Peptic Ulcer Disease (PUD)

A 45-year-old man presents with recurrent burning epigastric pain for 3 months. The pain is related to meals and is occasionally associated with nausea and bloating. He frequently uses NSAIDs for chronic back pain. On examination, there is mild epigastric tenderness without guarding or rigidity. Upper gastrointestinal endoscopy reveals a gastric ulcer. Biopsy testing is positive for Helicobacter pylori. Diagnosis?

Diagnosis is Peptic Ulcer Disease (PUD).

1. Definition

1. Peptic ulcer disease is a break in the gastric or duodenal mucosa extending through the muscularis mucosae into the submucosa or deeper.
2. It occurs when mucosal defensive mechanisms are overwhelmed by acid-peptic injury.
3. Major types:
1. Gastric ulcer
2. Duodenal ulcer

2. Etiology / Risk Factors

1. Two major causes:
1. Helicobacter pylori infection
2. NSAID use
2. Other risk factors and associations:
1. Aspirin
2. Smoking
3. Older age
4. Previous peptic ulcer or GI bleeding
5. Severe physiological stress in critically ill patients
6. Concomitant anticoagulants, antiplatelets, corticosteroids, or SSRIs may increase bleeding risk, particularly with NSAIDs
3. Rare causes:
1. Zollinger-Ellison syndrome
2. Crohn disease
3. CMV infection in immunocompromised patients

3. Pathophysiology

1. PUD results from an imbalance between aggressive factors and mucosal defenses.
2. Aggressive factors:
1. Gastric acid
2. Pepsin
3. H. pylori
4. NSAIDs
3. Protective factors:
1. Mucus-bicarbonate barrier
2. Prostaglandins
3. Adequate mucosal blood flow
4. Epithelial repair
4. H. pylori:
1. Colonizes gastric mucosa
2. Produces urease
3. Causes chronic gastritis
4. Disrupts mucosal defenses
5. Can alter gastrin and acid secretion
6. Predisposes to gastric and duodenal ulcers
5. NSAIDs:
1. Inhibit cyclooxygenase
2. Reduce prostaglandin synthesis
3. Decrease mucus and bicarbonate secretion
4. Impair mucosal blood flow and repair
5. Increase ulceration and bleeding risk

4. Clinical Features

4.1 Typical Features

1. Burning or gnawing epigastric pain
2. Dyspepsia
3. Nausea
4. Bloating
5. Early satiety
6. Symptoms may be related to meals

4.2 Gastric vs Duodenal Ulcer

1. Gastric ulcer
1. Pain may worsen with meals
2. May cause reduced food intake and weight loss
2. Duodenal ulcer
1. Pain may improve after eating
2. May recur several hours after meals or at night
3. These classical patterns are not sufficiently reliable for diagnosis or ulcer localization.

4.3 Features of Complications

1. Hematemesis or melena → upper GI bleeding
2. Sudden severe abdominal pain → perforation
3. Persistent vomiting and early satiety → gastric outlet obstruction
4. Dizziness, syncope, or hypotension → significant blood loss

5. Diagnosis

5.1 Diagnostic Approach

1. Evaluate:
1. Symptoms
2. NSAID/aspirin use
3. Previous ulcer disease
4. H. pylori status
5. Alarm features
2. Upper GI endoscopy (EGD) directly visualizes ulcers.
3. EGD allows:
1. Identification of ulcer location
2. Biopsy
3. Evaluation for malignancy
4. Endoscopic treatment of bleeding

5.2 H. pylori Testing

1. Noninvasive tests:
1. Urea breath test
2. Stool antigen test
2. Endoscopic tests:
1. Rapid urease test
2. Histology
3. Urea breath and stool antigen tests detect active infection.
4. Serology may remain positive after eradication and cannot reliably confirm active infection or cure.

5.3 Gastric Ulcer Biopsy

1. Gastric ulcers should be appropriately evaluated for malignancy.
2. The need for biopsy and follow-up endoscopy depends on:
1. Endoscopic appearance
2. Clinical context
3. Histopathology
4. Local guidelines
3. Duodenal ulcers are very rarely malignant and generally do not require routine biopsy for malignancy.

6. Alarm Features

1. GI bleeding
2. Iron-deficiency anemia
3. Unintentional weight loss
4. Persistent vomiting
5. Dysphagia or odynophagia
6. Palpable abdominal mass or lymphadenopathy
7. Features suggesting malignancy
8. Older age at new onset of dyspepsia

Age and alarm features guide the need for endoscopy. In younger patients, alarm features should be assessed individually rather than automatically mandating EGD.

7. Differential Diagnosis

1. Gastritis
2. Gastroesophageal reflux disease
3. Functional dyspepsia
4. Gastric malignancy
5. Pancreatitis
6. Biliary disease
7. Esophagitis
8. Mesenteric ischemia
9. Acute coronary syndrome

8. Management

8.1 Core Principle

1. Acid suppression → eradicate H. pylori → stop/reduce ulcerogenic drugs → treat complications

8.2 Acid Suppression

1. Proton pump inhibitors (PPIs) are the mainstay of ulcer healing.
2. Examples:
1. Omeprazole
2. Pantoprazole
3. Esomeprazole
3. Treatment duration depends on ulcer location, size, cause, complications, and continued NSAID exposure.

