What is the treatment approach for a patient diagnosed with infectious mononucleosis (mono)?

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Treatment of Infectious Mononucleosis

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

Primary Treatment Approach

Symptomatic Management

  • Provide adequate hydration, analgesics for pain, and antipyretics for fever control 1, 2
  • Activity should be guided by the patient's energy level rather than enforced bed rest 2
  • Fatigue, myalgias, and need for sleep may persist for several months after acute infection resolves 2

Medications NOT Recommended for Routine Use

  • Acyclovir does not ameliorate the course of infectious mononucleosis in otherwise healthy individuals and should not be used 1, 2
  • Antihistamines are not recommended for routine treatment 2
  • Corticosteroids are not recommended for routine treatment but should be reserved for specific severe complications 1, 2

Corticosteroid Use: When to Consider

Corticosteroids may be indicated only for severe complications including:

  • Respiratory compromise or impending airway obstruction 1, 2
  • Severe pharyngeal edema 2
  • Severe neurologic complications 1
  • Severe hematologic complications 1
  • Severe cardiac complications 1

Activity Restrictions

Patients must be withdrawn from contact or collision sports for at least 4 weeks after symptom onset 2

  • More conservative recommendations suggest avoiding contact sports or strenuous exercise for 8 weeks or while splenomegaly persists 3
  • This restriction is critical to prevent splenic rupture, which occurs in 0.1-0.5% of cases and is potentially life-threatening 3, 4

Special Population: Immunocompromised Patients

For immunocompromised patients with primary EBV infection, management differs significantly:

  • Reduce or discontinue immunomodulator therapy if possible 1
  • Antiviral therapy with ganciclovir or foscarnet may be considered in severe cases, though evidence is limited 1
  • These patients have increased risk of lymphoproliferative disorders and require careful monitoring 1
  • Discontinuation of immunosuppressive therapy may result in spontaneous regression of EBV-associated lymphoproliferative disease 1

Common Pitfalls to Avoid

  • Do not prescribe antibiotics empirically without ruling out streptococcal pharyngitis, as ampicillin/amoxicillin can cause a characteristic rash in 90% of patients with infectious mononucleosis 2
  • Do not use acyclovir thinking it will shorten disease course—it provides no benefit 1, 2
  • Do not allow return to contact sports before 4 weeks minimum, regardless of how well the patient feels 2
  • Do not use corticosteroids routinely for symptom relief—reserve only for life-threatening complications 1, 2

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

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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