Cytomegalovirus (CMV) Co-infection in Treatment-Refractory Immune Checkpoint Inhibitor-Associated Colitis: A Case...

Immune checkpoint inhibitors (ICIs) have been increasingly used for the treatment of various malignancies, and ICI-associated colitis is one of the most common side effects. Here we report a 55-year-old man with metastatic melanoma who was initially treated with nivolumab-relatlimab. Due to side effects, therapy was transitioned to ipilimumab, followed by combination ipilimumab and nivolumab. Ten days after the third dose of ipilimumab and nivolumab, he presented to the emergency department with nausea, vomiting, bloody diarrhea, and fever. Stool pathogen panel and Clostridioides difficile polymerase chain reaction (PCR) were negative. ICI-associated colitis was suspected clinically, and he was treated with steroids and then one dose of infliximab. However, his condition did not improve, and a colonoscopy was performed, which showed diffuse severe inflammation characterized by adherent blood, altered vascularity, erythema, friability, and granularity in the entire colon. Biopsy showed colonic mucosa with ulceration, cryptitis, crypt abscesses, dilated crypts with flattened epithelium, and focal crypt dropout. The histologic changes were compatible with ICI-associated colitis. Interestingly, cytomegalovirus (CMV) immunostaining showed scattered positive cells. Subsequent plasma CMV PCR was positive. The patient was treated with ganciclovir. The CMV viral load decreased after treatment, and his diarrhea improved. CMV co-infection in patients with treatment-refractory ICI-associated colitis is rare, and our case highlights the importance of clinicopathologic correlation in reaching the diagnosis.