Atrophic gastritis

Atrophic gastritis is a condition characterized by chronic inflammation of the gastric mucosa with atrophy, gland loss, and metaplastic changes. There are two types: autoimmune metaplastic atrophic gastritis (AMAG) and environmental metaplastic atrophic gastritis (EMAG), which is commonly caused by Helicobacter pylori (H. pylori). Patients with atrophic gastritis are often asymptomatic or may only experience nonspecific discomfort in the epigastric region. Important diagnostic steps include gastroscopy with biopsy and laboratory studies (e.g., gastrin). The therapeutic approach depends on the underlying etiology. AMAG is treated with vitamin B12 substitution, whereas individuals with EMAG will receive H. pylori eradication therapy. If left untreated, atrophic gastritis may lead to peptic ulcer disease or result in the development of various cancers.

Autoimmune metaplastic atrophic gastritis (AMAG)

• Associated with major histocompatibility haplotypes HLA-B8 and HLA-DR3
• Associated with other autoimmune diseases (e.g., autoimmune thyroiditis)

Environmental metaplastic atrophic gastritis (EMAG)

• Helicobacter pylori infection
  • Most important risk factor for chronic gastritis, including atrophic gastritis ^[2]
  • Colonizes mainly antrum of stomach
• Dietary factors
  • N-nitroso compounds
  • Alcohol intake
  • High salt intake

AMAG

• Autoimmune destruction of the parietal cells in the gastric corpus and fundus (autoantibodies against H⁺/K⁺ ATPase) → achlorhydria → increased release of gastrin (due to loss of negative feedback) → G cell hyperplasia → hypergastrinemia → hyperplasia of enterochromaffin-like cells → ↑ risk of carcinoid tumors.
• Achlorhydria impairs the intestinal absorption of inorganic iron → iron deficiency anemia (early manifestation)
• Autoantibodies against intrinsic factor → vitamin B12 deficiency → pernicious anemia

EMAG

• Colonization by H. pylori
  • Inflammation of the antrum → destruction of D cells → ↓ somatostatin → ↑ gastrin → ↑ production of gastric acids → duodenal ulcers ^[3][4]
  • Inflammation of the gastric body → local destruction of mucosa (via cytotoxins such as ammonia) → ↓ production of mucins and atrophy of the gastric glands → hypochlorhydria → hypergastrinemia and epithelial dysplasia → epithelial metaplasia → ↑ risk of gastric cancers ^[5]
• Diet: bacteria in the stomach metabolize nitrates present in food → formation of carcinogenic N-nitroso compounds → epithelial metaplasia → ↑ risk of gastric cancers

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General symptoms

• Hematemesis; (coffee-ground appearance or bright red), possibly melena
• Epigastric pain is possible.
• Nausea, vomiting
• Abdominal paresthesia and dyspepsia

Specific symptoms in AMAG

• Signs of anemia
  • E.g., pallor, fatigue (caused by iron deficiency anemia and/or pernicious anemia)
  • Features of vitamin B12 deficiency: triad of hematologic, neurologic, and gastrointestinal disorders
• Symptoms of other autoimmune diseases (e.g., goiter in Hashimoto thyroiditis)

Specific symptoms in EMAG

• Asymptomatic progression is common.
• Patients often have recurring ulcers (abdominal pain, dyspepsia)
• Symptoms often occur as a result of gastric or duodenal ulcer bleeding (see “Signs of GI bleeding”).

Helicobacter-associated atrophic gastritis frequently manifests with ulcerations. Atrophic gastritis of autoimmune origin does not.

