A 56-year-old Vietnamese woman presented to Blood Transfusion Hematology Hospital in February 2019 because of prolonged fever and fatigue. Her initial complete blood count (CBC) on admission was notable for severe anemia: hemoglobin (Hb) 60 g/L (120-175 g/L), mean corpuscular volume 72.9 fL (78-100), white blood cell count 9.65 G/L (4-10 G/L), neutrophils 55% (45%-75%), lymphocytes 20 % (20%-35%), monocytes 20% (4%-10%), platelet count 193 G/L (150-450 G/L). Human immunodeficiency virus (HIV) antibody, antinuclear antibody (ANA), Anti-double stranded DNA antibody (Anti ds-DNA), rheumatoid factor (RF), Coombs tests were negative. Other laboratory test results showed hypertriglyceridemia (565.49 mg/dL) (40-166 mg/dL), hyperferritinemia (3153.84 ng/ml) (10-280 ng/ml), increased soluble CD25 levels (3316.936U/ml) (Normal < 511.364 U/ml) and elevated lactate dehydrogenase (LDH) (592.34 U/L) (Normal < 248 U/L). Epstein-Barr virus (EBV) Detection by PCR (Polymerase Chain Reaction) result was positive. A lumbar puncture was performed which showed 14 white blood cell; 6 red blood cells; protein of 32.6 mg/dl (Normal < 45 mg/dL); glucose of 3.58 mmol/L (2.2-3.9 mmol/L) (serum glucose of 5.3 mmol/L) and Mycobacterium tuberculosis detection by PCR result was negative. Bone marrow aspirate cytology revealed red blood cell and platelet phagocytosis. Abdominopelvic CT scan and brain MRI were obtained showing hepatomegaly, splenomegaly and subacute bilateral pontine infarction (Fig. 1). Gastrointestinal and colorectal endoscopy were performed with unremarkable results. The diagnosis was established with Hemophagocytic syndrome probably secondary to Epstein-Barr virus (EBV) infection - Pontine infarction. The patient was treated with Aspirin (81mg/day) and Dexamethasone (5 mg/day). The fever was controlled and anemia improved partially over the next several weeks. She was continuously treated with Aspirin (81 mg/day) and Dexamethason (2 mg/day) after discharge from the hospital.
In May 2019, the patient was admitted to University Medical Center - Ho Chi Minh city due to acute weakness at the left side and slurred speech. She presented an expressive language impairment, short-term and long-term memory deficit, left central facial palsy and quadriparesis. CBC showed anemia, mild thrombocytopenia: WBC count 13.39 G/L (4-10 G/L), Hb 96 g/L (120-175 g/L), Platelets 142 G/L (150-450 G/L). Brain MRI showed multifocal cerebral infarcts located at left frontal lobe and bilateral corona radiata (Fig. 1). However, magnetic resonance angiography (MRA) of the brain revealed normal intracranial vasculature. Holter monitor, echocardiography, carotid Doppler, lower extremity venous Doppler ultrasound results were unremarkable. Cerebrospinal fluid (CSF) examination showed 19 white blood cell; 2000 red blood cells; protein of 95.22 mg/dL (Normal < 45 mg/dL); glucose of 3.6 mmol/L (2.2-3.9 mmol/L) (serum glucose of 6 mmol/L (3.9-6.4 mmol/L)), Lactate 4.139 mmol/l (1.1-2.4 mmol/L). Other CSF studies including CFS culture looking for bacteria and fungi, Herpes Simplex virus (HSV) PCR test, GeneXpert for the detection of Mycobacterium tuberculosis were all negative. The patient was treated with Dexamethasone and Plavix (75 mg/day) and discharged 7 days after the admission.
Ten days after discharge, the patient was readmitted with deteriorated neurological condition as noted by developing quadriplegia and a worsening level of consciousness. On examination at the time of admission, she was agitated and had visual hallucinations. Concurrently, she had developed low-grade fever without an identifiable source of infection. Laboratory tests showed anemia, thrombocytopenia: WBC count 9.01 G/L (4-10 G/L), Hb 78 g/L (120-175 g/L), Platelets 122 G/L (150-450 G/L) and elevated LDH (300 U/L) (Normal < 248 U/L). Brain MRI showed some recent small subcortical infarcts located at left frontal lobe when comparing with the brain MRI 2 weeks earlier. Intracranial high resolution vessel wall magnetic resonance imaging (HR-vwMRI) post-contrast T1W showed vessel wall thickening with moderate enhancement at the left PCA and bilateral MCA segments relevant to the cerebral infarction suggesting vasculitis (Fig. 2). Lumbar puncture was performed again and CSF examination showed: 13 white blood cell, neutrophils 10%, lymphocytes 90 %, 0 red blood cells; protein of 111.08 mg/dL (Normal < 45 mg/dL); glucose of 5.2 mmol/L (2.2-3.9 mmol/L) (serum glucose of 8.9 mmol/L (3.9-6.4 mmol/L)); lactate 4.139 mmol/L (1.1-2.4 mmol/L). CSF culture looking for bacteria and fungi, GeneXpert for the detection of Mycobacterium tuberculosis were all negative. An abdominal, pelvic and thoracic CT-Scan revealed splenomegaly, multiple bilateral small nodules of the lung, multiple liver lesions, multiple bilateral renal masses, gastric wall thickening and multiple nodules in the omentum (Fig. 3). Red blood cell and platelet phagocytosis was showed on bone marrow aspirate cytology. Gastrointestinal endoscopy was performed again showing mild congestive gastritis and Kaposi's sarcoma was doubted. The pathological findings of gastric tissue biopsy revealed large B cell lymphoma (Fig. 4). The patient was planned to start on chemotherapy but she developed septic shock from severe pneumonia and died 28 days after the definitive diagnosis.