Gastritis

Classification

• Acute H. pylori infection
• Other infectious: bacterial (phlegmonous), H. heilmannii, mycobacterial, syphilitic, viral (HSV, CMV), parasitic, fungal

• Type A (autoimmune, body-predominant)
• Type B (H. pylori-related, antral-predominant)
• Indeterminate (mixed/pangastritis)

• Lymphocytic (varioliform), eosinophilic, Crohn's-related, sarcoidosis, isolated granulomatous, Russell body gastritis, immune checkpoint inhibitor-induced

Topographic Patterns

Etiology & Pathogenesis

H. pylori Gastritis (Most Common)

• H. pylori is a gram-negative, helical/spiral-shaped, flagellated bacterium - the most common chronic bacterial infection in humans
• Over 50% of the world's population is infected (70-80% in developing nations)
• Key risk factor: low socioeconomic status in childhood; infection commonly acquired before age 10 in developing countries
• Infection triggers a persistent acute inflammatory infiltrate (neutrophils, lymphocytes, plasma cells, macrophages); despite robust host immune response, bacteria persist in most infected individuals
• Typically affects the antrum (diffuse antral gastritis), associated with increased gastric acid production
• Over time, the body/corpus can become involved (pangastritis), leading to glandular atrophy and mildly reduced acid secretion
• Host immune responses and bacterial virulence factors (e.g., CagA, VacA) determine whether infection stays antral or progresses to pangastritis and atrophy
• Induces MALT (mucosa-associated lymphoid tissue) that can give rise to B-cell MALTomas (lymphoma)

Autoimmune Gastritis (Type A)

• After H. pylori and NSAIDs, this is the third most common cause of chronic gastritis
• Involves primarily the fundus and body (oxyntic glands), with antral sparing
• Results in: glandular atrophy, decreased acid production, antral G-cell hyperplasia (due to loss of acid feedback), and vitamin B12 deficiency (due to loss of intrinsic factor)
• Anti-parietal cell antibodies directed against H+,K+-ATPase are present in >90% of pernicious anemia patients and ~50% of Type A gastritis patients
• Anti-intrinsic factor antibodies are more specific for Type A gastritis
• Strong autoimmune association: ~50% of pernicious anemia patients have thyroid antibodies; ~30% of thyroid disease patients have anti-parietal cell antibodies; also linked to vitiligo and Addison's disease
• Molecular mimicry between H. pylori LPS and H+,K+-ATPase is proposed as a possible trigger in some cases

NSAIDs and Alcohol

• Interfere with gastric mucosal protective mechanisms (prostaglandin synthesis, mucous layer, bicarbonate secretion)
• Cause acute mucosal injury; NSAIDs are a leading cause of chronic gastric damage with long-term use

Histologic Progression of Chronic Gastritis

1. Superficial gastritis - inflammatory infiltrate limited to lamina propria of surface mucosa; edema separates intact glands
2. Atrophic gastritis - infiltrate extends deeper, with progressive distortion and destruction of glands
3. Gastric atrophy - glandular structures are lost; paucity of inflammatory infiltrates; thinned mucosa with visible submucosal vessels on endoscopy
4. Intestinal metaplasia - gastric glands convert to small intestinal phenotype with goblet cells; a significant precancerous lesion (risk factor for gastric adenocarcinoma)

Acute Gastritis - Special Forms

Phlegmonous (Suppurative) Gastritis

• Infection of the submucosa and muscularis propria, often sparing the mucosa
• Causative organisms: gram-negative bacilli, anaerobes, gram-positive cocci (Group A streptococci), fungi (mucormycosis)
• Risk factors: alcoholism, immunocompromised states (AIDS, liver transplant), recent surgery, respiratory tract infection
• Presentation: septic appearance, acute upper abdominal pain, peritonitis, purulent ascites, fever, hypotension

Emphysematous Gastritis

• Severe form caused by gas-producing organisms: Clostridium perfringens, E. coli, S. aureus
• CT/plain films show gas in the gastric wall and portal venous system
• Can progress to gastric gangrene; potentially fatal
• Treatment: broad-spectrum antibiotics; may require gastrectomy if antibiotics fail

Complications

Uncommon Forms

• Lymphocytic (varioliform) gastritis - intense T-cell infiltration of surface epithelium; associated with celiac sprue; endoscopically shows thickened folds with central erosions; steroids/sodium cromoglycate with unclear results
• Eosinophilic gastritis - eosinophilic infiltration of any gastric layer; often with peripheral eosinophilia and systemic allergy; antrum predominantly involved, can cause outlet obstruction; treatment is glucocorticoids
• Granulomatous gastritis - seen in Crohn's disease, sarcoidosis, histoplasmosis, candidiasis, syphilis, TB; may require full-thickness surgical biopsy to exclude malignancy
• Russell body gastritis - mucosal lesion with pseudotumoral appearance; plasma cells with Russell bodies; strongly associated with H. pylori; resolves with H. pylori eradication
• Immune checkpoint inhibitor-induced gastritis - recognized complication of cancer immunotherapy; requires glucocorticoids and potentially IL-6 receptor blockers

Diagnosis

• Histology (endoscopic biopsy) is the gold standard - gastritis cannot be diagnosed from endoscopy alone
• H. pylori testing: urea breath test, stool antigen (non-invasive, preferred for confirmation of eradication); rapid urease test and histology on biopsy (invasive)
• Serology: anti-parietal cell and anti-intrinsic factor antibodies for autoimmune gastritis
• Serum markers: Pepsinogen I/II ratio, gastrin-17, and anti-H. pylori serology are used as non-invasive markers of gastric atrophy severity
• Imaging (CT): useful for emphysematous/phlegmonous gastritis (showing gas in gastric wall and portal venous system)

Treatment

H. pylori Eradication

• Rising clarithromycin and metronidazole resistance is significantly impacting eradication success
• Antibiotic susceptibility testing/culture-guided therapy is increasingly recommended
• H. pylori eradication before long-term NSAID use reduces risk of GI bleeding
• Eradication is recommended in: PUD, MALT lymphoma, early gastric cancer resection, unexplained iron-deficiency anemia, immune thrombocytopenic purpura, first-degree relatives of gastric cancer patients, patients with severe atrophic gastritis

Autoimmune/Chronic Gastritis

• Treatment is aimed at sequelae, not the underlying inflammation
• Pernicious anemia requires parenteral vitamin B12 supplementation (long-term)
• Endoscopic surveillance is recommended in atrophic gastritis (risk of adenocarcinoma)

Eosinophilic/Lymphocytic Gastritis

• Glucocorticoids are the primary treatment for eosinophilic gastritis (usually effective)
• Lymphocytic gastritis: H. pylori eradication if positive; glucocorticoids/sodium cromoglycate for others

Recent Evidence (2024-2026)