Atrophic Gastritis 

Updated: Dec 20, 2018
Author: Nafea Zayouna, MD; Chief Editor: BS Anand, MD 

Overview

Background

Atrophic gastritis is a histopathologic entity characterized by chronic inflammation of the gastric mucosa with loss of the gastric glandular cells and replacement by intestinal-type epithelium, pyloric-type glands, and fibrous tissue.[1] Atrophy of the gastric mucosa is the endpoint of chronic processes, such as chronic gastritis associated with Helicobacter pylori infection, other unidentified environmental factors, and autoimmunity directed against gastric glandular cells.[1] See the images below.

Atrophic gastritis. Helicobacter pylori–associated Atrophic gastritis. Helicobacter pylori–associated chronic active gastritis (Genta stain, 20x). Multiple organisms (brown) are observed adhering to gastric surface epithelial cells. A mononuclear lymphoplasmacytic and polymorphonuclear cell infiltrate is observed in the mucosa.
Atrophic gastritis. Intestinal metaplasia of the g Atrophic gastritis. Intestinal metaplasia of the gastric mucosa (Genta stain, 20x). Intestinal-type epithelium with numerous goblet cells (stained blue with the Alcian blue stain) replace the gastric mucosa and represent gastric atrophy. Mild chronic inflammation is observed in the lamina propria. This pattern of atrophy is observed both in Helicobacter pylori–associated atrophic gastritis and autoimmune gastritis.

The 2 main causes of atrophic gastritis result in distinct topographic types of gastritis, which can be distinguished histologically. H pylori–associated atrophic gastritis is usually a multifocal process that involves both the antrum and the oxyntic mucosa of the gastric corpus and fundus, whereas autoimmune gastritis essentially is restricted to the gastric corpus and fundus. Individuals with autoimmune gastritis[2] may develop pernicious anemia because of extensive loss of parietal cell mass and anti-intrinsic factor antibodies.

H pylori–associated atrophic gastritis is frequently asymptomatic, but individuals with this disease are at increased risk of developing gastric carcinoma, which may decrease following H pylori eradication.[3] Patients with chronic atrophic gastritis develop low gastric acid output and hypergastrinemia, which may lead to enterochromaffin-like (ECL) cell hyperplasia and carcinoid tumors.[4]

For patient education resources, see the Digestive Disorders Center, as well as Gastritis.

Pathophysiology

H pylori–associated atrophic gastritis

H pylori are gram-negative bacteria that colonize and infect the stomach. The bacteria lodge within the mucous layer of the stomach along the gastric surface epithelium and the upper portions of the gastric foveolae and rarely are present in the deeper glands (see the 3 images below).

Atrophic gastritis. Schematic representation of He Atrophic gastritis. Schematic representation of Helicobacter pylori–associated patterns of gastritis. Involvement of the corpus, fundus, and gastric antrum, with progressive development of gastric atrophy as a result of the loss of gastric glands and partial replacement of gastric glands by intestinal-type epithelium, or intestinal metaplasia (represented by the blue areas in the diagram) characterize multifocal atrophic gastritis. Individuals who develop gastric carcinoma and gastric ulcers usually present with this pattern of gastritis. Inflammation mostly limited to the antrum characterizes antral-predominant gastritis. Individuals with peptic ulcers usually develop this pattern of gastritis, and it is the most frequent pattern in the Western countries.
Patterns of atrophic gastritis associated with chr Patterns of atrophic gastritis associated with chronic Helicobacter pylori infection and autoimmune gastritis.
Atrophic gastritis. Helicobacter pylori–associated Atrophic gastritis. Helicobacter pylori–associated chronic active gastritis (Genta stain, 20x). Multiple organisms (brown) are observed adhering to gastric surface epithelial cells. A mononuclear lymphoplasmacytic and polymorphonuclear cell infiltrate is observed in the mucosa.

The infection is usually acquired during childhood and progresses over the lifespan of the individual if left untreated. The host response to the presence of H pylori is composed of a T-lymphocytic and B-lymphocytic response, followed by infiltration of the lamina propria and gastric epithelium by polymorphonuclear leukocytes (PMNs) that eventually phagocytize the bacteria.

