- Clinical science
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.
Prevalence in the general population:
- Autoimmune metaplastic atrophic gastritis (AMAG): ∼ 2–5%
- Environmental metaplastic atrophic gastritis (EMAG): strongly correlates with level of endemic H. pylori infection → increases with advancing age and affects the majority of elderly patients
Epidemiological data refers to the US, unless otherwise specified.
The Sydney system for the classification of chronic gastritis is the more general and comprehensive classification and takes into account localization, endoscopic imaging, etiology, inflammatory activity, and histological grading. The ABC classification is part of the Sydney system.
- Corpus gastritis
- Antral gastritis
Autoimmune gastritis (type A)
- Autoimmune gastritis is a rare condition overall
- In the US, people of Northern European descent and African Americans show a higher incidence compared to people of Asian or Hispanic origin.
- Bacterial gastritis (type B)
Chemical gastritis (type C)
- Type C gastritis is less frequently distinguished than types A and B and usually refers to chronic gastritis caused by chemical agents.
- Typical exogenous substances include drugs (particularly NSAIDs) and alcohol, bile reflux is an important endogenous factor.
- Special varieties
- Autoimmune gastritis (type A)
- Histopathological level of inflammation: acute, chronic, or chronic active
- Autoimmune destruction of the parietal cells
- Autoantibodies against intrinsic factor → vitamin B12 deficiency → pernicious anemia
- 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 case 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
- 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)
- 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
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
- Number and localization of necessary biopsy samples depend on the issue
- For detection of H. pylori: 2× antrum, 2× corpus; if the urease test is applied: 1× antrum and corpus each
- In case of vitamin B12 deficiency and suspected type A gastritis: 2× dome of fundus, 2× corpus
- In case of unspecific complaints in the epigastric region, visually inconspicuous endoscopy results and protracted course: diagnosis by exclusion via biopsy samples from distal duodenum (2×), antrum (2×), corpus (2×) and fundus (2×)
- Collection of biopsies
- 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 : culture of H. pylori requires a special nutrient broth and takes about 14 days. It may be conducted to test resistances (in exceptional cases!)
- Detection of H. pylori DNA by PCR: very sensitive and specific, but almost never used in daily clinical practice
- Interfering factors in H. pylori diagnostics (especially in the rapid urease test)
- Preexisting medication with PPIs: PPIs should preferably be discontinued two weeks prior to the test.
- Upper gastrointestinal bleeding: Verification methods are prone to interference if biopsies are taken in the context of bleeding or in the immediate vicinity of ulcerations
- Pre- and peripyloric biopsies: especially prone to interference in the case of bile reflux
- Preceding partial gastrectomy
- Gastric cancer and MALToma
- Mucosal atrophy and intestinal metaplasia revealed by histology
- Histology (gold standard) including staining and direct microscopic identification
H. pylori antigen detection in stool specimens
- On the basis of ELISA testing, involving monoclonal antibodies
- Suitable option as initial test (cost-effective)
- 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)
- H. pylori antigen detection in stool specimens
- Diagnosis is generally confirmed if two tests are positive.
- Duodenal ulcer: one positive result is sufficient
- Chronic active gastritis: if H. pylori is detected and signs of chronic active gastritis are observed simultaneously (infiltration of neutrophil granulocytes is characteristic), diagnosis is considered confirmed without further positive results.
- Positive culture: Detection by culture is sufficient for diagnosis in itself.
- Serum pepsinogen isoforms
- Pepsinogen I is only secreted by oxyntic glands of the gastric fundus and body, but pepsinogen II is secreted by all gastric glands (as well as by Brunner's glands of the duodenum)
- → Therefore, if gastritis (primarily) affects the gastric fundus, the ratio of the two isoforms in the serum changes.
