How should peptic ulcer disease be diagnosed and managed, including indications for upper endoscopy, appropriate Helicobacter pylori testing, and first‑line eradication regimens such as standard triple therapy, bismuth‑based quadruple therapy, and treatment for H. pylori‑negative or penicillin‑allergic patients?

Peptic Ulcer Disease: Diagnosis and Management

Indications for Upper Endoscopy

Perform upper endoscopy immediately in patients older than 55 years with new-onset dyspepsia, or in any patient with alarm symptoms (weight loss, progressive dysphagia, recurrent vomiting, gastrointestinal bleeding, or family history of gastric cancer), regardless of age. 1

• For patients younger than 55 years without alarm symptoms, a test-and-treat strategy for H. pylori is appropriate and cost-effective 1, 2
• Endoscopy should be preferred over upper gastrointestinal radiography because it has greater diagnostic accuracy and allows biopsy specimens to be obtained for H. pylori testing 1
• Patients requiring continuous long-term treatment with H2 receptor antagonists, acid pump inhibitors, or prokinetic drugs should undergo endoscopy 1
• Patients under 45 years with severe and persistent symptoms that do not respond to empirical treatment warrant endoscopy 1
• For suspected perforated peptic ulcer, CT scan is the preferred imaging modality; if unavailable, obtain chest/abdominal X-ray to detect free air 1

Helicobacter pylori Testing

Testing Methods and Timing

During active upper gastrointestinal bleeding, endoscopic biopsy testing for H. pylori yields false-negative rates of 25-55%, necessitating repeat testing after the acute episode. 3, 4

• Obtain gastric biopsies during endoscopy for H. pylori testing in all patients with peptic ulcer disease 1
• For non-invasive testing in younger patients without alarm symptoms, use urea breath test (88-95% sensitivity, 95-100% specificity) or stool antigen test (94% sensitivity, 92% specificity) 3, 2
• Serologic antibody testing is less accurate and cannot be used to confirm eradication, as antibodies remain positive for months to years after successful treatment 3, 2
• Testing should be performed off PPI therapy (ideally 2 weeks after stopping) to maximize accuracy, as PPIs suppress H. pylori and cause false-negative results 3

Confirmation of Eradication

Confirm H. pylori eradication in all patients with peptic ulcer disease using urea breath test or stool antigen test at least 4 weeks after completing therapy. 3, 4, 2

• Successful eradication reduces rebleeding rates from 26-62% down to 0-2% 3
• If eradication fails, initiate second-line therapy with a different regimen (typically levofloxacin-amoxicillin triple therapy for 10 days), then retest 4 weeks after completing the second course 3

First-Line Eradication Regimens

Standard Triple Therapy (First-Line)

For H. pylori eradication, use standard triple therapy: PPI (omeprazole 20 mg or equivalent) twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily for 14 days. 3, 5, 6, 2

• This regimen achieves eradication rates of 86-93% in areas with low clarithromycin resistance 7, 8
• Standard triple therapy is only recommended when local clarithromycin resistance is low 2
• Take amoxicillin at the start of meals to minimize gastrointestinal intolerance 5
• Take omeprazole before meals 6

Bismuth-Based Quadruple Therapy (Alternative First-Line or Second-Line)

In areas with high clarithromycin resistance or after triple therapy failure, use bismuth-based quadruple therapy: PPI (omeprazole 20-40 mg twice daily), bismuth subcitrate 120 mg four times daily, tetracycline 500 mg four times daily, and metronidazole 500 mg three times daily for 7-10 days. 3, 2, 9, 8

• Quadruple therapy achieves eradication rates of 82-89% as rescue treatment after triple therapy failure 9, 8
• This regimen shows similar efficacy to triple therapy when used as first-line treatment 8
• Side effects occur in approximately 9-11% of patients but are generally well-tolerated 9, 8

Sequential Therapy (Alternative)

• In areas with high clarithromycin resistance, sequential therapy may be considered as an alternative 3

Treatment for Special Populations

H. pylori-Negative Peptic Ulcer

For H. pylori-negative peptic ulcers, initiate high-dose PPI therapy (omeprazole 40 mg once daily) for 4-8 weeks, immediately discontinue NSAIDs if present, and perform repeat H. pylori testing outside the acute context due to high false-negative rates during active bleeding. 4, 6, 2

• For gastric ulcers specifically, perform repeat endoscopy at 6 weeks to confirm healing and exclude malignancy 4, 10
• For duodenal ulcers, endoscopic confirmation of healing is generally not necessary after treatment unless the patient needs to continue NSAIDs 3

Penicillin-Allergic Patients

For patients with penicillin allergy, use dual therapy: PPI (omeprazole 40 mg once daily) plus clarithromycin 500 mg three times daily for 14 days, followed by an additional 14 days of PPI 20 mg once daily for ulcer healing. 5, 6

• This regimen is specifically indicated for patients who are allergic or intolerant to clarithromycin or in whom clarithromycin resistance is known or suspected 5
• Alternative regimens include levofloxacin-based triple therapy 2

Post-Treatment Management

PPI Therapy Duration

After successful H. pylori eradication in uncomplicated duodenal ulcers, discontinue PPI therapy as rebleeding becomes extremely rare. 3, 4

• For gastric ulcers, continue PPI therapy (omeprazole 40 mg once daily) for 6-8 weeks until complete healing is confirmed on follow-up endoscopy 4, 10, 6
• After endoscopic treatment of bleeding peptic ulcer, administer IV PPI (80 mg bolus followed by 8 mg/hour infusion) for 72 hours, then switch to oral PPI 40 mg twice daily for 11 days, then 40 mg once daily for the remaining duration 4

Follow-Up Endoscopy

Perform repeat endoscopy at 6 weeks for all gastric ulcers to confirm healing and exclude malignancy; this is mandatory regardless of successful initial treatment. 4, 10

• Duodenal ulcers do not require follow-up endoscopy after successful H. pylori eradication unless NSAIDs must be continued 3
• During follow-up endoscopy for gastric ulcers, obtain multiple targeted biopsies from the antrum and body (at least 2 from each location) and additional biopsies from the ulcer site 10

Critical Pitfalls to Avoid

• Do not rely on a single negative H. pylori test during acute bleeding - false-negative rates reach 25-55% in this context 3, 4
• Do not use PPI therapy as a substitute for urgent endoscopy in patients with active bleeding - definitive endoscopic evaluation remains essential 3
• Do not assume gastric ulcer healing based on symptom resolution alone - endoscopic confirmation is mandatory to exclude malignancy 4, 10
• Do not discontinue PPI therapy prematurely - maintain for the full 6-8 weeks until healing is confirmed for gastric ulcers 4, 10
• Do not use serologic antibody testing to confirm eradication - antibodies persist long after successful treatment 3, 2