Significant damage associated with the release of bacterial and inflammatory toxic products is inflicted on the gastric epithelial cells, resulting in increasing cell loss or gastric atrophy over time. Weck published a study supporting their hypothesis that the association between H pylori and chronic atrophic gastritis was greatly underestimated due to the clearance of the infection in advanced stages of the disease.[5] These results suggest that the association is much stronger than estimated by most epidemiologic studies to date. Another study also reported that mannan-binding lectin allele (MBL2 codon 54 B) is associated with a higher risk of developing more severe gastric mucosal atrophy in H pylori–infected Japanese patients.[6]

During the process of gastric mucosal atrophy, some glandular units develop an intestinal-type epithelium, and intestinal metaplasia eventually occurs in multiple foci throughout the gastric mucosa when atrophic gastritis is fully established. Other glands are simply replaced by fibrous tissue, resulting in an expanded lamina propria.[7] Loss of gastric glands in the corpus, or corpus atrophy, reduces parietal cell numbers, which results in significant functional changes with decreased levels of acid secretion and increased gastric pH.[8] Hypochloridia or achloridia raises serum gastrin levels, thereby increasing the risk for the development of neuroendocrine tumors.[8] Studies have also reported that moderate alcohol consumption may be associated with atrophic gastritis by facilitating H pylori clearance.[9]

H pylori–associated chronic gastritis progresses with 2 main topographic patterns that have different clinicopathologic consequences.

The first is antral predominant gastritis. Inflammation that is mostly limited to the antrum characterizes antral predominant gastritis. Individuals with peptic ulcers usually develop this pattern of gastritis, and it is the most frequently observed pattern in Western countries.

The second is multifocal atrophic gastritis. Involvement of the corpus, fundus, and gastric antrum with progressive development of gastric atrophy (ie, loss of gastric glands) and partial replacement of gastric glands by intestinal-type epithelium (intestinal metaplasia) characterize multifocal atrophic gastritis. Individuals who develop gastric carcinoma and gastric ulcers usually have this pattern of gastritis. This pattern is observed more often in developing countries and in Asia.

Autoimmune atrophic gastritis

The development of chronic atrophic gastritis limited to corpus-fundus mucosa and marked diffuse atrophy of parietal and chief cells characterize autoimmune atrophic gastritis, as shown in the following two images.

Patterns of atrophic gastritis associated with chr Patterns of atrophic gastritis associated with chronic Helicobacter pylori infection and autoimmune gastritis.
Atrophic gastritis. Intestinal metaplasia of the g Atrophic gastritis. Intestinal metaplasia of the gastric mucosa (Genta stain, 20x). Intestinal-type epithelium with numerous goblet cells (stained blue with the Alcian blue stain) replace the gastric mucosa and represent gastric atrophy. Mild chronic inflammation is observed in the lamina propria. This pattern of atrophy is observed both in Helicobacter pylori–associated atrophic gastritis and autoimmune gastritis.

Autoimmune gastritis is associated with serum antiparietal and anti-intrinsic factor antibodies that cause intrinsic factor (IF) deficiency, which, in turn, causes decreased availability of cobalamin (vitamin B-12) and, eventually, pernicious anemia in some patients.

Palladino reported that methylenetetrahydrofolate reductase (MTHFR) polymorphisms may be associated with B12 deficiency and autoimmune atrophic gastritis.[10] Autoantibodies are directed against at least 3 antigens, including IF, cytoplasmic (microsomal-canalicular), and plasma membrane antigens. Two types of IF antibodies are detected (types I and II). Type I IF antibodies block the IF-cobalamin binding site, thus preventing the uptake of vitamin B12. Cell-mediated immunity also contributes to the disease.[11]

T-cell lymphocytes infiltrate the gastric mucosa and contribute to the epithelial cell destruction and resulting gastric atrophy. Stummvoll reported that Th17 cells induced the most destructive disease with cellular infiltrates composed primarily of eosinophils accompanied by high levels of serum IgE.[12] Polyclonal Treg also suppresses the capacity of Th1 cells and moderately suppresses Th2 cells, but it can suppress Th17-induced disease only at early time points.

The major effect of Treg was to inhibit the expansion of the effector T cells. However, effector cells isolated from protected animals were not anergic and were fully competent to proliferate and produce effector cytokines ex vivo.[12] The strong inhibitory effect of polyclonal Treg on the capacity of some types of differentiated effector cells to induce disease provides an experimental basis for the clinical use of polyclonal Treg in the treatment of autoimmune disease in humans.

