Journal of Advances in Medicine and Medical Research

Aims: Epstein-Barr virus (EBV) infection, or infectious mononucleosis, is usually a self-limited illness in young adults characterized by pharyngitis, fever, and lymphadenopathy. Atypical presentations may involve hepatic dysfunction, hematologic abnormalities, or rarely, splenic infarction. We report a case of EBV mononucleosis with multiple atypical features and a prolonged course.

Presentation of Case: A 33-year-old immunocompetent patient developed intermittent fever lasting 45 days at presentation, cholestatic hepatitis, hyperferritinemia, cytomegalovirus (CMV) IgM positivity, transient elevated smooth muscle and actin autoantibodies, and initially negative EBV serologies following recent travel to Japan. He was ultimately diagnosed with EBV mononucleosis. He improved with supportive management. Two weeks after discharge, he returned with left upper quadrant pain and was found to have splenomegaly and a splenic infarction. He was managed supportively and had stable recovery after discharge.

Discussion: This case illustrates several uncommon features of EBV infection, including cholestatic hepatitis, marked hyperferritinemia, transient autoimmune marker elevations, CMV IgM cross-reactivity, and delayed splenic infarction. The patient’s prolonged febrile course (>60 days) highlights the potential for EBV to mimic autoimmune, malignant, or hyperinflammatory syndromes.

Conclusion: EBV infection may rarely present with prolonged systemic illness, hepatic dysfunction, and splenic complications. Clinicians should consider EBV in the differential diagnosis of prolonged fever and cholestatic hepatitis, even when initial serologies are inconclusive.