S2276 Double Whammy: A Case Report of Immune Checkpoint Inhibitor Colitis and Concomitant CMV Colitis in a Patient on Nivolumab for Metastatic Melanoma

Introduction: Immune checkpoint inhibitors (ICI) are the standard of care for numerous malignancies. They are associated with immune-related adverse effects, with the GI tract being most commonly affected. Agents including nivolumab and ipilimumab have been shown to cause diarrhea due to colitis and/or enteritis in up to 40% of patients. Case Description/Methods: A 66-year-old man with a history of melanoma of the left face s/p Mohs surgery 7 years ago, presented to the ED with diarrhea. 6 months prior he was diagnosed with recurrent melanoma and cerebral metastasis, underwent resection, and was started on ICI therapy with ipilimumab/nivolumab and radiotherapy. After 2 cycles of ICI, he developed grade 2 diarrhea (4-6 stools/day). ICI was held and he was started on prednisone with suspicion for immune-mediated diarrhea. After an initial response to steroids, diarrhea recurred, with ≥ 7 stools/day. Stool PCR was positive for Yersinia and colonic biopsies showed neutrophilic infiltrate, suggestive of active colitis of infectious etiology. The patient clinically improved after a course of ciprofloxacin. Nivolumab was resumed, and 4 days later he presented to the ED with diarrhea that rapidly progressed to ∼20 stools/day (severe/grade 4). Stool GI PCR panel and Clostridioides difficile PCR was negative. IV methylprednisolone was started. Repeat colonoscopy showed pan-colonic diffuse congestion, and erythema. A 5 mm sessile descending polyp was snared. Histology revealed active chronic colitis with mononuclear infiltrate and attenuation of the colonic epithelium, supporting the diagnosis of ICI colitis. Low-grade CMV colitis was detected by IHC, with presence of CMV-positive cells within the colon biopsy and polyp specimens. The patient was started on a 3-week course of IV ganciclovir and trimethoprim / sulfamethoxazole for PJP prophylaxis. He was discharged on a tapering course of prednisone 40 mg with plans to repeat sigmoidoscopy in 4-6 weeks to assess healing (Figure 1). Discussion: Infectious etiology of diarrhea must be excluded before starting therapy for suspected ICI colitis. ICI colitis should be confirmed endoscopically before starting high-dose steroids. Systemic immunosuppression poses a risk of opportunistic infections and we found Yersinia and CMV in our patient on 2 different admissions. We wish to highlight the importance of excluding infectious etiologies before considering steroid failure in these patients. Infliximab and vedolizumab can be used in steroid-refractory cases, though caution must be employed in the setting of active infection.Figure 1.: A: Diffuse continuous congestion, erosions, erythema, friability noted in whole colon. B: Active chronic colitis with withering crypts, a crypt abscess, and crypt dropout. C: Crypt abscesses with marked attenuation of colonic epithelium. D: Immunohistochemical stain for cytomegalovirus, demonstrating the presence of several CMV positive cells within an inflammatory polyp.