The above findings led to an interesting study by Huter et al, who reported that antigen-specific-induced Treg are potent suppressors of autoimmune gastritis induced by both fully differentiated Th1 and Th17 effector cells. The investigators analyzed the suppressive capacity of different types of Treg to suppress Th1- and Th17-mediated autoimmune gastritis by comparing nTreg with polyclonal TGFbeta-induced WT Treg (iTreg) or TGFbeta-induced antigen-specific TxA23 iTreg in cotransfer experiments with Th1 or Th17 TxA23 effector T cells.[13] Th1-mediated disease was prevented by cotransfer of nTreg and also antigen-specific iTreg, whereas WT iTreg did not show an effect. However, Th17-mediated disease was only suppressed by antigen-specific iTreg. Preactivation of nTreg in vitro before the transfer did not increase their suppressive activity in Th17-mediated gastritis, supporting the investigators' hypothesis.[13]

Etiology

Atrophic gastritis usually is associated with either chronic H pylori infection or with autoimmune gastritis. The environmental subtype of atrophic gastritis corresponds mostly with H pylori–associated atrophic gastritis, although other unidentified environmental factors may play a role in the development of gastric atrophy. Yagi et al used magnifying endoscopy to distinguish atrophic gastritis caused by H pylori from autoimmune gastritis.[14]

Chronic gastritis caused by H pylori infection of the stomach

H pylori infection of the stomach is by far the most common cause of chronic atrophic gastritis.

The risk of atrophic gastritis is increased by 10-fold if an H pylori infection is present.

Whether H pylori infection follows the multifocal atrophic gastritis pathway or the nonatrophic antral gastritis pathway may be related to genetic susceptibility factors, environmental factors that modulate the host-bacterial interaction, or bacterial strains.

Although H pylori possessing the cag (cytotoxin-associated gene) pathogenicity island have been shown to have increased virulence, to cause higher levels of mucosal inflammation, and to be present more frequently in individuals infected with H pylori who develop gastric cancer, no specific virulence factors have been identified that might be useful to predict specific H pylori disease outcome.

Host factors or the effects of other environmental agents are likely to be the determinant elements modulating patterns of disease progression. For example, family relatives of individuals with gastric cancer develop pangastritis more frequently in response to H pylori infection and they also develop multifocal intestinal metaplasia more often, a preneoplastic lesion of the stomach and a component of H pylori–associated atrophic gastritis.

Autoimmune atrophic gastritis

Autoimmune atrophic gastritis is a type of chronic atrophic gastritis limited to the corpus-fundus mucosa and characterized by marked diffuse atrophy of the parietal and chief cells.

Autoimmune gastritis is associated with serum antiparietal and anti-IF antibodies that cause IF deficiency, which, in turn, causes decreased availability of cobalamin and, eventually, pernicious anemia in some patients.

In some families, the disease appears to be transmitted with an autosomal dominant pattern of inheritance.

A large population-based study by Zhang et al suggested that the presence of antigastric parietal cell antibodies (APCAs) may contribute to the development of chronic atrophic gastritis even in the absence of H pylori infection. The study, which included 9684 persons aged 50-74 years, reported an overall seroprevalence of APCA in this population of 19.5%, with a strong association found between the existence of APCAs and the presence of chronic atrophic gastritis. The more severe the disease, the greater the association with APCA was found. However, the link between APCAs and the severity of chronic atrophic gastritis was greatest in persons who were negative for H pylori.[15]

Epidemiology

United States data

The frequency of atrophic gastritis and the prevalence of chronic atrophic gastritis is not known because chronic gastritis frequently is asymptomatic[8] ; however, prevalence of atrophic gastritis parallels the 2 main causes of gastric atrophy, chronic H pylori infection (when the infection follows a course of multifocal atrophic gastritis) and autoimmune gastritis. In both conditions, atrophic gastritis develops over many years and is found later in life. The frequency of H pylori infection in the United States is similar to that found in other Western countries. In the United States, H pylori infection affects approximately 20% of persons younger than 40 years and 50% of those older than 60 years. However, subgroups of different ethnic backgrounds show different frequencies for the infection, which is more common in Asian, Hispanic, and African American persons.

