Epstein-Barr Virus Status and Subsequent Thiopurine Exposure Within a Paediatric Inflammatory Bowel Disease Population

Abstract

The use of thiopurine therapy in Epstein-Barr virus (EBV)-naı ¨ve inflammatory bowel disease (IBD) patients remains controversial due to a risk of EBV-associated complications. We evaluated EBV status and outcomes within our paediatric IBD population over an 8-year period; finding that 217 of 409 (53%) screened patients were seropositive for EBV at IBD diagnosis; that thiopurines were used in 189 of 217 (87%) seropositive and 159 of 192 (83%) seronegative patients (P ¼ 0.22); and that 7 of 192 (4%) previously seronegative patients subsequently tested positive for EBV with 6 of 7 (86%) patients having concurrently recorded thiopurine use. All six patients continued thiopurine with/without a period of cessation; no EBV-associated lymphoproliferative disorders/serious complications were recorded within our cohort. A significant proportion of our patients would not receive thiopurine therapy should their use be avoided in EBV-negative patients (47%) or seronegative males (30%). The small but significant risks of thiopurine treatment must be balanced against the potential benefits of successful IBD management; further research into this is required.

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

“…Independent of EBV status at the time of IBD diagnosis, a high proportion of children were treated with thiopurines (83.5%) and, during a mean follow-up time of 4.6 years, nine children with thiopurine therapy had proven EBV infection compared to three children without thiopurine treatment. In this cohort, in all of the primary EBV-infected children treatment with azathioprine was paused and subsequently restarted without any major complications reported, leading to the authors’ suggestion not to abandon thiopurine use as an effective maintenance treatment option for children with IBD [ 33 ]. We agree with Martinelli et al [ 34 ] and Kucharzik et al [ 25 ] and suggest that EBV serological testing should be performed prior to maintenance therapy and it should be carefully discussed with patients and their parents if thiopurine therapy should be used in their potentially EBV-naïve child, especially in male patients.…”

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

“…None of their patients developed EBVrelated complications or LDs over an 8-year period. 17 A multicenter cross-sectional described EBV seroprevalence in 495 patients with IBD, and demonstrated an overall seroprevalence of 72.8%, with, interestingly, 0% in patients under 5 years and less than 60% in patients under 30 years. 24 To our knowledge, these are currently the only studies describing the seroprevalence at the time of diagnosis of IBD in a pediatric population.…”

“…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 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 …”