Edoxaban-induced enterocolitis: The first case report demonstrating distinct endoscopic and histological features

Abstract

Direct oral anticoagulants (DOACs), including edoxaban, are widely used for stroke prevention in atrial fibrillation and venous thromboembolism. While gastrointestinal bleeding and diarrhea are recognized adverse effects, DOAC-induced enterocolitis has not been established as a distinct clinical entity. We report the first case of edoxaban-induced enterocolitis in a 75-year-old woman who developed bloody diarrhea and anorexia five days after starting edoxaban. Ileocolonoscopy revealed scattered redness, ulcers, and erosions in the terminal ileum, with diffuse edema and submucosal bleeding from the transverse colon to the rectum. Histopathology showed villous atrophy, lymphatic dilation, and lymphocyte-predominant infiltration in the ileum, along with crypt atrophy, mucosal edema, and hemorrhages in the colon. These findings were inconsistent with infectious, ischemic, vasculitic, or inflammatory bowel diseases, suggesting a drug-induced etiology. Given the acute onset and unique endoscopic and histopathological findings, edoxaban-induced enterocolitis was suspected. The patient's symptoms resolved three days after discontinuing edoxaban, and a follow-up ileocolonoscopy after 3 months showed complete mucosal healing. In accordance with the clinical course, we ultimately diagnosed this case as edoxaban-induced enteritis. Given the widespread use of DOACs, similar cases may be underrecognized, as unexplained bloody diarrhea in these patients often lacks detailed endoscopic evaluation. Further case reports and studies are needed to establish DOAC-induced enteritis as a distinct clinical entity. This case serves as a critical first step in recognizing DOAC-induced enterocolitis and highlights the need for increased awareness among clinicians.

Keywords: colonoscopy; direct oral anticoagulants; edoxaban; enterocolitis; gastrointestinal hemorrhage.

FIGURE 1

Endoscopic findings of the terminal ileum on the 11th day of edoxaban treatment. Scattered redness, shallow ulcers with irregular shape, and small erosions with spontaneous bleeding were observed.

FIGURE 2

Endoscopic findings of the colon on the 11th day of edoxaban treatment. (a) Transverse colon, (b) splenic flexure, (c) descending colon, and (d) sigmoid colon. Diffuse edema and intense redness which suggests submucosal bleeding were observed.

FIGURE 3

Histopathological findings of the ileum and descending colon. (a, b) In the terminal ileum, villous atrophy, lymphatic vessel dilation, and lymphocyte‐predominant infiltration were observed. (c, d) In the descending colon, crypt atrophy, lymphocyte‐predominant inflammatory infiltration, and mucosal edema with hemorrhage were noted.

FIGURE 4

Ileocolonoscopic findings 3 months after discontinuing edoxaban. (a) Terminal ileum and (b–d) colon. Follow‐up ileocolonoscopy 3 months after discontinuing edoxaban demonstrated complete mucosal healing.