Atrophic Gastritis Workup
- Author: Nafea Zayouna, MD; Chief Editor: BS Anand, MD more...
The diagnosis of atrophic gastritis can only be ascertained histologically. The endoscopic findings are not helpful for diagnosis, but endoscopy is essential to perform multiple gastric biopsy sampling. Obtain at least 2 biopsy samples from the gastric antrum, 2 from the corpus and 1 from the incisure, and submit to pathology in separate vials.
Decreased serum pepsinogen I levels and the ratio of pepsinogen I to pepsinogen II in the serum can be used to assess gastric atrophy. The finding of low pepsinogen I levels (<20 ng/mL) has a sensitivity of approximately 96.2% and a specificity of 97% for detection of fundus atrophy.
Identifying the underlying cause of atrophic gastritis and assessing specific complications can require several laboratory tests.
Diagnosis of H pylori–associated atrophic gastritis is made as follows:
Histologic examination of gastric biopsy with H pylori special stains: Histologic identification of H pylori is the standard method to assess if the organism is the underlying cause of atrophic gastritis. Histologic examination also helps evaluate the degree and distribution of atrophy, which helps identify the type of atrophic gastritis. Although histologic identification of H pylori is the standard approach to identify the infection, at late stages of extensive atrophic gastritis, the number of H pylori organisms is decreased markedly because intestinal metaplasia creates an unfavorable environment for H pylori. In these cases, other tests, such as the urea breath test (ie, with nonradioactive isotope 13C or with radioactive isotope 14C), and serologic evidence of infection may provide evidence for H pylori infection.
Rapid urease test from gastric biopsy tissue
Bacterial culture of gastric biopsy specimens: This usually is performed in the research setting or to assess antibiotic susceptibility in patients in whom first-line eradication therapy fails.
Serologic detection of anti- H pylori antibodies
Diagnosis of autoimmune gastritis is made as follows:
Antiparietal and anti-IF antibodies in the serum
Achlorhydria, both basal and stimulated, and hypergastrinemia
Low serum cobalamin (B-12) levels (<100 pg/mL)
Shilling test: Results may be abnormal and can be corrected by IF.
Upper GI endoscopy is essential to establish a diagnosis of atrophic gastritis. Areas of intestinal metaplasia may be recognized with endoscopy; perform sampling of multiple biopsy specimens.
Tissue sampling from both the gastric antrum and corpus is essential to establish the topography of gastritis and to identify atrophy and intestinal metaplasia, which may be patchy.
H pylori–associated atrophic gastritis
H pylori–associated atrophic gastritis can display different levels of severity, as demonstrated in the following images.
H pylori organisms are found within the gastric mucous layer and frequently accumulate in groups of bacteria at the apical side of gastric surface cells, occasionally in the lower portions of the gastric foveolae, and rarely within the deeper areas of the mucosa in association with glandular cells.
Patients with typical infection initially develop chronic active gastritis, in which H pylori organisms are observed in both the antrum and corpus (usually more numerous in the antrum). PMNs infiltrate the lamina propria, glands, surface, and foveolar epithelium, occasionally spilling into the lumen and forming small microabscesses. Lymphoid aggregates and occasional well-developed lymphoid follicles are observed expanding the lamina propria of the mucosa, and occasional lymphocytes permeate the epithelium.
In disease of longer duration, significant loss of gastric glands is observed, which is known as gastric atrophy. Gastric atrophy may result from the loss of gastric epithelial cells that were not replaced by appropriate cell proliferation or from replacement of the epithelium by intestinal-type epithelium (intestinal metaplasia). In advanced stages of atrophy associated with chronic H pylori infection, both the corpus and antrum display extensive replacement by intestinal metaplasia, which is associated with the development of hypochlorhydria. With the expansion of intestinal metaplasia, the numbers of H pylori detectable in the stomach decrease because H pylori are excluded from areas of metaplastic epithelium. This end stage is known as atrophic gastritis.
Autoimmune atrophic gastritis
The histologic changes vary in different phases of autoimmune atrophic gastritis (see the 2 images below).
During the early phase, multifocal diffuse infiltration of the lamina propria by mononuclear cells and eosinophils occurs, as does focal T-cell infiltration of oxyntic glands with glandular destruction. Focal mucous neck cell hyperplasia (ie, pseudopyloric metaplasia) and hypertrophic changes of parietal cells also are observed.
