What are the different etiologies of peptic ulcers?

Etiologies of Peptic Ulcer Disease

The primary causes of peptic ulcer disease are Helicobacter pylori infection (affecting approximately 42% of patients) and NSAID/aspirin use (36% of cases), with these two factors accounting for the vast majority of peptic ulcers. 1

Major Etiologic Categories

Helicobacter pylori Infection

• H. pylori is the main causative agent in gastroduodenal ulcer disease, representing the predominant mechanism worldwide 2
• The increasing incidence of H. pylori infection has fundamentally changed the epidemiology of peptic ulcer disease 3
• Approximately 1 in 5 peptic ulcers is associated with H. pylori infection 4
• Eradication of H. pylori reduces ulcer recurrence rates from 50-60% to 0-2% 1

NSAID and Aspirin Use

• NSAIDs and aspirin are the second most important pharmacologic causes, affecting acid secretion in the gastric mucosa 2
• NSAID use accounts for approximately 36% of peptic ulcer disease cases 1
• The combination of H. pylori infection and NSAID use synergistically increases the risk of bleeding ulcers more than sixfold 4
• Surreptitious NSAID usage is a cause of unexplained ulcer disease in up to 60% of patients 5

Corticosteroids

• Corticosteroids represent another important pharmacologic cause, affecting acid secretion in the gastric mucosa 2

Lifestyle and Environmental Factors

• Smoking contributes as a modifiable risk factor that alters gastric mucosal integrity 2
• High-salt-content diet contributes to altered gastric mucosal integrity 2
• Alcohol abuse has contributed to changing epidemiology of peptic ulcer disease 3

Stress Ulcers

• Stress ulcers occur particularly in critically ill patients in ICU settings or post-surgery 2
• Diagnosis may be obscured in sedated or unconscious patients 2

Hypersecretory States

• Zollinger-Ellison syndrome and other hypersecretory syndromes, although rare, must be excluded in refractory cases 6, 5
• Gastrinoma can present as intractable peptic ulcer disease progressing to gastric outlet obstruction despite maximal medical therapy 6

Iatrogenic Causes

• Endoscopic procedures including endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), and stricture dilation carry perforation risk 2
• ERCP-related perforations occur through multiple mechanisms with overall risk <1% but mortality of 7.8-9.9% 2

Infectious Causes (Geographic Variation)

• In low- and middle-income countries, typhoid fever (Salmonella enterica) is the most common cause of gastrointestinal perforation, with mortality ranging from 4.6% to 39%, particularly in children 2
• Abdominal tuberculosis affecting the ileocecal region can cause perforation, though less common in gastric locations 2

Traumatic Causes

• Blunt or penetrating trauma may cause immediate or delayed perforation through lacerations, transections, mural hematomas, or full-thickness contusions 2

Inflammatory Bowel Disease

• Crohn's disease can cause peptic ulcers, with focal chronic inflammation and architectural abnormalities in biopsies favoring this diagnosis 7, 5

Idiopathic Ulcers

• After excluding all known etiological factors, a group of patients with "idiopathic ulcers" remains 5
• These patients are characterized by postprandial hypersecretion of acid and hypergastrinemia with accelerated gastric emptying 8
• Idiopathic ulcers appear more resistant to standard therapy and can be associated with more frequent complications 5
• The interplay of factors may include genetic predisposition, altered acid secretion, rapid gastric emptying, defective mucosal defense mechanisms, psychological stress, and smoking 5

Critical Clinical Pitfalls

• Approximately 20% of patients with duodenal ulcers suffer recurrence despite successful H. pylori eradication, indicating the infection was not the actual cause 8
• When H. pylori infection and NSAID use coexist in a patient, it is not possible to establish which is the ulcer's cause 8
• As many as one-fifth of patients with ulcers may have the cause falsely attributed to H. pylori infection 8
• At least 20% of ulcer patients are H. pylori-negative upon original presentation in recent U.S. studies 8
• The proportion of non-H. pylori ulcer patients is larger than originally believed and likely to increase with declining incidence of H. pylori infection 8