Gastritis — inflammation of the gastric mucosa — and peptic ulcer disease (PUD) — mucosal defects extending through the muscularis mucosae of the stomach or duodenum — are among the most common gastrointestinal conditions worldwide. Together they affect an estimated 8-10% of the global population at some point in their lives. The two most important etiological factors are Helicobacter pylori infection and non-steroidal anti-inflammatory drug (NSAID) use, which account for the vast majority of cases. Understanding the distinction between gastritis subtypes, accurate diagnosis, and appropriate treatment is essential for preventing serious complications including gastrointestinal bleeding, perforation, and gastric malignancy.

Acute gastritis presents with sudden-onset epigastric pain, nausea, and sometimes vomiting, typically triggered by NSAIDs, alcohol, severe physiological stress (burns, sepsis, major surgery — so-called stress ulcers), or acute H. pylori infection. Histologically, it is characterized by neutrophilic infiltration of the mucosa. Chronic gastritis develops gradually and may be asymptomatic for years. H. pylori-associated chronic gastritis (type B) is the most prevalent form, affecting the antrum initially and progressing to the corpus over decades, potentially leading to atrophic gastritis, intestinal metaplasia, and increased gastric cancer risk. Autoimmune gastritis (type A) targets the parietal cells of the gastric body and fundus via anti-parietal cell and anti-intrinsic factor antibodies, resulting in achlorhydria, vitamin B12 malabsorption, and pernicious anemia. NSAID-induced gastropathy represents a chemical/reactive pattern (type C) caused by direct mucosal injury and prostaglandin depletion.

H. pylori is a gram-negative, microaerophilic, spiral-shaped bacterium that colonizes the gastric mucosa of approximately 50% of the world's population, with prevalence exceeding 80% in many developing countries. It produces urease (which neutralizes gastric acid by generating ammonia), vacuolating cytotoxin A (VacA), and cytotoxin-associated gene A protein (CagA) — virulence factors that damage the epithelium and trigger chronic inflammation. H. pylori infection is the primary cause of chronic active gastritis, duodenal ulcers (present in 90-95% of cases), gastric ulcers (60-70%), gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and is classified as a Class I carcinogen for gastric adenocarcinoma by the WHO. Transmission occurs primarily via the fecal-oral or oral-oral route, usually acquired in childhood.

NSAIDs cause gastrointestinal injury through two mechanisms: topical irritation due to their acidic properties, and systemic inhibition of cyclooxygenase-1 (COX-1), which reduces protective prostaglandin synthesis in the gastric mucosa. Prostaglandins normally stimulate mucus and bicarbonate secretion, maintain mucosal blood flow, and promote epithelial cell turnover. NSAID use increases the risk of peptic ulcers 3-5 fold and the risk of ulcer complications (bleeding, perforation) 4-6 fold. Risk factors for NSAID gastropathy include age over 65, history of peptic ulcer disease, concurrent use of corticosteroids or anticoagulants, high-dose or multiple NSAIDs, and H. pylori co-infection. COX-2 selective inhibitors (celecoxib) carry lower gastrointestinal risk but are not risk-free. Co-prescription of a proton pump inhibitor is recommended for patients with risk factors requiring chronic NSAID therapy.

Gastritis and peptic ulcers share overlapping symptoms: epigastric pain or burning, postprandial fullness, early satiety, nausea, and bloating. Duodenal ulcers classically produce hunger pain relieved by eating, while gastric ulcers may cause pain worsened by food intake. However, symptom patterns are unreliable for distinguishing the two. Up to 40% of patients with NSAID-related ulcers are asymptomatic until a complication occurs. Alarm features warranting urgent investigation include unintentional weight loss, dysphagia, persistent vomiting, evidence of gastrointestinal bleeding (hematemesis, melena, iron deficiency anemia), and age over 55 with new-onset dyspepsia.

Upper gastrointestinal endoscopy (esophagogastroduodenoscopy, EGD) is the gold standard for visualizing mucosal lesions, obtaining biopsies for histology, and ruling out malignancy. Endoscopy is indicated in patients with alarm features, those over 55 with new symptoms, and those failing empiric therapy. H. pylori testing can be non-invasive or invasive. Non-invasive tests include the urea breath test (UBT — sensitivity and specificity both exceeding 95%), stool antigen test (HpSA — comparable accuracy), and serology (useful for epidemiological studies but cannot distinguish active from past infection). Invasive tests performed during endoscopy include rapid urease test (CLO test), histological examination, and culture. Importantly, proton pump inhibitors, bismuth compounds, and antibiotics must be discontinued 2 weeks (PPIs) to 4 weeks (antibiotics/bismuth) before testing to avoid false-negative results.

