Epstein–Barr Virus-associated Lymphoma during Thiopurine and Anti-tumour Necrosis Factor Therapy: A Case Report

Abstract

Epstein–Barr virus (EBV)-associated lymphoproliferative disorders are uncommon but clinically important complications that may occur during immunosuppressive treatment for inflammatory bowel disease. Such events pose diagnostic and therapeutic challenges in clinical practice. Combination therapy with thiopurines and anti-tumour necrosis factor agents can impair immune surveillance and may favour EBV reactivation and lymphoproliferation. We report the case of a 39-year-old man with stenosing ileocolic Crohn’s disease, classified as A2L2B2 according to the Montreal classification, who developed EBV-positive diffuse large B-cell lymphoma during treatment with azathioprine and infliximab. The patient initially presented with mucohaemorrhagic diarrhoea and was subsequently diagnosed with Crohn’s disease after clinical, endoscopic, radiological and histological assessment. Combination therapy with infliximab and azathioprine was started in June 2021, after negative screening for hepatitis B, hepatitis C, human immunodeficiency virus and tuberculosis, and serology consistent with previous EBV infection. In August 2022, he was admitted with septic shock secondary to ileal perforation and underwent ileocaecal resection. Histopathological examination of the surgical specimen showed EBV-positive diffuse large B-cell lymphoma with tumour-free margins. Immunohistochemistry demonstrated CD20 and LMP1 positivity, absence of CD5 expression and a Ki-67 proliferation index of approximately 90%. Postoperative staging did not identify distant disease. The patient received four cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, with complete metabolic response on follow-up positron emission tomography. Subsequent recurrence of Crohn’s disease was managed with ustekinumab after multidisciplinary discussion. This case emphasises the need for careful risk–benefit assessment, clinical vigilance and coordinated management when prolonged combination immunosuppression is used in patients with Crohn’s disease, especially when severe intestinal complications occur.