Peptic Ulcer Disease – Causes, Symptoms, Diagnosis, Treatment and Ongoing care
- 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 Zollinger-Ellison syndrome.
- Gastric ulcer:
- Less common than duodenal ulcer in absence of nonsteroidal anti-inflammatory drugs (NSAIDs)
- Commonly located along lesser curvature of the antrum
- Esophageal ulcers: Located in the distal esophagus and usually secondary to gastroesophageal reflux disease (GERD); also seen with Zollinger-Ellison syndrome
- Ectopic gastric mucosal ulceration: May develop in patients with a Meckel’s diverticulum
- Predominant sex: Equal
- Predominant age:
- 70% of ulcers occur in patients between the ages of 25 and 64 years.
- Ulcer incidence increases with age.
- Peptic ulcer: 500,000 new cases/year
- Recurrence: 4 million/year
- Global incidence rate 0.1–0.19% (1)[A]
- Peptic ulcer: 1.8% in the US
- Lifetime prevalence is 5–10% for patients not infected with Helicobacter pylori; 10–20% if infected.
- H. pylori infection
- NSAID use
- Smoking cigarettes
- Family history of ulcers
- Zollinger-Ellison syndrome
- Medications: Corticosteroids (high-dose and/or prolonged therapy), bisphosphonates, potassium chloride, chemotherapeutic agents (e.g., IV fluorouracil)
Increased incidence of peptic ulcer disease (PUD) in families; familial clustering of H. pylori infection and inherited genetic factors reflecting response to the organism
- 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 (also not clear that COX-2-selective agents reduce major GI bleeding).
- If NSAIDs needed: Adjust ibuprofen dose to <1,200 mg/d to decrease risk of ulcerogenesis, and add proton pump inhibitor (PPI), misoprostol, or double-dose H2 blockers.
- To reduce ulcer risk, eradicate H. pylori before starting therapy with NSAIDs.
- Maintenance therapy with PPIs or H2 blockers is indicated for patients with a history of ulcer complications or recurrences, refractory ulcers, or persistent H. pylori infection.
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)
- 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 is ≤1%.
- Ulcerogenic drugs (e.g., NSAIDs)
- Hypersecretory syndromes (e.g., Zollinger-Ellison syndrome)
- Retained gastric antrum
- Less common: Crohn disease, vascular insufficiency, radiation therapy, cancer chemotherapy, smoking
Commonly Associated Conditions
- Zollinger-Ellison syndrome (gastrinoma)
- Multiple endocrine neoplasia type 1
- Carcinoid syndrome
- Chronic illness: Crohn disease, chronic obstructive pulmonary disease (COPD), chronic renal failure, hepatic cirrhosis, cystic fibrosis
- Hematopoietic disorders (rare): Systemic mastocytosis, myeloproliferative disease, hyperparathyroidism, polycythemia rubra vera
- Signs and symptoms:
- Episodic gnawing or burning epigastric pain
- Pain occurring after meals or on empty stomach
- Nocturnal pain
- Pain relieved by food intake, antacids, or antisecretory agents
- Nonspecific dyspeptic complaints: Indigestion, nausea, vomiting, loss of appetite, and heartburn
- Alarm symptoms:
- Anemia, hematemesis, melena, or heme-positive stool suggests bleeding.
- Vomiting and early satiety suggests obstruction.
- Anorexia or weight loss
- Persisting upper abdominal pain radiating to the back suggests penetration.
- Severe, spreading upper abdominal pain suggests perforation.
- NSAID-induced ulcers are often silent; perforation or bleeding may be initial presentation.
Physical exam for uncomplicated peptic ulcer may be unreliable and nonspecific: Epigastric tenderness (absent in at least 30% of older patients); guaiac-positive stool from occult blood loss
Diagnostic Tests & Interpretation
Initial lab tests
- Routine lab tests to consider when evaluating PUD:
- Complete blood count (CBC): Rule out anemia.
- Fecal occult blood test
- In patients with multiple or refractory ulcers, consider serum gastrin to rule out Zollinger-Ellison syndrome.
