Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

EBV may worsen immune checkpoint inhibitor–induced colitis

Key clinical point: For patients with immune checkpoint inhibitor–induced colitis, infection with Epstein-Barr virus (EBV) may increase risk of steroid-refractory disease and colon perforation.

Major finding: All EBV-positive patients had colon perforation, compared with no EBV-negative patients (P = .001).

Study details: A retrospective study involving 16 patients with immune checkpoint inhibitor–induced colitis.

Disclosures: The study was funded by the All Wales Lymphoma Panel. The investigators disclosed no conflicts of interest.


Pugh MR et al. Clin Gastroenterol Hepatol. 2019 Oct 11. doi: 10.1016/j.cgh.2019.09.031.


Immune checkpoint regulators (iCRs) have become common in the treatment for various cancers. Immune-related colitis (irColitis) is among the most common side effects of iCRs, as well as one of the most common etiologies of fatal toxicities from iCRs. However, much is still unknown on the pathophysiology behind irColitis or its complications. Pugh et al. performed detailed analyses of the potential role of Epstein-Barr virus (EBV) in irColitis. Rather than depend on serologies for EBV, the investigators utilized robust evaluation for colonic mucosal EBV with in situ hybridization, immunohistochemistry, and polymerase chain reaction. Interestingly, in the EBV-positive patients with endoscopic biopsies performed prior to perforation, EBV RNA were minimal or absent on endoscopic biopsies. This finding suggests EBV may be related to the immunosuppression used to treat the colitis rather than the primary driver of irColitis. This observation could have important clinical implications in using steroids for irColitis; we may be increasing the risk of perforation related to EBV by using steroids or other immunosuppression. While we need to interpret these findings with caution given the small sample size and comparisons between endoscopic biopsies and surgical specimens for EBV, this study highlights the potential role of EBV in steroid-refractory irColitis. An additional clinical implication from this study is that endoscopic biopsies did not identify patients who would eventually develop colonic perforation. We therefore cannot assume a patient with negative colonic biopsies for EBV is truly negative. Better means for assessing EBV status and predicting complications are still needed.

Jason K. Hou, MD, is assistant professor of medicine and gastroenterology; director of the GI and hepatology fellowship program; and director of research and IBD at Baylor College of Medicine, Houston. He is a staff physician in the department of gastroenterology, and medical director, IBD, at Michael E. DeBakey VA Medical Center, Houston. He has no conflicts of interest.