International data

An estimated 50% of the world's population is infected with H pylori, and, therefore, chronic gastritis is extremely common. H pylori infection is highly prevalent in Asia and in the developing countries, and multifocal atrophic gastritis is more prevalent in these areas of the world.

Autoimmune gastritis is a relatively rare disease, most frequently observed in individuals of northern European descent and in African Americans.

The prevalence of pernicious anemia resulting from autoimmune gastritis has been estimated as 127 cases per 100,000 members of the population in the United Kingdom, Denmark, and Sweden. The incidence of pernicious anemia is increased in patients with other immunological diseases, including Graves disease, myxedema, thyroiditis, and hypoparathyroidism.

Race-related demographics

H pylori–associated atrophic gastritis appears to be more common among Asian and Hispanic persons than people of other races.

In the United States, H pylori infection is more common among African Americans than white persons, a difference attributed to socioeconomic factors. However, whether higher rates of H pylori–associated atrophic gastritis are observed among African Americans has not been established.

Autoimmune atrophic gastritis is more frequent in individuals of northern European descent and African Americans and is much less frequent in southern Europeans and Asians.

Sex-related demographics

Atrophic gastritis affects both sexes similarly, as does H pylori.

Autoimmune gastritis has been reported to affect both sexes, with a female-to-male ratio of 3:1.

Age-related demographics

Atrophic gastritis is detected late in life, because it results from the effects of long-standing damage to the gastric mucosa.

H pylori–associated atrophic gastritis develops gradually, but extensive multifocal atrophy usually is detected in individuals older than 50 years.

Patients with autoimmune atrophic gastritis usually present with pernicious anemia, which typically is diagnosed in individuals aged approximately 60 years; however, pernicious anemia can be detected in children (juvenile pernicious anemia).

Prognosis

Atrophic gastritis is a progressive condition with increasing loss of gastric glands and replacement by foci of intestinal metaplasia over years.

Results from studies evaluating the evolution of atrophic gastritis after eradication of H pylori have been conflicting. Follow-up for up to several years after H pylori eradication has not shown regression of gastric atrophy in most studies, whereas other studies report improvement in the extent of atrophy.

Whether H pylori eradication in a patient with atrophic gastritis reduces the risk of development of gastric cancer is another important question. Available data are limited, but a prospective study in a Japanese population reported that H pylori eradication in patients with endoscopically-resected early gastric cancer resulted in decreased appearance of new early cancers, while intestinal-type gastric cancers developed in the control group without H pylori eradication.

These findings support an interventional approach, with eradication of H pylori if the organisms are detected in patients with atrophic gastritis, aiming at prevention of development of gastric cancer.

Morbidity/mortality

Mortality and morbidity associated with atrophic gastritis are related to specific clinicopathologic complications that may develop during the course of the underlying disease.

Similar to other individuals infected with H pylori, patients who develop atrophic gastritis may complain of dyspeptic symptoms. Individuals with either H pylori–associated atrophic gastritis or autoimmune atrophic gastritis carry an increased risk of developing gastric carcinoid tumors and gastric carcinoma. More recently, there is a case report from New York Mount Sinai Hospital involving synchronous gastric neuroendocrine tumor (NET) and duodenal gastrinoma with autoimmune chronic atrophic gastritis in the absence of H pylori infection.[16] The patient underwent transduodenal resection of the duodenal NETs, and subsequent followup over 2 years revealed no recurrence or metastasis from the gastric or duodenal disease.

The major effects of autoimmune gastritis are consequences of the loss of parietal and chief cells and include achlorhydria, hypergastrinemia, loss of pepsin and pepsinogen, anemia, and an increased risk of gastric neoplasms.

Autoimmune atrophic gastritis represents the most frequent cause of pernicious anemia in temperate climates. The risk of gastric adenocarcinoma appears to be at least 2.9 times higher in patients with pernicious anemia than in the general population. A recent study also reported an increased frequency of esophageal squamous carcinomas in patients with pernicious anemia.

Autoimmune atrophic gastritis and H pylori gastritis may also have a significant role in the development of unexplained or refractory iron deficient anemia.

