What is the management of Epstein-Barr Virus (EBV) infection?

Management of Epstein-Barr Virus (EBV) Infection

The management of EBV infection should focus on supportive care for uncomplicated cases, while implementing specific therapeutic strategies for severe manifestations like post-transplant lymphoproliferative disorders (PTLD), with rituximab being the first-line treatment for EBV-PTLD. 1

General Management of EBV Infection (Infectious Mononucleosis)

• Supportive care is the mainstay of treatment for uncomplicated EBV infection, including adequate rest, hydration, and antipyretics 2
• Activity reduction and bed rest as tolerated are recommended during the acute phase 2
• Patients should avoid contact sports or strenuous exercise for at least 8 weeks or while splenomegaly is present to prevent splenic rupture 2
• Monitor for hepatitis with liver function tests in symptomatic cases, as it is a common self-limiting complication 3
• Antiviral drugs (acyclovir, ganciclovir, foscarnet, cidofovir) are not effective against latent EBV and are not recommended for treatment of uncomplicated EBV infection 1

Management of EBV in High-Risk Populations (Post-Transplant)

Risk Assessment and Monitoring

• All allogeneic hematopoietic stem cell transplant (HSCT) patients and donors should be tested for EBV antibodies before transplantation 1
• For EBV-seronegative patients, an EBV-seronegative donor is preferred 1
• High-risk patients (those receiving T-cell depleted grafts, anti-thymocyte globulin, or with GvHD) should undergo prospective monitoring of EBV DNA-emia by quantitative PCR 1
• Begin screening no later than 4 weeks after HSCT and continue weekly for at least 4 months in high-risk patients 1
• Longer monitoring is recommended for patients with poor T-cell reconstitution (severe GvHD, haploidentical HSCT, T-cell depletion, ATG/alemtuzumab conditioning) 1

Prophylaxis Against EBV Disease

• B-cell depletion with prophylactic rituximab may reduce the risk of EBV DNA-emia in high-risk patients 1
• Prophylactic use of EBV-specific cytotoxic T lymphocytes (EBV-CTLs) should be considered as first-line prophylactic treatment when available 1
• Antiviral drugs, interferon, and intravenous immunoglobulin (IVIG) are not recommended for EBV prophylaxis 1

Preemptive Therapy for EBV DNA-emia

• Significant EBV DNA-emia without clinical symptoms is an indication for preemptive therapy with rituximab 1
• Rituximab (375 mg/m²) should be administered once weekly (typically 1-4 doses) until EBV DNA-emia negativity 1
• Combine rituximab with reduction of immunosuppression when possible 1
• Consider donor or third-party EBV-specific CTLs if available 1
• No specific threshold of EBV DNA-emia can be universally recommended for initiating preemptive therapy; local experience should guide center-specific cut-off values 1

Management of EBV-PTLD

First-Line Therapy

• Rituximab (375 mg/m²) administered once weekly is the treatment of choice for EBV-PTLD, with positive outcomes in approximately 70% of patients 1
• Reduction of immunosuppressive therapy should be combined with rituximab whenever possible 1
• Consider adoptive immunotherapy with donor or third-party EBV-specific CTLs if available 1
• Treatment should be initiated promptly due to the risk of rapidly growing high-grade lymphoid tumors and multi-organ impairment 1

Second-Line Therapy

• For rituximab failure, consider cellular therapy (EBV-specific CTLs or donor lymphocyte infusions) 1
• Chemotherapy ± rituximab is a potential option after failure of other methods 1
• Surgery, IVIG, interferon, and antiviral agents are not recommended for PTLD therapy 1

CNS EBV Disease

• Therapeutic options for CNS EBV-PTLD include rituximab ± chemotherapy, systemic or intrathecal rituximab monotherapy, anti-EBV T-cell therapy, or radiotherapy 1
• Chemotherapy protocols should be based on high-dose methotrexate and/or cytarabine or hydroxyurea, similar to primary CNS lymphoma protocols 1

Management of Chronic Active EBV Infection (CAEBV)

• CAEBV may initially respond to prednisolone and cyclosporine A with or without etoposide 4
• Allogeneic hematopoietic stem cell transplantation is the only curative treatment for CAEBV 4
• Early recognition and referral are crucial as patients with uncontrolled CAEBV have poor survival rates 4
• Consider CAEBV as a differential diagnosis in patients with persisting symptoms of infectious mononucleosis for more than 3 months 3

Complications and Special Considerations

• Airway compromise due to tonsillar enlargement should be treated with systemic corticosteroids during hospitalization 3
• Monitor for spontaneous splenic rupture, which occurs in 0.1-0.5% of patients with infectious mononucleosis, typically within 3 weeks of diagnosis 2, 3
• Ultrasonic assessment of spleen size may provide the best estimate of risk for return to physical activities 3
• Be aware of potential associations between EBV infection and lymphoproliferative cancers (particularly Hodgkin and Burkitt lymphomas), multiple sclerosis, and rheumatoid arthritis 3