During the florid phase of the disease, increased lymphocytic inflammation, oxyntic gland atrophy, and focal intestinal metaplasia occur. Diffuse involvement of the gastric corpus and fundus by chronic atrophic gastritis associated with intestinal metaplasia characterizes the end stage. Some patients present with gastric polyps, mostly nonneoplastic hyperplastic polyps and polypoid areas of preserved islands of relatively normal oxyntic mucosa that may appear polypoid endoscopically. The antrum is spared.
Yanaoka K, Oka M, Ohata H, et al. Eradication of Helicobacter pylori prevents cancer development in subjects with mild gastric atrophy identified by serum pepsinogen levels. Int J Cancer. 2009 Dec 1. 125(11):2697-703. [Medline].
Vannella L, Lahner E, Annibale B. Risk for gastric neoplasias in patients with chronic atrophic gastritis: a critical reappraisal. World J Gastroenterol. 2012 Mar 28. 18(12):1279-85. [Medline]. [Full Text].
Weck MN, Gao L, Brenner H. Helicobacter pylori infection and chronic atrophic gastritis: associations according to severity of disease. Epidemiology. 2009 Jul. 20(4):569-74. [Medline].
Tahara T, Shibata T, Wang FY, et al. Mannan-binding lectin B allele is associated with a risk of developing more severe gastric mucosal atrophy in Helicobacter pylori-infected Japanese patients. Eur J Gastroenterol Hepatol. 2009 Jul. 21(7):781-6. [Medline].
Gao L, Weck MN, Nieters A, Brenner H. Inverse association between a pro-inflammatory genetic profile and Helicobacter pylori seropositivity among patients with chronic atrophic gastritis: enhanced elimination of the infection during disease progression?. Eur J Cancer. 2009 Nov. 45(16):2860-6. [Medline].
Gao L, Weck MN, Stegmaier C, Rothenbacher D, Brenner H. Alcohol consumption and chronic atrophic gastritis: Population-based study among 9,444 older adults from Germany. Int J Cancer. 2009 Jun 2. 125(12):2918-22. [Medline]. [Full Text].
Palladino M, Chiusolo P, Reddiconto G, et al. MTHFR polymorphisms involved in vitamin B12 deficiency associated with atrophic gastritis. Biochem Genet. 2009 Oct. 47(9-10):645-50. [Medline].
Lahner E, Norman GL, Severi C, et al. Reassessment of intrinsic factor and parietal cell autoantibodies in atrophic gastritis with respect to cobalamin deficiency. Am J Gastroenterol. 2009 Aug. 104(8):2071-9. [Medline].
Stummvoll GH, DiPaolo RJ, Huter EN, et al. Th1, Th2, and Th17 effector T cell-induced autoimmune gastritis differs in pathological pattern and in susceptibility to suppression by regulatory T cells. J Immunol. 2008 Aug 1. 181(3):1908-16. [Medline]. [Full Text].
Huter EN, Stummvoll GH, DiPaolo RJ, Glass DD, Shevach EM. Pre-differentiated Th1 and Th17 effector T cells in autoimmune gastritis: Ag-specific regulatory T cells are more potent suppressors than polyclonal regulatory T cells. Int Immunopharmacol. 2009 May. 9(5):540-5. [Medline].
Massironi S, Cavalcoli F, Rossi RE, et al. Chronic autoimmune atrophic gastritis associated with primary hyperparathyroidism: a transversal prospective study. Eur J Endocrinol. 2013 May. 168(5):755-61. [Medline].
Yagi K, Nakamura A, Sekine A, Graham D. Features of the atrophic corpus mucosa in three cases of autoimmune gastritis revealed by magnifying endoscopy. Case Report Med. 2012. 2012:368160. [Medline]. [Full Text].
Zhang Y, Weck MN, Schottker B, et al. Gastric parietal cell antibodies, Helicobacter pylori infection, and chronic atrophic gastritis: evidence from a large population-based study in Germany. Cancer Epidemiol Biomarkers Prev. 2013 May. 22(5):821-6. [Medline].
Capella C, Fiocca R, Cornaggia M. Autoimmune gastritis. Graham DY, Genta RM, Dixon MF, eds. Gastritis. Philadelphia, Pa: Lippincott Williams; 1999. 79-96.
