Severe Gastritis after Administration of Nivolumab and Ipilimumab

Abstract

Immune checkpoint inhibitors such as ipilimumab, a cytotoxic T-lymphocyte-associated antigen-4 inhibitor, have been widely used for advanced malignancies. As these inhibitors improve antitumor immunity via T-cell modulation, immune-mediated adverse events associated with T-cell activation, such as colitis, might occur. Herein, we describe a 75-year-old Japanese woman with metastatic malignant melanoma who developed hemorrhagic gastritis after ipilimumab treatment. There was no macroscopic or clinical improvement of gastritis after proton pump inhibitor treatment. However, her condition improved after approximately 3 weeks of corticosteroid therapy and Helicobacter pylori eradication. This case suggests a potential association between severe gastritis and immune checkpoint inhibitor treatment. Although several reports have mentioned ipilimumab-associated colitis, gastritis is considered to be rare. In the present case, H. pylori-associated gastritis might have been exacerbated by the T-cell modulation effect of ipilimumab. To date, no report has clarified the mechanism by which ipilimumab modifies H. pylori infection. The present treatment course provides a helpful perspective for similar cases.

Keywords: Gastritis; Helicobacter pylori; Immune checkpoint inhibitor; Ipilimumab; Nivolumab.

Fig. 1

EGD on admission. a, b The stomach was diffusely erythematous and edematous. Despite the absence of ulcers, oozing hemorrhages with air infusion were seen. These findings were consistent with a fragile gastric mucosa (a: gastric body; b: antrum). c Magnifying observation of the gastric body with narrow-band imaging revealed destruction of the glandular structure of the surface. d In the gastric antrum, multiple round-shaped mucosae were seen. e The mucosal lesions were emphasized with indigo carmine spraying. f Narrow-band imaging revealed diffusely denuded areas of mucosa and residual mucosal islands, where the glandular structure was relatively intact (arrows). EGD, esophagogastroduodenoscopy.

Fig. 2

a Pathological findings of the gastric mucosa on admission and follow-up EGD before prednisone treatment. Magnification ×100. b Gastric biopsy showed total glandular atrophy and marked infiltration of lymphocytes and neutrophils in the lamina propria. Magnification ×400. c–e Follow-up EGD showed that a proton pump inhibitor alone had not improved the macroscopic findings of gastritis. Large mucosal defects and significant erythema with hemorrhage were noted. EGD, esophagogastroduodenoscopy.

Fig. 3

EGD after prednisone treatment. Erythema severity showed improvement when compared with the previous findings. Regenerating mucosa was observed mainly in the antral area. EGD, esophagogastroduodenoscopy.