Case Presentation: A 29-year-old Caucasian woman presented to the emergency department with fever, sore throat, epigastric and right upper quadrant abdominal pain of 5 days duration. Physical examination was positive for fever (40oC), tachycardia (heart rate 114 beats per minute), and a palpable liver and spleen on abdominal examination. Notable laboratory investigations included pancytopenia – platelet count was 79,000 /µL (130,000 – 400,000 /µL), hemoglobin 11 g/dL (12-16 g/dL) and WBC 2,900/µL (4, 800 – 10,800 /µL) with ANC 1,600 /µL (2,000 – 8,000 /µL). Liver enzymes were elevated, with AST 195 IU/L (13-39 IU/L), ALT 130 (7 – 52 IU/L), ALP 740 IU/L (34 – 104 IU/L), direct and total bilirubin 1.4mg/dL (0.0 – 0.2 mg/dL) and 2.1 mg/dL (0.3 – 1.0 mg/dL) respectively. EBV PCR and EBV serology (IgG & IgM) were positive consistent with recent primary infection. HIV screen was negative. Elevated D-dimer 6.41 µg/ml (<0.53 µg/ml), lactate dehydrogenase 761 IU/L (140 – 271 IU/L), low fibrinogen 117mg/dL (198 – 488 mg/dL) and elevated fibrin split products >10<40 µg/ml (<10 µg/ml) raised concern for concomitant DIC. Ferritin was elevated at 1020 ng/ml (normal:10-130 ng/ml), triglycerides were normal at 131mg/dL (<175 mg/dL). Abdominal ultrasound confirmed hepatosplenomegaly. An initial diagnosis of sepsis and DIC likely secondary to EBV infection was made and broad-spectrum antibiotics were initiated. Antibiotics were discontinued after blood cultures returned negative by day 3. Fevers and pancytopenia (hemoglobin dropped to 7.7 g/dL and ANC to 1000/µL) persisted until day 5 when bone marrow biopsy was obtained. Bone marrow biopsy results revealed mildly hypercellular marrow with prominent hemophagocytosis. A diagnosis of HLH was made on day 8 based on patient’s clinical, laboratory and bone marrow findings, and she was transferred to a tertiary institution. Interleukin 2 (IL-2) receptor level done after transfer was high normal at 999 pg/ml (<1033 pg/ml). Patient made a complete recovery with supportive care only. Follow-up laboratory testing post discharge showed resolution of all abnormalities.
Discussion: HLH is a rare life-threatening disorder of unregulated immune activation. It may be sporadic or familial, and usually has an underlying trigger including infections (most commonly EBV), lymphoproliferative disorders and rheumatologic disease. HLH presents similarly to sepsis, which often leads to delay in diagnosis and management, and is lethal in 20-60%. Diagnosis is made if 5 of 8 criteria are met, including fever (> 38.5 °C), splenomegaly, peripheral cytopenias (at least 2 cell lines; hemoglobin < 9 g/dL, absolute neutrophil count < 100/μL, platelets < 100,000/μL), hypertriglyceridemia and/or low fibrin, hemophagocytosis, low or absent NK activity, ferritin > 500 ng/ml and elevated IL-2 receptor are met. Our patient had 6 of 8. First line treatment for most cases includes etoposide and corticosteroids.
Conclusions: Clinicians need to consider HLH in the differential for patients presenting with sepsis, especially after a history of a triggering event like EBV.