Peptic Ulcer Disease

Peptic ulcer disease are erosions in the GI mucosa that extend through the muscularis propria. H. pylori is a common cause of peptic ulcer disease and was first elucidated by Marshall and Warren in 1984. They later won the 2005 Nobel Prize in Medicine for their work.

Etiology

• Common
  • H. pylori infection
  • NSAIDs
  • Medications 
• Rare: Zollinger-Ellison syndrome, malignancy, stress, and others
• Risk factors: smoking, alcohol, stress, spicy foods

Epidemiology

• Declining in developed countries
• Lifetime prevalence 5-10%

Pathogenesis

• Duodenal ulcers
  • Require acid and pepsin secretion in combination with an H. pylori infection or NSAID ingestion
  • Located on the inside of the upper portion of the small intestine (duodenum)
• Gastric ulcers: ulcers located on the inside of the stomach
• Due to decreased defensive factors, increased aggressive factors, or both
  • Defensive factors: mucosal bicarbonate, mucus, blood flow, growth factors, cell renewal, endogenous prostaglandins
  • Aggressive factors: hydrochloric acid, pepsins, ethanol, smoking, duodenal reflux, ischemia, NSAIDs, hypoxia, H. pylori infection
• H. pylori proposed mechanisms
  • Production of toxic mediators causing tissue injury (urease, cytotoxics, etc.)
  • Induction of mucosal immune response
  • Gastric metaplasia in the duodenum
• NSAIDs
  • Absorbed through stomach and small intestine
  • MOA: inhibit COX
    • COX is the rate-limiting step of prostaglandin synthesis in the GI tract
    • Prostaglandins promote gastric and duodenal mucosal protection from luminal acid and pepsin via multiple mechanisms (mucin, bicarb, blood flow, epithelial cell proliferation)

History

• Duodenal ulcer: burning, midepigastric pain relieved by food
• Gastric ulcer: burning, midepigastric pain within 15 – 30 minutes of a meal
• Recurrent episodes of quiescence and relapse
• Bleeding
• Bloating, belching, feelings of fullness
• Nausea 
• Vomiting
• Hematemesis
• Melena

Labs

• CBC
• LFTs
• Creatinine
• Amylase
• Calcium
• Gastrin, if ulcers are refractory to medical therapy or require surgery

Diagnosis

• H. pylori testing
  • H. pylori testing is recommended in all patients with suspected PUD
  • H. pylori invasive tests
    • Urease assay
      • Endoscopic biopsy from gastric body and antrum
      • > 90% sensitivity, 95 – 100% specificity
      • Sensitivity lowered in patients on PIs, H2-receptor antagonists, or antibiotics
    • Histology
      • Endoscopic biopsy of gastric mucosa
      • 95% sensitivity, 99% specificity
      • Sensitivity lowered in patients on PIs, H2-receptor antagonists, or antibiotics
      • Can assess severity of gastritis and confirm presence/absence of H. pylori
    • Culture
      • Culture of gastric mucosa
      • 80% sensitivity, 100% specificity
  • H. pylori noninvasive tests
    • Urea breath test
      • Based on ability of H. pylori to hydrolyze urea
      • > 95% sensitivity and specificity
      • Sensitivity lowered in patients on PIs, H2-receptor antagonists, or antibiotics → patients recommended to stop antibiotics for 4 weeks and PPIs for 2 weeks for optimal testing
    • Stool antigen
      • > 90% sensitivity, 86 – 92% specificity
      • > 90% accurate
    • Serology
      • 90% sensitivity, 76 – 96% specificity
      • Antibody titers can remain high for ≥ 1 year after H. pylori eradication
• Esophagogastroduodenoscopy (EGD)
  • Can biopsy during procedure
  • Acute ulcers have regular borders
  • Chronic ulcers have elevated borders with inflammation
• Upper GI radiography (barium swallow)
  • Barium within the ulcer craters
  • Helpful with determining location and depth of the ulcer

Treatment

• Medical treatment
  • H. pylori eradication
    • Triple therapy
      • PPI
      • 2 antibiotics: clarithromycin, amoxicillin (replace amoxicillin with metronidazole if the patient is allergic)
    • Quadruple therapy
      • PPI
      • 2 antibiotics: clarithromycin, amoxicillin (replace amoxicillin with metronidazole if the patient is allergic)
      • Bismuth
  • PPIs: more rapid healing than standard H2-receptor antagonists
  • H2-receptor antagonists
  • Antacids
  • Other recommendations: medications, lifestyle changes, smoking cessation, NSAID and aspirin discontinuation, avoiding coffee and alcohol
• Surgical intervention for PUD → goal: reduce gastric acid secretion
  • Truncal vagotomy
  • Selective vagotomy
  • Highly selective vagotomy [parietal cell vagotomy/proximal gastric vagotomy]
  • Truncal vagotomy and antrectomy
  • Partial gastrectomy

Relevant Information

• Strong association between MALT lymphoma and H. pylori. Regression of lymphomas has been shown after H. pylori eradication
• Most gastric ulcers (60%) occur on the lesser curvature of the stomach, near the incisura
• Most duodenal ulcers occur at the duodenal bulb
• Gastric ulcers rarely develop before 40 y/o; peak incidence is 55-65 y/o
• Gastric ulcers must be differentiated between gastric carcinoma and a benign ulcer. In contrast, duodenal ulcers are rarely malignant
• Concerning ulcer characteristics: large ulcer, ulcers with irregular border, ulcers with heaped-up borders

Types of Gastric Ulcers

Complications

• Upper GI bleed
• Gastric outlet obstruction 
• Fistulization
• Perforation: most occur along the anterior aspect of the lesser curvature

Differential Diagnoses

• Gastritis
• GERD
• Gastric cancer
• Pancreatitis
• Biliary colic
• Cholecystitis