- → Measurement of pepsinogen isoforms may provide a clue towards localization of gastric inflammation (AMAG: confined to gastric body and fundus; EMAG: distributed, but predominantly antrum)
- Vitamin B12 levels: decreased in AMAG
- Serum gastrin levels: increased in AMAG
- Serology : anti-intrinsic factor and anti-parietal cell antibodies
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
- Possibly detection of H. pylori (gram-negative, rod-shaped bacteria)
- G-cell hyperplasia (common in AMAG)
Patterns of affliction
- AMAG: lesions are confined to gastric body and fundus
- EMAG: lesions are distributed over gastric antrum (predominant), body, and fundus
- Etiology: various substances cause reactive gastritis
- Pathophysiology: interaction of direct noxae,NSAIDs, smoking, alcohol, and increased duodenogastric reflux → scattered infiltration of the gastric mucosa by lymphocytes and plasma cells → edema of the gastric mucosa → if and when the regenerative potential of the gastric mucosa is exceeded, erosions and ulcers develop. Also, glands in the corpus may atrophy, leading to decreased secretion of gastric acids and pepsinogen → hypochlorhydria, possibly leading to metaplasia and dysplasia
- Clinical features
- Avoid noxae (e.g., discontinue NSAIDs, abstaining from smoking and alcohol)
- Proton pump inhibitor (PPI) therapy
- Other substances: sucralfate, ursodeoxycholic acid, cholestyramine, prokinetic drugs
- If H. pylori is detected →
- Complications: gastric ulcers → bleeding, perforation
- Noninfectious granulomatous gastritis
- Localization: most commonly in the duodenum, thereafter in descending frequency in the gastric antrum and gastric corpus
- Other: e.g., vasculitis ,
- Etiology: obscure, frequently associated with allergic diseases
- Clinical signs
- Differential diagnosis: If symptoms of bronchial asthma, vasculitis, or eosinophilic myocarditis are observed: see → swift immunosuppression is necessary!
- If allergic diathesis has been confirmed: reduction diet eliminating milk, soy, eggs, wheat, and meat on a trial basis; thereafter selectively reestablish normal diet
- In symptomatic patients with predominant affliction of the mucosa: cromoglicic acid
- In case of stenoses, bleeding, or other complications:
- Full remission in most cases
- Chronic recurrent progression with low tendency for healing and high tendency for complications is possible.
- Etiology: obscure
- Clinical signs: epigastric pain, bleeding from the upper gastrointestinal tract, iron deficiency anemia
- Diagnostics: gastroscopy including biopsy samples from gastric corpus, gastric antrum, and duodenum
- Therapy: H. pylori eradication often leads to healing (even if H. pylori is not detectable)
- Definition: gastritis featuring massive enlargement of the mucosal folds
- Clinical features: dyspeptic symptoms (i.e., abdominal pain, nausea, vomiting, diarrhea, weight loss)
- Loss of protein → edema
- Malignant degeneration
- Therapy: if H. pylori is detected → eradication, otherwise symptomatic treatment and regular gastroscopic check-ups
The differential diagnoses listed here are not exhaustive.
- 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
- 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
- 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)
- Additionally, there are optional indications, which do not necessarily require eradication therapy (e.g.,if long-term NSAID administration is intended and H. pylori has been detected)
- Triple therapy: PPI + clarithromycin + amoxicillin or metronidazole
- Bismuth-containing quadruple therapy: PPI or an H2-receptor antagonist + bismuth + tetracycline + metronidazole
- In case of therapy failure or resistance to clarithromycin:
- Alternative: sequential therapy
- Vitamin B12 deficiency (→ pernicious anemia, funicular myelosis)
- Gastric adenocarcinoma
- Gastric : particularly carcinoid tumors (commonly featuring polypoid precursors)
- Esophageal squamous cell carcinoma
- Ulcerations in the stomach/duodenum (peptic ulcer disease) → upper gastrointestinal bleeding or perforation
- Gastric adenocarcinoma
- Extraintestinal manifestations (chronic urticaria, Parkinson's disease, migraine, immune thrombocytopenic purpura, iron deficiency anemia, rosacea)
We list the most important complications. The selection is not exhaustive.