Chronic Active Epstein–Barr Virus Associated Enteritis May Develop into a Precancerous Disease

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To the Editor:
Epstein–Barr virus (EBV) is reported to infect more than 90% of people,1 and plays an etiological role in many diseases.1–3 EBV infection with gastrointestinal tract involved is rare in immunocompetent adults, which is very challenging to differentiate from inflammatory bowel disease (IBD). Here we report a case of chronic active EBV-associated enteritis (CAEAE), which we believe to be the first such case reported in an immunocompetent man and finally developed into lymphoproliferative disease (LPD), a precancerous disease.
A 55-year-old man, with no personal and family history of immunodeficiency, was admitted in our hospital for fever and diarrhea for 4 times since 2004.
The 4 explosions happened in 2004, 2012, 2015, and 2016. Each time, he suffered from a 38°C to 41°C fever, followed by abdominal pain, diarrhea, (5–8 times/d, no visual blood) and dizziness. The B ultrasound reported a mild splenomegaly during the first admission. All the Laboratory tests showed similar results during all 4 admissions: mild leukocytosis, increased C-reactive protein levels, mild hypokalemia, positive occult blood stool, negative stool and blood culture, normal erythrocyte sedimentation rate, and a negative tuberculosis result. The CT scan found thickened terminal ileum wall with multiple small retroperitoneal and mesenteric lymph nodes exhibited and considered IBD. The colonoscopies all showed multiple superficial polymorphic ulcers covered with pus moss all over the terminal ileum and colon, resulting in partial luminal stenosis (Fig. 1A). The pathologists reported chronic active inflammation with large amount of neutrophils and lymphocytes infiltrated with normal tissue structure, partial cryptitis (Fig. 2A), and crypt abscess seen not sufficient to make a diagnosis of ulcerative colitis (UC). His symptoms all relieved in a month after mesalazine and supportive treatment for the previous 3 times. During the intermission, he had no complaint of gastrointestinal symptom. The colonoscopy reexamined 2 months after the second explosion showed a great improvement (Fig. 1B). EBV-infected enteritis was suspected after a careful review of his first 3 times of medical records. We performed an immunohistochemistry of EBV-encoded small RNA which was expressed in EBV-infected cells. EBV-encoded small RNA was positive in all the intestinal mucosa biopsies since 2004. Combined with his medical history, he was diagnosed with chronic active EBV-associated enteritis (CAEAE), instead of EBV infection secondary to UC. Before this, he has been misdiagnosed with UC for 11 years.
He was closely followed since the last discharge. One month ago, the patient suffered a fourth recurrence and the colonoscopy revealed multiple ulcers in the terminal ileum and the colon. The pathologists found a small lymphoproliferative lesion (Fig. 2B) in the rectum biopsy with an immunohistochemistry result of CD7++, CD20−, and EBV-encoded small RNA+. To exclude the diagnosis of lymphoma, we reexamined the colonoscopy and took 32 pieces of biopsies. None of the biopsies showed even a LPD change. He was diagnosed with EBV-associated enteritis accompanied with EBV-associated LPD. We speculate that CAEAE can turn into LPD, which is a precancerous condition to lymphoma4,5 (Fig. 2).
Chronic active EBV infection is a rare disorder, especially in gastrointestinal tract, which usually takes the form of LPD rather than a simple inflammation. There are only 3 cases of EBV-infected enteritis with no involvement of an underlying LPD in immunocompetent adult reported in the English literature worldwide till now.6–8 The patients all recovered from supportive treatment and the long-term follow-ups are unknown. We believe this to be the first reported case of CAEAE in an immunocompetent adult. The prognosis of CAEAE is unknown. We know that LPD is a precancerous condition5 and we have reported a case with LPD developed into lymphoma.

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