Atrophic gastritis

Atrophic gastritis is a condition characterized by chronic inflammation of the gastric mucosa with atrophy, gland loss, and metaplastic changes. It is classified into autoimmune metaplastic atrophic gastritis (AMAG) and environmental metaplastic atrophic gastritis (EMAG). Chronic infection with Helicobacter pylori (H. pylori) is the most common cause. Patients suffering from atrophic gastritis often do not display any symptoms or may only experience nonspecific discomfort in the epigastric region. Important diagnostic steps include gastroscopy with biopsy and laboratory studies (e.g., gastrin). Therapeutic emphasis depends on the underlying etiology: substitution of vitamin B₁₂ (AMAG) or H. pylori eradication therapy (helicobacter-associated atrophic gastritis). If left untreated, atrophic gastritis may lead to peptic ulcer disease or result in the development of various cancers.

• AMAG
  • Associated with major histocompatibility haplotypes HLA-B8 and HLA-DR3
  • Associated with other autoimmune diseases (e.g., autoimmune thyroiditis)
• EMAG
  • Helicobacter pylori infection (most important risk factor of atrophic gastritis overall)
  • Dietary factors (e.g., N-nitroso compounds , alcohol intake, high salt intake)

References:^[1][3]

AMAG

• Autoimmune destruction of the parietal cells
  • → Achlorhydria → increased release of gastrin (due to loss of negative feedback) → G cell hyperplasia → hypergastrinemia
    • Hypergastrinemia; may lead to hyperplasia of enterochromaffin-like cells and, consequently, to an increased risk of carcinoid tumors.
• Autoantibodies against intrinsic factor → vitamin B₁₂ deficiency → pernicious anemia

EMAG

• Helicobacter-associated: colonization by H. pylori → decreased production of mucins → increased production of gastric acids → inflammation primarily of the antrum; → ascending propagation → shift of the corpus-antrum border → in cases of chronification: atrophy of the gastric glands → hypochlorhydria (not achlorhydria) and epithelial metaplasia → increased risk of gastric cancers
• Diet: bacteria in the stomach metabolize nitrates present in food → formation of N-nitroso compounds (carcinogenic) → epithelial metaplasia → increased risk of gastric cancers

References:^[1][3]

• Intensity of symptoms may be inconsistent and vary widely
  • Hematemesis; (coffee-ground appearance or bright red in color), possibly melena
  • Epigastric pain is possible
  • Nausea, vomiting
  • Abdominal paresthesia and dyspepsia
• Additionally in AMAG
  • Anemia: iron deficiency (early) and pernicious anemia (late)
    • Achlorhydria impairs the intestinal absorption of inorganic iron → iron deficiency anemia
    • Lack of intrinsic factor → vitamin B₁₂ deficiency → pernicious anemia
      • Features of Vitamin B12 deficiency: triad of hematologic, neurologic, and gastrointestinal disorders (see vitamin B₁₂ deficiency)
  • Evidence of other autoimmune diseases (e.g., Hashimoto's thyroiditis)
• Additionally in EMAG
  • Asymptomatic progression is common
  • Symptoms often a consequence of gastric or duodenal ulcer bleeding

References:^[1][3][4]

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

• Collection of biopsies
  • For histology: 2 biopsy samples from the antrum (peripyloric and angular incisure) and corpus (lesser curvature and greater curvature) each
  • For the urease test: 1 biopsy sample from antrum and corpus each
• Applied methods: As a rule, there should always be a combination of two methods.
  • Histology (gold standard) including staining and direct microscopic identification
    • Curved, flagellated gram-negative rod
  • Rapid urease test: detection of ammonia production by the urease of H. pylori
  • Culture and resistogram
• 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 post-treatment
  • Positive 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 case of chronic bleeding (any type): possibly microcytic anemia
  • In AMAG: possibly macrocytic anemia
• Serum pepsinogen isoforms
• Vitamin B₁₂ levels: decreased in AMAG
• Serum gastrin levels: increased in AMAG
• Serology : anti-intrinsic factor and anti-parietal cell antibodies

References:^[1][3][5][6]

• Chemical gastritis
  • Etiology: various substances cause reactive gastritis
    • Drugs, particularly NSAIDs (additional intake of glucocorticoids and/or SSRIs further increases the risk)
    • Alcohol (especially high-proof and if consumed regularly)
    • Nicotine
  • Clinical features
    • General symptoms of chronic gastritis (epigastric pain; , nausea; , vomiting, hematemesis, melena, dyspepsia)
    • Complaints of varying intensity are common
  • Therapy
    • Avoid harmful substances (e.g., discontinue NSAIDs, abstaining from smoking and alcohol)
    • Proton pump inhibitor (PPI) therapy
    • If H. pylori is detected → Helicobacter pylori eradication therapy
  • Complications: gastric ulcers → bleeding, perforation
• Noninfectious granulomatous gastritis
  • Crohn disease
    • Localization: most commonly in the duodenum, thereafter in descending frequency in the gastric antrum and gastric corpus
    • Diagnosis
      • Endoscopy: normal findings are frequent
      • Biopsy
  • Other: e.g., sarcoidosis, vasculitis
• Ménétrier's disease
  • Definition: gastritis featuring massive enlargement of the mucosal folds
  • Clinical features: dyspeptic symptoms (i.e., abdominal pain, nausea, vomiting, diarrhea, weight loss)
  • Diagnostics
    • Endoscopy: prominent rugae in the gastric fundus
    • Biopsy: foveolar hyperplasia and parietal cell atrophy
  • Complications:
    • Loss of protein → edema
    • Malignant degeneration
  • Therapy: if H. pylori is detected → eradication, otherwise symptomatic treatment and regular gastroscopic check-ups

References:^[7][8]

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

AMAG

• Vitamin B12 replacement therapy (parenteral)
• If H. pylori is detected: attempt to eradicate → may lead to healing
• Risk of malignant degeneration requires regular endoscopic check-ups

Helicobacter-associated atrophic gastritis

Helicobacter pylori eradication therapy with proton pump inhibitors (PPIs) at twice the standard dose + 2 antibiotics (+ possibly bismuth) for a minimum of 7 (possibly 10) days , thereafter continue one PPI at standard dose

• Indications ;
  • Test-and-treat strategy; : for patients that are < 55 years old; , suffer from uninvestigated dyspepsia; , and have no record of "alarm features" (e.g., bleeding)
  • Active peptic ulcer disease
  • History of peptic ulcer disease
  • MALT lymphoma: disease may be cured by sole H. pylori eradication in stage I (success rate of 80%), in stage II eradication therapy as part of a therapeutic framework)
• First-line therapies
  • Triple therapy: PPI + clarithromycin + amoxicillin or metronidazole
  • Bismuth containing quadruple therapy: PPI or an H₂-receptor antagonist + bismuth + tetracycline + metronidazole

References:^[4][9][6]

AMAG

• Vitamin B₁₂ deficiency (→ pernicious anemia, 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 (chronic urticaria, Parkinson's disease, migraine, immune thrombocytopenic purpura, iron deficiency anemia, rosacea)

Helicobacter-associated atrophic gastritis frequently presents with ulcerations. Atrophic gastritis of autoimmune origin does not!
References:^{[1][3][10][11]}

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