Case Presentation: Epstein-Barr virus (EBV) infection in young adults is typically a straightforward diagnosis characterized by fever, sore throat, and lymphadenopathy. However, EBV can be a master of disguise, presenting outside this classic triad and masquerading as primary hepatobiliary or hematologic disease. We describe a patient who presented with hepatitis, pancytopenia, and warm autoimmune hemolytic anemia (AIHA), illustrating how EBV can mimic more serious pathology and trigger rare complications.
Discussion: A 24-year-old previously healthy female presented to the hospital with five days of right upper quadrant pain, nausea, vomiting, and profound fatigue. She reported a mild sore throat and subjective fever but denied rash. On exam, she was tachycardic and appeared ill, with right upper quadrant tenderness and a negative Murphy’s sign.Initial laboratory studies showed a hepatocellular pattern of liver injury (ALT/AST in the 500s U/L, ALP 171 U/L, total bilirubin 1.8 mg/dL) and leukopenia with a WBC of 1.64 x 109/L. A broad workup was initiated, including a heterophile antibody (Monospot) test, viral hepatitis panel, and autoimmune markers. By hospital day two, transaminases worsened to the 700s U/L and pancytopenia evolved with a WBC of 1.95 x 10^9/L, absolute neutrophil count of < 1000 cells/mm3. hemoglobin 10.9 g/dL, platelets 131 x 10^9/L. Hemolysis was suspected based on elevated LDH and reduced haptoglobin. The heterophile and hepatitis panel returned negative. The differential expanded to include tick-borne infection, other viral illnesses, autoimmune hepatitis, and hematologic malignancy. Infectious Disease and Gastroenterology were consulted. Recommendations included extensive infectious testing, such as EBV serologies, leptospirosis, malaria, other zoonotics, and a comprehensive autoimmune evaluation.In the interim, she was managed supportively with intravenous fluids, antiemetics, and analgesics. Over the next 72 hours, her condition began to improve. The final piece of the diagnostic puzzle fell into place when EBV-specific serologies returned positive with viral capsid antigen (VCA) IgM 40.01 U/mL, VCA IgG 29.90 U/mL, and nuclear antigen over 600 U/mL. A direct antiglobulin test was positive for IgG, confirming warm AIHA. A diagnosis of acute EBV infection with associated hepatitis, pancytopenia, and AIHA was made.
Conclusions: This diagnostic journey offers a few vital lessons for the Internal Medicine physician. EBV is a great mimic, our patient’s predominant symptoms were nausea, abdominal pain, and hepatitis rather than the classic mono triad. Atypical presentations can lead to unnecessary testing and initial misdirection. Additionally, a negative heterophile test should not prematurely exclude EBV as demonstrated in our patient. The sensitivity may be as low as 50% in the first week, and a false-negative rate of up to 25% has been recorded overall. (1) When clinical suspicion remains high, EBV-specific serologies such as VCA IgM, VCA IgG, and EBNA are critical to correctly identify the infection. (2) For hemodynamically stable patients with EBV hepatitis and mild AIHA, supportive care is an appropriate and often sufficient strategy, as many cases resolve spontaneously. However, progressive or severe hemolysis may necessitate treatments with corticosteroids or rituximab. Our patient improved with supportive care alone.