Enhancer of Zeste Homolog 1 and 2 Inhibitor-Induced Colitis Mimicking Immune Checkpoint Inhibitor-Induced Colitis.

An 80-year-old woman with relapsed nodal T-follicular helper cell lymphoma, not otherwise specified, developed severe watery diarrhea during valemetostat therapy. Colonoscopy revealed diffuse mucosal erythema and edema, and a biopsy showed lymphoplasmacytic infiltration, crypt abscesses, and apoptotic bodies, consistent with immune checkpoint inhibitor-induced colitis. Immunohistochemistry revealed CD3-positive T cell predominance with abundant CD8-positive cells. Diarrhea improved after discontinuation of the drug without additional therapy. To the best of our knowledge, this is the first reported case of enhancer of zeste homolog 1 and 2 (EZH1/2) inhibitor-induced colitis. EZH1/2 inhibition may lead to T cell-mediated intestinal injury through epigenetic dysregulation; therefore, patients receiving EZH1/2 inhibitors who develop persistent diarrhea should undergo early endoscopic and histological evaluations.