Differential diagnosis and management of immune checkpoint inhibitor-induced colitis: A comprehensive review

Abstract

Immune checkpoint inhibitors (ICIs) are a new class of cancer pharmacotherapy consisting of antibodies that block inhibitory immune regulators such as cytotoxic T lymphocyte antigen 4, programmed cell death 1 and programmed death-ligand 1. Checkpoint blockade by ICIs reactivates a tumor-specific T cell response. Immune-related adverse events can occur in various organs including skin, liver, and gastrointestinal tract. Mild to severe colitis is the most common side effect with some experiencing rapid progression to more serious complications including bowel perforation and even death. Prompt diagnosis and management of ICI-induced colitis is crucial for optimal outcome. Unfortunately, its clinical, endoscopic and histopathologic presentations are non-specific and overlap with those of colitis caused by other etiologies, such as infection, medication, graft-versus-host disease and inflammatory bowel disease. Thus, a definitive diagnosis can only be rendered after these other possible etiologies are excluded. Sometimes an extensive clinical, laboratory and radiologic workup is required, making it challenging to arrive at a prompt diagnosis. Most patients experience full resolution of symptoms with corticosteroids and/or infliximab. For ICI-induced colitis that is treatment-refractory, small scale studies offer alternative strategies, such as vedolizumab and fecal microbiota transplantation. In this review, we focus on the clinical features, differential diagnosis, and management of ICI-induced colitis with special attention to emerging treatment options for treatment-refractory ICI-induced colitis.

Keywords: Immune checkpoint inhibitor, Immune checkpoint inhibitor-induced colitis, Infliximab, Vedolizumab, Graft-versus-host disease, Inflammatory bowel disease

Core Tip: Colitis is the most common adverse effect associated with immune checkpoint inhibitor (ICI) therapy. Its clinical, endoscopic and histopathologic presentations overlap with those of colitis caused by other etiologies, including infection, other medications and graft-versus-host disease. Patients often present with diarrhea, abdominal pain and variable endoscopic findings ranging from normal or mild inflammation to ulcerations. Microscopically, acute colitis pattern of injury is the most common finding. ICI-induced colitis is a diagnosis of exclusion. Its current first-line treatment is corticosteroids, followed by infliximab for steroid-refractory colitis. Vedolizumab and fecal microbiota transplantation are promising options for treatment-refractory ICI-induced colitis.