Can you get non-Epstein-Barr Virus (EBV) mononucleosis more than once?

Non-EBV Mononucleosis Can Occur Multiple Times

Yes, non-EBV mononucleosis can recur multiple times as it does not confer lifelong immunity like EBV infection typically does. 1

Causes of Non-EBV Mononucleosis

Non-EBV mononucleosis can be caused by several pathogens, including:

• Human Herpesvirus-6 (HHV-6)
• Cytomegalovirus (CMV)
• Other viral agents

Research has shown that double infections with EBV and other viruses like HHV-6 are common, occurring in approximately 39.5% of infectious mononucleosis cases 2. This suggests that what appears clinically as mononucleosis may often involve multiple pathogens.

Diagnostic Considerations

When evaluating recurrent mononucleosis-like symptoms, consider:

1. Serological testing: The standard panel should include:

   • Viral Capsid Antigen (VCA) IgM
   • VCA IgG
   • Epstein-Barr Nuclear Antigen (EBNA) IgG 1

2. PCR testing: For active viral replication, quantitative PCR can detect viral loads in peripheral blood 1

3. Testing for other pathogens: When EBV tests are negative but symptoms persist, test for CMV, HHV-6, and other potential causes 2

Clinical Presentation

Non-EBV mononucleosis presents similarly to EBV mononucleosis with:

• Fever
• Tonsillar pharyngitis
• Lymphadenopathy
• Fatigue
• Possible periorbital/palpebral edema
• Potential splenomegaly (in ~50% of cases) 3

Management Approach

For recurrent non-EBV mononucleosis:

1. Supportive care: This remains the mainstay of treatment

   • Adequate rest
   • Hydration
   • Avoidance of contact sports for at least 8 weeks or while splenomegaly is present 1, 3

2. Activity restriction: Reduce activity and recommend bed rest as tolerated 3

3. Monitoring for complications: Be vigilant for:

   • Splenic rupture (0.1-0.5% of cases)
   • Chronic fatigue syndrome (occurs in 5-6% of patients) 1, 3

Important Considerations

• Immune function assessment: Patients with recurrent mononucleosis-like symptoms may have defects in virus-specific immunity even with normal general immune parameters 4

• Immunocompromised patients: These individuals are at higher risk for reactivation and complications, particularly those on immunosuppressive therapy like anti-TNF agents 1

• Persistent symptoms: Some patients may experience symptoms for months or years after initial infection, possibly related to specific immune defects against the causative virus 4

Prevention Strategies

Since non-EBV mononucleosis can recur, prevention measures include:

• Frequent handwashing
• Avoiding sharing utensils, glasses, or food
• Avoiding close contact with infected individuals during acute illness
• Covering coughs and sneezes 1

Remember that while EBV mononucleosis typically confers lifelong immunity, non-EBV causes of mononucleosis do not necessarily provide the same protection, making recurrence possible.