Management of Infectious Mononucleosis
Infectious mononucleosis is a self-limited disease requiring supportive care only; antivirals like acyclovir provide no benefit in otherwise healthy individuals and should not be used. 1, 2
General Management Approach
Supportive Care (Mainstay of Treatment)
- Provide symptomatic treatment including adequate hydration, antipyretics for fever, and analgesics for pain. 2, 3
- Allow activity as tolerated based on the patient's energy level rather than enforcing strict bed rest. 3
- Advise patients that fatigue may persist for up to three months but typically resolves spontaneously. 4
Activity Restrictions
- Patients must avoid contact sports and strenuous exercise for at least 4-8 weeks from symptom onset or while splenomegaly persists. 2, 4, 3
- This restriction is critical to prevent splenic rupture, which occurs in 0.1-0.5% of cases and is potentially life-threatening. 4
Medications NOT Recommended
Antivirals
- Acyclovir does not ameliorate the course of infectious mononucleosis in immunocompetent patients despite inhibiting EBV replication in vitro. 1, 2
- A meta-analysis of 5 clinical trials demonstrated no benefit from acyclovir therapy. 1
- Other antivirals (ganciclovir, foscarnet, valacyclovir) similarly have no proven role in established disease in otherwise healthy individuals. 5, 2
Corticosteroids
- Corticosteroids are NOT recommended for routine treatment of uncomplicated infectious mononucleosis. 2, 3
- Reserve corticosteroids only for life-threatening complications including:
Antihistamines
- Antihistamines are not recommended for routine treatment. 3
Special Population: Immunocompromised Patients
Risk Assessment
- Immunocompromised patients face increased risk of severe disease, lymphoproliferative disorders, and hemophagocytic syndrome. 5, 2
- Primary EBV infection poses particular threat in patients on thiopurines, with reports of fatal infectious mononucleosis-associated lymphoproliferative disorders. 5
Management Modifications
- Reduce or discontinue immunomodulator therapy if possible when primary EBV infection occurs. 5, 2
- Discontinuation of immunosuppressive therapy may result in spontaneous regression of EBV-associated lymphoproliferative disease. 2
- In severe primary EBV infection in immunocompromised patients, consider antiviral therapy with ganciclovir or foscarnet despite limited supporting evidence. 5, 2
- Seek specialist consultation for suspected lymphoproliferative disease. 5
Diagnostic Confirmation When Needed
Initial Testing
- Heterophile antibody test (Monospot) is the most widely used initial test, becoming positive between days 6-10 after symptom onset. 5, 2
- Sensitivity is 87% and specificity is 91%, but false-negatives are common in children under 10 years and early in infection. 5, 2
Confirmatory Testing
- When clinical suspicion remains high despite negative heterophile test, obtain EBV serologic testing including VCA IgM, VCA IgG, and EBNA antibodies. 5, 2
- VCA IgM present without EBNA antibodies indicates recent primary infection. 5, 2
Infection Control Measures
Contagious Period
- Main contagious period extends approximately 7-10 days from symptom onset. 6
- Patients should avoid close contact with others during this period. 6
Transmission Prevention
- Emphasize hand hygiene with soap and water. 6
- Avoid sharing personal items that may contain saliva including towels, pillows, eating utensils, and drinking containers. 6
Common Pitfalls to Avoid
- Do not prescribe acyclovir or other antivirals for uncomplicated infectious mononucleosis in immunocompetent patients—they provide no benefit. 1, 2
- Do not use corticosteroids routinely; reserve only for specific life-threatening complications. 2, 3
- Do not allow return to contact sports before 4-8 weeks or while splenomegaly persists due to splenic rupture risk. 2, 4, 3
- Be aware that symptoms may be minimal in immunocompromised patients receiving corticosteroids. 2