What is the recommended treatment for infectious mononucleosis (mono)?

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Last updated: November 13, 2025View editorial policy

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Treatment of Infectious Mononucleosis

Treatment for infectious mononucleosis is entirely supportive, as aciclovir does not ameliorate the course of the disease in otherwise healthy individuals. 1

Supportive Care Measures

The mainstay of management consists of:

  • Adequate hydration, analgesics, and antipyretics for symptom relief 2
  • Activity modification guided by the patient's energy level rather than enforced bed rest 2
  • Rest as tolerated with gradual return to normal activities 3
  • Avoidance of contact or collision sports for at least 4 weeks (some sources recommend 8 weeks) after symptom onset or while splenomegaly persists 3, 2

Role of Corticosteroids

Corticosteroids should be reserved exclusively for airway obstruction or severe pharyngeal edema causing respiratory compromise. 1

The evidence does not support routine corticosteroid use:

  • Insufficient evidence exists for steroid efficacy in symptom control for uncomplicated infectious mononucleosis 4
  • Across multiple trials, no sustained benefit was found in 8 of 10 assessments of health improvement with steroid therapy 4
  • While two trials showed reduced sore throat at 12 hours with steroids, this benefit was not maintained beyond the initial period 4
  • Serious complications have been documented with prolonged steroid use, including polymicrobial bacteremia, septic shock, pulmonary septic emboli, and orbital cellulitis 5
  • Adverse events reported include respiratory distress and acute onset of diabetes, though causality is uncertain 4

Antiviral Therapy

Aciclovir is not recommended as it does not improve clinical outcomes in immunocompetent patients with infectious mononucleosis 1

Management in Special Populations

For immunocompromised patients:

  • Reduce or discontinue immunomodulator therapy if possible when primary EBV infection is suspected 1
  • Obtain complete blood count, blood film, and liver function tests in patients on immunosuppressive therapy 1
  • Specialist consultation is required due to increased risk of EBV-associated lymphoproliferative disease 1

Expected Clinical Course

  • Most patients have an uneventful recovery with spontaneous resolution 3
  • Fatigue may persist for several months after acute infection resolves, but typically improves within three months 3, 2
  • Spontaneous splenic rupture occurs in 0.1 to 0.5% of cases and represents the most feared complication 3, 6

Prevention Measures

  • Avoid sharing personal items contaminated with saliva and practice hand hygiene during outbreaks in close community settings 1

References

Guideline

Diagnosis and Treatment 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

Steroids for symptom control in infectious mononucleosis.

The Cochrane database of systematic reviews, 2015

Research

Diagnosis and treatment of infectious mononucleosis.

American family physician, 1994

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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