Because of the complexity of the topic and change in dogma after H pylori discovery, reference search pre-1990 was mainly through book chapters, monographs, and review articles, including selective search of original publications. For 1990–2008, the PubMed database was used to retrieve key articles on various and specific aspects of peptic ulcer disease. Search terms were “ulcer”, “peptic ulcer”, “gastric ulcer”, “duodenal ulcer”, “epidemiology”, “ulcer pathogenesis”, “H pylori”, “H pylori
SeminarPeptic ulcer disease
Introduction
Peptic ulcer disease embraces both gastric and duodenal ulcers and has been a major threat to the world's population over the past two centuries, with a high morbidity and substantial mortality. Epidemiological data for this disease and its complications have shown striking geographical variations in incidence and prevalence. Development of ulcer disease and death from it has been associated with the birth of urbanisation and was interpreted as a birth-cohort event with the peak of disease in those born during the late 19th century.1, 2 Our understanding of the disease changed greatly with the discovery of Campylobacter pyloridis (renamed Helicobacter pylori in 1989 because of a revised taxonomic classification) in 1982 by Warren and Marshall.3, 4 This discovery switched the notion from an acid-driven disease to an infectious disease, opening a huge area for intensive research that resulted in the reconciliation of previously suggested mechanisms of pathogenesis.
The fall of the acid dogma in peptic ulcer disease, which had found its undisputed acceptance during and after the introduction of histamine H2-receptor antagonists, led to the present therapeutic principle. Maintenance acid-suppressive therapy for duodenal ulcer, which followed decades of dominance of surgical interventions (subtotal gastric resections, several forms of vagotomy), was replaced with a short-term antibiotic regimen targeting eradication of H pylori infection.5, 6 H pylori eradication as cure of peptic ulcer received its full recognition when the Nobel Prize for Medicine and Physiology was awarded to Warren and Marshall in 2005. This recognition has not, however, closed the chapter on peptic ulcers. The management of ulcer disease and its complications remains a clinical challenge. Additionally, non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin are an increasingly important cause of ulcers and their complications even in H pylori-negative patients.7, 8 Other rare causes of ulcer disease in the absence of H pylori, NSAIDs, and aspirin also exist.
Section snippets
Clinical manifestations and diagnosis
The predominant symptom of uncomplicated peptic ulcer is epigastric pain, which can be accompanied by other dyspeptic symptoms such as fullness, bloating, early satiety, and nausea. In patients with duodenal ulcer, epigastric pain occurs typically during the fasting state or even during the night and is usually relieved by food intake or acid-neutralising agents. Roughly a third of these patients also have heartburn, mostly without erosive oesophagitis.9 Chronic ulcers can be asymptomatic.10 In
Pathogenesis
Panel 1 shows an aetiological classification of peptic ulcers. The complex and multifactorial pathogenesis of peptic ulcer has been studied over several decades, and results from an imbalance of aggressive gastric luminal factors acid and pepsin and defensive mucosal barrier function. Several environmental and host factors contribute to ulcer formation by increasing gastric acid secretion or weakening the mucosal barrier.18, 19, 20 Among environmental factors, smoking, excessive alcohol use,
H pylori-positive ulcer
Epidemiological studies revealed a very strong association between H pylori infection and duodenal and gastric ulcers. The ultimate proof of H pylori as the main cause of ulcer disease was the permanent cure of peptic ulcers by eradication of the infection.30, 31 More than 50% of the world's population has a chronic H pylori infection of the gastric mucosa, yet only 5–10% of those infected develop ulcers. Factors determining whether the infection will produce disease are the pattern of
NSAID-induced ulcer
Topical injury by ion trapping78 and reduction of mucus gel hydrophobicity79 was once thought to be an important mechanism of NSAID-induced gastric damage. Later, NSAIDs were shown to damage the stomach mainly by suppression of gastric prostaglandin synthesis.80 The discovery of two isoforms of cyclo-oxygenase (COX), COX-1 and COX-2, sparked an enormous drive by the pharmaceutical industry to develop COX-2-selective NSAIDs as gastric-sparing anti-inflammatory analgesics. Now, good evidence
Management
Since Karl Schwarz's109 dictum of no acid, no ulcer, development of medical therapies has targeted gastric acid secretion and mucosal defence mechanisms. Many drugs have been used to treat ulcers, but few early treatments stood the test of time (table 1). The most successful classes of drugs were those inhibiting gastric acid secretion. H2-receptor antagonists revolutionised treatment of peptic ulcer, healing ulcers and keeping them in remission when given as maintenance therapy.110, 111 They
Treatment for H pylori-positive ulcer
Treatment for H pylori-associated ulcer disease is mainly directed at eradication of infection. Eradication is usually achieved with a combination of acid-inhibiting therapy and antibiotics. Antibacterial therapy alone does result in healing, but the process is accelerated by addition of acid suppressants (ie, PPIs).74 The Maastricht Consensus Report provides recommendations on management of H pylori infection (panel 2).6
H pylori eradication is equally effective in both duodenal and gastric
Treatment for NSAID-induced ulcer
NSAIDs, including low-dose aspirin, are the most important cause of ulcer complications in developed countries where prevalence of H pylori infection is falling. In patients who develop uncomplicated peptic ulcers while on NSAIDs, more than 90% of gastric or duodenal ulcers heal with 8 weeks of standard-dose H2-receptor antagonists (eg, ranitidine 150 mg twice a day), provided that NSAIDs are discontinued.129 However, healing of gastric ulcers will be greatly impaired if patients continue to
H pylori-negative NSAID-negative ulcer
Ulceration of the gastric or duodenal mucosa in the absence of H pylori infection and NSAID or aspirin usage is rare.149, 150, 151, 152, 153, 154 However, because of the falling prevalence of H pylori infection and resulting ulcers, the proportion of ulcers that are unrelated to this infection is likely to increase and several rare causes need specific attention. The most important consideration in a patient with gastric or duodenal ulcer, negative H pylori test, and negative NSAID or aspirin
Search strategy and selection criteria
References (160)
- et al.
