What is the management and treatment of infectious mononucleosis?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: December 20, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Management and Treatment of Infectious Mononucleosis

Supportive care is the mainstay of treatment for infectious mononucleosis, as antiviral agents like acyclovir provide no benefit in otherwise healthy individuals. 1, 2

General Management Approach

Symptomatic treatment forms the foundation of care:

  • Antipyretics for fever management 2
  • Activity reduction and bed rest as tolerated 3
  • Patients must avoid contact sports or strenuous exercise for 8 weeks or while splenomegaly persists to prevent splenic rupture 3
  • Spontaneous splenic rupture occurs in 0.1-0.5% of cases and represents the most feared, potentially life-threatening complication 3, 4

Antiviral Therapy: Not Recommended

Acyclovir does not ameliorate the course of infectious mononucleosis in immunocompetent patients despite inhibiting EBV replication in vitro. 5, 1, 2 A meta-analysis of 5 clinical trials demonstrated no clinical benefit, and its use is not recommended for uncomplicated cases. 5

Corticosteroid Use: Reserved for Specific Complications

Corticosteroids should NOT be used routinely but are indicated only for severe complications: 1, 2

  • Severe upper airway obstruction 6
  • Neurologic complications (encephalomyelitis, increased intracranial pressure) 5, 6
  • Immune-mediated hematologic complications (severe anemia, thrombocytopenia) 6
  • Cardiac complications 2

The evidence for corticosteroid efficacy comes primarily from anecdotal reports, and they should be used judiciously given limited supporting data. 5, 6

Management in Immunocompromised Patients: A Different Approach

In immunocompromised patients with primary EBV infection, immunomodulator therapy should be reduced or discontinued if possible. 1, 2

For severe primary EBV infection in immunocompromised patients, consider antiviral therapy with ganciclovir or foscarnet despite limited supporting evidence: 1, 2

  • This population has increased risk of lymphoproliferative disorders and hemophagocytic syndrome 1
  • Primary EBV infection poses particular threat in patients on thiopurines, with reports of fatal infectious mononucleosis-associated lymphoproliferative disorders 1
  • Specialist consultation should be sought for suspected lymphoproliferative disease 1
  • Discontinuation of immunosuppressive therapy may result in spontaneous regression of EBV-associated lymphoproliferative disease 2

Critical Pitfalls to Avoid

Splenic rupture prevention is paramount:

  • Enforce strict activity restrictions for minimum 8 weeks 3
  • Athletes may take 3-6 months to regain top form despite clinical recovery 7
  • Contact sports must be avoided until spleen returns to normal size 3, 7

Diagnostic considerations:

  • False-negative heterophile tests are common early in infection (first 6-10 days) and in children under 10 years 1, 2
  • If clinical suspicion remains high with negative heterophile test, proceed to EBV-specific serologic testing (VCA IgM, VCA IgG, EBNA) 1, 2

Immunocompromised patients may present with minimal symptoms, particularly those on corticosteroids, requiring higher index of suspicion. 2

References

Guideline

Diagnostic Approach to Infectious Mononucleosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Management of Infectious Mononucleosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Infectious Mononucleosis: An Updated Review.

Current pediatric reviews, 2024

Research

Diagnosis and treatment of infectious mononucleosis.

American family physician, 1994

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.