Cytomegalovirus and Epstein-Barr Virus reactivation in steroid-refractory immune checkpoint inhibitor colitis

Introduction: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation are known complications in immunocompromised hosts, particularly transplant recipients. However, their occurrence and clinical implications in patients with solid tumors remain underexplored. The introduction of immune checkpoint inhibitors (ICIs) has transformed cancer therapy, but immune-related adverse events (irAEs), including colitis, are increasingly recognized. The potential role of viral reactivation in exacerbating these toxicities is not well established. Cases Presentation: We report two cases of patients with solid tumors treated with ICIs who developed severe, refractory immune-related colitis. Extensive evaluation revealed markedly elevated CMV and EBV viral loads in colonic biopsies, confirmed by histopathology. Both patients showed significant clinical and endoscopic improvement following antiviral therapy with ganciclovir, highlighting the role of CMV and EBV in modulating the severity of ICI-induced colitis. Conclusions: CMV and EBV reactivation may contribute to the persistence or worsening of ICI-induced colitis. Early recognition and treatment of viral reactivation in patients with irAEs may improve outcomes. Clinical judgment and serial viral monitoring are essential for guiding management decisions.