Cytomegalovirus Esophagitis in a Patient on Ocrelizumab: A Case Report on Diagnostic and Management Challenges in Selective B-Cell Depletion

Background Ocrelizumab, an anti-CD20 monoclonal antibody for relapsing-remitting multiple sclerosis (RRMS), selectively depletes B cells while theoretically preserving T-cell immunity. Cytomegalovirus (CMV) infection is considered rare on ocrelizumab monotherapy (0.03 per 100 patient-years). CMV esophagitis poses diagnostic challenges due to symptom overlap with reflux disease and cardiac pathology. Case A 38-year-old male with RRMS on ocrelizumab for three years presented with postprandial chest and epigastric pain, dysphagia, and decreased appetite. He had no additional immunosuppressive risk factors. Cardiac workup was unremarkable, and transient improvement with acid suppression delayed further evaluation. Esophagogastroduodenoscopy revealed a large esophageal ulcer extending into the stomach and duodenum. Histopathology demonstrated characteristic CMV "owl's eye" inclusions confirmed by immunohistochemistry. Management and Outcome The patient completed valganciclovir 900 mg twice daily for three weeks with complete symptom resolution. Ocrelizumab was continued, with no recurrence or MS relapse during follow-up. Discussion B-cell depleting therapies can predispose to viral complications even without broad immunosuppression, as impaired humoral immunity facilitates viral spread. With in-hospital mortality rates reaching 18.2% for CMV esophagitis, early recognition is critical. Atypical esophageal symptoms following unremarkable cardiac evaluation in these patients warrant prompt endoscopy with biopsy rather than prolonged empiric therapy. This case demonstrates that CMV esophagitis can occur on selective B-cell depleting monotherapy without traditional risk factors, underscoring the need for high clinical suspicion for opportunistic infections in patients on targeted immunomodulatory therapies. Prompt tissue diagnosis is essential for appropriate management and prevention of life-threatening complications.