Treatment of Infectious Mononucleosis
Infectious mononucleosis in otherwise healthy adolescents and young adults requires only supportive care; antiviral agents and corticosteroids are not recommended for routine use. 1
Primary Management Approach
Supportive care is the cornerstone of treatment:
Rest and activity modification: Patients should reduce activity and rest as tolerated, avoiding contact sports or strenuous exercise for 8 weeks from symptom onset or while splenomegaly persists to prevent splenic rupture (which occurs in 0.1-0.5% of cases). 2
Symptomatic relief: Provide adequate analgesia for pharyngitis and fever using acetaminophen or NSAIDs. 3
Hydration and nutrition: Encourage adequate fluid intake and soft foods if dysphagia is present. 2
What NOT to Do
Avoid routine pharmacological interventions:
Antiviral agents (acyclovir, valacyclovir) have no proven benefit in treating infectious mononucleosis in immunocompetent patients and should not be prescribed. 1, 4
Corticosteroids should NOT be used routinely for uncomplicated infectious mononucleosis, as they lack evidence for symptom control and carry risks of serious complications including septic shock and secondary infections. 1, 5
Avoid empirical antibiotics without confirming bacterial superinfection, as ampicillin/amoxicillin causes a characteristic maculopapular rash in 90% of patients with infectious mononucleosis. 1
Corticosteroid Use: Reserved for Life-Threatening Complications Only
Corticosteroids may be beneficial ONLY in specific severe complications:
- Severe airway obstruction or pharyngeal edema requiring intervention 1, 4
- Severe hematologic complications (e.g., severe thrombocytopenia, hemolytic anemia) 3
- Neurologic complications (e.g., encephalitis, Guillain-Barré syndrome) 3
The evidence strongly suggests that the risks of prolonged steroid therapy (including septic shock, polymicrobial bacteremia, and septic emboli) outweigh any potential benefits in uncomplicated cases. 5
Special Populations: Immunocompromised Patients
Management differs significantly in immunosuppressed patients:
Reduce or discontinue immunomodulator therapy if possible when primary EBV infection occurs. 1
Consider antiviral therapy with ganciclovir or foscarnet in severe primary EBV infection in immunosuppressed patients, despite lack of robust supporting evidence. 1
Obtain specialist consultation immediately for investigation and management, as these patients face increased risk of lymphoproliferative disorders, hemophagocytic syndrome, and severe disease. 1
Monitor closely with full blood count, blood film, liver function tests, and EBV serology. 1
Activity Restrictions and Return-to-Play
Specific guidance on physical activity:
Restrict vigorous physical activity for 3-8 weeks from symptom onset to reduce splenic rupture risk. 6
Avoid contact sports for at least 8 weeks or until splenomegaly has completely resolved on physical examination. 2
Use shared decision-making to determine exact timing of return to athletic activity based on individual clinical course. 7
Common Pitfalls to Avoid
Do not prescribe steroids for symptom control in uncomplicated cases—this practice lacks evidence and carries significant risks. 5
Do not use antibiotics empirically for sore throat without confirming bacterial coinfection (such as Group A Streptococcus), as this may cause unnecessary rash and antibiotic exposure. 1
Do not allow early return to contact sports even if the patient feels better—splenic rupture can occur weeks after symptom onset. 2