Correa P. Human gastric carcinogenesis: a multistep and multifactorial process-- First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 1992 Dec 15. 52(24):6735-40. [Medline].
Dixon MF, Genta RM, Yardley JH. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996 Oct. 20(10):1161-81. [Medline].
Dore MP, Leandro G, Realdi G, Sepulveda AR, Graham DY. Effect of pretreatment antibiotic resistance to metronidazole and clarithromycin on outcome of Helicobacter pylori therapy: a meta-analytical approach. Dig Dis Sci. 2000 Jan. 45(1):68-76. [Medline].
Franceschi F, Genta RM, Sepulveda AR. Gastric mucosa: long-term outcome after cure of Helicobacter pylori infection. J Gastroenterol. 2002. 37 Suppl 13:17-23. [Medline].
Gao L, Weck MN, Raum E, et al. Sibship size, Helicobacter pylori infection and chronic atrophic gastritis: a population-based study among 9444 older adults from Germany. Int J Epidemiol. 2010 Feb. 39(1):129-34. [Medline].
Graham DY. Therapy of Helicobacter pylori: current status and issues. Gastroenterology. 2000 Feb. 118(2 Suppl 1):S2-8. [Medline].
Graham DY, Belson G, Abudayyeh S, et al. Twice daily (mid-day and evening) quadruple therapy for H. pylori infection in the United States. Dig Liver Dis. 2004 Jun. 36(6):384-7. [Medline].
Hershko C, Hoffbrand AV, Keret D, et al. Role of autoimmune gastritis, Helicobacter pylori and celiac disease in refractory or unexplained iron deficiency anemia. Haematologica. 2005 May. 90(5):585-95. [Medline].
Inoue T, Uedo N, Ishihara R, et al. Autofluorescence imaging videoendoscopy in the diagnosis of chronic atrophic fundal gastritis. J Gastroenterol. 2010 Jan. 45(1):45-51. [Medline].
Konturek PC, Konturek SJ, Brzozowski T. Helicobacter pylori infection in gastric cancerogenesis. J Physiol Pharmacol. 2009 Sep. 60(3):3-21. [Medline].
Krasinskas AM, Abraham SC, Metz DC, et al. Oxyntic mucosa pseudopolyps: a presentation of atrophic autoimmune gastritis. Am J Surg Pathol. 2003 Feb. 27(2):236-41. [Medline].
Laiyemo AO, Kamangar F, Marcus PM, et al. Atrophic gastritis and the risk of incident colorectal cancer. Cancer Causes Control. 2010 Jan. 21(1):163-70. [Medline].
Leung WK, Kim JJ, Kim JG. Microsatellite instability in gastric intestinal metaplasia in patients with and without gastric cancer. Am J Pathol. 2000 Feb. 156(2):537-43. [Medline].
Malfertheiner P, Megraud F, O'Morain C, et al. Current concepts in the management of Helicobacter pylori infection--the Maastricht 2-2000 Consensus Report. Aliment Pharmacol Ther. 2002 Feb. 16(2):167-80. [Medline].
Rugge M, Genta RM. Staging and grading of chronic gastritis. Hum Pathol. 2005 Mar. 36(3):228-33. [Medline].
Shin CM, Kim N, Lee HS, et al. Validation of diagnostic tests for Helicobacter pylori with regard to grade of atrophic gastritis and/or intestinal metaplasia. Helicobacter. 2009 Dec. 14(6):512-9. [Medline].
Sipponen P, Harkonen M, Alanko A, et al. Diagnosis of atrophic gastritis from a serum sample. Clin Lab. 2002. 48(9-10):505-15. [Medline].
Vaananen H, Vauhkonen M, Helske T, et al. Non-endoscopic diagnosis of atrophic gastritis with a blood test. Correlation between gastric histology and serum levels of gastrin-17 and pepsinogen I: a multicentre study. Eur J Gastroenterol Hepatol. 2003 Aug. 15(8):885-91. [Medline].
Whittingham S, Mackay IR. Autoimmune gastritis: historical antecedents, outstanding discoveries, and unresolved problems. Int Rev Immunol. 2005 Jan-Apr. 24(1-2):1-29. [Medline].