Complications

The multifocal atrophic gastritis that develops in some individuals with H pylori infection is associated with increased risk of the following:

  • Gastric ulcers
  • Gastric adenocarcinoma

The corpus-restricted atrophic gastritis that develops in patients with autoimmune gastritis is associated with an increased risk of the following:

  • Pernicious anemia
  • Gastric polyps
  • Gastric adenocarcinoma
 

Presentation

History

Atrophic gastritis represents the end stage of chronic gastritis, both infectious and autoimmune. In both cases, the clinical manifestations of atrophic gastritis are those of chronic gastritis, but pernicious anemia is observed specifically in patients with autoimmune gastritis and not in those with H pylori–associated atrophic gastritis.

H pylori-associated atrophic gastritis

Acute H pylori infection usually is not detected clinically, but experimental infection results in a clinical syndrome characterized by epigastric pain, fullness, nausea, vomiting, flatulence, malaise, and, sometimes, fever. The symptoms resolve in approximately a week, regardless of whether or not H pylori organisms are eliminated.

Persistence of the organism causes H pylori chronic gastritis, which usually is asymptomatic or may manifest as epigastric pain and, rarely, nausea, vomiting, anorexia, or significant weight loss. Symptoms associated with complications of chronic H pylori–associated atrophic gastritis may develop, including gastric ulcers and gastric adenocarcinoma.

Autoimmune atrophic gastritis

The clinical manifestations of autoimmune atrophic gastritis primarily are related to the deficiency of cobalamin, which is not absorbed adequately because of IF deficiency resulting from severe gastric parietal cell atrophy. The disease has an insidious onset and progresses slowly. Cobalamin deficiency affects the hematological, GI, and neurologic systems.

Hematologic manifestations

The most significant manifestation is megaloblastic anemia, but, rarely, purpura due to thrombocytopenia may develop. Symptoms of anemia include weakness, light-headedness, vertigo and tinnitus, palpitations, angina, and symptoms of congestive heart failure.

GI manifestations

The lack of cobalamin is associated with megaloblastosis of the GI tract epithelium. Patients sometimes complain of a sore tongue. Anorexia with moderate weight loss, occasionally associated with diarrhea may result from the malabsorption associated with megaloblastic changes in the epithelium of the small intestine.

Neurologic manifestations

These result from demyelination, followed by axonal degeneration and neuronal death. The affected sites include peripheral nerves, posterior and lateral columns of the spinal cord, and the cerebrum. Signs and symptoms include numbness and paresthesias in the extremities, weakness, and ataxia. Sphincter disturbances may be present. Mental function disturbances vary from mild irritability to severe dementia or psychosis. Neurologic disease may occur in patients with normal hematocrit and normal red cell parameters.

Anemia

Patients with pernicious anemia have an increased frequency of gastric polyps and have a 2.9-fold increase in gastric cancer.

Additionally, patients with autoimmune atrophic gastritis and H pylori infection may manifest iron deficient anemia that may be refractory to oral iron treatment. H pylori eradication in combination with continued oral iron therapy has been shown to result in a significant increase in hemoglobin levels.

Primary hyperparathyroidism

Massironi et al found evidence of a noncausal association between chronic autoimmune atrophic gastritis (CAAG) and primary hyperparathyroidism (PHPT). In a prospective study, they evaluated the prevalence of PHPT in 107 patients with CAAG and the prevalence of CAAG in 149 patients with sporadic PHPT. The results indicate that PHPT is about three-fold more prevalent in patients with CAAG than in the general population and that CAAG is about four-fold more prevalent in patients with PHPT than in the general population.[17]

Physical Examination

Physical examination is of little contributory value in atrophic gastritis; however, some findings are associated specifically with the complications of H pylori–associated atrophic gastritis and autoimmune atrophic gastritis.

In uncomplicated H pylori–associated atrophic gastritis, clinical findings are few and nonspecific. Epigastric tenderness may be present. If gastric ulcers coexist, guaiac-positive stool may result from occult blood loss.

Findings in a patient with autoimmune atrophic gastritis result from the development of pernicious anemia and neurologic complications.

With severe cobalamin deficiency, the patient is pale and has slightly icteric skin and eyes. The pulse is rapid, and the heart may be enlarged. Auscultation usually reveals a systolic flow murmur.