- Indications for H. pylori testing: New-onset PUD, history of PUD, persistent symptoms after empirical antisecretory therapy, gastric mucosa–associated lymphoid tissue (MALT) lymphoma, uninvestigated dyspepsia in patients <50 years of age without alarm symptoms
- H. pylori diagnostic tests: False-negative results may occur if patient was recently treated with antibiotics, bismuth, or PPIs; or in patients with active bleeding:
- Noninvasive tests:
- Serology antibody: Most commonly used for testing in primary care but slow to normalize after treatment, so cannot be used to document successful eradication (sensitivity 85%, specificity 79%) (2)[A]
- Urea breath test: Identifies active H. pylori infection; also used for posttreatment testing (sensitivity >95%, specificity >90%) (2)[A]
- Stool antigen: Can be used for screening and posttreatment testing (sensitivity 91%, specificity 94%) (2)[A]
- Invasive tests:
- Upper endoscopy with gastric biopsy, which can be evaluated with Steiner stain for direct visualization of organism (sensitivity >95%, specificity >95%) (2)[A]
- Rapid urease test: Conducted on gastric biopsies (sensitivity 93–97%, specificity 95%) (2)[A]
- Noninvasive tests:
Barium or Gastrografin contrast radiography (double-contrast hypotonic duodenography): Indicated when endoscopy is unsuitable or not feasible
Indications for upper endoscopy: Patients with suspected peptic ulcers who are >55 years of age, those who have alarm symptoms, and those with ulcers that do not respond to treatment (3)[A]
Functional dyspepsia, gastritis, GERD, biliary colic, pancreatitis, cholecystitis, Crohn disease, intestinal ischemia, variant angina pectoris, GI malignancy
- Acid suppression: PPIs: 1st line:
- Omeprazole 20 mg/d p.o.; lansoprazole 30 mg/d p.o.; rabeprazole 20 mg/d p.o.; esomeprazole 40 mg/d p.o.; or pantoprazole 40 mg/d p.o.
- Administer PPIs before breakfast.
- PPIs are not associated with an increased risk for major congenital birth defects, spontaneous abortions, or preterm delivery (4)[A].
- H2 blockers: Ranitidine or nizatidine 150 mg p.o. b.i.d. or 300 mg p.o. at bedtime, cimetidine 400 mg p.o. b.i.d. or 800 mg p.o. at bedtime, famotidine 150 mg p.o. b.i.d. or 300 mg p.o. at bedtime
- Treat ulcers for 6–8 weeks or until healing is confirmed in patients with complicated ulcers.
- PPIs heal peptic ulcers more rapidly and should not be taken with H2 blockers.
- Optimal H. pylori eradication regimens (2)[A]: Triple therapy: 2 antibiotics plus a PPI × 14 days: Omeprazole 20 mg p.o. b.i.d., or lansoprazole 30 mg p.o. b.i.d., or pantoprazole 40 mg p.o. b.i.d., or rabeprazole 20 mg p.o. b.i.d., or esomeprazole plus clarithromycin 500 mg p.o. b.i.d. plus amoxicillin 1 g p.o. b.i.d. or metronidazole 500 mg p.o. b.i.d. in patients with allergy to amoxicillin:
- Triple and quadruple therapy have similar eradication rates for primary H. pylori infection (5)[A].
- Bacterial resistance: Clarithromycin 10%, amoxicillin 1.4%, metronidazole 37%: Culture-guided choice of triple therapy is more clinically and cost effective.
- Treatment of H. pylori–negative ulcers (usually due to NSAIDs):
- Discontinue NSAID use
- Treat acutely with PPIs for 4–8 weeks; may use longer as maintenance for patients with recurrent or complicated ulcers or in patients who require long-term aspirin or NSAID use.
- Renal insufficiency: Decrease H2 blocker dosage by 50%.
- Cimetidine: Avoid with theophylline, warfarin, phenytoin, and lidocaine.
- Proton pump inhibitors may decrease bone density. Obtain interval bone densitometry with long-term PPI use.
- Omeprazole may decrease efficacy of clopidogrel. May wish to use H2 blockers or an alternative PPI (6).
- For H. pylori eradication: Use 2nd-line therapy if 1st line fails (2)[A]:
- Bismuth quadruple therapy × 14 days:
- Bismuth subsalicylate 525 mg p.o. q.i.d. plus
- Metronidazole 500 mg p.o. q.i.d. plus
- Tetracycline 500 mg p.o. q.i.d. plus
- PPI × 14 days
- Alternative 2nd-line therapy:
- Levofloxacin 250 mg p.o. b.i.d. plus
- Amoxicillin 1,000 mg p.o. b.i.d. plus
- PPI p.o. b.i.d.
- Another alternative salvage therapy:
- Rifabutin 300 mg p.o. daily plus
- Amoxicillin 1,000 mg p.o. b.i.d. plus
- PPI p.o. b.i.d.
- Bismuth quadruple therapy × 14 days:
- Alternative ulcer-healing drugs: Sucralfate 1 g p.o. q.i.d. or 2 g p.o. b.i.d. × 4–8 weeks
- Precautions: Renal insufficiency:
- Reduce H2 blocker dosage by 50%.
- Avoid magnesium-containing antacids.
- Significant possible interactions:
- Cimetidine inhibits cytochrome P450 isozymes (avoid with theophylline, warfarin, phenytoin, and lidocaine).
- Omeprazole may prolong elimination of diazepam, warfarin, and phenytoin.
- Sucralfate reduces absorption of tetracycline, norfloxacin, ciprofloxacin, and theophylline; leads to subtherapeutic levels.
