Case Presentation: A previously healthy 54-year-old man presented with three days of fever, right upper-quadrant abdominal (RUQ) pain, and non-bloody diarrhea after returning from a trip to Massachusetts. He worked in an outdoor occupation with frequent interstate travel. Initial evaluation showed a temperature of 37.8 °C, mild RUQ tenderness, hemoglobin 13.8 g/dL, WBC 2.47 × 10³/µL with 24.8% bands, platelets 105 × 10³/µL, ALT 58 U/L, and AST 102 U/L. Blood cultures were negative. Abdominal imaging demonstrated mild enterocolitis. He was discharged after stool testing identified norovirus, and the empiric antibiotics were discontinued.Eleven days later, he returned with persistent fevers, chills, night sweats, and recurrent abdominal pain. Repeat infectious evaluation, including testing for tuberculosis, Lyme disease, Babesia, viral hepatitides, CMV, Brucella, and dengue, was negative. Liver enzymes continued to rise, eventually peaking in the 600 U/L range. Epstein–Barr virus (EBV) serology demonstrated positive viral capsid antigen IgM and IgG, as well as EBNA (nuclear antigen) IgG, and he was managed for acute EBV infection. However, EBV DNA testing was negative. A tick-borne disease panel subsequently returned positive for Anaplasma phagocytophilum by polymerase chain reaction. Doxycycline was initiated with rapid clinical improvement and normalization of liver enzymes.
Discussion: Human granulocytic anaplasmosis (HGA) may present with fever, cytopenias, transaminitis, gastrointestinal symptoms, or other non-specific manifestations, often prompting broad diagnostic evaluation. Norovirus infection can also produce abdominal pain, diarrhea, and low-grade fever, making concomitant disease difficult to recognise. As molecular stool panels and multiplex serologies become more common in hospital medicine, clinicians increasingly encounter multiple simultaneous positive results. Hickam’s dictum, “patients can have as many diseases as they please”, highlights the need to avoid premature diagnostic closure when test results appear to explain only part of the presentation.This case was further complicated by positive EBV IgM in the absence of compatible clinical features. EBV serologies may cross-react in other infections due to polyclonal B-cell activation, leading to false-positive viral capsid IgM. Reported triggers include parvovirus B19, hepatitis A, toxoplasmosis, Lyme disease, HIV, and tick-borne illnesses. Understanding EBV antibody kinetics is essential; the presence of EBV nuclear antigen IgG only two weeks into symptoms makes acute EBV unlikely. In this case, a false-positive EBV IgM obscured the underlying diagnosis of anaplasmosis.
Conclusions: Hospitalists frequently evaluate patients with non-specific febrile illnesses and multiple abnormal laboratory findings. This case illustrates the importance of maintaining a broad differential diagnosis and applying Hickam’s dictum when confronted with potentially misleading laboratory results. In our patient, Norovirus likely caused true gastrointestinal symptoms, while anaplasmosis produced persistent fever and transaminitis. EBV serology proved misleading due to false-positive IgM. When serologic findings and clinical presentation diverge, confirmatory molecular testing should be pursued to avoid diagnostic delay and ensure timely treatment.