Testing Recommendations for Symptomless EBV Exposure
Routine testing for asymptomatic individuals with known EBV exposure is not recommended in the general population, but serological screening should be performed before initiating immunosuppressive therapy, particularly in younger patients and those starting purine analogues or biologics. 1
General Population Without Planned Immunosuppression
- No testing is indicated for asymptomatic individuals with EBV exposure who are not planning to start immunosuppressive medications 2, 3
- The vast majority of the population (95%) will be infected with EBV at some point in life, and most infections are asymptomatic or subclinical 4
- Testing in the absence of symptoms or planned immunosuppression provides no actionable clinical information 2
Pre-Immunosuppression Screening (Critical Context)
The British Society of Gastroenterology (2025) recommends EBV serological screening before starting purine analogues, biologics, and small molecule therapies, particularly given the risk of severe complications in seronegative patients 1
High-Risk Populations Requiring Screening:
- Patients under 30 years of age: Seroprevalence drops to 90.8% in this age group, with 29% of patients aged 18-25 years being seronegative 1
- Patients planned for purine analogue therapy: 92% of EBV-positive lymphomas in IBD patients occurred in those exposed to purine analogues 1
- Patients planned for combination immunosuppression: Combination therapy with purine analogues and biologics confers greater lymphoma risk (0.69 per 1000 person-years) than monotherapy 1
Rationale for Pre-Treatment Screening:
- Primary EBV infection in immunocompromised patients can lead to severe complications including viral colitis, chronic active EBV infection, haemophagocytic lymphohistiocytosis, and B- or T/NK-cell lymphomas 1
- EBV-positive lymphoma risk is significantly elevated with purine analogues (HR 5.28,95% CI 2.01-13.9) 1
Interpretation of Results in Asymptomatic Individuals
- Positive EBV IgG (>8.0) without IgM: Indicates past infection and immunity; no further action needed 2, 3
- Positive EBNA with negative IgM: Confirms remote past infection (months to years ago) with established immunity 3
- Negative serology in young patients: Identifies individuals at risk for primary infection during immunosuppression who require risk-benefit discussion 1
Important Caveats
- Poor concordance exists between blood and tissue EBV DNA counts, so serological testing remains the standard for screening asymptomatic individuals 1
- Risk-benefit discussions are essential for seronegative patients before starting immunosuppression, as there is uncertainty about optimal management strategies 1
- Chronic active EBV infection requires persistent symptoms, unusual antibody patterns (VCA-IgG ≥1:640, EA-IgG ≥1:160), and elevated viral load (>10^2.5 copies/mg DNA in peripheral blood mononuclear cells); it cannot be diagnosed in truly asymptomatic individuals 1