Do ulcerative colitis and checkpoint inhibitor-induced colitis have similar pathological features?

From the Guidelines

Ulcerative colitis and checkpoint inhibitor-induced colitis share some pathological features, but checkpoint inhibitor-induced colitis often has more prominent apoptosis, a more diffuse distribution throughout the colon, and can affect the upper GI tract, which is uncommon in ulcerative colitis. Both conditions involve inflammation of the colon with similar endoscopic appearances, including erythema, loss of vascular pattern, granularity, friability, and ulcerations. Histologically, both can show crypt abscesses, lamina propria expansion with inflammatory cells, and epithelial damage. However, checkpoint inhibitor-induced colitis frequently shows increased CD8+ T-cell infiltration and lacks the basal plasmacytosis typical of ulcerative colitis, as noted in studies such as 1.

Some key differences between the two conditions include:

• The distribution of colitis, with checkpoint inhibitor-induced colitis often involving the descending colon more frequently than other parts of the colon 1
• The presence of more prominent apoptosis and a more diffuse distribution of inflammation in checkpoint inhibitor-induced colitis
• The potential for checkpoint inhibitor-induced colitis to affect the upper GI tract, which is less common in ulcerative colitis
• The distinct immune cell infiltrates, with checkpoint inhibitor-induced colitis showing increased CD8+ T-cell infiltration and lacking basal plasmacytosis typical of ulcerative colitis

These distinctions are important for proper diagnosis and management, as treatment approaches differ despite some overlap in the use of corticosteroids and immunosuppressants, such as infliximab at 5-10 mg/kg or vedolizumab, as discussed in guidelines like 1 and 1. Checkpoint inhibitor colitis may require discontinuation of the causative immunotherapy and specific immunosuppressive regimens.

From the Research

Similarities in Pathology

• Ulcerative colitis and checkpoint inhibitor-induced colitis have been found to share similar pathological features, including heavy infiltration of CD8+ T cells 2.
• The immune cell infiltration pattern in checkpoint inhibitor-induced colitis is more similar to ulcerative colitis than to colonic acute graft-versus-host disease or colonic Crohn's disease, with a deep band-like CD4+ T cell infiltration pattern and a superficial band-like CD68+ cell infiltration pattern in both 2.
• Endoscopically and histologically, there is a significant overlap between immune-mediated colitis (IMC) and inflammatory bowel disease, although more neutrophilic inflammation without chronic inflammation is usually present in IMC 3.

Key Features of Checkpoint Inhibitor-Induced Colitis

• Checkpoint inhibitor-induced colitis can lead to severe dehydration or intestinal perforation, and its diagnosis and management are crucial for optimal outcome 4, 5.
• The incidence of immune-mediated colitis (IMC) ranges from 1%-25% depending on the type of ICI and if used in combination 3.
• Corticosteroids are recommended for grade 2 or more severe colitis, while holding the immunotherapy, and infliximab can be used in cases of corticosteroid failure 3, 5.

Comparison with Inflammatory Bowel Disease

• Checkpoint inhibitor-induced colitis shares many of the same phenotypical, serological, and histological characteristics of both Crohn's disease and ulcerative colitis, suggesting that it may represent a new inflammatory bowel disease phenotype 6.
• The pathology of checkpoint inhibitor-induced colitis is similar to an inflammatory bowel disease (IBD) flare, with endoscopic lesions and histopathological features that are similar to those of IBD 5.