Epstein–Barr Virus Prevalence at Diagnosis and Seroconversion during Follow-Up in Pediatric Inflammatory Bowel Disease

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.

Epstein–Barr virus seroprevalence and viral load at disease onset in children with inflammatory bowel disease

“…In addition, our local seroprevalence of EBV was slightly lower when compared with rates previously reported in children with IBD. [15][16][17]23 Bachman et al reported a seroprevalence of EBV of 53% in their cohort of 194 children with IBD on serology at the time of diagnosis. 16 Of the seronegative patients, 17% showed a seroconversion at a mean of 4.3 years after diagnosis.…”

“…[15][16][17]23 Bachman et al reported a seroprevalence of EBV of 53% in their cohort of 194 children with IBD on serology at the time of diagnosis. 16 Of the seronegative patients, 17% showed a seroconversion at a mean of 4.3 years after diagnosis. They report three patients who developed malignancy, though noted no association with EBV infection.…”

“…They report three patients who developed malignancy, though noted no association with EBV infection. 16 Harris et al reported a seroprevalence at diagnosis of 53%, with 87% of these being treated with thiopurines, as well as 83% of the seronegative patients. None of their patients developed EBVrelated complications or LDs over an 8-year period.…”

“…15 More recently, Bachman et al and Harris et al demonstrated seroprevalence of 53% at the time of diagnosis in pediatric IBD patients and seroconversion rate of 17% in initially EBV-negative patients. 16,17 It has increasingly become common practice for pediatric gastroenterologists to assess seropositivity for EBV at the time of diagnosis of IBD. The goal of this clinical practice is to prevent possible complications of thiopurine therapy, such as lymphomas and other LPDs, in seronegative patients who are at risk of developing a primary EBV infection during their treatment.…”

“…and Harris et al . demonstrated seroprevalence of 53% at the time of diagnosis in pediatric IBD patients and seroconversion rate of 17% in initially EBV‐negative patients 16,17 …”