Causes of Peptic Ulcer Disease
The two principal causes of peptic ulcer disease are Helicobacter pylori infection (affecting approximately 42% of patients) and NSAID/aspirin use (affecting approximately 36% of patients), with gastric acid serving as an essential aggravating factor rather than a primary cause 1.
Primary Etiologic Factors
Helicobacter pylori Infection
H. pylori gastritis is an infectious disease responsible for many peptic ulcers and represents a major causative factor 2. The bacterium has been identified in approximately 42% of patients with peptic ulcer disease 1. Importantly, eradicating H. pylori decreases peptic ulcer recurrence rates dramatically from approximately 50-60% to 0-2% 1, confirming its causal role.
NSAID and Aspirin Use
NSAID use has surpassed H. pylori as the most commonly identified risk factor among patients with bleeding ulcers, found in 53% of such patients 3. NSAIDs and aspirin are etiologic factors in approximately 36% of people with peptic ulcer disease 1. The mechanism involves direct mucosal injury and systemic prostaglandin inhibition.
Even low-dose aspirin (81-325 mg/day) increases the risk for GI bleeding 2-4 times 3. When aspirin is combined with NSAIDs, the relative risk of GI bleeding increases to more than 10 times that seen with either agent alone 3.
Synergistic Risk Factors
The combination of H. pylori infection and NSAID use synergistically increases the risk of bleeding ulcers more than sixfold 4. This represents a critical clinical consideration, as patients with both risk factors face substantially elevated complications.
Secondary Contributing Factors
Gastric Acid
Gastric acid is an aggravating factor rather than a primary cause—gastric acid alone can hardly develop peptic ulcers 5. However, acid suppression remains the cornerstone of treatment because ulcers cannot heal in an acidic environment.
Stress
Mental and physical stress is considered one of four important factors in peptic ulcer development 5. Notably, research from the 1995 Hanshin-Awaji earthquake showed that 83.2% of patients who developed stress ulcers were infected with H. pylori 5, suggesting that stress ulcers predominantly develop in those already infected with the bacterium.
Risk Factors for NSAID-Related Ulcers
The most significant risk factors include:
- History of previous peptic ulcer (odds ratio as high as 13.5) 3
- History of NSAID-related GI complications
- Advanced age (increases risk by approximately 4% per year) 3
- Concomitant use of corticosteroids or anticoagulants
- High-dose NSAIDs or combinations of NSAIDs including aspirin
- Concurrent use of coxibs and over-the-counter products 3
Idiopathic Ulcers
Patients who do not use NSAIDs and are H. pylori negative are considered to have idiopathic peptic ulcers 6. These represent a minority of cases after the two primary causes are excluded.
Clinical Implications
The declining prevalence of peptic ulcer disease over the past 20 years is attributed to improved H. pylori management, more conservative NSAID use, and widespread proton pump inhibitor availability 7. Discontinuing NSAIDs heals 95% of ulcers and reduces recurrence from 40% to 9% 1, while H. pylori eradication essentially eliminates recurrence risk when successful.