Treatment of Infectious Mononucleosis
Treatment of infectious mononucleosis is primarily supportive, with antivirals and corticosteroids not recommended for routine use in immunocompetent patients. 1
Supportive Care (Mainstay of Treatment)
Symptomatic management includes:
- Adequate hydration, antipyretics for fever, and analgesics for pain control 2, 3
- Rest as tolerated based on the patient's energy level—enforced bed rest is not recommended and may actually delay recovery 3, 4
- Activity should be guided by the patient's symptoms, with evidence suggesting that allowing patients out of bed as soon as they feel able leads to quicker recovery 4
Medications NOT Recommended
Antivirals have no proven benefit:
- Acyclovir and other antiviral agents provide no benefit in treating infectious mononucleosis in otherwise healthy individuals and should not be used routinely 1
- This recommendation is consistent across multiple guidelines despite the viral etiology 2, 5
Corticosteroids are reserved only for specific severe complications:
- May be beneficial only for severe airway obstruction or pharyngeal edema requiring intervention 1
- Should be used for severe neurologic, hematologic, or cardiac complications 2
- Not recommended for routine symptom management 3, 5
Avoid empirical antibiotics:
- Do not prescribe antibiotics without confirming bacterial superinfection, as ampicillin/amoxicillin can cause a characteristic rash in patients with infectious mononucleosis 1
Activity Restrictions
Contact sports and strenuous exercise must be avoided:
- Patients should avoid contact or collision sports for at least 3-4 weeks from symptom onset 5
- Some guidelines recommend extending this to 8 weeks or until splenomegaly resolves 6
- This precaution is critical to prevent splenic rupture, which occurs in 0.1-0.5% of cases and is potentially life-threatening 6
Special Populations: Immunocompromised Patients
Management differs significantly in immunosuppressed individuals:
Immunomodulator adjustment:
- Immunosuppressive therapy should be reduced or discontinued if possible when primary EBV infection occurs 1, 7
- This is particularly important for patients on thiopurine therapy, where fatal infectious mononucleosis-associated lymphoproliferative disorders have been reported 7
Consider antiviral therapy in severe cases:
- Antiviral therapy with ganciclovir or foscarnet may be considered in severe primary EBV infection in immunosuppressed patients, despite lack of strong supporting evidence 1, 2
- Specialist consultation is essential for investigation and management of immunocompromised patients with primary EBV infection 1
Specific scenarios requiring immunosuppression discontinuation:
- Discontinue immunosuppressive therapy in cases of symptomatic infectious mononucleosis, EBV-related mucocutaneous ulceration, and severe complications 8
Clinical Pitfalls to Avoid
Common errors in management:
- Do not prescribe antihistamines—they have no proven benefit 3
- Do not enforce strict bed rest, as this may prolong recovery time 4
- Do not use antivirals in immunocompetent patients expecting clinical benefit 1, 5
- Do not overlook the need for prolonged activity restriction to prevent splenic rupture 6
Expected Course and Follow-up
Recovery timeline:
- Most patients have an uneventful recovery with symptoms resolving within a few weeks 6, 9
- Fatigue, myalgias, and need for sleep may persist for several months after acute infection resolves 3
- Approximately 10-20% of patients may develop a distinct fatigue syndrome following infectious mononucleosis 4
- Poor physical functioning and lengthy convalescence predict chronic ill health 4