Esophagogastroduodenoscopy and biopsy

• Diagnostic test of choice
• To evaluate the gastric mucosa and collect biopsy samples from the gastric antrum and corpus, possibly also from the fundus

Helicobacter pylori diagnostics

Indications ^[6]

• Dyspepsia (method depends on patient characteristics)
  • H. pylori test-and-treat strategy: urea breath test (in patients ≤ 60 years of age without alarm features of gastritis) ^[6][7]
  • EGD with biopsies or rapid urease testing (in patients > 60 years of age or with ≥ 1 alarm feature of gastritis)
• Low-grade MALT lymphoma
• Peptic ulcer disease (active or positive history without prior eradication)
• Endoscopically resected early gastric cancer

PPIs should be discontinued at least 2 weeks prior to testing for H. pylori to minimize false-negative rates. ^[8]

Modalities

As a rule, at least two methods should be employed. The diagnosis is generally confirmed if two tests are positive.

• Invasive methods
  • Collection of biopsy samples
    • For histology: 2 biopsy samples from the antrum (peripyloric and angular incisure) and 2 samples from the corpus (lesser curvature and greater curvature)
    • For the urease test: 1 biopsy sample from the antrum and 1 sample from the corpus
  • Histology (gold standard) including staining and direct microscopic identification shows curved, flagellated gram-negative rods
  • Rapid urease test: detection of ammonia production by the urease of H. pylori
  • Culture and resistogram: culture of H. pylori requires a special nutrient broth
  • Detection of H. pylori DNA by PCR: very sensitive and specific, but almost never used in daily clinical practice
• Non-invasive methods
  • H. pylori stool antigen test: detects the presence of H. pylori antigens in a stool sample
    • Can be used for diagnosis of H. pylori infection and proof of eradication after treatment
    • Suitable option as initial test (cost-effective)
  • Urea breath test: detection of a labeled carbon isotope in breath samples
  • Serum IgG antibodies against H. pylori: H. pylori antibodies may be detected even after eradication → test indicates (past) exposure, not necessarily current infection (lower specificity)

Additional tests

• Hematology
  • In cases of chronic bleeding (any type): possibly microcytic anemia
  • In AMAG: possibly macrocytic anemia
• Serum pepsinogen isoforms
• Vitamin B12 levels: ↓ in AMAG
• Serum gastrin levels: ↑ in AMAG
• Serology
  • Anti-intrinsic factor
  • Anti-parietal cell antibodies

Microscopy findings

The following microscopic findings may be seen in both types of atrophic gastritis.

• Chronic inflammation → granulocytic infiltrations in the mucosa, lymphocytic infiltrations in the submucosa
• Mucosal thinning
• Loss of glands
• Epithelial metaplasia
  • (Pseudo)pyloric: replacement of parietal and chief cells in oxyntic glands by mucus-secreting cells, which are usually present in the pyloric region
  • Intestinal: replacement of epithelial cells in the oxyntic or antral mucosa by intestinal epithelium cells (e.g., goblet cells)
• Possible detection of H. pylori (gram-negative, rod-shaped bacteria)
• G-cell hyperplasia (common in AMAG)

Patterns of affliction

• AMAG: Lesions are confined to the gastric body and fundus.
• EMAG: Lesions first manifest in the gastric antrum (predominant), then spread to body and fundus.

Chemical gastritis ^[9]

• Definition: a chemical injury of the gastric mucosa that may be caused by several drugs or other substances
• Common etiologies: NSAIDs, aspirin , alcohol, caffeine, corrosive substances , certain supplements , bile reflux
• Pathophysiology: direct mucosal injury → edema → hyperemia → erosion → ulceration
• Clinical features
  • Typical symptoms of gastritis (i.e., dyspepsia, epigastric pain)
  • Nausea/vomiting
  • Hematemesis/melena
• Therapy
  • Discontinue NSAIDs, abstain from smoking and alcohol, and avoid other substances that may worsen symptoms (e.g., caffeine, iron supplements)
  • Acid suppression: proton pump inhibitor (PPI) therapy
• Complications: gastric ulcers → bleeding, perforation

Granulomatous gastritis ^[9][10]

• Definition: the presence of multiple granulomas in the gastric mucosa, may be infectious or noninfectious
• Etiology
  • Infectious granulomatous gastritis: e.g., tuberculosis , syphilis, Whipple disease, histoplasmosis, anisakis
  • Noninfectious granulomatous gastritis : e.g., Chron disease , sarcoidosis, granulomatosis with polyangiitis, foreign body

