Treatment of Infectious Mononucleosis
Infectious mononucleosis is primarily managed with supportive care alone, as antiviral therapy with acyclovir does not provide clinical benefit and is not recommended. 1
Primary Treatment Approach
Supportive Care (Mainstay of Treatment)
- Rest and activity modification based on the patient's energy level should guide activity; enforced bed rest is not necessary 2
- Adequate hydration is essential 2
- Analgesics and antipyretics for symptom relief (fever, sore throat, myalgias) 2
- Symptom duration: Fatigue and myalgias may persist for several months after acute infection resolves, but most symptoms resolve within 2-3 weeks 3, 2
Activity Restrictions
- Avoid contact or collision sports for at least 4 weeks after symptom onset due to risk of splenic rupture 2
- Continue sports restriction for 8 weeks or while splenomegaly persists, whichever is longer 3
- Splenic rupture occurs in 0.1-0.5% of cases and is the most feared complication 3
Antiviral Therapy: Not Recommended
- Acyclovir inhibits EBV replication in vitro but provides no clinical benefit in infectious mononucleosis based on meta-analysis of 5 clinical trials 1
- A Cochrane review of antivirals (acyclovir, valomaciclovir, valacyclovir) found very low quality evidence with no clinically meaningful benefit 4
- While viral shedding may be suppressed during treatment, this effect is not sustained after treatment stops and does not translate to clinical improvement 4
- Acyclovir is not recommended for routine treatment of infectious mononucleosis 1
Corticosteroid Therapy: Limited Indications Only
When Corticosteroids May Be Indicated
- Airway obstruction or impending airway compromise 1
- Severe pharyngeal edema 2
- Increased intracranial pressure in cases with neurologic complications 1
- Respiratory compromise 2
Evidence Against Routine Corticosteroid Use
- A Cochrane review found insufficient evidence for routine steroid use in infectious mononucleosis 5
- Only 2 of 10 health improvement assessments showed benefit, with reduced sore throat at 12 hours that was not maintained 5
- Corticosteroids are not recommended for routine treatment of uncomplicated infectious mononucleosis 2
- Potential adverse events include respiratory distress and acute onset of diabetes, though causality is uncertain 5
When Corticosteroids Are Used
- Consider only in severe cases with specific complications (airway obstruction, severe pharyngeal edema) 1, 2
- Some case reports suggest benefit in multi-organ involvement, but this remains controversial 6
Special Populations: Immunocompromised Patients
Patients on Immunosuppressive Therapy
- Careful clinical assessment is warranted with full blood count, blood film, liver function tests, and EBV serology 1
- Consider reducing or discontinuing immunomodulator therapy if possible 1
- In severe primary EBV infection in immunocompromised 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 1
- Seek specialist advice for investigation and management of suspected lymphoproliferative disease or lymphoma 1
Monitoring and Follow-Up
- Monitor for complications: hepatosplenomegaly, hematological abnormalities, neurological symptoms, and signs of splenic rupture 3
- Reassess clinical status if symptoms worsen or fail to improve within expected timeframe 3
- Fatigue may persist for 3 months in most patients; infectious mononucleosis is a risk factor for chronic fatigue syndrome 3
Common Pitfalls to Avoid
- Do not prescribe antibiotics unless bacterial superinfection is documented; ampicillin/amoxicillin causes rash in 90% of IM patients 3
- Do not use acyclovir routinely—it provides no clinical benefit despite in vitro activity 1, 4
- Do not use corticosteroids routinely—reserve only for life-threatening complications 5, 2
- Do not allow premature return to contact sports—maintain 4-8 week restriction to prevent splenic rupture 3, 2