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 29, 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

Infectious mononucleosis is a self-limited disease requiring supportive care only, with no role for antiviral therapy in immunocompetent patients. 1

Primary Treatment Approach

Supportive Care (Mainstay of Treatment)

  • Provide antipyretics for fever control and analgesics for pain relief 1
  • Ensure adequate hydration throughout the illness 2
  • Allow activity as tolerated based on the patient's energy level rather than enforcing strict bed rest 2
  • Advise patients that fatigue may persist for several months after acute symptoms resolve 2

Activity Restrictions

  • Patients must avoid contact sports and strenuous exercise for 8 weeks from symptom onset or until splenomegaly resolves, whichever is longer 3
  • This restriction is critical to prevent splenic rupture, which occurs in 0.1-0.5% of cases and represents the most feared complication 3, 4
  • Athletes typically recover faster than non-athletes, though elite athletes may require 3-6 months to regain peak performance 5

Medications NOT Recommended for Routine Use

Antiviral Agents

  • Acyclovir does not ameliorate the course of infectious mononucleosis in immunocompetent individuals and should not be used 6, 1
  • Despite inhibiting EBV replication in vitro, a meta-analysis of 5 clinical trials showed no clinical benefit 7
  • Antiviral agents (ganciclovir, foscarnet) have no proven role in established disease in immunocompetent patients 6

Corticosteroids

  • Corticosteroids are NOT recommended for routine treatment 1, 2
  • Reserve corticosteroids only for specific severe complications including: 6, 1
    • Severe neurologic complications (encephalomyelitis, increased intracranial pressure)
    • Severe hematologic complications
    • Severe cardiac complications
    • Respiratory compromise or severe pharyngeal edema threatening airway patency 2
  • Anecdotal reports suggest benefit in neurologic complications of EBV infection, but this requires confirmation 7

Management in Immunocompromised Patients

Critical Differences in Approach

  • Reduce or discontinue immunomodulator therapy if possible when primary EBV infection is diagnosed 6, 1
  • This is particularly important for patients on thiopurines, where fatal infectious mononucleosis-associated lymphoproliferative disorders have been reported 6
  • Discontinuation of immunosuppressive therapy may result in spontaneous regression of EBV-associated lymphoproliferative disease 1

Antiviral Therapy Consideration

  • In severe primary EBV infection in immunocompromised patients, consider antiviral therapy with ganciclovir or foscarnet despite limited supporting evidence 6, 1
  • This represents an exception to the general rule against antivirals, reserved only for severe cases in immunosuppressed individuals
  • Seek specialist consultation for suspected lymphoproliferative disease 6

Important Clinical Pitfalls

Diagnostic Considerations

  • Symptoms in immunocompromised patients may be minimal, particularly in those receiving corticosteroids 1
  • Immunocompromised patients have increased risk of severe disease, lymphoproliferative disorders, and hemophagocytic syndrome 6
  • Monitor these high-risk patients more aggressively 6

Splenic Rupture Recognition

  • Splenic rupture is rare but potentially life-threatening, occurring in 0.1-0.5% of cases 3, 4
  • Almost never fatal if diagnosed early 5
  • Maintain high clinical suspicion in patients with abdominal pain during the acute illness or recovery period

Recovery Expectations

  • Most patients have an uneventful recovery with complete resolution 3
  • Fatigue may be profound but typically resolves within 3 months 3
  • Infectious mononucleosis is a risk factor for chronic fatigue syndrome 3

References

Guideline

Management of Infectious Mononucleosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Epstein-Barr virus infectious mononucleosis.

American family physician, 2004

Research

Infectious Mononucleosis: An Updated Review.

Current pediatric reviews, 2024

Research

Diagnosis and treatment of infectious mononucleosis.

American family physician, 1994

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

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.