What are the treatment recommendations for a patient diagnosed with infectious mononucleosis (mono)?

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Management of Infectious Mononucleosis

Treatment for infectious mononucleosis is entirely supportive, with no role for antiviral therapy in otherwise healthy individuals. 1, 2

Supportive Care Measures

  • Provide symptomatic relief with antipyretics (acetaminophen or ibuprofen) for fever and throat pain 2, 3
  • Ensure adequate hydration throughout the illness course 3
  • Allow patient-guided activity levels rather than enforcing strict bed rest; patients allowed out of bed as soon as they felt able reported quicker recovery 4
  • Advise rest as tolerated based on the patient's energy level, as fatigue may persist for several months 3, 5

Activity Restrictions

Patients must avoid contact sports and strenuous exercise for at least 3-4 weeks from symptom onset to prevent splenic rupture, which occurs in 0.1-0.5% of cases and is potentially life-threatening 6, 3, 5. The risk of splenic rupture persists even after clinical recovery 7.

  • Restrict contact or collision sports for 4 weeks minimum after onset of symptoms 3
  • Extend restrictions to 8 weeks or until splenomegaly resolves if splenomegaly is documented 6
  • Use shared decision-making to determine exact timing of return to athletic activity 5

Medications to Avoid

  • Do not prescribe aciclovir routinely, as it does not ameliorate the course of infectious mononucleosis in healthy individuals 1, 2
  • Avoid routine corticosteroids for uncomplicated cases 2, 3
  • Do not prescribe antihistamines for routine treatment 3

When Corticosteroids Are Indicated

Reserve corticosteroids exclusively for life-threatening complications 1, 3:

  • Airway obstruction or impending airway compromise 1
  • Severe pharyngeal edema causing respiratory compromise 1
  • Severe neurologic complications 2
  • Severe hematologic complications 2
  • Severe cardiac complications 2

Special Instructions for Immunocompromised Patients

If the patient is on immunosuppressive therapy, reduce or discontinue immunomodulators if possible 1, 2. These patients require:

  • Specialist consultation due to increased risk of EBV-associated lymphoproliferative disease 1
  • Laboratory monitoring including complete blood count, blood film, and liver function tests 1
  • Consider antiviral agents (ganciclovir or foscarnet) in severe primary EBV infection in immunocompromised patients, though evidence is limited 2

Infection Control Measures

  • Advise avoiding sharing personal items contaminated with saliva (cups, utensils, toothbrushes) 1
  • Practice hand hygiene during outbreaks in close community settings 1
  • Explain that EBV is transmitted primarily through saliva and close personal contact 6, 5

Common Pitfalls to Avoid

  • Do not enforce strict bed rest, as this does not improve outcomes and patient-guided activity leads to faster recovery 4
  • Do not prescribe antibiotics unless there is documented bacterial superinfection; ampicillin/amoxicillin will cause a rash in 90% of mononucleosis patients 3
  • Do not allow premature return to sports, as splenic rupture can occur even after clinical recovery and has resulted in fatal hemorrhage 7
  • Do not dismiss persistent fatigue as it may last several months and is a risk factor for chronic fatigue syndrome 6, 3

Expected Clinical Course

  • Most patients have uneventful recovery with resolution of acute symptoms within 2-4 weeks 6
  • Fatigue, myalgias, and need for sleep may persist for several months after acute infection resolves 3
  • Monitor for complications including splenic rupture (most feared), airway obstruction, and rarely neurologic or hematologic complications 6, 5

References

Guideline

Diagnosis and Treatment of 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

Epstein-Barr virus infectious mononucleosis.

American family physician, 2004

Research

Recovery from infectious mononucleosis: a case for more than symptomatic therapy? A systematic review.

The British journal of general practice : the journal of the Royal College of General Practitioners, 2002

Research

Infectious Mononucleosis: Rapid Evidence Review.

American family physician, 2023

Research

Infectious Mononucleosis: An Updated Review.

Current pediatric reviews, 2024

Research

Surgical implications of infectious mononucleosis.

American journal of surgery, 1981

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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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