Severe steroid refractory gastritis induced by Nivolumab: A case report

Vindum, Helene Hjorth; Agnholt, Jørgen; Nielsen, A.W. Moelby; Nielsen, M. B.

doi:10.3748/wjg.v26.i16.1971

Cited by 23 publications

(19 citation statements)

References 15 publications

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“…Clinically, patients in our cohort with CPI-assGastritis showed a heterogeneous pattern of disease with a wide spectrum of epigastric symptoms ranging from mild malaise and nausea to severe epigastric pain and vomiting. In contrast to previously published case series, 60% of our patients experienced extreme weight loss ( 9 , 11 , 15 , 17 , 18 ). In the present study, all patients received dual CPI before the development of gastritis.…”

Section: Discussioncontrasting

confidence: 99%

“…However, the development of CPI-assGastritis is not solely associated with dual CPI. Several case reports in the literature describe gastritis after anti-PD1 monotherapy ( 11 , 17 , 18 ). Nevertheless, it is important for oncologists to be aware that dual CPI certainly increases the likelihood of developing CPI-assGastritis, especially because new indications for dual CPI are currently advancing rapidly.…”

Section: Discussionmentioning

confidence: 99%

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Apoptotic Gastritis in Melanoma Patients Treated With PD-1-Based Immune Checkpoint Inhibition – Clinical and Histopathological Findings Including the Diagnostic Value of Anti-Caspase-3 Immunohistochemistry

et al. 2021

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BackgroundGastritis induced by checkpoint inhibitors (CPI) is a rare but severe drug-related side effect. The reference standard for confirming CPI-associated gastritis (CPI-assGastritis) is histopathological assessment; however, the histopathological features of CPI-assGastritis are not yet adequately defined.Materials and MethodsGastric biopsies of melanoma patients with histopathologically suspected CPI-assGastritis were compared with gastric biopsies of patients with inflammation free gastric mucosa (IFGM), type A, B, and C gastritis with respect to apoptosis count and predominant histopathological features. Immunohistochemical anti-caspase-3 staining was performed to identify apoptosis. Quantification was performed by manually counting the number of apoptotic events per 10 high-power fields (HPF). Clinical symptoms, treatment, and follow-up data of patients with CPI-assGastritis were examined. The nonparametric Mann–Whitney U test was used for statistical testing.ResultsFive melanoma patients (three women, two men; median age: 45 years) were treated with PD-1-based CPI. The patients reported epigastric pain, weight loss, nausea, and vomiting. Histologically, the patients with CPI-assGastritis showed a partly lymphocytic, partly granulocytic inflammatory infiltrate. Manual counting of apoptotic cells in biopsy tissue slides stained against caspase 3 revealed a median of 6 apoptotic events/10 HPF (95% CI, 2.75-17.30) in the patients with CPI-assGastritis. Results for the comparison cohort (patients n = 21) were a median of 1 apoptotic event/10 HPF (95% CI, 0.5–4.5) for type-A gastritis (six patients), a median of 2 apoptotic events/10 HPF (95% CI, 0–4.5) for type-B gastritis (five patients), and no apoptosis for IFGM and type-C gastritis (five patients). Patients with CPI-assGastritis had a significantly higher apoptosis count than patients with IFGM (p<0.01), type A (p<0.05), B (p<0.05), and C gastritis (p<0.01). None of the CPI-assGastritis biopsies showed evidence of Helicobacter pylori. All CPI-assGastritis patients responded to systemic treatment with corticosteroids.ConclusionCPI-assGastritis manifests with nonspecific symptoms but histologically shows a high number of apoptotic events, which can best be visualized by anti-caspase-3 immunohistochemistry. This histopathological feature may help to histologically differentiate CPI-assGastritis from other forms of gastritis and inform decision-making regarding its optimal management.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Apoptotic Gastritis in Melanoma Patients Treated With PD-1-Based Immune Checkpoint Inhibition – Clinical and Histopathological Findings Including the Diagnostic Value of Anti-Caspase-3 Immunohistochemistry

et al. 2021

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“…There are various cases of gastritis reported in literature after ICI treatment, and while most of them responded to corticosteroids, there were some of them refractory to this therapy. A 16-year-old melanoma patient treated with nivolumab developed steroid-refractory gastritis that responded only to infliximab therapy [24]. Pembrolizumab has been found to induce autoimmune gastritis in a melanoma patient, five years after start of therapy [26] contributing to the multitude of late-onset ICI related events.…”

