Peptic Ulcer Disease

Etiology and Risk Factors

Risk rises with previous ulcer or bleeding, older age, higher-dose or multiple NSAIDs, and concurrent aspirin, anticoagulants, or glucocorticoids. Corticosteroid-associated ulcer risk is particularly important when combined with NSAIDs. Smoking can further impair healing. Ordinary stress or spicy meals may alter symptom perception but should not be presented as the primary causes of most peptic ulcers (Chaudhry & Corder, 2026).

Epidemiology and Clinical Context

Population context: H. pylori exposure, prior ulcer history, and NSAID or aspirin use change ulcer probability. Older age, a previous complicated ulcer, concomitant antithrombotics, and serious comorbidity make bleeding and treatment decisions more consequential; absence of typical pain does not exclude a serious ulcer complication (Mills & Ciorba, 2019; Rej et al., 2023).

Pathophysiology

Mechanism: acid-pepsin injury versus mucosal defense

Acid and pepsin are injurious when the epithelial barrier, mucus-bicarbonate layer, mucosal circulation, and restitution cannot adequately protect tissue. H. pylori alters inflammatory signaling and the regulation of acid secretion. NSAIDs impair prostaglandin-mediated defenses, principally through cyclooxygenase inhibition, even when acid secretion remains normal. These mechanisms can coexist, increasing the risk of ulceration or hemorrhage (Chaudhry & Corder, 2026; Mills & Ciorba, 2019).

• In antral-predominant H. pylori infection, reduced somatostatin restraint and increased gastrin can increase acid delivery to the duodenum, promoting ulcer formation in susceptible mucosa.
• With corpus-predominant H. pylori inflammation or atrophy, loss of mucosal integrity and parietal-cell function may predominate; gastric ulcer risk does not require acid hypersecretion.
• NSAID-associated prostaglandin deficiency decreases bicarbonate, mucus, and local perfusion. The resulting tissue is susceptible to injury from normal levels of luminal acid and pepsin.
• Continued injury may progress from superficial disruption to a crater, vascular erosion, transmural perforation, or fibrosis that narrows the gastric outlet (Mills & Ciorba, 2019; Norris, 2020).

Clinical Manifestations

Typical symptoms are recurrent epigastric burning, gnawing discomfort, nausea, or dyspepsia. Symptoms poorly predict the presence, location, or severity of an ulcer. Older adults may first present with melena, hematemesis, anemia, perforation, or obstruction without preceding ulcer pain (Mills & Ciorba, 2019).

Diagnostic Evaluation

Evaluation: choose tests based on risk

• Gastrointestinal bleeding, progressive anemia, persistent vomiting, or weight loss warrant expedited evaluation and upper endoscopy when appropriate. Suspected perforation with peritoneal signs requires emergency imaging and surgical assessment; diagnostic endoscopy should not delay or replace that pathway (Chaudhry & Corder, 2026).
• When endoscopy is not otherwise necessary, urea breath testing or stool antigen testing assesses active H. pylori infection. Recent acid suppression, antibiotics, or bismuth may reduce test sensitivity; arrange appropriate medication holds according to the testing protocol.
• A gastric ulcer requires consideration of tissue sampling and interval endoscopic confirmation of healing when indicated to avoid overlooking malignancy or a nonhealing lesion. Assessment is individualized to ulcer appearance, biopsy results, and clinical course.

Expected Findings

Gastric versus duodenal ulcer

Domain	Gastric ulcer	Duodenal ulcer
Main mechanism	Defective mucosal protection commonly prominent; H. pylori and NSAIDs are frequent contributors.	H. pylori-associated acid delivery and impaired duodenal defense often important; NSAIDs can also cause ulcers.
Pain pattern	May occur shortly after meals, but patterns are variable and unreliable for diagnosis.	Classically occurs after meals or overnight and may improve with food, but many patients do not fit this pattern.
Endoscopy	Permits assessment of ulcer features, biopsy when appropriate, and exclusion of gastric malignancy.	Confirms diagnosis and evaluates complications; biopsy decisions depend on indication.
Safety concern	Hemorrhage, perforation, outlet obstruction, or an underlying malignant lesion.	Hemorrhage, perforation, or obstruction. Clinical pain may be absent even with serious disease.

Diagnostic Limitations and Reassessment

Symptoms poorly predict the presence, location, or severity of an ulcer (Mills & Ciorba, 2019).

Treatment and Management

Problem	Reasoned management priority
H. pylori-positive ulcer	Use an effective multidrug eradication regimen selected using current resistance and prior antibiotic-exposure information; plan adherence support and test of cure. Acid suppression alone does not eliminate recurrence risk from persistent infection.
NSAID-associated ulcer	Stop the offending NSAID if possible and use acid suppression to heal injury. If antiplatelet or NSAID therapy must continue, balance thrombotic and GI risk and consider protective strategies.
Ulcer without either typical exposure	Reconsider false-negative H. pylori tests, hidden NSAID use, malignancy, severe acid hypersecretion, or another uncommon cause.
Active bleed, perforation, or obstruction	Stabilization and urgent endoscopic, surgical, or procedural management take priority over routine outpatient eradication treatment.