Lymphocytic gastritis ^[9][11][12]

• Definition: a lymphocytic infiltration (predominantly CD8) of the gastric mucosa, unspecific to any particular disease, likely explained by autoimmune or allergic inflammation.
• Clinical features: Symptoms are unspecific, ranging from dyspepsia to GI bleeding.
• Diagnostics: infiltration of lymphocytes in biopsies of the gastric mucosa ^[12]
• Treatment: varies according to suspected underlying etiology
• Subtype: varioliform gastritis ^[11][9]
  • Description: a severe form of lymphocytic gastritis with thickened folds noted on endoscopy, capped by small nodules with a central depression or erosion
  • Clinical features: anorexia, rapid weight loss, and features of a protein-losing gastropathy (e.g., hypoproteinemia, hypoalbuminemia, edema).

Eosinophilic gastritis ^[9][13]

• Etiology: uncertain, frequently associated with allergic diseases, blood eosinophilia, and ↑ IgE
• Clinical features: Symptoms are unspecific, ranging from dyspepsia to GI bleeding.
• Diagnostics: Endoscopic features are uncertain and diagnosis is confirmed with histopathology.
• Management
  • Elimination diet
  • Oral swallowed steroids
  • Immunosuppression with glucocorticoids should be considered in severe cases
  • PPI for symptomatic control

Ménétrier disease ^[11]

• Definition: gastritis featuring massive enlargement of the mucosal folds
• Pathophysiology
  • Foveolar hyperplasia leads to:
    • Increased mucus production → loss of protein
    • Atrophy of parietal cells → decreased gastric acid production
    • Hyperplasia of gastric rugae
• Clinical features
  • Dyspeptic symptoms (i.e., abdominal pain, nausea, vomiting, diarrhea, weight loss)
  • Protein-loss gastropathy → hypoalbuminemia and peripheral edema
• Diagnostics
  • Endoscopy: prominent rugae in the gastric fundus
  • Biopsy: foveolar hyperplasia and parietal cell atrophy
  • CT: thick, convoluted rugae (resemble cerebral gyri)
• Complications
  • Peripheral edema
  • Malignant degeneration
• Management
  • All patients should follow a high-protein diet
  • Pharmacological therapy is not well established
  • Consider surgical therapy (total gastrectomy) for severe cases with persistent protein loss
  • If H. pylori is detected, eradication

A horse with a WAVEEy MANE: Weight loss, Anorexia, Vomiting, Edema, and Epigastric pain are the most important clinical features of MÉNétriere disease.

The differential diagnoses listed here are not exhaustive.

General

• Avoid intake of substances that may exacerbate ongoing inflammation (e.g., alcohol, NSAIDs).
• Symptomatic treatment with proton pump inhibitors (PPIs), antacids, sucralfate, or H2-receptor blockers

Sucralfate should not be given simultaneously with PPIs and/or H2 antagonists because it is activated by an acidic environment.

AMAG

• Vitamin B12 replacement therapy (parenteral)
• If H. pylori is detected: attempt to eradicate (may lead to healing)
• Because there is a risk of malignant degeneration, regular endoscopic check-ups are required.

Helicobacter-associated atrophic gastritis

• See “H. pylori eradication therapy” below.

AMAG

• Vitamin B12 deficiency; (leading to pernicious anemia, which potentially causes funicular myelosis)
• Gastric adenocarcinoma
• Gastric neuroendocrine tumors: particularly carcinoid tumors (commonly featuring polypoid precursors)
• Esophageal squamous cell carcinoma

EMAG

• Ulcerations in the stomach/duodenum (peptic ulcer disease) → upper gastrointestinal bleeding or perforation
• Gastric adenocarcinoma
• Gastric MALT lymphoma
• Extraintestinal manifestations (e.g., chronic urticaria, Parkinson disease, migraine, immune thrombocytopenic purpura, iron deficiency anemia, rosacea) ^[16]

We list the most important complications. The selection is not exhaustive.