What is the recommended treatment for mononucleosis?

Treatment of Infectious Mononucleosis

Infectious mononucleosis requires supportive care only—antiviral therapy with acyclovir provides no clinical benefit and is not recommended for routine use. 1, 2

Primary Management: Supportive Care

The cornerstone of treatment is symptomatic management without pharmacologic intervention:

• Adequate hydration, analgesics, and antipyretics form the basis of care 3
• Activity should be guided by the patient's energy level—enforced bed rest is not necessary 3
• Avoid contact or collision sports for at least 3-4 weeks from symptom onset due to splenic rupture risk (occurs in 0.1-0.5% of cases) 4, 5
• Fatigue may persist for several months after acute infection resolves, which is normal 3, 6

Why Antivirals Don't Work

Despite acyclovir's ability to inhibit EBV replication in vitro, clinical reality differs:

• Meta-analysis of 5 clinical trials showed no benefit of acyclovir in treating infectious mononucleosis in otherwise healthy individuals 7, 1, 2
• Acyclovir is explicitly not recommended for routine treatment 7, 2
• This lack of efficacy likely reflects that symptomatic disease is driven by immune response rather than active viral replication 2

Corticosteroids: Only for Life-Threatening Complications

Corticosteroids have an extremely limited role:

• Use only for severe airway obstruction or impending airway compromise from pharyngeal edema 7, 1, 2, 3
• Consider for increased intracranial pressure in patients with neurologic complications 7, 2
• Not recommended for routine symptom management 3, 5

Critical Pitfall: Avoid Ampicillin/Amoxicillin

• Do not prescribe empirical antibiotics without confirming bacterial superinfection 1
• Ampicillin or amoxicillin causes a characteristic rash in 90-100% of patients with infectious mononucleosis, which can confuse the clinical picture 1

Special Population: Immunocompromised Patients

Management differs substantially in immunosuppressed individuals:

• Reduce or discontinue immunomodulator therapy if possible when primary EBV infection occurs 7, 1, 2
• Obtain full blood count, blood film, liver function tests, and EBV serology for comprehensive assessment 7, 2
• Consider ganciclovir or foscarnet in severe primary EBV infection in immunosuppressed patients, despite lack of strong supporting evidence 1, 2
• Seek specialist consultation for investigation and management, particularly if lymphoproliferative disease or lymphoma is suspected 1, 2

The increased lymphoma risk in immunosuppressed patients (particularly those on thiopurines) is small but real, with EBV-associated post-transplant lymphoproliferative disorder-like presentations being the primary concern 7.

Monitoring for Complications

Watch for these serious complications requiring intervention:

• Splenic rupture (0.1-0.5% incidence)—the most feared complication 4, 6
• Airway compromise from severe pharyngeal edema 1, 2
• Neurologic complications including encephalitis or increased intracranial pressure 7, 2
• Severe hepatitis with markedly elevated liver enzymes 5