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Epstein-Barr Virus Prevalence at Diagnosis and Seroconversion during Follow-Up in Pediatric Inflammatory Bowel
Jennifer Bachmann1, Giang Le Thi1, Annecarin Brückner1
1Department of Pediatrics, Division of Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, 80337 Munich, Germany.
Insights
Nearly half of pediatric inflammatory bowel disease (IBD) patients are Epstein-Barr virus (EBV)-naïve at diagnosis. These children face an increased risk of severe EBV infection and complications like hemophagocytic lymphohistiocytosis during immunosuppressive therapy.
Area of Science:
- Pediatric Gastroenterology
- Infectious Diseases
- Immunology
Background:
- Primary Epstein-Barr virus (EBV) infection in pediatric inflammatory bowel disease (IBD) patients on thiopurines is linked to higher risks of malignancy and hemophagocytic lymphohistiocytosis (HLH).
- Understanding EBV seroprevalence and seroconversion in this vulnerable population is crucial for risk stratification and management.
Purpose of the Study:
- To determine Epstein-Barr virus (EBV) seroprevalence at diagnosis and seroconversion rates during follow-up in a pediatric inflammatory bowel disease (IBD) cohort.
- To investigate the association between EBV status, immunosuppressive therapy, and clinical outcomes including severe EBV infection, HLH, and malignancy.
Main Methods:
- Retrospective analysis of EBV serology and patient data from a single-center IBD cohort.
- Prospective retesting of EBV-seronegative patients at diagnosis.
- Correlation of EBV status with thiopurine exposure and clinical complications.
Main Results:
- Of 402 pediatric IBD patients, 194 (48%) had EBV serology at diagnosis; 53% were EBV-positive.
- Among 92 EBV-seronegative patients, 17% showed seroconversion during a mean follow-up of 4.3 years.
- Three azathioprine-treated children developed symptomatic EBV infection, two with signs of HLH; three malignancies occurred, not clearly EBV-related.
Conclusions:
- Approximately 50% of pediatric IBD patients are susceptible to primary EBV infection at diagnosis.
- These EBV-naïve patients are at risk for severe EBV infection and potentially life-threatening complications, including HLH, during immunosuppressive therapy.
- Close monitoring of EBV status in pediatric IBD patients undergoing immunosuppression is warranted.
Abstract:
Primary Epstein-Barr virus infection in pediatric patients with inflammatory bowel disease during immunomodulation with thiopurines has been associated with increased risk for malignancies or hemophagocytic lymphohistiocytosis. We determined Epstein-Barr virus (EBV) seroprevalence at inflammatory bowel disease (IBD) diagnosis and seroconversion during follow-up in a large single center cohort of children with IBD. EBV serology results and patient characteristics were retrospectively retrieved from the hospital documentation system. EBV seronegative patients at IBD diagnosis were prospectively retested. We report on IBD patients with symptomatic active EBV infection and a complicated disease course, and those diagnosed with malignancy with respect to EBV status and drug exposure. Of 402 patients, 194 (48%) had available EBV serology results at time of IBD diagnosis at a median of 12 years (IQR 9-14 years). Thereof, 102 (53%) were EBV-positive. Of 92 EBV-negative patients, 66 were retested and 17% showed a seroconversion at a mean follow-up time of 4.3 years (SD 3 years). Three children treated with azathioprine experienced acute clinically relevant EBV infection 2, 2.5, and 4 years after IBD diagnosis, two developed signs of hemophagocytic lymphohistiocytosis. Three cases of malignancy occurred in the cohort, though none seemed to be triggered by EBV. In conclusion, almost 50% of pediatric IBD patients were EBV-naïve following diagnosis and may be at increased risk to develop severe EBV infection during immunosuppressive therapy, potentially associated with complications such as hemophagocytic lymphohistiocytosis or malignancy.
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