What is the diagnosis and treatment for a patient with sore throat, nausea, erythema of the tonsils, lymphadenopathy, and positive mononucleosis test results?

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Diagnosis and Management of Infectious Mononucleosis

Diagnosis

This patient has infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV), confirmed by the positive heterophile antibody test, and requires supportive care only—no antibiotics or antivirals are indicated. 1

The clinical presentation is classic for IM with:

  • Sore throat and tonsillar erythema (pharyngitis) 2, 3
  • Lymphadenopathy (axillary in this case, though cervical is more typical) 3, 4
  • 14-day duration of symptoms 3
  • Nausea (common systemic symptom) 2
  • Positive heterophile antibody test (the "monospot" test) 1

Diagnostic Confirmation

A positive heterophile antibody test is diagnostic for EBV infection and no further EBV-specific testing is required. 1 The monospot test has 71-90% accuracy for diagnosing IM, though it can be falsely negative in up to 25% of cases during the first week of illness. 5 Since this patient has had symptoms for 14 days, the positive result is reliable. 1

If the heterophile test had been negative despite high clinical suspicion, you would need to perform EBV-specific serologic testing for IgG and IgM antibodies to viral capsid antigen (VCA) and antibodies to Epstein-Barr nuclear antigen (EBNA). 1, 6 Recent primary EBV infection shows VCA IgM positive with EBNA antibodies negative. 1

Why Not Streptococcal Pharyngitis?

While this patient has pharyngitis, antimicrobial therapy is of no proven benefit for acute pharyngitis except when caused by Group A streptococci. 2 The Infectious Diseases Society of America guidelines emphasize that EBV is a frequent cause of acute pharyngitis accompanied by generalized lymphadenopathy, which distinguishes it from typical streptococcal pharyngitis. 2 The 14-day duration and positive heterophile test confirm viral etiology, making bacterial testing unnecessary. 2, 7

Treatment Approach

Supportive Care (Mainstay of Treatment)

Treatment consists exclusively of symptomatic management with adequate hydration, analgesics, antipyretics, and rest guided by the patient's energy level. 3, 5

  • Provide adequate hydration 3
  • Use analgesics and antipyretics for symptom relief 3
  • Allow activity level to be guided by patient's energy—do not enforce strict bed rest 3
  • Advise that fatigue may persist for several months after acute infection resolves 3

What NOT to Use

Corticosteroids, acyclovir, and antihistamines are not recommended for routine treatment of infectious mononucleosis. 3 Corticosteroids should only be considered for respiratory compromise or severe pharyngeal edema. 3 Antivirals do not reduce the length or severity of illness. 5

Do not prescribe antibiotics—this is a viral infection and antibiotics provide no benefit while contributing to antimicrobial resistance. 2

Activity Restrictions

The patient must avoid contact sports and strenuous exercise for at least 4 weeks (some sources recommend 8 weeks) after symptom onset due to risk of splenic rupture. 3, 4 Splenic rupture occurs in 0.1-0.5% of patients and is potentially life-threatening. 4 Splenomegaly occurs in approximately 50% of IM cases. 4

Common Pitfalls to Avoid

  • Do not prescribe amoxicillin or ampicillin—these antibiotics cause a characteristic maculopapular rash in 90% of IM patients and may lead to misdiagnosis of drug allergy. 3
  • Do not rely solely on a negative heterophile test to rule out IM, especially early in illness (first week), as false-negative rates are high. 1, 5
  • Do not allow return to sports before 4 weeks minimum, even if the patient feels better, due to splenic rupture risk. 3, 4
  • Do not perform unnecessary EBV-specific antibody testing when the heterophile test is already positive. 1

Expected Clinical Course

Most patients have an uneventful recovery with spontaneous resolution. 4 Fatigue, myalgias, and need for sleep may persist for several months after the acute infection resolves. 3 The illness is generally benign and self-limited. 4

References

Guideline

Diagnostic Approach to Infectious Mononucleosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Epstein-Barr virus infectious mononucleosis.

American family physician, 2004

Research

Infectious Mononucleosis: An Updated Review.

Current pediatric reviews, 2024

Research

Common questions about infectious mononucleosis.

American family physician, 2015

Guideline

Differentiating Viral and Bacterial Pharyngitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 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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