Celiac Disease After Administration of Immune Checkpoint Inhibitors: A Case Report

Our plain-English summary of Celiac Disease After Administration of Immune Checkpoint Inhibitors: A Case Report, by J. Leblanc, S. Hoibian, A. Boucraut, et al (Frontiers in Immunology, 2021).

The study

• Authors: J. Leblanc, S. Hoibian, A. Boucraut, J.P. Ratone, L. Stoffaes, D. Dano, D. Louvel-Perrot, B. Chanez, A.S. Chretien, A. Madroszyk, P. Rochigneux
• Journal: Frontiers in Immunology
• Published: 2021;12:799666
• Type of article: Case report
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Immune checkpoint inhibitors (ICI) reinvigorate the immune system to recognize and destroy tumor cells. Because of this biological mechanism, patients might develop autoimmune toxicities, notably in the digestive tract (most frequently, hepatitis or colitis). A 70-year-old man with relapsed mesothelioma was treated with nivolumab in 3rd line. He was hospitalized for watery and foul-smelling diarrhea. He underwent gastrointestinal endoscopy, showing duodenitis and villous atrophy and measurement of serum IgA antibodies to tissue transglutaminase (tTG-IgA+), leading to the diagnosis of ICI-induced celiac disease. He was treated with steroids, proton pump inhibitors, and a gluten-free diet. If ICI-induced celiac disease is rare in the literature, increasing reports suggest that celiac disease might represent an underestimated ICI toxicity. This case highlights the necessity of complementary investigation (including tTG-IgA and endoscopic biopsies) in patients with atypical digestive symptoms during immunotherapy.

Copyright © 2021 Leblanc, Hoibian, Boucraut, Ratone, Stoffaes, Dano, Louvel-Perrot, Chanez, Chretien, Madroszyk and Rochigneux.

In plain English

This case report from Marseille, France, described a 70-year-old man with epithelioid malignant pleural mesothelioma diagnosed in 2017. It concerns a side effect of cancer treatment and does not discuss asbestos exposure. After earlier chemotherapy, he was given nivolumab, an immune checkpoint inhibitor, as third-line treatment in March 2021. Two days after the second infusion he had grade 3 diarrhea and vomiting, and he was later hospitalized. His colon was normal, but the duodenum (the upper small intestine) was severely inflamed. Biopsies showed changes of celiac disease, including marked villous atrophy. Blood antibodies to tissue transglutaminase were positive (128 U/ml; lab norm 10 U/ml). Nivolumab was stopped, and he was treated with proton pump inhibitors, steroids and a gluten-free diet. Two months later he reported improvement and weight gain, and a repeat endoscopy found the duodenal inflammation and ulcerations healed. Seven months after his last infusion his cancer was stable. He had type 1 diabetes, which the authors said probably made celiac disease more likely. The authors concluded that this toxicity is probably underdiagnosed. They noted that a single case cannot be generalized.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (with a brief review of previously published cases in the discussion)
• Who was studied: One 70-year-old man with epithelioid malignant pleural mesothelioma, first seen in July 2017, treated at the Paoli-Calmettes Institute, Marseille, France
• Exposure: Nivolumab (an anti-PD-1 immune checkpoint inhibitor), 240 mg every 2 weeks as third-line treatment from March 2021, after earlier cisplatin-pemetrexed, carboplatin-pemetrexed and vinorelbine. No asbestos exposure is described.
• Main results:
  • After the second nivolumab infusion the patient developed asthenia, vomiting and grade 3 diarrhea
  • Upper endoscopy showed major duodenitis with diffuse superficial ulcerations; ileocolonoscopy with biopsies was normal
  • Intestinal biopsies showed lesions of celiac disease, including increased intraepithelial T lymphocytes, crypt hyperplasia and marked villous atrophy
  • Serum IgA antibodies to tissue transglutaminase were positive at 128 U/ml (lab norm 10 U/ml)
  • Anti-endomysial IgA antibodies were positive at 80 U/ml (lab norm 10 U/ml)
  • The patient stayed in hospital for 2 weeks and nivolumab was stopped; treatment included proton pump inhibitors, steroids and a gluten-free diet
  • Two months later the patient reported good clinical improvement and weight gain; a control endoscopy found complete healing of the duodenal inflammation and ulcerations
  • Seven months after the last nivolumab infusion the patient still had stable disease without further systemic treatment
  • The patient had a history of type 1 diabetes; the authors stated he was therefore probably more likely to present with celiac disease
• The authors' conclusion: The authors concluded that immune checkpoint inhibitor-induced celiac disease is probably underdiagnosed, and that patients with atypical digestive symptoms during this treatment need further investigation (endoscopy with biopsy and a tTG-IgA blood test).
• Limitations the authors state:
  • As a single-patient case report, the findings cannot be generalized
  • Specialized data such as genetic markers for celiac disease (HLA subtypes) and detailed immune infiltration were not available

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Mesothelioma, Nivolumab (Opdivo), Endoscopy, Immunotherapy.

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