INTRODUCTION: Cytomegalovirus (CMV) enteritis is a common infection in immunocompromised patients. In the gastrointestinal tract, CMV infections are often seen in the esophagus and colon; only rarely do they involve the small bowel. We present a case of acute CMV pan-ileitis confirmed on histopathology. CASE DESCRIPTION/METHODS: A 77-year-old man with previous history of high-grade muscle-invasive urothelial carcinoma treated with resection, biweekly chemotherapy, and radiation presented with sub-acute non-bloody watery diarrhea up to 10 times per day. Symptoms were not associated with fever, melena, hematochezia or abdominal pain. Initial laboratory values were notable for elevated inflammatory markers and an elevated fecal calprotectin without leukopenia (Table 1). A CT scan of the abdomen and pelvis revealed pan-ileitis. Initial clinical management focused on possible infectious ileitis versus undiagnosed Crohn’s disease. He was empirically treated for bacterial enteritis with ceftriaxone and metronidazole, without improvement after completing a one-week course. Colonoscopy then was performed and showed erythema, edema, and ulceration at the Terminal ileum (TI) (Figure 1). Pathology showed fibrin-inflammatory exudates and lymphoplasmocytic infiltrates in the lamina propria, with mild architectural distortion (Figure 2). Viral immunostains demonstrated CMV inclusion bodies. Due to these results, he then was started on oral valganciclovir and discharged home. Subsequent serum immunoglobulin test results confirmed elevated levels of both CMV IgM and IgG. DISCUSSION: The usual presentation of CMV enteritis includes abdominal pain, vomiting or diarrhea, with only rare reports of ileal perforation. Arriving at this diagnosis can be challenging, especially in the absence of immunosuppression or pathognomonic punched-out ulcerations. CMV enteritis also can mimic both infectious and ischemic colitis. Current guidelines recommend treating active CMV enteritis with antiviral therapy, regardless of whether the patient is immunocompromised. Previous reports have suggested there can be prolonged and persistent infection with lack of spontaneous resolution, even in young immunocompetent individuals. In addition, there is an increased mortality rate in immunosuppressed patients with CMV infection. Thus, patients undergoing biologic or chemotherapy who are diagnosed with CMV enteritis should receive appropriate treatment as soon as possible.Table 1.: WBC: white blood cell count; AST: aspartate aminotransferase; ALT: alanine aminotransferase; LDH: lactate dehydrogenase; CRP: C-reactive protein; TB: tubercolosis; IBD: inflammatory bowel diseaseFigure 1.: A. Colonoscopy showing ulcerated mucosa and surrounding erythema in the Terminal Ileum. B. Inflammation characterized by erythema in the Terminal Ileum.Figure 2.: Low power Hematoxylin and eosin shows granulation tissue, inflammation; B,C. higher power hematoxylin and eosin shows and infected endothelial cell with nuclear and cytoplasmic inclusions D. shows positive immune-histochemical staining for CMV.