 

DDx

Diagnostic Considerations

Chronic atrophic gastritis with intestinal metaplasia is recognized to be a precancerous lesion that can evolve toward low- and high-grade intraepithelial lesions and gastric cancer, particularly those involving H pylori infection.[1] Clinicians must identify patients at risk of developing gastric carcinoma to increase clinical surveillance, early recognition, and prompt treatment. At present, the Operative Link on Gastritis Assessment (OLGA) staging system appears to be the most reliable and powerful system for identifying these high-risk patients.[1]

Autoimmune atrophic gastritis has been associated with thyroid diseases, type 1 diabetes mellitus, Addison disease, chronic spontaneous urticaria, myasthenia gravis, vitiligo, and perioral cutaneous autoimmune conditions (eg, erosive oral lichen planus).[2] Thus, in the setting of any autoimmune condition and increased autoimmune disease clustering, clinicians should rule out concomitant autoimmune conditions.[2]

Differential Diagnoses

 

Workup

Approach Considerations

2018 ASGE guidelines

Guidelines for sedation and anesthesia in gastrointestinal endoscopy were released in January 2018 by the American Society for Gastrointestinal Endoscopy (ASGE).[18]

It is recommended that all patients undergoing endoscopic procedures be evaluated to assess their risk of sedation related to preexisting medical conditions.

The combination of an opioid and benzodiazepine is recommended to be a safe and effective regimen for achieving minimal to moderate sedation for upper endoscopy and colonoscopy in patients without risk factors for sedation-related adverse events.

It is suggested to use an appropriate adjunctive agent (eg, diphenhydramine, promethazine, or droperidol) in combination with conventional sedative drugs in select clinical circumstances.

Providers should undergo specific training in the administration of endoscopic sedation and possess the skills necessary for the diagnosis and management of sedation-related adverse events, including rescue from a level of sedation deeper than that intended.

Recommend the routine monitoring of blood pressure, oxygen saturation, and heart rate in addition to clinical observation for changes in cardiopulmonary status during all endoscopic procedures using sedation. Supplemental oxygen administration should be considered for moderate sedation and should be administered during deep sedation. Supplemental oxygen should be administered if hypoxemia is anticipated or develops.

Suggest that capnography monitoring be considered for patients undergoing endoscopy targeting deep sedation.

Anesthesia provider–administered sedation should be considered for complex endoscopic procedures or patients with multiple medical comorbidities or at risk for airway compromise.

It is suggested that endoscopists use propofol-based sedation (endoscopist-directed or anesthesia-provider administered) when it is expected to improve patient safety, comfort, procedural efficiency, and/or successful procedure completion.

Laboratory Studies

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 incisura, 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. The reported best cut-off pepsinogen I value for patients with atrophic gastritis appears to be 40 mcg/L, with a 90% sensitivity, 67% specificity, 69% accuracy, and 92% negative predictive value, whereas the reported best cut-off value for the ratio of pepsinogen I to pepsinogen II appears to be 8, with a 71% sensitivity, specificity, and accuracy each, and an 86% negative predictive value.[19]

The combination of pepsinogen, gastrin-17 and anti- H pylori antibodies serological assays appears to be a reliable tool for the diagnosis of atrophic gastritis.[20] In a systematic review and meta-analysis of data from 20 studies (1995-2016) comprising 4241 subjects, investigators found a 27% prevalence of atrophic gastritis, a 74.7% summary sensitivity, a 95.6% sensitivity, and a 91% negative predictive value.[20]

Other laboratory findings may include the following[8] :

  • Elevated serum gastrin levels
  • Microcytic, hypochromic anemia (which may precede the development of megaloblastic, vitamin B12-associated anemia)
  • Vitamin B12 deficiency (which may elevated homocysteine levels)

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.

Procedures

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.

Histologic Findings

H pylori–associated atrophic gastritis

H pylori–associated atrophic gastritis can display different levels of severity, as demonstrated in the following images.

