Peptic Ulcer Disease


Peptic ulcer disease (PUD) is characterized by defects in the stomach and/or duodenal mucosa, leading to inflammation of the underlying tissue by gastric acid and pepsin.


  • Duodenal ulcer: most common form of PUD; usually located in the proximal duodenum
  • Multiple ulcers/ulcers distal to the second portion of duodenum and/or jejunum raise possibility of gastrinoma (Zollinger-Ellison syndrome [ZES]).
  • Gastric ulcer: less common than duodenal ulcer in absence of NSAID use; often located along lesser curvature of the antrum
  • Esophageal ulcers: located in the distal esophagus; usually secondary to gastroesophageal reflux disease (GERD); also seen with gastrinoma
  • Ectopic gastric mucosal ulceration: may develop with Meckel diverticulum


The incidence and prevalence have decreased in high-income countries including United States (1).


  • Duodenal ulcers: more common in men
  • Predominant age: 70% of ulcers occur between ages 25 and 64 years. Duodenal/gastric ulcer incidence increases with age.
  • Peptic ulcer: 500,000 new cases per year
  • Recurrence: 4 million per year
  • Global incidence rate 0.1–0.19%; overall decrease from improved sanitary conditions, effective treatment, and careful NSAIDs use
  • Lifetime risk globally: 5–10%

<10% in the general population; lifetime prevalence is higher (10–20%) in Helicobacter pylori–positive patients, compared to the general population (5–10%).

Etiology and Pathophysiology

Increased incidence in families due to familial clustering of H. pylori infection and inherited genetic factors reflecting response to organism.

Risk Factors

  • Most common cause: H. pylori infection
  • NSAIDs use (including aspirin and COX-2 inhibitors): second most common cause; those with regular use have risk of concomitant H. pylori infection.
  • Other medication use: corticosteroids (high dose; prolonged therapy), bisphosphonates, potassium chloride, clopidogrel, sirolimus chemotherapeutic agents
  • Hypersecretion syndromes: gastrinoma (ZES), systemic mastocytosis, cystic fibrosis, hyperparathyroidism, carcinoid syndrome, antral G-cell hyperplasia
  • Others: tobacco use, alcohol use, stress (e.g., acute illness, ventilator support, extensive burns, head injury), radiation therapy

General Prevention

  • Educate patients about harmful agents like NSAIDs, aspirin, alcohol, tobacco, and caffeine.
  • Discontinue NSAIDs and use acetaminophen instead when appropriate, or add proton pump inhibitor (PPI) in patients with previous NSAID-related ulcer.
    • If NSAIDs are necessary, use the lowest possible dose with a PPI or misoprostol.
    • To reduce ulcer risk, consider testing for and eradicating H. pylori.
  • Maintenance therapy with PPIs or H2 blockers: indicated if history of ulcer complications, recurrences, refractory ulcers, or persistent H. pylori infection
  • Consider maintenance PPI treatment in patients with H. pylorinegative, non–NSAID-induced ulcer.
  • H. pylori infection: present in 95% of duodenal and 70% of gastric ulcers; annual risk of duodenal ulcer in those with infection is ≤1%.
  • Strong association exists between obesity and PUD; counsel patients on weight loss

Commonly Associated Conditions

  • Gastrinoma (ZES); multiple endocrine neoplasia type 1; carcinoid syndrome
  • Chronic illness: Crohn disease, chronic obstructive pulmonary disease, chronic renal failure, hepatic cirrhosis, cystic fibrosis
  • Hematopoietic disorders (rare): systemic mastocytosis, myeloproliferative disease, hyperparathyroidism, polycythemia rubra vera

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