Differential Diagnosis

• Single most likely diagnosis
  • Infectious Mononucleosis (IM) due to Epstein-Barr Virus (EBV): The patient had a viral illness 2 years ago with a positive heterophile agglutination test but was negative for EBV antibodies at that time, which could indicate a false negative or a very early infection. The current presentation with another viral illness and a positive heterophile agglutination test, along with initial negative EBV antibody tests, suggests the possibility of acute EBV infection, as the repeat EBV antibody results are pending and may turn positive, confirming the diagnosis.
• Other Likely diagnoses
  • Cytomegalovirus (CMV) infection: Although the patient is negative for CMV antibodies (both IgM and IgG), CMV can cause a mononucleosis-like syndrome. However, the positive heterophile agglutination test is more commonly associated with EBV.
  • Other viral infections: Such as adenovirus or human herpesvirus 6 (HHV-6), which can cause similar clinical presentations but are less likely to cause a positive heterophile agglutination test.
• Do Not Miss (ddxs that may not be likely, but would be deadly if missed.)
  • Hemophagocytic Lymphohistiocytosis (HLH): A rare but potentially life-threatening condition that can be triggered by viral infections, including EBV. It requires prompt recognition and treatment.
  • Lymphoma: Although rare in this context, lymphoma can present with systemic symptoms similar to those of infectious mononucleosis and is a critical diagnosis not to miss.
• Rare diagnoses
  • Toxoplasmosis: Can cause a mononucleosis-like syndrome but is less common and typically associated with exposure to cats or undercooked meat.
  • Brucellosis: A zoonotic infection that can cause systemic symptoms but is rare and usually associated with specific exposures (e.g., to livestock).