Sintilimab-induced severe erosive hemorrhagic gastritis and pyloric obstruction: a case report and literature review

Abstract

Immune checkpoint inhibitors could restore immune surveillance to attack tumor through targeting CTLA-4, PD-1 or PD-L1, and have achieved huge success. However, immune-related adverse events (irAEs) have been attracting attention as their application is expanding. Gastritis is relatively rare as a subtype of irAEs, particularly severe gastritis. Guidelines on its clinical management still remain undefined due to limited data. Sintilimab is a PD-1 inhibitor approved in China. Here we offer a case of sintilimab-induced severe erosive hemorrhagic gastritis and pyloric obstruction. Conventional proton pump inhibitors and mucosal protective agents did not take effect, so glucocorticoid was chosen. This severe gastritis was successfully cured finally. Our report describing its clinical performances, endoscopic characteristics and treatments, could assist clinicians to better know this rare irAE.

Plain language summary

Immune checkpoint inhibitors are a type of drug which fight cancer through enhancing the body's immunity. They have significant anti-tumor effects. The side effects of these medications, called immune-related adverse events (irAEs), are becoming more obvious as more and more patients undergo immunotherapy. Sintilimab is an immune checkpoint inhibitor approved in China. This case report discusses an irAE in a patient treated with sintilimab. The patient suffered from gastritis, with severely erosive bloody inflammation and a narrow outflow tract of the stomach. Inhibiting stomach acid and protecting mucosa are classical methods to treat gastritis, but neither worked in this case. However, the patient was successfully treated with glucocorticoids, a type of steroid used to treat inflammation. Gastritis is an uncommon irAE for patients treated with immune checkpoint inhibitors and we are short of credible instructions to timely recognize and manage it. This case report might be valuable for other clinicians looking to treat patients with similar symptoms.

Tweetable abstract

A rare case of Sintilimab-induced irAE presented severe diffuse gastritis with pyloric obstruction and responded well to immunosuppression with glucocorticoid.

Executive summary

• Immune checkpoint inhibitors (ICIs) could affect normal organs apart from tumor lesions through targeting CTLA-4/PD-1-expressing immune cells, resulting in side effects called immune-related adverse events (irAEs).

• Immunosuppression with glucocorticoid is generally recommended for various irAEs of grade 2 and greater severities.

• Gastric damage is a relatively rare subtype of irAEs and there are currently no clinical guidelines to instruct its management.

• This case of sintilimab-related gastritis presented with nausea, vomiting and epigastric pain, endoscopically characterized by a pyloric obstruction, extensively diffuse erythema and erosion with thick coating or necrosis attached to fragile mucosa.

• The patient responded well to glucocorticoid and benefitted from a naso–jejunal tube, which supplied enteral nutrition and an outstretched force to withstand the strictured pylorus.

• One of the histopathological findings of ICI-related gastritis is increased lymphocytes in lamina propria or epithelium.

• COVID-19 infection might further aggravate irAEs through upregulating ICI-induced immune responses.

• It is expected to collect more clinical data to assist clinicians in timely diagnosing and dealing with ICI-related gastritis.

Keywords: :

• gastritis
• immune-related adverse events
• immune checkpoint inhibitors
• PD-1
• sintilimab

Author contributions

Y Chen and W Xiong designed the case report. W Xiong wrote and reviewed the manuscript. Z Yang collected the patient's data and analyzed the endoscopy images.

Financial disclosure

The authors receive funding from the National Natural Science Foundation of China (No.82303708) and the Key Research and Development Project of Jiangxi Province Science and Technology Department (20203BBGL73164). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Informed consent disclosure

The authors state that they have obtained verbal and written informed consent from the patient/patients for the inclusion of their medical and treatment history within this case report.

Additional information

Funding

The authors receive funding from the National Natural Science Foundation of China (No.82303708) and the Key Research and Development Project of Jiangxi Province Science and Technology Department (20203BBGL73164).