Autoimmune atrophic gastritis—pathogenesis, pathology and management

Abstract

Autoimmune gastritis is a chronic progressive inflammatory condition that results in the replacement of the parietal cell mass by atrophic and metaplastic mucosa. A complex interaction of autoantibodies against the parietal cell proton pump and sensitized T cells progressively destroy the parietal cells, inducing hypochlorhydria and then achlorhydria, while autoantibodies against the intrinsic factor impair the absorption of vitamin B12. The resulting cobalamin deficiency manifests with megaloblastic anaemia and neurological and systemic signs and symptoms collectively known as pernicious anaemia. Previously believed to be predominantly a disease of elderly women of Northern European ancestry, autoimmune gastritis has now been recognized in all populations and ethnic groups, but because of the complexity of the diagnosis no reliable prevalence data are available. For similar reasons, as well as the frequent and often unknown overlap with Helicobacter pylori infection, the risk of gastric cancer has not been adequately assessed in these patients. This Review summarizes the epidemiology, pathogenesis and pathological aspects of autoimmune metaplastic atrophic gastritis. We also provide practical advice for the diagnosis and management of patients with this disease.

Key Points

  • Atrophic gastritis can be associated with long-standing Helicobacter pylori infection (multifocal atrophic gastritis) and with an autoimmune process that progressively destroys the oxyntic mucosa (autoimmune atrophic gastritis)

  • Both types of atrophic gastritis are underdiagnosed, in part because of inadequate biopsy sampling

  • Autoimmune atrophic gastritis progresses from a mild chronic inflammation of the gastric corpus to an advanced stage associated with a severe form of vitamin B12 deficiency anaemia known as pernicious anaemia

  • Traditionally, autoimmune atrophic gastritis has been viewed as a disease affecting predominantly elderly women of Northern European descent, but growing evidence suggests that there might be no racial specificity

  • The diagnosis of autoimmune gastritis rests on the demonstration of its characteristic histopathological features and the demonstration of autoantibodies against intrinsic factor and parietal cells

  • Management of the early stages of autoimmune atrophic gastritis is focused on the prevention of vitamin B12, folate and iron deficiencies

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Figure 1: Atrophic gastritis.
Figure 2: Resected stomach from a patient with end-stage autoimmune atrophic gastritis.
Figure 3: Typical histopathological features of autoimmune atrophic gastritis.
Figure 4: Atrophic corpus mucosa.
Figure 5: Endocrine-like-cell dysplasia.
Figure 6: A small neuroendocrine tumour (carcinoid) in the stomach of a patient with autoimmune atrophic gastritis.
Figure 7: Autoimmune gastritis in a biopsy sample obtained from the corpus mucosa.
Figure 8: Algorithm to be followed when the unexpected diagnosis of autoimmune gastritis is suggested in the histopathology report.
Figure 9: Endoscopic appearance of the gastric corpus in a patient with end-stage autoimmune gastritis.

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R. M. Genta and W. L. Neumann contributed to researching data for the article, discussion of content, writing, and reviewing/editing the manuscript before submission. E. Coss and M. Rugge researched data for the article, made substantial contributions to discussion of content and reviewed/edited the manuscript before submission.

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Correspondence to Robert M. Genta.

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Competing interests

William L. Neumann is employed by Pathologists Bio-Medical Labs, Dallas, TX, a private, hospital-based pathology practice. At the time of writing, Dr Neumann was a Gastrointestinal Pathology Fellow at the University of Texas Southwestern, Dallas; the fellowship was partially funded by Miraca Life Sciences, where he was based at the time. Robert M. Genta is an employee of Miraca Life Sciences, a private pathology referral laboratory based in Irving, Texas. Dr Genta is also a professor of Pathology and Medicine (Division of Gastroenterology) at the University of Texas Southwestern Medical Center at Dallas. The other authors declare no competing interests.

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Neumann, W., Coss, E., Rugge, M. et al. Autoimmune atrophic gastritis—pathogenesis, pathology and management. Nat Rev Gastroenterol Hepatol 10, 529–541 (2013). https://doi.org/10.1038/nrgastro.2013.101

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