What is the recommended management for infectious mononucleosis?

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Last updated: February 13, 2026View editorial policy

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Management of Infectious Mononucleosis

Infectious mononucleosis is a self-limited disease requiring primarily supportive care, with no role for antiviral therapy in immunocompetent patients. 1, 2

Supportive Treatment Approach

The cornerstone of management is symptomatic treatment with activity restriction to prevent splenic rupture. 1, 3

Activity Restrictions

  • Patients must avoid contact sports and strenuous exercise for 8 weeks from symptom onset or until splenomegaly resolves, whichever is longer. 1, 3
  • Bed rest as tolerated is recommended during the acute phase. 3
  • Splenic rupture occurs in 0.1-0.5% of cases and represents the most feared complication. 1, 3

Symptomatic Relief

  • Adequate analgesia for sore throat and fever management. 4
  • Hydration and rest during the acute illness phase. 3

Role of Antiviral Therapy

Antiviral agents (acyclovir, valacyclovir, valganciclovir) have no proven benefit in immunocompetent patients with infectious mononucleosis and are NOT recommended. 5, 1, 2

  • A Cochrane systematic review found that while antivirals may reduce time to clinical recovery by 5 days, this difference is of questionable clinical significance given the wide confidence intervals and very low quality of evidence. 2
  • Antivirals suppress viral shedding only while on treatment, with no sustained effect after discontinuation. 2
  • Meta-analysis of 5 clinical trials showed no benefit of acyclovir in treating infectious mononucleosis. 5

Exception: Immunocompromised Patients

In immunocompromised patients with severe primary EBV infection, consider antiviral therapy with ganciclovir or foscarnet despite limited supporting evidence. 5, 1

  • Reduce or discontinue immunomodulator therapy if possible. 5, 1
  • Seek specialist consultation for suspected lymphoproliferative disease. 1
  • Patients on thiopurines face particular risk of fatal infectious mononucleosis-associated lymphoproliferative disorders. 1

Corticosteroid Use

Corticosteroids should be reserved ONLY for specific life-threatening complications, not for routine management. 1, 6

Indications for Corticosteroids

  • Upper airway obstruction (primary indication). 1, 6, 4
  • Possibly immune-mediated severe anemia or thrombocytopenia. 6
  • Selected cases of neurologic complications with increased intracranial pressure. 5

Corticosteroids should NOT be used for uncomplicated infectious mononucleosis or to hasten routine symptom resolution. 1, 6

Monitoring and Follow-Up

Clinical Monitoring

  • Most patients recover within weeks to months without sequelae. 3, 6
  • Fatigue may persist in approximately 10% of patients at 6-month follow-up. 2
  • Monitor for complications including neurologic, hematologic, hepatic, and respiratory manifestations. 6

Important Caveats

  • Avoid prescribing ampicillin or amoxicillin, as these cause a characteristic maculopapular rash in 90% of patients with infectious mononucleosis. 3
  • Patients remain contagious for approximately 7-10 days from symptom onset. 7
  • Advise patients to avoid sharing personal items contaminated with saliva (utensils, drinking containers, towels). 7

Key Clinical Pitfall

The most critical management error is failing to counsel patients about activity restriction, which can lead to preventable splenic rupture. 1, 3 This complication, though rare, is potentially life-threatening and entirely avoidable with proper patient education about the 8-week restriction period.

References

Guideline

Diagnostic Approach to Infectious Mononucleosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Antiviral agents for infectious mononucleosis (glandular fever).

The Cochrane database of systematic reviews, 2016

Research

Infectious Mononucleosis: An Updated Review.

Current pediatric reviews, 2024

Research

Infectious mononucleosis in adolescents.

Pediatric annals, 1991

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Primary Transmission of Infectious Mononucleosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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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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