What is the recommended treatment for mononucleosis?

Treatment of Infectious Mononucleosis

The treatment of infectious mononucleosis is primarily supportive, focusing on adequate rest, hydration, analgesics, and antipyretics, with activity guided by the patient's energy level rather than enforced bed rest. 1, 2

Core Management Principles

Supportive Care (First-Line Treatment)

• Symptomatic management is the mainstay of therapy, including adequate hydration, analgesics for pain relief, and antipyretics for fever control 2, 3
• Activity modification should be patient-directed based on energy levels rather than mandatory bed rest, as enforced bed rest is not recommended 2
• Fatigue management is essential, as profound fatigue typically resolves within three months, though myalgias and need for sleep may persist for several months after acute infection 1, 2

What NOT to Use

• Acyclovir and other antiviral agents have no proven benefit in treating infectious mononucleosis in otherwise healthy individuals and are not recommended for routine use 4, 5, 2
• Antihistamines are not recommended for routine treatment 2
• Corticosteroids should not be used routinely and should be avoided unless benefits clearly outweigh potential risks 5, 2

Specific Indications for Corticosteroid Therapy

Corticosteroids may be beneficial only in specific severe complications:

• Severe airway obstruction or pharyngeal edema requiring intervention 4, 5, 2
• Respiratory compromise threatening airway patency 2

The evidence consistently shows that steroid therapy is indicated specifically for airway obstruction, but has no role in routine management 4. This represents a narrow therapeutic window where corticosteroids provide benefit.

Activity Restrictions and Splenic Precautions

Patients must avoid contact sports and strenuous exercise for at least 4-8 weeks:

• Minimum 4 weeks from symptom onset is the standard recommendation 2
• Extended to 8 weeks or until splenomegaly resolves (whichever is longer) for maximum safety 1
• This precaution addresses the risk of spontaneous splenic rupture, which occurs in 0.1-0.5% of cases and is potentially life-threatening 1

Special Populations Requiring Modified Management

Immunocompromised Patients

• Immunomodulator therapy should be reduced or discontinued if possible when primary EBV infection occurs 4
• In severe primary EBV infection in immunosuppressed patients, antiviral therapy with ganciclovir or foscarnet may be considered despite lack of supporting evidence, as these agents are more potent than acyclovir for replicative EBV infection (though more toxic) 4
• Specialist consultation is essential for investigation and management 4

Patients on Thiopurine Therapy

• Careful clinical assessment is warranted with full blood count, blood film, liver function tests, and EBV serology 4
• Primary EBV infection poses particular threat in this population, with reports of fatal infectious mononucleosis-associated lymphoproliferative disorders 4

Clinical Monitoring

Key parameters to monitor:

• Symptom resolution timeline: Most symptoms resolve in 2-3 weeks 3
• Splenomegaly persistence: Present in approximately 50% of cases and dictates return to physical activity 1
• Hepatomegaly: Occurs in approximately 10% of cases 1
• Protracted courses: Some patients experience prolonged clinically active infection requiring extended supportive care 6

Important Clinical Pitfalls

• Do not prescribe antibiotics empirically without confirming bacterial superinfection, as this may cause rash (particularly with ampicillin/amoxicillin)
• Do not clear patients for contact sports prematurely, as splenic rupture is the most feared complication 1
• Do not use corticosteroids for routine symptom management, as potential risks outweigh benefits in uncomplicated cases 5
• Recognize that heterophile antibody tests have false-negative results early in infection, requiring EBV-specific serologic testing when clinical suspicion remains high 2