分钟。体格检查发现一名急症面容的女性，有巩膜黄染、肝脾肿大以及可触及的颈部和腋窝淋巴结肿大。全血细胞计数显示全血细胞减少，血红蛋白59 g/L（正常120 - 160 g/L），白细胞计数2.7×10⁹/L（正常4 - 10.5×10⁹/L），血小板计数50×10⁹/L（正常150 - 450×10⁹/L）。白细胞分类计数包括58%中性粒细胞（正常38% - 77%），其中杆状核未成熟中性粒细胞升高至45%（正常<14%），16%淋巴细胞（正常20% - 48%），7%单核细胞（正常<12%），无嗜酸性粒细胞（正常<6%）。血涂片显示红细胞大小不均、异形红细胞症和低色素性。凝血检查显示D - 二聚体水平升高至1.39 μg/mL（正常<0.45 μg/mL），凝血酶原时间延长至34.4秒（正常11 - 15秒），活化部分凝血活酶时间延长至55.6秒（正常25 - 34秒），国际标准化比值延长至3.31（正常<1.1），纤维蛋白原低至60 mg/dL（正常>200 mg/dL）。血脂检查显示胆固醇114 mg/dL（正常125 - 200 mg/dL），甘油三酯207 mg/dL（正常30 - 150 mg/dL），高密度脂蛋白胆固醇10 mg/dL（正常40 - 60 mg/dL），低密度脂蛋白胆固醇63 mg/dL（正常<100 mg/dL）。其他实验室异常包括铁蛋白升高至6513 ng/mL（正常10 - 150 ng/mL）和乳酸脱氢酶升高至1071单位/L（正常95 - 240单位/L）。可溶性白细胞介素 - 2受体α水平升高至60727单位/mL（正常223 - 710单位/mL）。氟脱氧葡萄糖 - 正电子发射断层扫描（FDG - PET）显示气管旁、肺门、盆腔、腹部和隆突下淋巴结内有异常示踪剂定位，以及FDG - PET阳性的肝脾肿大。骨髓活检显示骨髓细胞增多（细胞含量95%），有三系造血、噬血细胞、多型浆细胞增多和T细胞淋巴细胞增多，同时EBV潜伏膜蛋白 - 1免疫组化染色阳性。EBV定量DNA PCR显示>100万拷贝。这些发现符合EBV感染继发HLH的诊断。尽管采用HLH - 94方案进行了强化治疗，但患者在漫长的住院过程后因病死亡。
