peptic ulcer disease (PUD)

Classification

endoscopic classification

• grade 1A: pulsatile bleeding
• grade 1B: oozing blood
• grade 2A: non-bleeding visible vessel (pigmented protruberance)
• grade 2B: adherent clot
• grade 2C: flat pigmented spot
• grade 3: clean ulcer base

Etiology

• Helicobacter pylori infection*
  • associated with 90-95% of duodenal ulcers
  • associated with 70-90% of gastric ulcers
  • decreasing as cause of peptic ulcer
    • only 17% of peptic ulcers H pylori positive
  • major cause of chronic active gastritis
• non-steroidal anti-inflammatory drugs (NSAIDs)*
  • may cause gastric (antral) or duodenal ulcers
  • addition of steroids potentiates risk of PUD
  • accounts for majority of PUD not associated with H pylori
  • presence of Helicobacter pylori
    • does not confer additional risk
    • does confer additional risk
  • glucocorticoids also risk factor
• ethacrynic acid
• severe physiologic stress
  • burns
  • CNS trauma
  • surgery
  • severe medical illness
• psychosocial stress
  • low stress resilience is a marker of risk
• hypersecretory states
  • gastrinoma (Zollinger-Ellison syndrome)
  • multiple endocrine neoplasia (MEN)-1
  • antral G cell hyperplasia
  • systemic mastocytosis
  • basophilic leukemia
• viral infection
  • Herpes
  • Cytomegalovirus
• radiation
• chemotherapy
• vascular insufficiency: crack cocaine
• duodenal obstruction
• diseases associated with peptic ulcer disease (PUD)
  • cirrhosis of the liver
  • chronic obstructive pulmonary disease
  • renal failure
  • renal transplantation
• smoking & alcohol are risk factors
• anticoagulation is a risl factor for bleeding
• 50% of peptic ulcer idiopathic

* H pylori & NSAIDs cause > 90% of peptic ulcers

Pathology

• a break in the gastric or duodenal mucosa >= 5 mm
• imbalance between protective & injurious factors
  • protective factors: mucous, bicarbonate (alkaline tide), mucosal blood flow, prostaglandins, hydrophobic mucosal layer, restitution, epithelial renewal
  • injurious factors: H. pylori, acid, pepsin, bile acids, smoking, ethanol, NSAIDs, steroids, stress

Genetics

• familial tendency
• increased frequency in persons with blood group O

Clinical manifestations

• patients commonly asymptomatic at diagnosis
  • up to 20% of patients
  • peptic ulcer often detected during evaluation for positive fecal occult blood
  • elderly patients are more likely to be asymptomatic & have an increased risk of GI bleeding, especially if taking NSAIDs
• epigastric pain & tenderness
  • gnawing or burning pain
  • onset of pain 1-3 hours after meals
  • pain relieved by antacids
  • pain may occur at night
  • pain may radiate to back
  • pain is generally intermittent
  • duodenal ulcer more likely than gastric ulcer to cause pain that awakens patient at night
• nausea/vomiting:
  • vomiting may be related to gastric outlet obstruction
• dyspepsia: belching, bloating, distention, fatty food intolerance
• heartburn
• anorexia/weight loss
• hematemesis
• melena

Diagnostic criteria

• endoscopic diagnosis
  • a break in the gastric or duodenal mucosa >= 5 mm

Laboratory

• fecal occult blood:
  • guaiac-positive stool may initiate diagnostic workup
• complete blood count (CBC)
• INR if anticoagulation
• serum chemistries
  • serum creatinine
  • serum calcium, serum albumin
  • serum gastrin in recurrent, refractory PUD or in patients with a family history of Zollinger-Ellison (ZE) syndrome
• diagnostic tests for Helicobacter pylori (test all patients)
  • serology for H pylori IgG antibodies
  • urease breath test
  • H pylori stool antigen assay
  • gastric biopsy during upper GI endoscopy
  • predictive value of H pylori testing without EGD is low
• secretin-stimulation test
  • used in conjunction with serum gastrin
  • distinguish ZE from other hypergastrinemic states
    • achlorhydria
    • pharmacologic agents
      • proton-pump inhibitors
      • H2 receptor antagonists
• measurement of gastric acid secretion
  • used in conjunction with serum gastrin & secretin-stimulation test
  • distinguish ZE from other hypergastrinemic states
  • not useful by itself in evaluation of PUD

Diagnostic procedures

• esophagogastroduodenoscopy (EGD) is gold standard
  • indications
    • patients > 55 years or other alarm features of dyspepsia
    • upper GI bleed (INR < 2.5)
    • repeat upper GI endoscopy for treated peptic ulcers not routinely indicated
      • repeat upper endoscopy reserved for
        • persistent symptoms after 8-12 weeks of therapy
        • ulcers of unknown cause
        • if no gastric biopsy obtained during initial upper GI endoscopy
  • a break in the gastric or duodenal mucosa >= 5 mm
  • patients < 55 years of age with dyspepsia may be treated empirically without EGD
  • procedure
    • identify gastric ulcers, duodenal ulcers
    • biopsy all gastric ulcers to rule out malignancy
    • test for Helicobacter pylori
    • endoscopic therapy indicated for active bleeding (grade 1) or visible blood vessel within ulcer (grade 2A)
  • for high-risk peptic ulcers (grade 1A-2B), observe patient in hospital for 72 hours
  • for low risk peptic ulcers, treat with PPI, refeed within 24 hours, early hospital discharge
    • no benefit of observing for 24 hours in hospital
  • duodenal ulcers are low risk for malignancy
    • biopsy unnecessary unless refractory to therapy

