Chronic active EBV infection in refractory enteritis with longitudinal ulcers with a cobblestone appearance: an autopsied case report

Abstract

Background Chronic active Epstein–Barr virus infection (CAEBV) is defined as Epstein–Barr virus (EBV)-positive T/NK cell-related neoplasia, and its major clinical symptom is systemic inflammation presenting as infectious mononucleocytosis, whereas enteritis and diarrhea are minor clinical symptoms. The complex mixture of tumorigenic processes of EBV-positive cells and physical symptoms of systemic inflammatory disease constitutes the varied phenotypes of CAEBV. Herein, we describe a case of CAEBV that was initially diagnosed as Crohn’s disease (CD) based on ileal ulcers and clinical symptoms of enteritis. Case presentation A 19-year-old woman complained of abdominal pain and fever. Blood examination showed normal blood cell counts without atypical lymphocyte but detected modest inflammation, hypoalbuminemia, slight liver dysfunction, and evidence of past EBV infection. The esophagogastroduodenoscopic findings were normal. However, colonoscopy revealed a few small ulcers in the terminal ileum. The jejunum and ileum also exhibited various forms of ulcers, exhibiting a cobblestone appearance, on capsule endoscopy. Based on these clinical findings, she was strongly suspected with CD. In the course of treatment by steroid and biologics for refractory enteritis, skin ulcers appeared about 50 months after her initial hospital visit. Immunohistology of her skin biopsy revealed proliferation of EBV-encoded small RNA (EBER)-positive atypical lymphocytes. We retrospectively assessed her previous ileal ulcer biopsy before treatment and found many EBER-positive lymphocytes. Blood EBV DNA was also positive. Therefore, she was diagnosed with extranodal NK/T-cell lymphoma with CAEBV-related enteritis rather than CD. She was treated with cyclosporine and prednisolone combination therapy for CAEBV-related systemic inflammation and chemotherapy for malignant lymphoma. Unfortunately, her disease continued to progress, leading to multiple organ failure and death at the age of 23 years. Conclusion Clinicians need to remember the possibility of CAEBV as a differential diagnosis of refractory enteritis. Enteritis with intestinal ulcer is a rare symptom of CAEBV, and it is impossible to acquire a definitive diagnosis by ulcer morphology only. In cases where the possibility of CAEBV remains, tissue EBVR expression should be checked by in situ hybridization and blood EBV DNA.

Clinical Analysis of Chronic Active Epstein–Barr Virus Infection Involving the Gastrointestinal Tract

“…There have been few reports on CAEBV with gastrointestinal tract involvement. A previous report found that gastrointestinal involvement accounted for only 8% of CAEBV patients and mainly manifested as diarrhea and abdominal pain, 15 similar to IBD. In this study, patients with gastrointestinal involvement accounted for 20.8% of CAEBV patients in the same period.…”

Clinical Analysis of Chronic Active EBV Infection Involving Gastrointestinal Tract

“…There have been few reports on CAEBV with gastrointestinal tract involvement. A previous report found that gastrointestinal involvement accounted for only 8% of CAEBV patients and mainly manifested as diarrhea and abdominal pain 13 . Which was similar to IBD.…”

Impact of Epstein–Barr virus infection in patients with inflammatory bowel disease

“…Although no international criteria for the threshold of EBV load to determine active EBV infection have been established, prior CAEBV cases series found that patients often had more than 105 copies/mL of EBV DNA in peripheral blood, more than 100 EBV+ cells/HPF in surgery samples, and more than 30 EBV+ cells/HPF in biopsy samples, which provides support for clinicians for a correct diagnosis ( 91 , 93 ). Because CAEBV usually has a poor prognosis and has the potential to progress to hemophagocytic lymphohistiocytosis or malignant NK/T lymphoma, especially when involving T or NK cells in Asian populations, early diagnosis of the disease is important, and the only proven curative treatment for the disease is hematopoietic stem cell transplantation ( 94 , 95 ). Intestinal lymphoma is a common differential diagnosis for IBD in clinical practice, but misdiagnosis in cases of EBV-positive primary intestinal lymphoma is not uncommon, especially primary EBV-positive intestinal NK/T-cell lymphomas (NKTCLs).…”