What are the differences between gastro‑oesophageal reflux disease (GERD) and peptic ulcer disease (PUD), and what is the initial management for each?

GERD vs Peptic Ulcer Disease: Key Differences and Initial Management

GERD and peptic ulcer disease are distinct acid-related disorders that differ fundamentally in pathophysiology, location, complications, and treatment approach—GERD results from failure of the anti-reflux barrier allowing gastric contents to reflux into the esophagus, while peptic ulcer disease involves focal mucosal breaks in the stomach or duodenum, typically driven by Helicobacter pylori infection or NSAID use. 1

Pathophysiology and Location

GERD is caused by failure of the anti-reflux barrier, primarily through transient lower esophageal sphincter relaxations, combined with impaired protective mechanisms including esophageal peristalsis, salivation, and gastric emptying. 2 The disease affects the esophagus, with gastric acid and other gastric contents refluxing upward into the esophageal lumen. 2

Peptic ulcer disease involves focal mucosal breaks (ulcers) in the stomach or duodenum, with H. pylori infection being the primary driver in most cases. 1 Unlike GERD, peptic ulcers represent actual tissue destruction rather than inflammation from refluxed contents. 1

Clinical Presentation

GERD Symptoms

• Typical symptoms: Heartburn (retrosternal burning) and regurgitation are approximately 70% sensitive and specific for objective GERD. 2
• Extraesophageal manifestations: Chronic cough, laryngitis, asthma, globus sensation, and dental erosions may occur, though these respond less reliably to acid suppression than typical symptoms. 1
• Nocturnal symptoms: Nighttime heartburn or regurgitation that disturbs sleep is common. 2

Peptic Ulcer Disease Symptoms

• Epigastric pain is the predominant symptom, often described as "ulcer-like dyspepsia" with pain that may be relieved or worsened by food. 1
• Alarm features such as dysphagia, anemia, weight loss, or gastrointestinal bleeding warrant immediate endoscopy. 1, 2
• Patients may present with complications including perforation, bleeding, or gastric outlet obstruction. 1

Natural History and Complications

GERD is a chronic relapsing condition that does not typically progress to peptic ulceration but can lead to erosive esophagitis, strictures, Barrett's esophagus, and esophageal adenocarcinoma in severe cases. 3, 4 Approximately 30% of GERD patients have visible mucosal damage (erosive esophagitis), while 70% have non-erosive reflux disease (NERD). 5

Peptic ulcer disease carries risk of life-threatening complications including hemorrhage, perforation, and mortality if untreated, particularly when H. pylori is not eradicated. 1 Successful H. pylori eradication eliminates the issue of peptic ulcer mortality. 1

Diagnostic Approach

GERD Diagnosis

• Empiric PPI trial is appropriate initial management for patients with typical symptoms (heartburn, regurgitation) without alarm features—endoscopy is not required upfront. 2, 6
• Upper endoscopy is indicated after 8–12 weeks of optimized PPI therapy if symptoms persist, or immediately if alarm features are present. 2
• Ambulatory pH monitoring (off PPI) is reserved for patients with persistent symptoms despite optimized therapy, to objectively confirm GERD and assess symptom-reflux association. 1, 2

Peptic Ulcer Disease Diagnosis

• H. pylori testing (via stool antigen, urea breath test, or endoscopic biopsy) is essential, as eradication is the cornerstone of peptic ulcer management. 1
• Upper endoscopy is the gold standard for diagnosing peptic ulcers and should be performed in patients with alarm symptoms or those requiring confirmation before long-term therapy. 1
• "Test and treat" strategy for H. pylori in dyspeptic patients is cost-effective and eliminates ulcer mortality risk. 1

Initial Management

GERD First-Line Treatment

Pharmacologic therapy:

• Initiate a standard-dose PPI once daily (e.g., omeprazole 20 mg, lansoprazole 30 mg, esomeprazole 40 mg, pantoprazole 40 mg) taken 30–60 minutes before breakfast for 4–8 weeks. 2, 7, 6
• PPIs are the most effective first-line pharmacological treatment for GERD, superior to H2-receptor antagonists and antacids for both healing esophagitis and achieving symptomatic relief. 2, 7
• If symptoms persist after 4 weeks, escalate to twice-daily PPI dosing (one dose before breakfast, one before dinner) for an additional 4–8 weeks. 2, 6

Lifestyle modifications:

• Weight loss is the single most effective lifestyle intervention for overweight or obese patients (BMI ≥25 kg/m²), with the strongest evidence for efficacy. 2
• Elevate the head of the bed by 6–8 inches for patients with nocturnal symptoms. 2
• Avoid lying down for 2–3 hours after meals to reduce esophageal acid exposure. 2
• Identify and avoid individual trigger foods (coffee, chocolate, alcohol, spicy foods, citrus, high-fat meals) through detailed dietary history. 2

Peptic Ulcer Disease First-Line Treatment

H. pylori eradication therapy:

• Test all dyspeptic patients for H. pylori using stool antigen, urea breath test, or endoscopic biopsy. 1
• Eradicate H. pylori in all positive patients using triple or quadruple therapy regimens (PPI + antibiotics). 1
• Eradication eliminates peptic ulcer mortality risk, even though some patients may have residual dyspeptic symptoms. 1

Acid suppression:

• Full-dose PPI therapy (e.g., omeprazole 20 mg once daily) is first-choice therapy for H. pylori-negative peptic ulcers and for healing ulcers during eradication therapy. 1
• PPI therapy ensures healing of both H. pylori-positive and H. pylori-negative peptic ulcers. 1

Management of residual symptoms:

• After successful H. pylori eradication, patients with persistent epigastric pain (ulcer-like dyspepsia) should receive full-dose PPI therapy, as these symptoms are likely acid-related. 1
• The approach to subsequent therapy after eradication is the same as for H. pylori-negative patients, individualized based on predominant symptoms. 1

Treatment Escalation and Long-Term Management

GERD

• After symptom control, titrate PPI to the lowest effective dose that maintains relief. 2
• For patients without confirmed erosive esophagitis or Barrett's esophagus, consider gradual dose reduction or on-demand PPI strategy once symptoms are stable. 2
• If PPI therapy extends beyond 12 months without objective confirmation, offer repeat endoscopy with prolonged pH monitoring to reassess the need for continued therapy. 2
• Surgical options (laparoscopic fundoplication, magnetic sphincter augmentation) are reserved for patients who meet strict criteria: ≥3 months of failed intensive medical therapy, objective documentation of pathological GERD, positive symptom-reflux association, preserved esophageal peristalsis, and significant quality-of-life impairment. 2, 6

Peptic Ulcer Disease

• Confirm H. pylori eradication 4–6 weeks after completion of therapy using urea breath test or stool antigen (not serology). 1
• Long-term PPI maintenance is generally not required after successful H. pylori eradication unless the patient has H. pylori-negative ulcers or ongoing NSAID use. 1
• If symptoms recur, repeat H. pylori testing and consider endoscopy to assess for ulcer recurrence or alternative diagnoses. 1

Critical Pitfalls to Avoid

• Do not confuse GERD with peptic ulcer disease—they require different diagnostic and therapeutic approaches, particularly regarding H. pylori testing and eradication. 1
• Do not perform routine endoscopy for typical GERD symptoms without alarm features; empiric PPI therapy is appropriate initial management. 2
• Do not continue empiric PPI therapy indefinitely without objective testing if symptoms persist beyond 8–12 weeks of optimized treatment. 2
• Do not fail to test for H. pylori in patients with peptic ulcer disease or ulcer-like dyspepsia, as eradication eliminates mortality risk. 1
• Do not use metoclopramide as monotherapy or adjunctive therapy for GERD due to its unfavorable risk-benefit profile, including risk of tardive dyskinesia. 2
• Do not add nocturnal H2-receptor antagonists to twice-daily PPI therapy, as there is no evidence of improved efficacy and tachyphylaxis develops within 6 weeks. 2