Radiology

• upper GI series

Complications

• gastrointestinal bleeding (15%)
  • hematemesis, melena, hematochezia
  • risk of rebleeding is highest in the 1st 72 hours after endoscopic therapy
  • risk of rebleeding is higher in idiopathic peptic (30%) than peptic ulcers due to H pylori (7%) or NSAIDs (3%)
  • oral esomeprazole noninferior to IV esomeprazole after endoscopic treatment of bleeding peptic ulcer
• perforated peptic ulcer, gastric perforation, intestinal perforation
  • sudden severe abdominal pain, peritoneal signs, shock
• obstruction: gastric outlet obstruction, intestinal obstruction
  • nausea/vomiting, early satiety, succussion splash
• penetration
  • gradual increase in abdominal pain frequency & severity
  • may present as acute pancreatitis

• disease interaction of psychosocial stress with peptic ulcer

Differential diagnosis

• gastroesophageal reflux disease (GERD)
• dyspepsia without ulcer (gastroduodenitis)
  • pharmacologic agents
  • theophylline
  • digitalis
  • caffeine
• biliary tract disease
• pancreatitis
• musculoskeletal
• carcinoma
  • gastric
  • duodenal (rare)
  • pancreatic
• Crohn's disease
• infectious agents
  • giardiasis
  • tuberculosis
  • Mycobacterium avium-intracellulare
• sarcoidosis
• Menetrier's disease
• lymphoma

Management

• test for & treat Helicobacter pylori if positive; then, empiric treatment with proton pump inhibitor (PPI) for patients < 55 years & no alarm features of dyspepsia
• stop & avoid NSAIDs
  • aspirin may be continued in combination with proton pump inhibitor in patients with cardiovascular disease (see antiplatelet therapy below)
    • restart aspirin 1-7 days after initiation of proton pump inhibitor
      • restart day 1 ok, restart in 10 days is too late
  • if no alternative to NSAID, use COX-2 inhibitor plus a PPI QD
• smoking cessation
• endoscopy as indicated (see Diagnostic-procedures)
  • patients with low-risk peptic ulcer may be fed within 24 hours, receive daily proton pump inhibitor & discharged from hospital
• proton pump inhibitors (PPI)
  • once daily oral PPI
    • hemodynamically stable patient with hematemesis & a clean-based gastric ulcer with no active bleeding (low risk)
    • oral PPI noninferior to IV PPI after endoscopic treatment of bleeding peptic ulcer
  • duration of therapy
    • high risk
      • high-dose PPI IV infusion or IV push BID for 3 days after successful endoscopic therapy (strong recommendation) & BID for 2 weeks (weak recommendation)
    • low risk: oral QD for 4-8 weeks
    • idiopathic bleeding ulcers require indefinite duration of PPI therapy due to risk of rebleeding
  • 80-100% healing of ulcer after completion of therapy
  • omeprazole (Prilosec) 20-40 mg QD
  • lansoprazole (Prevacid) 15-30 mg QD
  • addition of H2-receptor antagonist may be synergistic (see proton pump inhibitor)
• H2-receptor antagonist
  • duration of therapy 6-8 weeks
  • 90-95% healing of ulcer after completion of therapy
  • cimetidine (Tagamet) 400 mg BID or 800 mg QHS
  • famotidine (Pepcid) 20 mg BID or 40 mg QHS
  • nizatidine (Axid) 150 mg BID or 300 mg QHS
  • ranitidine (Zantac) 150 mg BID or 300 mg QHS
• prostaglandins
  • inhibit acid secretion by inhibiting activation of adenylate cyclase in gastric parietal cells by histamines
  • used primarily as prophylactic agents, not recommended for routine treatment of PUD
  • Misoprostol (Cytotec) 200 ug QID
• antimuscarinic agents:
  • pirenzipine
  • telenzipine
  • not approved for used in the US
• antacids
• cytoprotective agents
  • sucralfate (Carafate) 1 g QID or 2 g BID for 6-8 weeks
  • bismuth subsalicylate
• nitrates (Isordil, nitroglycerin) may protect against bleeding ulcers
• avoid excess alcohol
• stress-reduction
• surgery for peptic ulcer complications
• blood transfusion only if blood hemoglobin < 7 g/dL (conditional recommendation)
• follow-up:
  • endoscopy to document healing of gastric ulcer & to rule-out gastric cancer
  • repeat endoscopy not needed in the absence of complications
    • low risk peptic ulcers due to NSAIDs in younger patients < 55 years
    • duodenal ulcers (low risk of malignancy)
  • 1 year recurrence rate < 10% if Helicobacter pylori is eradicated
  • follow-up H pylori testing (proof of eradication)
    • urease breath test or
    • H pylori stool antigen testing
    • H pylori serology maintains elevated titers > 1 year after successful eradication
• antiplatelet therapy
  • combination aspirin 80 mg + proton pump inhibitor in patients with healed peptic ulcers is safer than clopidogrel (Plavix)
  • aspirin-related ulcers will heal with proton pump inhibitor regardless of whether aspirin is continued or switched to clopidogrel
  • restarting low-dose aspirin 3-5 days after upper GI bleed reduces 30-day mortality 10-fold in patients with cardiovascular disease, while increasing rebleeding rates only 2-fold
  • restart aspirin 1-7 days after resolution of bleeding & initiation of proton pump inhibitor if peptic ulcer related to aspirin use for secondary prophylaxis for cardiovascular disease
• restart anticoagulation after resolution of bleeding
  • restart anticoagulation in 7 days

More general terms

• gastrointestinal ulcer
• chronic gastrointestinal disease

More specific terms

• duodenal ulcer
• gastric ulcer
• perforated peptic ulcer

Additional terms

• antiulcer agent
• dyspepsia (indigestion)
• Helicobacter pylori
• NSAID gastropathy

Patient information

peptic ulcer disease patient information