What is the management and treatment of infectious mononucleosis?

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Management and Treatment of Infectious Mononucleosis

Primary Treatment Approach

Supportive care is the mainstay of treatment for infectious mononucleosis, with no role for antiviral therapy in otherwise healthy individuals. 1, 2

Core Management Strategy

Symptomatic Treatment

  • Antipyretics for fever control (acetaminophen or NSAIDs) 2
  • Rest as tolerated with activity reduction during acute illness 3
  • Adequate hydration and nutrition 3
  • Throat lozenges or analgesics for pharyngitis 3

Activity Restrictions

  • Avoid contact sports and strenuous exercise for 8 weeks or until splenomegaly resolves 3
  • This restriction is critical given the 0.1-0.5% risk of spontaneous splenic rupture, which is the most feared and potentially life-threatening complication 3, 4
  • Athletes may return to contact sports only when the spleen returns to normal size, though elite athletes may require 3-6 months to regain peak performance 5

Medications: What NOT to Use

Antiviral Agents

  • Aciclovir does NOT ameliorate the course of infectious mononucleosis in otherwise healthy individuals 1, 2
  • Antiviral therapy has no proven benefit in uncomplicated cases 6

Corticosteroids

  • NOT recommended for routine treatment 2, 6
  • Reserve corticosteroids only for specific severe complications: 1, 2, 6
    • Severe upper airway obstruction with impending respiratory compromise
    • Severe neurologic complications (e.g., encephalitis, Guillain-Barré syndrome)
    • Immune-mediated severe anemia or thrombocytopenia
    • Severe cardiac complications (e.g., myocarditis)
  • Use corticosteroids judiciously as they should not be given for uncomplicated disease 6

Special Population: Immunocompromised Patients

Critical Management Differences

Immunocompromised patients require aggressive intervention with reduction or discontinuation of immunosuppressive therapy when primary EBV infection occurs. 7, 1, 2

Specific Interventions

  • Reduce or discontinue immunomodulator therapy (e.g., thiopurines, anti-TNF agents) if clinically feasible 7, 1, 2
  • Consider antiviral therapy with ganciclovir or foscarnet in severe primary EBV infection in immunocompromised patients, despite limited supporting evidence 7, 1, 2
  • These agents are more potent than aciclovir for replicative EBV infection but carry greater toxicity 7
  • Seek specialist consultation for suspected lymphoproliferative disease 7

Risk Context

  • Patients on thiopurines have a 5.28-fold increased hazard ratio for lymphoproliferative disorders 7
  • Primary EBV infection during immunosuppression poses particular threat, with reported fatal cases of infectious mononucleosis-associated lymphoproliferative disorders in young patients on azathioprine 7
  • Discontinuation of immunosuppressive therapy may result in spontaneous regression of EBV-associated lymphoproliferative disease 7, 2

Monitoring and Follow-Up

Clinical Monitoring

  • Monitor for complications including splenic rupture, airway obstruction, neurologic manifestations, and hematologic abnormalities 3, 4
  • Fatigue typically resolves within 3 months but can be profound 3
  • Infectious mononucleosis is a risk factor for chronic fatigue syndrome 3

Laboratory Monitoring

  • Routine laboratory monitoring is not necessary in uncomplicated cases 3
  • In immunocompromised patients with primary EBV infection, obtain full blood count, blood film, liver function tests, and EBV serology 7

Common Pitfalls to Avoid

  • Do not prescribe ampicillin or amoxicillin as these cause a characteristic maculopapular rash in 90% of patients with infectious mononucleosis 3
  • Do not allow premature return to contact sports before splenomegaly resolves, as splenic rupture can be fatal if not diagnosed early 3, 4
  • Do not use corticosteroids for uncomplicated disease despite patient or family pressure for faster recovery 6
  • Do not assume negative heterophile test excludes diagnosis early in illness (first 6-10 days) or in children under 10 years 1, 2

Expected Clinical Course

  • Most patients have an uneventful recovery with spontaneous resolution over weeks to months 3, 6
  • The illness is generally benign and self-limited 3
  • Prompt diagnosis prevents unnecessary investigations and treatments while minimizing complications 3

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.

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