CHAPTER 16
Peptic ulcer disease

Jonathan R. White¹, Krish Ragunath^1,2, and John C. Atherton¹

¹ University of Nottingham, Nottingham, UK

² Curtin University, Perth, WA, Australia

Peptic ulcer disease (PUD) remains a common cause of morbidity and mortality in the 21st century. Through the endoscope (Figure 16.1), a peptic ulcer is identified as a mucosal break in the stomach or duodenum with depth. The arbitrary criterion (used in most clinical trials) is that an ulcer has a diameter of 5 mm or larger, and lesions smaller than 5 mm are designated erosions. The leading causes of peptic ulcer disease are Helicobacter pylori infection (Figures 16.2–16.4) and use of nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin (Figures 16.5 and 16.6). Rarer causes include malignancy, hypersecretory states such as gastrinoma, other drugs, infections, and vascular and inflammatory disorders. The incidence of peptic ulcer disease has decreased in many countries following falling prevalence of H. pylori infection, but peptic ulcers remain an important clinical issue due to the rise in use of NSAIDs as well as aspirin for cardiovascular disease prevention. Other drugs associated with a modest risk of peptic ulceration are glucocorticoids, clopidogrel, selective serotonin uptake inhibitors, and bisphosphonates.

Specific diets such as spicy food, alcohol or caffeine play no clear role in the development of peptic ulcer disease. Conversely, population‐based studies in USA and Denmark show that mental health issues such as severe stress, depressed mood, suicidal ideation, and psychological counseling were associated with a higher prevalence of PUD. Stress‐related mucosal disease (ulceration, mucosal erosions) occurs in around three‐quarters of patients within a few days of acute major illnesses, and largely relates to the severity of the acute illness (including organ transplantation, head injuries, and burns) or multisystem failure.

The most common complication of peptic ulcer disease is hemorrhage.

Helicobacter pylori‐related peptic ulcer disease

Helicobacter pylori colonizes the gastric mucosa of over 50% of the world’s population and is an important etiological factor in both duodenal and gastric ulceration. H. pylori is also an important cause of gastric adenocarcinoma and mucosa‐associated lymphoid tissue (MALT) lymphoma. H. pylori provokes both local and systemic inflammatory responses, which are essential in the pathogenesis of H. pylori‐induced disease. Disease risk in an infected individual is determined by a combination of host susceptibility (e.g., gene encoding interleukin‐1β, or a weak regulatory T cell response increases the level of inflammation induced by H. pylori), environmental factors, and bacterial virulence factors. When the balance between mucosal damaging agents and the integrity of mucosal defenses is disturbed, peptic ulceration may occur (Figure 16.7). Eradication of H. pylori cures related ulcers and prevents their recurrence.

Microbiological culture for identification of H. pylori is not routinely recommended and is not available in most centers although it is useful to guide eradication therapy in cases of treatment failure. If culture is not possible, there are now molecular, PCR‐based tests for antibiotic resistance, most notably clarithromycin and fluoroquinolones, which can be performed on gastric biopsy specimens directly without prior culture of H. pylori.

Table 16.1 shows a summary of the most recent international guidelines for the management of Helicobacter pylori.

Nonsteroidal antiinflammatory drug‐related peptic ulcer disease

Increasing NSAID and aspirin use has led to an increase in the relative proportion of gastric to duodenal ulcers (Figures 16.8–16.12). NSAID ulcers are more likely than H. pylori ulcers to develop complications such as bleeding. NSAIDs prevent synthesis of essential prostaglandins that are required for mucosal integrity and are also directly toxic to the mucosa. The type of agent, dose, patient age, and other cofactors may influence who develops ulcers. The overall risk of peptic ulcer disease is increased 20‐fold by NSAID use.