- Endoscopy indicated for patients over the age of 50 with new onset of dyspeptic symptoms, those who do not respond to treatment, and those of any age with alarm symptoms such as bleeding and weight loss (7)[A]
- At endoscopy:
- Biopsy of stomach for H. pylori testing
- Biopsy of margin of gastric ulcer to confirm benign etiology
- Interventions to stop active bleeding, or prevent rebleeding in those with certain stigmata include injection with epinephrine, heater probe treatment, or placement of endoscopic clips.
- Indications for surgery: Ulcers that are refractory to treatment and patients at high risk for complications (e.g., transplant recipients, patients dependent on steroids or NSAIDs); surgery also may be needed acutely for treatment of perforation and bleeding that is refractory to endoscopic therapy.
- Surgical options:
- Duodenal ulcers: Truncal vagotomy and drainage (pyloroplasty or gastrojejunostomy), selective vagotomy (preserving the hepatic and/or celiac branches of the vagus) and drainage, or highly selective vagotomy
- Gastric ulcers: Partial gastrectomy, Billroth I or II
- Laparoscopy or open patching of perforated ulcers (8)
- Discontinue ulcerogenic agents (e.g., NSAIDs).
- Bleeding peptic ulcers:
- Stable patient: Give PPI to reduce transfusion requirements, need for surgery, and duration of hospitalization (3)[A].
- Unstable patients: Fluid or packed red blood cell resuscitation followed by emergent EGD; use IV PPI
- Perforated peptic ulcers: Free peritoneal perforation with bacterial peritonitis is a surgical emergency.
- H. pylori eradication: Expected in >90% (with double antibiotic regimen): Confirm eradication by urea breath test.
- Acute duodenal ulcer: Monitor clinically.
- Acute gastric ulcer: Confirm healing via endoscopy after 12 weeks if biopsy not done initially to confirm that lesion is benign.
After H. pylori eradication:
- Low ulcer relapse rate; if relapse, consider surreptitious use of NSAIDs
- Reinfection rates <1% per year
- Low risk of rebleeding
- Decreased NSAID ulcer recurrence
- Hemorrhage: Up to 25% of patients (initial presentation in 10%)
- Perforation <5% of patients
- Gastric outlet obstruction: Up to 5% of duodenal or pyloric channel ulcers; male predilection found
- Risk of gastric adenocarcinoma increased in H. pylori–infected patients
1. Sung JJ, Kuipers EJ, El-Serag HB. Systematic review: update on the global incidence and prevalence of peptic ulcer disease. Aliment Pharmacol Ther. 2009.
2. Saad R, Chey WD. A clinician’s guide to managing Helicobacter pylori infection. Cleve Clin J Med. 2005;72:109–10, 112–3, 117–8 passim
3. Ramakrishnan K, Salinas RC. Peptic ulcer disease. Am Fam Physician. 2007;76:1005–12.
4. Gill SK, O’Brien L, Einarson TR, et al. The Safety of Proton Pump Inhibitors (PPIs) in Pregnancy: A Meta-Analysis. Am J Gastroenterol. 2009;104:1541–5.
5. Luther J, Higgins PD, Schoenfeld PS, et al. Empiric quadruple vs. triple therapy for primary treatment of Helicobacter pylori infection: Systematic review and meta-analysis of efficacy and tolerability. Am. J. Gastroenterol. 2010;105:65–73.
6. Johnson DA et al. Safety of proton pump inhibitors: current evidence for osteoporosis and interaction with antiplatelet agents. Curr Gastroenterol Rep.2010;12:167–74.
7. ASGE Standards of Practice Committee, Banerjee S, Cash BD, et al. The role of endoscopy in the management of patients with peptic ulcer disease.Gastrointest. Endosc. 2010;71:663–8.
8. Bertleff MJ, Lange JF et al. Perforated Peptic Ulcer Disease: A Review of History and Treatment. Digestive surgery. 2010;27:161–169.
- 530.20 Ulcer of esophagus without bleeding
- 531.90 Gastric ulcer, unspecified as acute or chronic, without mention of hemorrhage or perforation, without mention of obstruction
- 533.90 Peptic ulcer of unspecified site, unspecified as acute or chronic, without mention of hemorrhage or perforation, without mention of obstruction
- 532.90 Duodenal ulcer, unspecified as acute or chronic, without hemorrhage or perforation, without mention of obstruction
- 13200003 peptic ulcer (disorder)
- 6129004 peptic ulcer of esophagus (disorder)
- 397825006 gastric ulcer (disorder)
- 51868009 duodenal ulcer disease (disorder)
- In patients with PUD, H. pylori should be eradicated to assist in healing and to reduce the risk of gastric and duodenal ulcer recurrence (3)[A].
- In patients with peptic ulcers, PPIs provide acid suppression, healing rates, and symptom relief superior to other antisecretory therapies (3)[A].
- Upper endoscopy is indicated in patients with suspected peptic ulcers who are >55 years of age, those who have alarm symptoms, and those who do not respond to treatment (3)[A].