What are the primary recommendations for managing a patient with mononucleosis (mono)?

Management of Infectious Mononucleosis

Supportive care is the cornerstone of treatment for infectious mononucleosis, with activity restriction being the most critical intervention to prevent splenic rupture. 1, 2

Diagnostic Confirmation

Before initiating management, confirm the diagnosis appropriately:

• Heterophile antibody test (Monospot) is the initial diagnostic test of choice, becoming positive between days 6-10 after symptom onset 1, 2
• If clinical suspicion remains high despite negative Monospot, order EBV-specific serology: VCA IgM, VCA IgG, and EBNA antibodies 1, 2
• VCA IgM present without EBNA antibodies confirms recent primary infection 1, 2
• Expect false-negative heterophile tests early in infection (first week) and in children under 10 years 2, 3
• Complete blood count typically shows >50% lymphocytes with >10% atypical forms 4, 5

Primary Treatment Approach

Supportive Care (All Patients)

• Antipyretics for fever control (acetaminophen or NSAIDs) 2, 3
• Adequate hydration 3
• Rest as tolerated - do not enforce strict bed rest; let the patient's energy level guide activity 3
• Analgesics for pharyngitis pain 2, 3

Activity Restriction (Critical for Safety)

Withdraw patients from contact or collision sports for at least 3-4 weeks from symptom onset 2, 3, 6, 5

• This restriction is non-negotiable due to splenic rupture risk, which occurs in 0.1-0.5% of cases and can be fatal 4, 7
• Splenic rupture typically occurs within the first month but risk persists after clinical recovery 7
• Extend restriction to 8 weeks if splenomegaly is still present on examination 4
• Use shared decision-making for return to activity timing, but prioritize safety 5

Medications NOT Recommended for Routine Use

Antivirals

• Aciclovir does NOT improve outcomes in otherwise healthy individuals 1, 2, 3
• Reserve antiviral therapy (ganciclovir or foscarnet) only for severe cases in immunocompromised patients 1, 2

Corticosteroids

• NOT recommended for routine treatment 1, 2, 3
• Reserve corticosteroids only for specific severe complications: respiratory compromise, severe pharyngeal edema, severe neurologic complications, severe hematologic complications, or cardiac complications 2, 3

Antihistamines

• Not recommended for routine treatment 3

Special Population: Immunocompromised Patients

These patients require heightened vigilance and modified management:

• Reduce or discontinue immunomodulator therapy if possible when primary EBV infection is diagnosed 1, 2
• Consider antiviral therapy with ganciclovir or foscarnet in severe cases, despite limited supporting evidence 2
• Monitor carefully for lymphoproliferative disorders, as risk is significantly increased 1, 2
• Symptoms may be minimal in patients receiving corticosteroids, making diagnosis challenging 2
• Discontinuation of immunosuppressive therapy may result in spontaneous regression of EBV-associated lymphoproliferative disease 2

Monitoring and Follow-Up

• Fatigue may persist for 3 months after acute infection resolves; counsel patients accordingly 4, 3
• Monitor for splenic rupture warning signs: acute left upper quadrant pain, left shoulder pain (Kehr sign), hemodynamic instability 4, 7
• Infectious mononucleosis is a risk factor for chronic fatigue syndrome 4

Critical Pitfalls to Avoid

• Do not clear patients for contact sports prematurely - splenic rupture can be fatal and has caused deaths in young patients at home 7
• Do not rely solely on negative heterophile test early in illness - false negatives are common in the first week 2, 3
• Do not prescribe routine corticosteroids - reserve only for life-threatening complications 2, 3
• Do not assume symptoms are minimal in immunocompromised patients on corticosteroids - maintain high clinical suspicion 2