Case Presentation: A 68-year man presented to the hospital due to 2 weeks of acute abdominal pain with nausea, vomiting, diarrhea and the inability to tolerate his jejunostomy tube feeds, resulting in 20lbs of weight loss. Past medical history includes Stage 4 gastric adenocarcinoma, coronary artery disease, and hypertension. After diagnosis of gastric cancer 1 year prior to presentation, the patient underwent induction therapy with FOLFOX, then FOLFIRI, and then switched to immunotherapy with Pembrolizumab due to intolerance of his prior treatment courses. He completed his 6th cycle of immunotherapy 3 weeks prior to presentation and the patient tolerated all prior infusions. When the patient’s symptoms started, outpatient infectious stool testing of clostridium difficile, stool ova and parasites and gastrointestinal PCR panel were negative. Further workup revealed an elevated calprotectin (538μg/g) and lactoferrin (232.9μg/g). Exam findings showed that the patient’s abdominal pain was not reproducible and there was no rebound tenderness or guarding. Laboratory testing showed a leukocytosis (11.45 cells/L), metabolic acidosis (HCO3 21mEq/L), and hypoalbuminemia (3.0 g/dL). Infectious workup with cultures was negative. Computed Tomography of the abdomen/pelvis with contrast revealed extensive pneumatosis of the right colon with peri-colonic gas extending towards the central mesentery. These findings were consistent with pneumatosis intestinalis, colitis and a bowel perforation. The patient’s vitals were stable without any evidence of peritoneal signs; therefore, medical management for immunotherapy induced colitis was started with IV steroids without surgical intervention. A QuantiFERON test was obtained in case second line therapy with a TNF alpha inhibitor was required.

Discussion: Pembrolizumab induced colitis is a common immune related adverse event (IrAE) that can occur in patients undergoing systemic immunotherapy and ranges from mild to severe. However, the complication of bowel perforation is a rare and life threatening IrAE that occurs in about 1-1.5 % of all immunotherapy induced colitis cases. This case was unique in that the patient’s objective findings showed extensive pneumatosis intestinalis with stable vitals and a non-toxic appearance allowing for medical management. Despite concerning imaging, the patient responded to steroid therapy and did not require second line agents. Although, escalation was not required, it is essential to obtain a QuantiFERON test in case anti-TNF alpha therapy is needed. The use of immunotherapies, such as PD1 inhibitors like Pembrolizumab is increasing in frequency as their mechanism allows augmentation of host T cell function, improving immune mediated destruction of malignant cells. While this mechanism is an effective method for suppressing incurable cancers, it also comes with the risk of unintended immune mediated damage.

Conclusions: With the increased use of immunotherapies, the frequency of patients presenting to the hospital with complications will increase. This case demonstrates the clinical presentation, workup, and management of a patient with a Grade 4 immunotherapy induced colitis that required treatment with steroids. It provides the importance of obtaining key laboratory tests, such as lactoferrin, calprotectin and QuantiFERON, as well as the need to consider immune mediated injury when patients on these medications come to the hospital with a localizing chief complaint and evidence of inflammation.