Mayo Clinic Graduate Medical Education Rochester, Minnesota
Introduction: Immune Checkpoint Inhibitors (ICIs) have become a common treatment for multiple malignancies. Side effects involving the gastrointestinal (GI) tract include an IBD-like enteritis or colitis. However, most of these described side effects occur during or soon after the discontinuation of ICI therapy. In this report, we describe a rare case of Crohn’s disease diagnosed over three years after the completion of pembrolizumab therapy.
Case Description/Methods: A 71-year-old white male without significant co-morbidities diagnosed with melanoma of the trunk with nodal metastases and initiated on pembrolizumab treatment. During 20 months of successful ICI treatment, he did not experience dose-limiting adverse effects. Over a year after discontinuation of ICI, he developed mild epigastric pain and diarrhea. Upper endoscopy with biopsies demonstrating superficial gastritis and chronic duodenitis with normal villous architecture. A colonoscopy without terminal ileum examination was unremarkable. The gastritis and duodenitis were attributed to NSAID use which was then discontinued. However, he continued to have intermittent abdominal pain, diarrhea, and developed an unintentional fifteen-pound weight loss. Three years after pembrolizumab discontinuation, a CT enterography demonstrated multiple small bowel strictures concerning for Crohn’s disease. Laboratory work up revealed a CRP of 34.2, hemoglobin of 11.6 (MCV 88.2), and no evidence of vitamin D or B12 deficiencies. Ultimately, anterograde double balloon enteroscopy revealed ulcers in the jejunum with associated strictures. Biopsies displayed active, chronic enteritis with ulceration. No dysplasia was detected and CMV immunostaining was negative. He was diagnosed with stricturing jejunal Crohn’s Disease and was started on vedolizumab with subsequent clinical and radiographic response.
Discussion: Cases of de novo IBD following ICI therapy have been reported and are believed to arise due to induced autoimmunity as well as distortion of the gut microbiome. This case’s clinical, radiographic, endoscopic, and histologic data support a diagnosis of Crohn’s disease. However, previous reports of ICI-associated IBD also reported acute colitis/enteritis that required ICI termination. This case is atypical as the patient experience no acute ICI related side effects. In summary, this case serves as an example of potential GI-related, long-term autoimmune implications of ICI therapy, even in patients without acute side effects.
