What is the treatment for infectious mononucleosis (mono)?

Treatment for Infectious Mononucleosis (Mono)

The mainstay of treatment for infectious mononucleosis is supportive care, including adequate hydration, analgesics, antipyretics, and adequate rest, as routine use of antivirals and corticosteroids is not recommended. 1, 2, 3

Diagnosis Confirmation

Before initiating treatment, confirm the diagnosis with:

• Clinical presentation: Look for the classic triad of:

  • Fever
  • Tonsillar pharyngitis
  • Lymphadenopathy (particularly posterior cervical)
  • Fatigue (often profound)
  • Periorbital/palpebral edema (in ~33% of patients)

• Laboratory testing:

  • Complete blood count with differential (look for >40% lymphocytes and >10% atypical lymphocytes)
  • Heterophile antibody test (Monospot) - sensitivity 87%, specificity 91% 3
  • For negative Monospot cases: EBV-specific antibody testing (VCA IgM, VCA IgG, EBNA IgG) 1

Treatment Algorithm

1. Supportive Care (First-line)

• Rest: Allow activity as tolerated based on energy levels; enforced bed rest is not necessary 2, 4
• Hydration: Ensure adequate fluid intake 2, 4
• Pain management:
  • Acetaminophen for fever and mild pain
  • NSAIDs (e.g., ibuprofen, loxoprofen) for pain, fever, and inflammation
    • May be particularly effective in patients with atopic predispositions 5

2. Activity Restrictions

• Avoid contact sports or strenuous exercise for at least 8 weeks or while splenomegaly is present 2
• This is critical to prevent splenic rupture, which occurs in 0.1-0.5% of patients 2

3. Special Considerations

• For severe cases with complications:

  • Airway obstruction/severe pharyngeal edema: Consider corticosteroids 1, 4
  • Respiratory compromise: Consider corticosteroids 1, 4
  • Severe or persistent cases: Consider antiviral therapy (acyclovir, valacyclovir) 1, 6

• For immunocompromised patients:

  • Higher risk for complications and lymphoproliferative disorders 1
  • May require closer monitoring and earlier intervention
  • Consider specialist consultation

What Not To Do

• Do not routinely prescribe:
  • Corticosteroids (except for specific complications noted above)
  • Acyclovir or other antivirals (except in severe/persistent cases)
  • Antihistamines 4
  • Antibiotics (unless there is evidence of bacterial superinfection)

Expected Course and Follow-up

• Most patients recover completely without specific treatment
• Fatigue, myalgias, and increased need for sleep may persist for several months 4
• Approximately 5-6% of patients may develop post-infectious fatigue syndrome 1
• Monitor for potential complications:
  • Splenic rupture (most serious acute complication)
  • Hepatitis
  • Hematologic abnormalities
  • Neurological complications

Pitfalls and Caveats

1. False-negative heterophile antibody tests are common early in the course of infection and in children under 5 years 4, 3

2. Splenic rupture risk necessitates clear patient education about avoiding contact sports and trauma to the abdomen

3. Prolonged symptoms are common and do not necessarily indicate complications or need for additional treatment

4. Antibiotics should be avoided unless there is clear evidence of bacterial superinfection; ampicillin/amoxicillin can cause a maculopapular rash in EBV-infected patients

5. Immunocompromised patients require closer monitoring due to higher risk of complications and lymphoproliferative disorders 1