What to do if mononucleosis (mono) is not improving?

Management of Non-Improving Infectious Mononucleosis

For patients with infectious mononucleosis that is not improving, clinical reassessment is necessary to rule out complications, and hospitalization should be considered if there are signs of respiratory compromise, severe pharyngeal edema, or worsening symptoms after 5 days of supportive care.

Initial Reassessment

When mononucleosis symptoms are not improving, a thorough clinical reassessment is essential to:

• Confirm the diagnosis through laboratory testing if not already done

  • Complete blood count with differential (looking for >40% lymphocytes and >10% atypical lymphocytes) 1
  • Heterophile antibody test (Monospot) - note that false negatives can occur early in illness 2, 1
  • Consider EBV viral capsid antigen antibody testing if heterophile test is negative 1, 3
  • Liver function tests (elevated liver enzymes increase suspicion for mono) 1

• Evaluate for complications requiring intervention:

  • Upper airway obstruction/severe pharyngeal edema
  • Splenic rupture (occurs in 0.1-0.5% of cases) 4
  • Neurological complications
  • Hematologic complications
  • Hepatic involvement

Management Algorithm

Step 1: Assess Severity and Complications

• Respiratory status: Check for signs of upper airway obstruction, respiratory distress, or severe pharyngeal edema
• Abdominal examination: Assess for splenomegaly and tenderness
• Neurological assessment: Check for signs of meningitis, encephalitis, or other neurological involvement
• Hydration status: Evaluate for signs of dehydration due to poor oral intake

Step 2: Management Based on Findings

For Mild to Moderate Persistent Symptoms (No Complications)

• Continue supportive care:
  • Adequate hydration
  • Analgesics for pain control
  • Antipyretics for fever
  • Rest guided by energy levels (not enforced bed rest) 2
  • Avoid contact sports for at least 8 weeks or while splenomegaly is present 4

For Severe Pharyngeal Edema/Upper Airway Obstruction

• Consider corticosteroids (though not recommended for routine treatment) 2, 1
• If minimal improvement with corticosteroids, consider hospitalization 5
• In cases of life-threatening airway obstruction unresponsive to medical management, acute tonsillectomy may be considered 6

For Suspected Splenic Rupture

• Immediate hospitalization
• Surgical consultation
• Abdominal imaging

Step 3: Timeframe for Improvement Assessment

• Most patients should show clinical improvement within 2-3 days of appropriate supportive care 5
• If no improvement is observed after 5 days or if the patient's condition worsens, hospitalization should be considered 5
• Fatigue may persist for several months and is not necessarily a sign of complications 2, 4

Special Considerations

• Prolonged fatigue: May persist for months after acute infection and is not necessarily a sign of complications 2
• Immunocompromised patients: Higher risk for severe disease and complications; lower threshold for hospitalization 1
• Recurrent symptoms: Consider secondary bacterial infection (especially streptococcal pharyngitis) or other viral infections 2

Common Pitfalls to Avoid

• Unnecessary antibiotics: Avoid prescribing antibiotics unless there is clear evidence of a secondary bacterial infection
• Premature return to contact sports: This increases risk of splenic rupture; patients should avoid contact sports for at least 8 weeks or while splenomegaly is present 4
• Overlooking complications: Always reassess for potential complications when symptoms are not improving
• Enforced bed rest: Allow activity as tolerated based on the patient's energy level 2

Remember that while most cases of infectious mononucleosis resolve spontaneously with supportive care, persistent symptoms warrant careful reassessment to rule out complications that may require more aggressive intervention.