Atrophic gastritis. Schematic representation of He Atrophic gastritis. Schematic representation of Helicobacter pylori–associated patterns of gastritis. Involvement of the corpus, fundus, and gastric antrum, with progressive development of gastric atrophy as a result of the loss of gastric glands and partial replacement of gastric glands by intestinal-type epithelium, or intestinal metaplasia (represented by the blue areas in the diagram) characterize multifocal atrophic gastritis. Individuals who develop gastric carcinoma and gastric ulcers usually present with this pattern of gastritis. Inflammation mostly limited to the antrum characterizes antral-predominant gastritis. Individuals with peptic ulcers usually develop this pattern of gastritis, and it is the most frequent pattern in the Western countries.
Patterns of atrophic gastritis associated with chr Patterns of atrophic gastritis associated with chronic Helicobacter pylori infection and autoimmune gastritis.
Atrophic gastritis. Helicobacter pylori–associated Atrophic gastritis. Helicobacter pylori–associated chronic active gastritis (Genta stain, 20x). Multiple organisms (brown) are observed adhering to gastric surface epithelial cells. A mononuclear lymphoplasmacytic and polymorphonuclear cell infiltrate is observed in the mucosa.
Atrophic gastritis. Intestinal metaplasia of the g Atrophic gastritis. Intestinal metaplasia of the gastric mucosa (Genta stain, 20x). Intestinal-type epithelium with numerous goblet cells (stained blue with the Alcian blue stain) replace the gastric mucosa and represent gastric atrophy. Mild chronic inflammation is observed in the lamina propria. This pattern of atrophy is observed both in Helicobacter pylori–associated atrophic gastritis and autoimmune gastritis.

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).

Patterns of atrophic gastritis associated with chr Patterns of atrophic gastritis associated with chronic Helicobacter pylori infection and autoimmune gastritis.
Atrophic gastritis. Intestinal metaplasia of the g Atrophic gastritis. Intestinal metaplasia of the gastric mucosa (Genta stain, 20x). Intestinal-type epithelium with numerous goblet cells (stained blue with the Alcian blue stain) replace the gastric mucosa and represent gastric atrophy. Mild chronic inflammation is observed in the lamina propria. This pattern of atrophy is observed both in Helicobacter pylori–associated atrophic gastritis and autoimmune gastritis.

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.

On routine gastric body biopsies, the histologic features of autoimmune metaplastic atrophic gastritis may be identifiable but subtle. In a subset of patients whose histologic findings consist of metaplasia, full-thickness chronic inflammation, and/or oxyntic destruction, it may be prudent to include a note in the medical record that suggests laboratory testing and/or close clinical followup.[21]

 

Treatment

Medical Care

Once atrophic gastritis is diagnosed, treatment can be directed (1) to eliminate the causal agent, which is a possibility in cases of H pylori–associated atrophic gastritis; (2) to correct complications of the disease, especially in patients with autoimmune atrophic gastritis who develop pernicious anemia (in whom vitamin B-12 replacement therapy is indicated); or (3) to attempt to reverse the atrophic process.

No consensus from different studies exists regarding the reversibility of atrophic gastritis; however, removal of H pylori from the already atrophic stomach may block further progression of the disease. Until recently, specific recommendations for H pylori eradication were limited to peptic ulcer disease. At the Digestive Health Initiative International Update Conference on H pylori held in the United States, the recommendations for H pylori testing and treatment were broadened. H pylori testing and eradication of the infection also were recommended after resection of early gastric cancer and for low-grade mucosa-associated lymphoid tissue lymphoma.

If H pylori is identified as the underlying cause of gastritis, subsequent eradication now is almost generally an accepted practice. Protocols for H pylori eradication require a combination of antimicrobial agents and antisecretory agents, such as a proton pump inhibitors (PPIs), ranitidine bismuth citrate (RBC), or bismuth subsalicylate. Despite the combinatorial effect of drugs in regimens used to treat H pylori infection, cure rates remain, at best, 80-95%.

Lack of patient compliance and antimicrobial resistance are the most important factors influencing poor outcome. Currently, the most widely used and efficient therapies to eradicate H pylori are triple therapies (recommended as first-line treatments) and quadruple therapies (recommended as second-line treatment when triple therapies fail to eradicate H pylori). In both cases, the best results are achieved by administering therapy for 10-14 days, although some studies have recommended the duration of treatment of 7 days. The accepted definition of cure is no evidence of H pylori 4 or more weeks after ending the antimicrobial therapy.

Triple therapy, with indicated adult dose

Twice-a-day (bid) PPI or RBC triple therapies include lansoprazole (Prevacid), 30 mg PO bid; omeprazole (Prilosec), 20 mg PO bid; or RBC (Tritec), 400 mg bid. Antibiotic therapy includes clarithromycin (Biaxin), 500 mg PO bid; amoxicillin, 1000 mg PO bid; or metronidazole, 500 mg PO bid.

