Metachronous Esophageal Ulcers after Immune-mediated Colitis Due to Immune Checkpoint Inhibitor Therapy: A Case Report and Literature Review

Abstract

Although cases of gastrointestinal toxicity of pembrolizumab have been reported, cases of acute immune-mediated colitis accompanied with metachronous esophageal disorders (esophagitis and ulcer) are rare. We herein report a case of acute colitis and metachronous esophageal ulcers due to an immune-related adverse event following concomitant pembrolizumab chemotherapy for lung adenocarcinoma. To our knowledge, there have so far been no reports of cases in which both acute immune-mediated colitis and metachronous esophageal ulcers developed. We therefore report the details of this case along with a review of the pertinent literature.

Keywords: ICI; immune-mediated colitis; metachronous esophageal ulcer; pembrolizumab; steroid administration.

Figure 1.

Colonoscopic findings by a former doctor. The examination indicated a mass lesion revealed a steeply rising in the sigmoid colon. The tumor margin was composed of normal mucosa, and only the central recess area was reddish and accompanied by vascular atypia.

Figure 2.

Colonoscopic findings. The examination indicated circumferential edematous changes, dark-purple rough mucosa, mucous adhesion, and erosion in the intestinal tract on the oral side of the sigmoid colon 30 cm from the anal margin.

Figure 3.

Abdominal contrast-enhanced computed tomographic findings. Severe, continuous circumferential wall thickening was observed from the ascending colon to the sigmoid colon. Submucosal edema was particularly significant. Furthermore, increased adipose tissue density concentration around the intestinal tract and mild ascites retention in the pelvic cavity were observed.

Figure 4.

Histopathological findings in the sigmoid colon. The examination revealed surface layer erosion and hemorrhaging, and mild lymphocyte infiltration in the lamina propria (arrow). Only a few apoptosis-like changes were observed; there were no crypt abscesses, and neutrophil inflammation was mild (a). Immunohistochemical staining showed no bias in CD4- and CD8-positive T cells (b) (the scale bar shows 50 μm).

Figure 5.

Colonoscopic findings on 15 days of steroid treatment. Follow-up colonoscopy showed improved mucosal findings of the sigmoid colon.

Figure 6.

Esophagogastroduodenoscopic findings on day 100 of steroid treatment. Shallow and extensive map-like ulcers were observed extending from the upper esophagus 17 cm from the incisor to the gastric junction of the esophagus. The ulcer margin was reddish, and a regenerated epithelium was observed.

Figure 7.

Esophagogastroduodenoscopic findings on day 107 of steroid treatment. Follow-up esophagogastric duodenoscopy showed healing of the esophageal ulcer.