Definition and Epidemiology

Peptic ulcer disease (PUD) is a pathologic, destructive, chronic disorder characterized by ulceration of the gastric and duodenal mucosa. The two common causes of peptic ulcers in the United States are Helicobacter infections (Helicobacter pylori) and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). During the last decades of the 20th century, the incidence of PUD declined dramatically. This decline is attributed to the discovery and effective use of acid suppressants and the treatment of H. pylori infections. However, gastric and duodenal ulcers continue to have a serious impact on the economics of health care and society because of recurrence rates, increased office visits, medication costs, diagnostic costs, and patient quality-of-life concerns. Therefore it is essential to obtain a thorough health history, to identify potential risk factors, and to provide a cost-effective diagnosis and treatment plan.

PUD may be defined as a full-thickness defect in the mucosa of the stomach or duodenum caused by an imbalance both in the amount of acid and pepsin production and in the ability of the gastric and duodenal lining to protect itself. It is estimated that approximately 4.5 million people in the United States are affected annually, and the hospitalization rate for PUD is approximately 30 patients per 100,000 cases. Lifetime prevalence is estimated at 11% to 14% in males and 8% to 11% in females.¹ H. pylori, a spiral, flagellated, gram-negative, rod-shaped bacterium, was first identified and linked to gastritis in the 1980s and is a major causative organism in the development of ulcer disease. With the discovery of the bacterium, the treatment of PUD has changed from acid suppression to eradication of the bacterium. Excluding individuals who are using NSAID therapy, 61% of duodenal ulcers and 63% of gastric ulcers have been found to test positive for H. pylori.¹

The second most common cause of PUD is the use of NSAIDs and low-dose aspirin. NSAIDs are commonly prescribed medications and available over the counter. As many as 30% of individuals taking NSAIDs will have adverse gastrointestinal (GI) events. Increasing the risk of an adverse event in individuals using NSAID therapy are a previous history of PUD, advanced age, long-term NSAID use, comorbidities, and concurrent use of anticoagulants.¹ Because of advancing age and the increased prevalence of osteoarthritis, the risk of PUD is significant in older patient populations. The discovery of cyclooxygenase 1 (COX-1) and COX -2 led to the development of COX-2–selective NSAIDs as an alternative therapy. COX-2 inhibitors are generally considered safer for the GI tract; however, this class of medication, which is commonly prescribed for arthritis pain, can also cause gastric or duodenal ulcer formation and has been linked to adverse cardiovascular events.²

Other risk factors for the development of PUD include family history, cigarette smoking, chronic obstructive pulmonary disease, major trauma, oral steroids, bisphosphonate therapy, caffeine ingestion, alcohol, cirrhosis, and physiologic stress. Certain conditions and genetic factors have also been identified as risk factors for the development of PUD. Zollinger-Ellison syndrome, antral G cell hyperplasia, cystic fibrosis, short bowel syndrome, hyperparathyroidism, and noncompliance with an H. pylori treatment regimen are documented in the development of PUD.¹

Pathophysiology

The function of the GI tract is the digestion of food and absorption of nutrients. This process is achieved by high concentrations of acid and pepsin that are secreted from the parietal cells of the stomach. The surface of the mucosa secretes alkaline mucus that protects the mucosa from self-digestion. Under normal conditions, a balance is present between gastric acid secretion and gastroduodenal mucosal defense. However, when this system is interrupted, the protective tissue is damaged, and erosion or ulcer formation occurs. A peptic ulcer can affect one or all layers of the gastric lining or duodenum. Gastric ulcers are commonly found distal to the junction between the antrum and the acid secretory mucosa. Duodenal ulcers are primarily located in the duodenal bulb or at the pyloric duodenal junction. Most patients with duodenal ulcers have impaired bicarbonate secretion, which is associated with H. pylori.³ Reduction of the production of acid and pepsin is key to the promotion of healing and prevention of recurrence. Spontaneous remissions and exacerbations are commonly associated with PUD.

H. pylori, a spiral, flagellated organism, is acquired through the orofecal route. Once it is ingested, H. pylori attaches to the gastric mucosa, colonizes the entire gastric epithelium, and produces local tissue injury that results in the release of cytotoxins and proteases. NSAID therapy has been shown to damage the gastric mucosa by suppression of gastric prostaglandin synthesis. Acid suppression continues to be the key component in the management of NSAID-associated PUD.

Clinical Presentation

Although some patients are asymptomatic, the most common presenting chief complaint is epigastric pain or dyspepsia. Upper abdominal pain or discomfort is the most common presentation, with pain centered in the epigastrium. This discomfort is often described as a sharp, burning, aching, gnawing pain occurring 2 to 5 hours after meals or in the middle of the night. The patient will report that the pain is usually relieved with the ingestion of food or antacids; however, the symptoms are recurrent, with episodes lasting from hours to days to months. Peptic ulcers may be associated with food provoking symptoms. Patients may report pain with eating, postprandial belching, fullness, fatty food intolerance, nausea, and vomiting. Changes in the intensity, duration, or location of the pain may indicate penetration or perforation of an ulcer.⁴