Clinical Review

Challenges in the Management of Peptic Ulcer Disease



From the University of Alabama at Birmingham, Birmingham, AL.


Objective: To review current challenges in the management of peptic ulcer disease.

Methods: Review of the literature.

Results: Peptic ulcer disease affects 5% to 10% of the population worldwide, with recent decreases in lifetime prevalence in high-income countries. Helicobacter pylori infection and nonsteroidal anti-inflammatory drug (NSAID) use are the most important drivers of peptic ulcer disease. Current management strategies for peptic ulcer disease focus on ulcer healing; management of complications such as bleeding, perforation, and obstruction; and prevention of ulcer recurrence. Proton pump inhibitors (PPIs) are the cornerstone of medical therapy for peptic ulcers, and complement testing for and treatment of H. pylori infection as well as elimination of NSAID use. Although advances have been made in the medical and endoscopic treatment of peptic ulcer disease and the management of ulcer complications, such as bleeding and obstruction, challenges remain.

Conclusion: Peptic ulcer disease is a common health problem globally, with persistent challenges related to refractory ulcers, antiplatelet and anticoagulant use, and continued bleeding in the face of endoscopic therapy. These challenges should be met with PPI therapy of adequate frequency and duration, vigilant attention to and treatment of ulcer etiology, evidence-based handling of antiplatelet and anticoagulant medications, and utilization of novel endoscopic tools to obtain improved clinical outcomes.

Keywords: H. pylori; nonsteroidal anti-inflammatory drugs; NSAIDs; proton pump inhibitor; PPI; bleeding; perforation; obstruction; refractory ulcer; salvage endoscopic therapy; transcatheter angiographic embolization.

A peptic ulcer is a fibrin-covered break in the mucosa of the digestive tract extending to the submucosa that is caused by acid injury (Figure 1). Most peptic ulcers occur in the stomach or proximal duodenum, though they may also occur in the esophagus or, less frequently, in a Meckel’s diverticulum.1,2 The estimated worldwide prevalence of peptic ulcer disease is 5% to 10%, with an annual incidence of 0.1% to 0.3%1; both rates are declining.3 The annual incidence of peptic ulcer disease requiring medical or surgical treatment is also declining, and currently is estimated to be 0.1% to 0.2%.4 The lifetime prevalence of peptic ulcers has been decreasing in high-income countries since the mid-20th century due to both the widespread use of medications that suppress gastric acid secretion and the declining prevalence of Helicobacter pylori infection.1,3

Peptic ulcer in duodenum

Peptic ulcer disease in most individuals results from H. pylori infection, chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, or both. A combination of H. pylori factors and host factors lead to mucosal disruption in infected individuals who develop peptic ulcers. H. pylori–specific factors include the expression of virulence factors such as CagA and VacA, which interact with the host inflammatory response to cause mucosal injury. The mucosal inflammatory response is at least partially determined by polymorphisms in the host’s cytokine genes.1,4 NSAIDs inhibit the production of cyclooxygenase-1-derived prostaglandins, with subsequent decreases in epithelial mucous formation, bicarbonate secretion, cell proliferation, and mucosal blood flow, all of which are key elements in the maintenance of mucosal integrity.1,5 Less common causes of peptic ulcers include gastrinoma, adenocarcinoma, idiopathic ulcers, use of sympathomimetic drugs (eg, cocaine or methamphetamine), certain anticancer agents, and bariatric surgery.4,6

This article provides an overview of current management principles for peptic ulcer disease and discusses current challenges in peptic ulcer management, including proton pump inhibitor (PPI) therapy, refractory ulcers, handling of antiplatelet and anticoagulants during and after peptic ulcer bleeding, and ulcer bleeding that continues despite salvage endoscopic therapy.


We searched MEDLINE using the term peptic ulcer disease in combination with the terms current challenges, epidemiology, bleeding, anticoagulant, antiplatelet, PPI potency, etiology, treatment, management, and refractory. We selected publications from the past 35 years that we judged to be relevant.


Next Article: