Peptic Ulcer Disease

Detailed Overview

PUD is primarily driven by Helicobacter pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). The imbalance between protective factors (mucus, bicarbonate, prostaglandins) and aggressive factors (gastric acid, pepsin) leads to tissue necrosis and ulceration. If left untreated, it can lead to severe complications such as hemorrhage, perforation, or gastric outlet obstruction. Proper eradication of H. pylori and cessation of offending agents are central to achieving long-term healing and preventing recurrence.

Epidemiology & Demographics

Global prevalence is estimated at 5-10%. Incidence of duodenal ulcers is higher in younger populations (30-55 years), while gastric ulcers peak in older patients (55-70 years). Males and females are affected equally, though historical data showed a male predominance.

Etiological Mechanism

The two primary etiologic factors are H. pylori infection (responsible for ~90% of duodenal and 70-90% of gastric ulcers) and NSAID use. Zollinger-Ellison syndrome (gastrinoma) is a rare cause.

Primary Causes

H. pylori bacterial colonization, chronic NSAID/aspirin therapy, hypersecretory states (Zollinger-Ellison syndrome), viral infections (CMV, HSV in immunocompromised), and Crohn's disease involving the upper GI tract.

• H. pylori infection: Colonizes the gastric mucosa, inducing chronic inflammation and altering acid secretion.
• NSAID use: Inhibits COX-1, depleting mucosal prostaglandins needed for cytoprotection.
• Smoking: Impairs mucosal blood flow and healing, increasing the risk of ulcer recurrence.
• Advanced age: Associated with increased NSAID use and age-related decline in mucosal defense.

In H. pylori-associated PUD, the bacteria produce urease to survive the acidic environment and cytotoxins (like VacA and CagA) that damage epithelial cells. The resulting chronic active gastritis increases gastrin release (especially in antral-predominant gastritis), leading to hypersecretion of gastric acid. This excess acid overloads duodenal buffering, causing duodenal metaplasia and subsequent ulceration. In NSAID-associated PUD, systemic inhibition of cyclooxygenase-1 (COX-1) drastically reduces the synthesis of mucosal prostaglandins, which normally stimulate mucus and bicarbonate secretion and maintain mucosal blood flow.

Characteristic Clinical Presentation

• Epigastric Pain: Burning or gnawing pain, classically relieved by food or antacids in duodenal ulcers, but often worsened by food in gastric ulcers.
• Dyspepsia: Bloating, early satiety, and nausea after meals.
• Nocturnal Pain: Pain that awakens the patient from sleep, typically occurring between midnight and 3 AM, highly suggestive of duodenal ulcers.
• Melena: Black, tarry stools indicating upper GI bleeding in complicated PUD.

Physical Examination Signs

• Epigastric tenderness on deep palpation without guarding or rebound (uncomplicated PUD).
• Guarding and board-like abdominal rigidity (indicative of perforation).
• Tachycardia and orthostatic hypotension (suggestive of significant GI hemorrhage).
• Succussion splash (suggestive of gastric outlet obstruction).

• Gastrointestinal Hemorrhage: Occurs in 15% of patients; presents with hematemesis or melena.
• Perforation: Free air under the diaphragm; high mortality if not surgically managed promptly.
• Gastric Outlet Obstruction: Edema or stricture formation at the pylorus, causing intractable vomiting.

Diagnostic Criteria & Guidelines

Diagnosis is definitively established via esophagogastroduodenoscopy (EGD) showing a mucosal break >5 mm in diameter, with biopsy confirmation for H. pylori status and ruling out malignancy in gastric ulcers.

Differential Diagnosis

• Gastroesophageal Reflux Disease (GERD)
• Gastric Cancer
• Biliary Colic / Cholelithiasis
• Acute Pancreatitis

Laboratory Tests & Biomarkers

• Urea Breath Test: Positive (confirms active H. pylori infection, sensitivity >95%).
• Stool Antigen Test: Positive for H. pylori antigen.
• Hemoglobin/Hematocrit: Decreased (e.g., Hb <10 g/dL) if chronic or acute bleeding is present.
• Fasting Serum Gastrin: Markedly elevated (>1000 pg/mL) in suspected Zollinger-Ellison syndrome.

Imaging Modalities & Findings

• EGD (Endoscopy): Visualization of a discrete mucosal defect, usually in the antrum or duodenal bulb, often with a clean base or signs of recent bleeding (visible vessel/clot).
• Upright Chest X-ray: Pneumoperitoneum (free air under the right hemidiaphragm) if perforation has occurred.

• Uncomplicated
  Intact mucosal defect without evidence of bleeding, perforation, or obstruction.
• Complicated - Bleeding
  Ulcer eroding into an underlying blood vessel (e.g., gastroduodenal artery).
• Complicated - Perforated
  Full-thickness ulceration resulting in pneumoperitoneum and chemical peritonitis.

Second-Line & Adjunctive Therapy

Levofloxacin-based salvage therapy: PPI BID + Amoxicillin 1 g BID + Levofloxacin 500 mg daily for 10-14 days.

Surgical & Procedural Management

Endoscopic therapy (epinephrine injection + thermal coagulation or clipping) for bleeding ulcers. Surgical interventions like Graham patch closure for perforated ulcers, or highly selective vagotomy for refractory cases.

Recommended Lifestyle Changes

• Strict cessation of smoking to promote ulcer healing.
• Avoidance of NSAIDs and cyclooxygenase-2 (COX-2) inhibitors.
• Limiting alcohol intake, which can exacerbate mucosal irritation.
• Eating smaller, more frequent meals if experiencing dyspepsia.

Patient Counseling & Advice

Inform patients that completing the full 14-day course of H. pylori eradication therapy is critical to prevent resistance and recurrence. Warn about harmless dark stools associated with bismuth therapy.

Follow-Up & Monitoring Schedule

Perform urea breath test or stool antigen test at least 4 weeks after completion of antibiotic therapy and 2 weeks after holding PPI to confirm H. pylori eradication. Repeat EGD in 8-12 weeks for gastric ulcers to document healing and exclude malignancy.

Preventive Strategies

Test and treat H. pylori before starting long-term NSAID therapy. Use a PPI prophylactically in patients at high risk (e.g., history of ulcer, age >65, concurrent corticosteroid or anticoagulant use) who must remain on NSAIDs.

Excellent with successful H. pylori eradication, with recurrence rates dropping from >60% to <5-10%. Mortality in uncomplicated PUD is negligible, but perforated ulcers carry a 5-10% mortality rate.