Description

• Duodenal ulcer:
  • Most common form of peptic ulcer
  • Usually located in the proximal duodenum
  • Multiple ulcers or ulcers distal to the second portion of duodenum raise possibility of gastrinoma (Zollinger-Ellison syndrome).
• Gastric ulcer:
  • Less common than duodenal ulcer in absence of NSAID use
  • Commonly 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 in patients with a Meckel's diverticulum

Epidemiology

• Predominant sex: Male = Female
• Predominant age:
  • 70% of ulcers occur in patients ages 25–64.
  • Ulcer incidence increases with age.
• Peptic ulcer: 500,000 new cases/yr
• Recurrence: 4 million/yr
• Global incidence rate: 0.1–0.19%

• Peptic ulcer: 1.8% in the US
• Lifetime prevalence is 5–10% for patients not infected with Helicobacter pylori; 10–20% if infected.

Risk Factors

• H. pylori infection
• NSAID use
• Smoking cigarettes
• Family history of ulcers
• Gastrinoma
• Medications: Corticosteroids (high-dose and/or prolonged therapy), bisphosphonates, potassium chloride, chemotherapeutic agents (e.g., IV fluorouracil)

Genetics
Increased incidence of peptic ulcer disease (PUD) in families is likely due to familial clustering of H. pylori infection and inherited genetic factors reflecting response to the organism.

General Prevention

• NSAID ulcers: Avoid salicylates and NSAIDs:
  • Alternatives include acetaminophen and tramadol. COX-2 inhibitor use (e.g., celecoxib) is controversial due to potential cardiac safety risks.
  • If NSAIDs are needed, adjust the ibuprofen dose to <1,200 mg/d to decrease risk of ulcerogenesis, and add a proton pump inhibitor (PPI) or H₂ blocker.
  • To reduce ulcer risk, consider testing for and eradicating H. pylori before starting therapy with NSAIDs.
• Maintenance therapy with PPIs or H₂ blockers is indicated for patients with a history of ulcer complications, recurrences, refractory ulcers, or persistent H. pylori infection.
• Should also consider maintenance PPI treatment in patients with H. pylori negative, non–NSAID-induced ulcer.

Pathophysiology

Imbalance between aggressive factors (e.g., gastric acid, pepsin, bile salts, pancreatic enzymes) and defensive factors maintaining mucosal integrity (e.g., mucus, bicarbonate, blood flow, prostaglandins, growth factors, cell turnover)

Etiology

• May be multifactorial
• H. pylori infection: 90% of duodenal ulcers and 70–90% of gastric ulcers:
  • Lifetime risk for PUD in H. pylori–infected people: 10–20%
  • Annual risk of developing duodenal ulcer in H. pylori–infected people: ≤1%
• Ulcerogenic drugs (e.g., NSAIDs)
• Hypersecretory syndromes (e.g., gastrinoma)
• Retained gastric antrum
• Less common: Crohn disease, vascular insufficiency, radiation therapy, cancer chemotherapy, smoking

Commonly Associated Conditions

• Gastrinoma (Zollinger-Ellison syndrome)
• Multiple endocrine neoplasia type 1
• Carcinoid syndrome
• Chronic illness: Crohn's disease, chronic obstructive pulmonary disease (COPD), chronic renal failure, hepatic cirrhosis, cystic fibrosis
• Hematopoietic disorders (rare): Systemic mastocytosis, myeloproliferative disease, hyperparathyroidism, polycythemia rubra vera