(972) Immune Checkpoint Inhibitor Enterocolitis Leading to Metabolic Derangements From Severe Diarrhea

Introduction: Immune checkpoint inhibitors (ICIs) are novel cancer therapeutics that have gained traction over the past several years due to their increased efficacy and improved side effect profile when compared to traditional chemotherapeutics. While usually well tolerated, they can trigger autoimmune reactions leading to significant end organ dysfunction1. Here we present a case of enterocolitis secondary to the combination therapy of ipilimumab/nivolumab leading to life threatening metabolic derangements.

Description: Patient is a 63-year-old male with history of renal cell carcinoma receiving ipilimumab/nivolumab infusions as an outpatient who presented to the hospital with several weeks of worsening diarrhea and confusion. He was found to have significant metabolic abnormalities from the diarrhea including a non-anion gap metabolic acidosis with a pH of 7.1, HCO3 of 8, and a potassium of 2.5. CT Abdomen pelvis showed enterocolitis. He was admitted to the ICU and aggressively treated with oral and IV fluid resuscitation as well as aggressive electrolyte replacement. Infectious workup was negative and methylprednisolone was started for presumed check point inhibitor enterocolitis. EGD was done with biopsy consistent with duodenitis. The patient's mental status improved with treatment of the metabolic derangements, but he continued to have high volume diarrhea of up to 13L per day for several days. He was given two doses of infliximab before finally starting to show improvement in the diarrhea. He continued to improve over the following days and subsequently discharged on a course of steroids without further issues. Further treatment with ipilimumab/nivolumab was discontinued.

Discussion: As ICIs become more common, familiarity with their adverse effects is important for ICU clinicians. Reportedly, up to 33% of patients develop diarrhea after starting ICIs, but most cases are mild and self-limited. Ipilimumab/nivolumab combination therapy carried a 2.7% risk of serious gastrointestinal adverse effects requiring hospitalization2. In addition to steroids and stopping the offending agent, treatment is largely supportive with fluid and electrolyte replacement. Immune system modulators infliximab or vedolizumab can be used in refractory cases3.