Section: Discussionmentioning

confidence: 99%

“…We found five cases of ulcerative esophagitis after nivolumab, pembrolizumab, ipilimumab or durvalumab therapy for different types of cancer [19][20][21][22][23], with patients presenting different outcomes from well-responders to corticosteroids to fatal events. Unusual cases of gastritis were reported, such as steroid refractory [24] or neutrophilic gastritis [25] under nivolumab therapy. Lymphocytic gastritis (acute form at five years after introduction of ICI [26]), [27] and cytomegalovirus (CMV) gastritis [28] induced by pembrolizumab were reported.…”

Section: Gastrointestinal Tract Toxicitymentioning

confidence: 99%

Digestive Toxicities Secondary to Immune Checkpoint Inhibition Therapy – Reports of Rare Events. A Systematic Review

Radulescu

Crişan

Grapa

et al. 2021

JGLD

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Background and Aims: While immune checkpoint inhibitors therapy (ICI) is exceedingly effective, these drugs are associated with various immune-related adverse effects. As gastrointestinal, hepatic or pancreatic toxicity becomes more common, various reports of rare adverse effects have emerged, leading to a significant clinical and prognostic impact. We aimed to provide a systematic review of mainly case-reports on rare events, to help physicians to make an accurate and fast diagnosis. Methods: We performed a systematic review of the literature, using established MeSH terms: “immune checkpoint inhibitors”, “gastrointestinal tract”, “gastrointestinal diseases”, “liver”, “pancreas”, “nivolumab”, “ipilimumab”, the subheadings “adverse effects”, “toxicity” and the supplementary concepts “pembrolizumab”, “tremelimumab”, “atezolizumab”, “avelumab”, “durvalumab”, with defined inclusion criteria. Results: From 419 manuscripts initially selected, 74 reports of rare adverse events were included in our review. Special cases of neutrophilic gastritis, hemorrhagic gastritis, or even perforations were described at upper digestive tract. Different types of colitis were found secondary to ICI such as pseudomembranous, granulomatous, collagenous and microscopic colitis or even inflammatory bowel disease. In terms of liver toxicity, we found rare reports of cholangitis, granulomatous hepatitis, lipodystrophy and hepatic sinusoidal obstruction syndrome. Pancreas toxicity was rarely reported as severe pancreatitis, exocrine failure and diabetes mellitus. Conclusion: Although a complete check-up of every organ at every routine visit may not be practical, focus on symptoms, targeted laboratory and imaging testing may reveal rare organ damage. Raising awareness of the uncommon toxicities related to the immunotherapy is essential, as some rare events can lead to fatal outcomes.

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“…We searched PubMed from the database's inception to June 2020 with the following search terms: “ultrasonography”, “immune checkpoint inhibitor”, and “gastritis”. Only a few cases reporting imaging findings of ICI‐induced gastritis using PET‐CT and CT were found 19‐24 . Onuki et al (2018) reported a case of severe upper gastrointestinal tract disorder in patients with non‐small cell lung cancer following pembrolizumab administration 22 .…”

Section: Discussionmentioning

confidence: 99%

A case of immune checkpoint inhibitor‐associated gastroenteritis detected by ultrasonography

Omotehara

Nishida

Yamanashi

et al. 2021

J of Clinical Ultrasound

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While immune checkpoint inhibitors (ICIs) have antitumor effects, they also have characteristic side effects, including colitis. However, gastritis has rarely been reported. We report a case of a patient with lung adenocarcinoma who presented with epigastric pain and diarrhea following pembrolizumab administration. Sonography of the abdomen demonstrated diffuse, although mild, gastric wall thickening (mainly in the submucosa), as well as a slight decrease in echogenicity throughout the gastric wall. While the mucosal surface was relatively smooth, color Doppler examination showed increased vascularity. Esophagogastroduodenoscopy and pathological examination confirmed the diagnosis of ICI‐related gastroenteritis.

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Severe steroid refractory gastritis induced by Nivolumab: A case report

Cited by 23 publications

References 15 publications

Apoptotic Gastritis in Melanoma Patients Treated With PD-1-Based Immune Checkpoint Inhibition – Clinical and Histopathological Findings Including the Diagnostic Value of Anti-Caspase-3 Immunohistochemistry

Apoptotic Gastritis in Melanoma Patients Treated With PD-1-Based Immune Checkpoint Inhibition – Clinical and Histopathological Findings Including the Diagnostic Value of Anti-Caspase-3 Immunohistochemistry

Digestive Toxicities Secondary to Immune Checkpoint Inhibition Therapy – Reports of Rare Events. A Systematic Review

A case of immune checkpoint inhibitor‐associated gastroenteritis detected by ultrasonography

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