Proton pump inhibitors (PPIs) are the mainstay of acid-suppressive therapy. They irreversibly inhibit the hydrogen-potassium ATPase (proton pump) in gastric parietal cells, reducing acid secretion by up to 99%. Omeprazole (20-40 mg daily), pantoprazole (40 mg daily), and esomeprazole (20-40 mg daily) are the most commonly prescribed. PPIs should be taken 30-60 minutes before breakfast for optimal efficacy. For uncomplicated duodenal ulcers, 4 weeks of PPI therapy achieves healing rates exceeding 95%; gastric ulcers typically require 8 weeks. H2-receptor antagonists such as ranitidine (note: withdrawn in many markets due to NDMA contamination concerns; famotidine 20-40 mg twice daily is the current preferred H2 blocker) provide less potent acid suppression but may be used for mild symptoms or as step-down therapy after PPI-induced healing.

Eradication of H. pylori is indicated in all infected patients with peptic ulcer disease, MALT lymphoma, after endoscopic resection of early gastric cancer, and in first-degree relatives of gastric cancer patients. Standard triple therapy consists of a PPI (e.g., omeprazole 20 mg twice daily) plus amoxicillin (1 g twice daily) plus clarithromycin (500 mg twice daily) for 14 days. However, rising clarithromycin resistance (exceeding 15-20% in many regions) has reduced efficacy. Bismuth quadruple therapy — PPI plus bismuth subsalicylate (or subcitrate) plus metronidazole plus tetracycline for 14 days — is recommended as first-line in areas with high clarithromycin resistance or as second-line after triple therapy failure. Concomitant therapy (PPI + amoxicillin + clarithromycin + metronidazole for 14 days) is another effective option. Eradication should be confirmed with UBT or stool antigen test at least 4 weeks after completing treatment.

Sucralfate — a complex of aluminum hydroxide and sulfated sucrose — forms a protective barrier over ulcerated mucosa by binding to positively charged proteins in the ulcer base. It is administered 1 g four times daily on an empty stomach. Bismuth subsalicylate has both cytoprotective and antimicrobial properties against H. pylori. Misoprostol, a synthetic prostaglandin E1 analog, can prevent NSAID-induced ulcers but is limited by gastrointestinal side effects (diarrhea) and is contraindicated in pregnancy. Dietary modifications — avoiding alcohol, caffeine, spicy foods, and eating smaller frequent meals — may provide symptomatic relief, though evidence for specific dietary interventions is limited.

Upper gastrointestinal bleeding is the most common complication, occurring in 15-20% of peptic ulcer patients over their lifetime. It presents with hematemesis (vomiting blood or coffee-ground material), melena (black tarry stools), or both, and may cause hemodynamic instability. Emergency endoscopy with hemostatic therapy (epinephrine injection, thermal coagulation, clipping) is the first-line intervention. Perforation — a full-thickness breach of the gastric or duodenal wall — occurs in 2-10% of ulcers and presents as sudden severe epigastric pain with peritoneal signs (board-like rigidity, absent bowel sounds); free air under the diaphragm on upright chest X-ray is diagnostic. Perforation requires emergency surgical repair. Gastric outlet obstruction due to chronic scarring at the pylorus or duodenal bulb presents with recurrent vomiting, early satiety, and weight loss, and may require endoscopic balloon dilation or surgery.

Prevention centers on H. pylori eradication, judicious NSAID use, and gastroprotection with PPIs when chronic NSAID therapy is unavoidable. Patients with complicated ulcer disease should be tested and treated for H. pylori and should avoid NSAIDs when possible. For those requiring long-term low-dose aspirin for cardiovascular protection, co-prescription of a PPI reduces ulcer risk. Smoking cessation accelerates ulcer healing and reduces recurrence. Patients with autoimmune gastritis require lifelong vitamin B12 monitoring and replacement, and periodic endoscopic surveillance for gastric neoplasia. Long-term PPI use warrants periodic reassessment, as potential risks include Clostridioides difficile infection, hypomagnesemia, vitamin B12 deficiency, and a small increased risk of gastric fundic gland polyps.

For more information on specific medications discussed in this article, explore the PillsCard drug pages: omeprazole, pantoprazole, esomeprazole, ranitidine, sucralfate, bismuth subsalicylate, amoxicillin, and clarithromycin. Always consult your physician or pharmacist before starting or changing medications for gastritis or ulcer disease.