Current eradication decision: For treatment-naive adults with H. pylori infection when antibiotic susceptibility is unknown, the 2024 ACG guideline recommends 14 days of optimized bismuth quadruple therapy. Prior macrolide or fluoroquinolone exposure, allergies, feasibility of the complex dosing schedule, and previous eradication attempts affect regimen selection. Do not select empiric clarithromycin- or levofloxacin-containing salvage regimens without documented susceptibility (Chey et al., 2024).

Verify eradication and ensure appropriate healing follow-up

After every H. pylori treatment course, confirm eradication with urea breath testing or fecal antigen testing at least four weeks after completion of antibiotics and bismuth; withhold PPIs or potassium-competitive acid blockers for at least two weeks before testing when clinically feasible. An H2-receptor antagonist or antacid can bridge symptoms if appropriate. Serology cannot establish eradication. Persistent ulceration or symptoms require assessment for false-negative testing, reinfection, ongoing NSAID exposure and alternate causes, including neoplasia (Chey et al., 2024).

Gastric ulcer biopsy and follow-up endoscopy are individualized to appearance, histology, healing and residual concern for malignancy; routine surveillance is usually unnecessary for a healed, uncomplicated duodenal ulcer. During acute GI bleeding, the ACG-CAG guideline suggests continuing cardiac aspirin used for secondary cardiovascular prevention. If it was interrupted, the guideline suggests resumption on the day endoscopic hemostasis is confirmed. These recommendations do not apply to aspirin used for primary prevention (Abraham et al., 2022; American Society for Gastrointestinal Endoscopy, 2010).

Complications and Red Flags

Complication discrimination

Presentation	Mechanism and urgency
Melena, hematemesis, tachycardia, orthostasis	Ulcer may erode a vessel; evaluate hemorrhage and hemodynamic stability.
Sudden severe rigid abdomen or rebound tenderness	Possible free perforation and chemical or infectious peritonitis; emergency evaluation.
Persistent postprandial emesis, early satiety, dehydration	Inflammatory narrowing or fibrosis causing gastric outlet obstruction.
Multiple recurrent or treatment-resistant ulcers with diarrhea	Consider a hypersecretory condition such as Zollinger-Ellison syndrome in the appropriate context.

Clinical Reasoning Priorities

A patient with osteoarthritis and daily high-dose ibuprofen presents with new iron-deficiency anemia but minimal abdominal discomfort. The absence of classic epigastric pain does not exclude PUD. The clinician must assess bleeding and malignancy risk, review aspirin/anticoagulant coexposure, determine whether H. pylori testing is indicated, and address the NSAID rather than prescribing indefinite acid suppression without an etiologic plan.

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References

Abraham, N. S., Barkun, A. N., Sauer, B. G., Douketis, J., Laine, L., Noseworthy, P. A., Telford, J. J., & Leontiadis, G. I. (2022). American College of Gastroenterology-Canadian Association of Gastroenterology clinical practice guideline: Management of anticoagulants and antiplatelets during acute gastrointestinal bleeding and the periendoscopic period. The American Journal of Gastroenterology, 117(4), 542–558. https://doi.org/10.14309/ajg.0000000000001627

American Society for Gastrointestinal Endoscopy. (2010). The role of endoscopy in the management of patients with peptic ulcer disease. https://www.asge.org/docs/default-source/education/practice_guidelines/doc-the-role-of-endoscopy-in-the-management-of-patientswith-peptic-ulcer-disease.pdf

Chaudhry, F., & Corder, M. M. (2026). Peptic ulcer disease. In M. A. Chisholm-Burns, J. M. Kolesar, P. M. Malone, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed., Chapter 19). McGraw Hill.

Chey, W. D., Howden, C. W., Moss, S. F., Morgan, D. R., Greer, K. B., Grover, S., & Shah, S. C. (2024). ACG clinical guideline: Treatment of Helicobacter pylori infection. American Journal of Gastroenterology, 119(9), 1730–1753. https://doi.org/10.14309/ajg.0000000000002968

Mills, J. C., & Ciorba, M. A. (2019). Gastrointestinal disease. In G. D. Hammer & S. J. McPhee (Eds.), Pathophysiology of disease: An introduction to clinical medicine (8th ed., Chapter 13). McGraw-Hill Education.

Norris, T. L. (2020). Porth’s essentials of pathophysiology (5th ed.). Wolters Kluwer.

Rej, A., Chew, T. S., & Sanders, D. S. (2023). Gastroenterology. In I. D. Penman, S. H. Ralston, M. W. J. Strachan, & R. P. Hobson (Eds.), Davidson’s principles and practice of medicine (24th ed., pp. 781–858). Elsevier.