What is the management approach for a patient with Epstein-Barr Virus (EBV) infection presenting with gastrointestinal (GI) symptoms?

Management of EBV Infection with Gastrointestinal Symptoms

For immunocompetent patients with EBV and GI symptoms, provide supportive care and monitor clinically, as these manifestations are typically self-limited and resolve within weeks without specific antiviral therapy. 1, 2

Initial Clinical Assessment

Determine the patient's immune status immediately, as this fundamentally changes management:

• Immunocompetent patients: Primary EBV infection with GI symptoms (esophagitis, gastritis, cholecystitis) typically resolves spontaneously with supportive care alone 1, 2, 3
• Immunocompromised patients (post-transplant, on thiopurines, anti-TNF therapy): Require aggressive diagnostic workup and potential intervention due to risk of EBV-associated post-transplant lymphoproliferative disorder (PTLD) 4

Diagnostic Workup Based on Immune Status

For Immunocompromised Patients with GI Symptoms

Perform endoscopy urgently when GI symptoms occur in immunosuppressed patients, as this is essential for diagnosing EBV-PTLD 4:

• Physical examination for fever, tonsillitis, adenopathy, and organomegaly 4
• Endoscopy with tissue biopsy is mandatory for histological examination, including EBER in situ hybridization and/or immunohistochemistry for viral antigens 4
• PET-CT/CT imaging to assess for nodal versus extranodal disease 4
• Quantitative EBV DNA PCR from whole blood, plasma, or serum 4
• Complete blood count with differential 5

For Immunocompetent Patients with GI Symptoms

Obtain EBV serology (IgM and IgG) and consider endoscopy only if symptoms are severe or persistent 1, 2:

• Dynamic EBV serology showing shift from IgM to IgG positivity confirms primary infection 1
• Peripheral blood smear looking for atypical lymphocytes 2
• Liver function tests, as mild transaminitis is common 3
• Endoscopy with biopsy if severe dysphagia, persistent symptoms, or concern for alternative diagnosis 1, 2

Management Algorithm

Immunocompetent Patients

Provide symptomatic treatment only:

• Anti-emetics and antidiarrheals (e.g., loperamide) for nausea, vomiting, or diarrhea 4
• Monitor QTc if using anti-emetics, as many prolong QT interval 4
• Proton pump inhibitors for esophagitis or gastritis 1, 2
• No antiviral therapy indicated, as antivirals have no proven role in primary EBV infection with GI manifestations 4
• Symptoms typically resolve within 2-8 weeks without intervention 1, 2, 3

Immunocompromised Patients (Post-Transplant, IBD on Immunosuppression)

Reduce or discontinue immunosuppression immediately if possible, combined with rituximab for proven or probable EBV-PTLD 4:

• Rituximab 375 mg/m² once weekly is first-line therapy for EBV-PTLD 4
• Administer 1-4 doses until EBV DNA-emia negativity 4
• Reduction of immunosuppression must be combined with rituximab whenever feasible 4
• For patients on thiopurines with suspected primary EBV infection, discontinue thiopurine therapy immediately due to risk of fatal hemophagocytic syndrome and lymphoproliferative disorders 4

Special Considerations and Pitfalls

Do not use antiviral agents (acyclovir, ganciclovir, foscarnet) for EBV-PTLD or primary EBV infection, as they have no proven efficacy against latent EBV infection and are not recommended 4:

• Antivirals only work against productive viral replication, not the latent infection driving PTLD 4
• Exception: In severe primary EBV infection with systemic complications, ganciclovir or foscarnet may be considered despite lack of evidence, but specialist consultation is required 4

Avoid misdiagnosing EBV gastritis as gastric lymphoma:

• EBV gastritis can present with dense atypical lymphoid infiltrates mimicking lymphoma 2
• Key distinguishing features: polyclonal pattern on gene rearrangement, positive EBV IgM serology, and spontaneous resolution 2
• EBER in situ hybridization on gastric biopsies confirms EBV etiology 2

For IBD patients on immunosuppression:

• The British Society of Gastroenterology notes that routine EBV screening prior to thiopurine therapy remains controversial in adults 4
• However, in pediatric IBD patients who are EBV-seronegative, there may be justification for avoiding thiopurines due to higher risk from primary infection 4
• Risk of hemophagocytic syndrome and lymphoma on thiopurines is not restricted to young males; females are also at risk 4

Monitoring and Follow-up

For immunocompromised patients, monitor EBV DNA-emia weekly during treatment:

• Continue monitoring for at least 4 months post-transplant, as EBV doubling time can be as short as 56 hours 4
• More frequent sampling warranted if EBV DNA levels are rising 4

For immunocompetent patients with resolved symptoms:

• Follow-up endoscopy at 2 months if initial presentation was severe, to confirm mucosal healing 2
• No routine EBV DNA monitoring needed in immunocompetent individuals 4