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.
Highlights
IntroductionInflammatory bowel disease (IBD) has become a global disease with increasing incidence, in the pediatric population [1,2]
A difference was seen in the timepoint of diagnosis, with patients without Epstein–Barr virus (EBV) testing being diagnosed with inflammatory bowel disease (IBD) mainly before 2014 (92% vs. 48%)
About 50% of pediatric IBD patients were EBV-naïve at diagnosis and 30% of pediatric
Summary
Inflammatory bowel disease (IBD) has become a global disease with increasing incidence, in the pediatric population [1,2]. Since there is no cure for IBD, a high proportion of the patients may require immunosuppressive therapies for decades or even lifelong to control the intestinal inflammation. Two meta-analyses described a four-to-six-fold higher incidence of lymphoproliferative diseases in IBD patients treated with azathioprine or 6-mercaptopurine compared to patients not receiving thiopurines and the general population [3,4]. The CESAME study, i.e., a French nationwide cohort study including 19,486 IBD patients with a median follow-up of 35 months (IQR 29–40), revealed a significant association between thiopurine therapy and lymphoproliferative disorders with an adjusted hazard ratio of 5.28 (p = 0.0007) [5]
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