Civilisation and peptic ulcer
Lancet
(1962) - et al.
Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration
Lancet
(1984) - et al.
Gastroduodenal defence mechanisms
Abnormalities of acid secretion in patients with duodenal ulcer
Gastroenterology
(1978)- et al.
Epidemiology of peptic ulcer disease
- et al.
Stressful life events, acid hypersecretion, and ulcer disease
Gastroenterology
(1983) - et al.
Peptic ulcers after the Hanshin-Awaji earthquake: increased incidence of bleeding gastric ulcers
Am J Gastroenterol
(1998) - et al.
Cure of duodenal ulcer associated with eradication of Helicobacter pylori
Lancet
(1990) - et al.
Cure of Helicobacter pylori-associated ulcer disease through eradication
Baillieres Best Pract Res Clin Gastroenterol
(2000) - et al.
The role of gastrin in ulcer pathogenesis
Baillieres Best Pract Res Clin Gastroenterol
(2000)
The acid response to gastrin distinguishes duodenal ulcer patients from Helicobacter pylori-infected healthy subjects
Gastroenterology
Effect of Helicobacter pylori on gastric somatostatin in duodenal ulcer disease
Lancet
Helicobacter pylori infection and abnormalities of acid secretion in patients with duodenal ulcer disease
Gastroenterology
A mechanism by which Helicobacter pylori infection of the antrum contributes to the development of duodenal ulcer
Gastroenterology
Pathogenesis of gastric metaplasia of the human duodenum: role of Helicobacter pylori, gastric acid, and ulceration
Gastroenterology
Expression of interleukin 8 and CD54 by human gastric epithelium after Helicobacter pylori infection in vitro
Gastroenterology
Patterns of inflammation linked to ulcer disease
Baillieres Best Pract Res Clin Gastroenterol
Surface hydrophobicity of gastric mucosa in Helicobacter pylori infection: effect of clearance and eradication
Gastroenterology
Demonstration of a phospholipid-rich zone in the human gastric epithelium damaged by Helicobacter pylori
Gastroenterology
Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration
J Biol Chem
Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori
Gastroenterology
Importance of Helicobacter pylori oipA in clinical presentation, gastric inflammation, and mucosal interleukin 8 production
Gastroenterology
Genetics of duodenal and gastric ulcer
Clin Gastroenterol
Contribution of HLA-DQA gene to host's response against Helicobacter pylori
Lancet
The MACH2 study: role of omeprazole in eradication of Helicobacter pylori with 1-week triple therapies
Gastroenterology
Duodenal ulcer healing by eradication of Helicobacter pylori without anti-acid treatment: randomised controlled trial
Lancet
Eradication of Helicobacter pylori reduces the possibility of rebleeding in peptic ulcer disease
Gastrointest Endosc
Gastric mucosal hemorrhage in dogs. Effects of acid, aspirin, and alcohol
Gastroenterology
Peptic ulcer and bleeding events associated with rofecoxib in a 3-year colorectal adenoma chemoprevention trial
Gastroenterology
NSAIDs, Coxinbs CINOD and H2S-releasing NSAIDs, what lies beyond the horizon?
Dig Liver Dis
The mucoid cap over superficial gastric damage in the rat. A high-pH microenvironment dissipated by nonsteroidal antiinflammatory drugs and endothelin
Gastroenterology
Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage
Gastroenterology
Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs
Lancet
Effects of Helicobacter pylori and nonsteroidal anti-inflammatory drugs on peptic ulcer disease: a systematic review
Clin Gastroenterol Hepatol
Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis
Lancet
Stratifying the risk of NSAID-related upper gastrointestinal clinical events: results of a double-blind outcomes study in patients with rheumatoid arthritis
Gastroenterology
Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers
Lancet
Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with non-steroidal anti-inflammatory drugs: a randomised trial
Lancet
Causes underlying the birth-cohort phenomenon of peptic ulcer: analysis of mortality data 1911–2000, England and Wales
Int J Epidemiol
Unidentified curved bacilli on gastric epithelium in active chronic gastritis
Lancet
Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in peptic ulcer disease
JAMA
Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report
Gut
Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. A meta-analysis
Ann Intern Med
Risk of upper gastrointestinal complications among users of traditional NSAIDs and COXIBs in the general population
Gastroenterology
Impact of Helicobacter pylori eradication on heartburn in patients with gastric or duodenal ulcer disease—results from a randomized trial programme
Aliment Pharmacol Ther
Asymptomatic peptic ulcer disease
Br Med J (Clin Res Ed)
Acute upper gastrointestinal haemorrhage in west of Scotland: case ascertainment study
BMJ
Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. Steering Committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage
BMJ
Epidemiology of hospitalization for acute upper gastrointestinal hemorrhage: a population-based study
Am J Gastroenterol
Helicobacter pylori infection and perforated peptic ulcer prevalence of the infection and role of antimicrobial treatment
Helicobacter
Cited by (662)
Biochemical evaluation with symptoms of gastrointestinal tract manifestations – A systemic review
2024, Journal of King Saud University - ScienceCT Assessment of Complications From Gastric or Duodenal Ulcers
2024, RadiologiaSodium alginate-based smart gastro-retentive drug delivery system of revaprazan loaded SLNs; Formulation and characterization
2023, International Journal of Biological MacromoleculesEvaluation of Abdominal Emergencies
2023, Surgical Clinics of North AmericaSafety of surfactant excipients in oral drug formulations
2023, Advanced Drug Delivery Reviews