Does a 17-year-old female with a 3-week history of sore throat and fatigue, initially treated for strep, with a positive Epstein-Barr Virus (EBV) nuclear antigen (EBNA) and negative IgM, have infectious mononucleosis?

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Serologic Interpretation: This Patient Does NOT Have Acute Infectious Mononucleosis

This 17-year-old female does not have acute infectious mononucleosis based on her serologic profile. The presence of positive EBNA (Epstein-Barr nuclear antigen) with negative IgM indicates past EBV infection, not current acute disease 1, 2.

Understanding the Serologic Pattern

Why This is NOT Acute Mononucleosis

  • EBNA positivity is the key finding that excludes acute infection - EBNA antibodies appear late in EBV infection (typically 3-6 months after acute illness) and persist indefinitely, indicating remote past infection 2

  • The diagnostic pattern for acute IM requires: positive VCA IgM, positive or negative VCA IgG, and absent EBNA 1, 2

  • Her positive EBNA with negative IgM demonstrates she had EBV infection in the past (likely months to years ago) and has developed immunity 1

What the Positive VCA IgG Means

  • VCA IgG >8.0 without accompanying IgM indicates past infection rather than acute or recent infection 1

  • This pattern (positive VCA IgG + positive EBNA + negative IgM) represents remote past EBV exposure with established immunity 2

Clinical Implications and Next Steps

Alternative Diagnosis Required

  • Her current 3-week illness of sore throat and fatigue must have another cause since the serology excludes acute mononucleosis 3

  • Consider other etiologies including:

    • Persistent or recurrent streptococcal pharyngitis (despite initial treatment) 4
    • Cytomegalovirus infection 5
    • Toxoplasmosis 5
    • Other viral pharyngitis 5

When Heterophile Testing Would Have Been Useful

  • The heterophile antibody test has 87% sensitivity and 91% specificity for acute IM but can be false-negative in the first week of illness 3

  • In this case, a heterophile test would likely have been negative given the serologic pattern showing past rather than acute infection 4

Important Caveat About Chronic Active EBV

  • The guidelines you're seeing about chronic active EBV (CAEBV) are not applicable here - CAEBV requires persistent IM-like symptoms, unusual antibody patterns with markedly elevated VCA and EA titers (VCA-IgG ≥1:640, EA-IgG ≥1:160), and exclusion of other diseases 6

  • CAEBV is a rare, serious condition characterized by chronic symptoms (persistent fever, lymphadenopathy, hepatosplenomegaly) lasting months, not the 3-week presentation described here 6

Management Recommendation

Reassess for alternative diagnoses - repeat throat culture or rapid strep testing, consider monospot if not already done (though expect negative result), and evaluate for other causes of prolonged pharyngitis and fatigue 4, 5. The positive EBNA definitively rules out acute mononucleosis as the cause of her current symptoms 1, 2.

References

Guideline

Epstein-Barr Virus Infection Diagnosis and Interpretation

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Infectious Mononucleosis: Rapid Evidence Review.

American family physician, 2023

Research

Common questions about infectious mononucleosis.

American family physician, 2015

Research

Epstein-Barr virus infectious mononucleosis.

American family physician, 2004

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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