What Causes Gastric Ulcers
Gastric ulcers are caused primarily by two factors: Helicobacter pylori infection and nonsteroidal anti-inflammatory drug (NSAID) use, which together account for nearly all cases. 1, 2
Primary Etiologic Agents
Helicobacter pylori Infection
- H. pylori is the main causative agent in gastroduodenal ulcer disease and represents the predominant mechanism worldwide. 1
- The bacterium is found in 53% of patients presenting with bleeding ulcers, though this represents a shift from historical patterns where NSAIDs have become increasingly prevalent. 3, 1
- Among those with latent H. pylori infection, the risk of developing an ulcer is approximately 1% per year (1 per 100 patient-years) independent of NSAID use. 4
NSAID and Aspirin Use
- NSAIDs and aspirin are the second most important pharmacologic causes, affecting acid secretion and disrupting gastric mucosal integrity. 1
- NSAID use has surpassed H. pylori as the most commonly identified risk factor in some populations, particularly in developed countries where H. pylori prevalence is declining. 3
- Approximately 1 in 5 peptic ulcers is associated with H. pylori infection, with most of the remainder due to NSAID use. 5
Synergistic Interaction Between H. pylori and NSAIDs
- The combination of H. pylori infection and NSAID use synergistically increases the risk of bleeding ulcers more than sixfold. 5
- H. pylori infection increases the risk of upper GI complications in NSAID users by 2- to 4-fold. 4, 1, 6
- When aspirin is combined with NSAIDs in the presence of H. pylori, the relative risk of GI bleeding increases to more than 10 times that seen with either agent alone. 3, 6
Additional Contributing Factors
Corticosteroids
- Corticosteroids represent another important pharmacologic cause that affects acid secretion in the gastric mucosa. 1
- Concomitant corticosteroid use increases ulcer risk in NSAID users. 3, 6
Anticoagulants and Antiplatelet Agents
- Warfarin and other anticoagulants significantly increase ulcer complication risk, particularly when combined with NSAIDs. 1, 6
- Concomitant use of low-dose aspirin (≤325 mg) or other antiplatelet agents increases NSAID-related GI risk. 6
Lifestyle and Dietary Factors
- Smoking contributes as a modifiable risk factor that alters gastric mucosal integrity. 1
- High-salt-content diet contributes to altered gastric mucosal integrity. 1
- Alcohol abuse has contributed to changing epidemiology of peptic ulcer disease. 1
Stress Ulcers
- Stress ulcers occur particularly in critically ill patients in ICU settings or post-surgery, representing a distinct pathophysiologic mechanism. 1
Key Mechanistic Pathways
- Both H. pylori and NSAIDs induce ulcers through shared mechanisms: decreased pH, imbalance between apoptosis and proliferation, reduction in mucosal blood flow, and recruitment of polymorphonuclear cells in distinct compartments. 7
- The severity of NSAID-induced gastrointestinal toxicity correlates with the anti-inflammatory potency of the agent; high-potency NSAIDs (e.g., piroxicam) cause more ulceration than lower-potency agents (e.g., ibuprofen). 6
Critical Clinical Pitfall
A common error is assuming that gastric ulcers in NSAID users are solely NSAID-induced. Both NSAIDs and H. pylori are independent risk factors, and in an individual patient with an ulcer, one cannot be certain which factor is responsible—both risks should be addressed if present. 8 This is particularly important because H. pylori eradication alone is insufficient for secondary prevention of NSAID-induced ulcers in patients who continue NSAID therapy. 7, 9