8.3 H. pylori Eradication

1. All patients with confirmed H. pylori infection should receive eradication therapy.
2. When antibiotic susceptibility is unknown, optimized bismuth quadruple therapy for 14 days is the preferred empiric regimen.
3. Optimized bismuth quadruple therapy:
1. PPI twice daily
2. Bismuth four times daily
3. Tetracycline 500 mg four times daily
4. Metronidazole 500 mg three or four times daily
5. Duration: 14 days
4. Alternative regimens in appropriate patients include:
1. Rifabutin-based triple therapy
2. Vonoprazan-amoxicillin dual therapy
5. Avoid empiric clarithromycin-containing or levofloxacin-containing regimens unless susceptibility is demonstrated.

8.4 Confirm Eradication

1. Test of cure is required in all treated patients.
2. Preferred methods:
1. Urea breath test
2. Stool antigen test
3. Biopsy-based testing when indicated
3. Perform testing at least 4 weeks after completion of therapy.
4. Before testing:
1. Hold PPI/PCAB for 2 weeks
2. Hold antibiotics and bismuth for 4 weeks
5. These measures reduce the risk of false-negative results.

8.5 NSAID-Associated Ulcer

1. Stop NSAIDs if possible
2. Treat with a PPI
3. Test for and eradicate H. pylori if present
4. If NSAIDs must continue:
1. Use the lowest effective dose
2. Consider a COX-2 selective NSAID when appropriate
3. Provide PPI gastroprotection in high-risk patients

9. Management of Complications

9.1 Upper GI Bleeding

1. Initial management:
1. Airway, breathing, circulation
2. IV access
3. Hemodynamic resuscitation
4. CBC, coagulation studies, renal function, and blood grouping/crossmatch as appropriate
2. After appropriate resuscitation and stabilization, hospitalized patients with UGIB generally undergo upper endoscopy within 24 hours.
3. High-risk bleeding ulcers require:
1. Endoscopic hemostasis
2. PPI therapy

9.2 Perforation

1. Presents with sudden severe abdominal pain
2. May cause:
1. Peritonitis
2. Free intraperitoneal air
3. Requires:
1. Resuscitation
2. IV antibiotics
3. Acid suppression
4. Urgent surgical evaluation

9.3 Gastric Outlet Obstruction

1. Presents with:
1. Persistent vomiting
2. Early satiety
3. Abdominal distension
2. Management may include:
1. Gastric decompression
2. IV fluids and electrolyte correction
3. PPI therapy
4. Endoscopic or surgical treatment depending on the cause

10. Monitoring

1. Assess symptom improvement
2. Monitor for GI bleeding
3. Confirm H. pylori eradication
4. Review NSAID/aspirin requirement
5. Monitor hemoglobin if bleeding or anemia is present
6. Follow-up endoscopy may be required for gastric ulcers, depending on clinical and endoscopic findings

11. Complications

1. Upper GI bleeding, most common major complication
2. Perforation
3. Penetration into adjacent organs
4. Gastric outlet obstruction
5. Recurrent ulceration
6. Iron-deficiency anemia

12. Prevention

1. Diagnose and eradicate H. pylori
2. Avoid unnecessary NSAIDs
3. Use the lowest effective NSAID dose
4. Use PPI gastroprotection in high-risk NSAID users
5. Avoid smoking
6. Review medications that increase GI bleeding risk

13. Key Clinical Insight

1. Epigastric pain + NSAID use or H. pylori infection = suspect PUD
2. Hematemesis/melena, sudden severe abdominal pain, or persistent vomiting = evaluate for complicated PUD

14. Key Exam Points

1. Two major causes = H. pylori + NSAIDs
2. PUD extends through the muscularis mucosae into the submucosa or deeper
3. H. pylori produces urease
4. NSAIDs → ↓ prostaglandins → ↓ mucus/bicarbonate + impaired mucosal protection
5. EGD = direct visualization and allows biopsy/treatment
6. Gastric ulcers require appropriate evaluation for malignancy
7. Urea breath test or stool antigen = preferred noninvasive tests for active H. pylori
8. Preferred empiric H. pylori regimen when susceptibility is unknown = optimized bismuth quadruple therapy for 14 days
9. Avoid empiric clarithromycin or levofloxacin regimens unless susceptibility is demonstrated
10. Always confirm H. pylori eradication
11. Test of cure → ≥4 weeks after therapy, off PPI/PCAB for 2 weeks and antibiotics/bismuth for 4 weeks
12. PPI = mainstay of ulcer healing
13. Most common major complication = upper GI bleeding
14. UGIB → stabilize first, then generally EGD within 24 hours
15. Sudden severe abdominal pain → suspect perforation
16. Persistent vomiting → consider gastric outlet obstruction
17. Gastric vs duodenal meal-related pain patterns are classical but not diagnostically reliable