Case Presentation: A 19-year-old female presented with 1 month of worsening abdominal pain, 3 weeks of fevers / chills, 1 week of nausea/vomiting, and 4 days of rash. Her abdominal pain was intermittent, stabbing, diffuse, and worsening in severity. She also had daily chills and fevers (maximum temperature of 38.9 °C). Her emesis was non-bilious and non-bloody. Her rash was pruritic and started on her upper chest and progressed to her trunk, arms, legs, and palms. She had a history of celiac disease.On presentation, her temperature was 37.6 °C, blood pressure was 111/79 mmHg, and pulse was 76 bpm. Physical exam revealed cervical lymphadenopathy, diffuse abdominal tenderness, and a macular rash on her palms, upper/lower extremities, trunk, and abdomen. Labs demonstrated elevated AST (994 U/L), ALT (1,974 U/L), total bilirubin (4.5 mg/dL), direct bilirubin (3.1 mg/dL), alkaline phosphate (223 U/L); negative antinuclear antibody, anti-smooth muscle antibody, anti-mitochondrial antibody, anti-liver-kidney microsomal-1 antibodies, hepatitis A / B / C / E serologies, HIV antigen / antibody, SARS-CoV-2 PCR, Lyme IgM / IgG, Rocky Mountain Spotted Fever IgG, Ehrlichia IgG, and Cytomegalovirus (CMV) IgG and viral load; and positive Epstein-Barr virus (EBV) IgM / IgG / viral load (347 IU/mL). Her liver ultrasound with doppler was unremarkable. Her fever, nausea, and vomiting resolved immediately prior to admission. Her rash resolved on hospital day 4. At admission she was started on empiric doxycycline for tick-borne disease, but this was discontinued after 4 days and upon return of the aforementioned negative serologies. With supportive care, her liver function abnormalities all began to trend towards normal. The cause of her acute hepatitis was infection with EBV.

Discussion: Over 95% of adults worldwide have been infected with EBV.1 Infectious mononucleosis (IM) due to EBV classically causes fever, pharyngitis, hepatosplenomegaly, lymphadenopathy, abdominal pain, and mild liver enzyme elevation.1,2 Typically, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) will elevate to 2-3 times the upper limit of normal; a minority of cases present with elevation of 5-10 times the upper limit of normal.3,4 Rarer symptoms of EBV include jaundice and rash, both found in around 5% of infected patients.1,2In this case, the patient presented with typical infectious mononucleosis symptoms of fever, lymphadenopathy, and abdominal pain; she also had the more atypical rash. Most interesting was her vastly elevated aminotransferases; her AST and ALT were 25 and 35 times the normal upper limit, respectively. The diagnosis of acute hepatitis from EBV infection was made based on positive EBV serologies and viral load, extensive diagnostics ruling out other potential etiologies, and her improvement with only supportive care.EBV is a rare causative agent of acute hepatitis. Most often, the associated hepatitis is mild, clinically undetectable, and resolves with supportive care. Very rarely, however, EBV infection can result in significantly elevated aminotransferases and progression to liver failure.

Conclusions: With the high prevalence of EBV cases, the general internist must maintain a high index of suspicion for EBV hepatitis in patients presenting with classic IM symptoms as well as atypical symptoms such as rash, jaundice, and severely elevated liver transaminases. Recognition of EBV infection as a potential cause of acute hepatitis can help guide the corresponding diagnostic work-up and therapeutic plan.