Pack kits containing combination triple therapies are available as combinations of lansoprazole, amoxicillin, and clarithromycin (PrevPac) and bismuth subsalicylate, tetracycline, and metronidazole (Helidac). PrevPac contains drug combinations in the dosage recommended as first-line treatment by the Maastricht 2-2000 Consensus report from Europe. Note the following:

  • PrevPac components include lansoprazole (Prevacid), 30 mg PO bid; clarithromycin (Biaxin), 500 mg PO bid; and amoxicillin, 1000 mg PO bid.

  • Helidac triple-therapy components include bismuth subsalicylate, 525 mg (two 262.4-mg chewable tabs) 4 times per day (qid); metronidazole, 250 mg qid; and tetracycline HCL, 500 mg qid.

Quadruple therapy, with indicated adult dose

Quadruple therapy, with indicated adult dose is a PPI bid, including lansoprazole (Prevacid), 30 mg PO bid or omeprazole (Prilosec), 20 mg PO bid, and antibiotics, including tetracycline HCl, 500 mg PO qid; bismuth subsalicylate, 120 mg PO qid; and metronidazole, 500 mg PO 3 times per day (tid).

Handle subsequent H pylori eradication failures on a case-by-case basis.

Prevention

Epidemiologic studies of H pylori–associated chronic gastritis show that acquisition of the infection is associated with large crowded households and lower socioeconomic status.

Well-defined measures to prevent infection are not established.

Long-Term Monitoring

Guidelines for follow-up care for cases of atrophic gastritis are not established.

If the patient was treated for H pylori infection, confirm eradication. Perform evaluation of eradication at least 4 weeks after the end of treatment. Eradication may be assessed by noninvasive methods, such as the urea breath test.

Follow-up care may be individualized depending on the findings during endoscopy. For example, if dysplasia is found at endoscopy, increased surveillance is necessary.

 

Medication

Medication Summary

Best results are achieved with 10- to 14-day protocols using combination therapies, with eradication in 80-95% of the cases.

Antibiotics

Class Summary

Antimicrobial activity against most H pylori strains. Rare resistant strains have been reported.

Amoxicillin (Amoxil, Trimox)

Semisynthetic penicillin, an analogue of ampicillin. Interferes with the synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Clarithromycin (Biaxin)

Semisynthetic macrolide antibiotic. Inhibits bacterial growth, possibly by blocking the dissociation of peptidyl t-RNA from ribosomes, causing arrest of RNA-dependent protein synthesis.

Tetracycline (Sumycin)

Active against gram-positive and gram-negative organisms and mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit(s). Yellow, odorless, crystalline powder. Potency is affected in solutions of pH < 2.0 and is destroyed rapidly by alkali hydroxide solutions.

Metronidazole (Flagyl)

Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents (except for C difficile enterocolitis).

Proton pump inhibitors

Class Summary

A substituted benzimidazole (a compound that inhibits gastric acid secretion) is the active ingredient. PPIs do not exhibit anticholinergic or H2 antagonistic activities but suppress acid secretion by specific inhibition of the H+/K+ -ATPase enzyme system on the secretory surface of parietal cells.

Omeprazole (Prilosec)

Decreases gastric acid secretion by inhibiting the parietal cell H+/K+ -ATP pump.

Lansoprazole (Prevacid)

Decreases gastric acid secretion by inhibiting parietal cell H+/K+ -ATP pump.

Esomeprazole (Nexium)

S-isomer of omeprazole. Inhibits gastric acid secretion by inhibiting H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells.

Bismuth compounds

Class Summary

The components of bismuth-containing therapies, including bismuth subsalicylate, metronidazole, clarithromycin, and tetracycline, individually have demonstrated in vitro activity against most susceptible strains of H pylori.

Bismuth subsalicylate (Bismatrol, Pepto-Bismol)

Highly insoluble salt of trivalent bismuth and salicylic acid. More than 80% of salicylic acid is absorbed from oral doses of bismuth subsalicylate chewable tabs.

Ranitidine bismuth citrate (Tritec)

Combination of ranitidine (inhibits H2 receptor in gastric parietal cells, which reduces gastric acid secretion, gastric volume, and hydrogen concentrations) and bismuth citrate. Do not administer as monotherapy.

Administer 30 min prior to sucralfate.