Introduction
Background
Peptic ulcer disease (PUD) is a common disorder that affects millions of individuals in the United States each year. PUD has a major impact on our health care system by accounting for roughly 10% of medical costs for digestive diseases. In the last two decades, major advances have been made in the understanding of the pathophysiology of PUD, particularly regarding the role of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs). This has led to important changes in diagnostic and treatment strategies, with the potential for improving the clinical outcome and for decreasing health care costs.
Pathophysiology
Peptic ulcers are defects in the gastric or duodenal mucosa that extend through the muscularis mucosa. H pylori infection and NSAID use are the most common etiologic factors. Other, less common causes are hypersecretory states, such as Zollinger-Ellison syndrome, G-cell hyperplasia, mastocytosis, and basophilic leukemias.
Under normal conditions, a physiologic balance exists between peptic acid secretion and gastroduodenal mucosal defense. Mucosal injury and, thus, peptic ulcer occur when the balance between the aggressive factors and the defensive mechanisms is disrupted. Aggressive factors, such as NSAIDs, H pylori, alcohol, bile salts, acid, and pepsin, can alter the mucosal defense by allowing back diffusion of hydrogen ions and subsequent epithelial cell injury. The defensive mechanisms include tight intercellular junctions, mucus, mucosal blood flow, cellular restitution, and epithelial renewal.
Frequency
United States
- One-year point prevalence is 1.8%. Lifetime prevalence is approximately 10%. PUD affects approximately 4.5 million people annually.
International
The frequency of PUD in other countries is variable and determined primarily by association with the major causes of PUD: H pylori and NSAIDs.1
Mortality/Morbidity
Medical office visits and hospitalizations for PUD have decreased in the last few decades. The mortality rate, which has decreased modestly in the last few decades as well, is approximately 1 death per 100,000 cases. The hospitalization rate is approximately 30 patients per 100,000 cases.
Sung et al examined the rate of bleeding-related versus non-bleeding–related causes of mortality in 577 patients with peptic ulcer bleeding.2 The causes of death were classified as follows:
- Bleeding-related mortality
- Death from uncontrolled bleeding
- Death during surgery for uncontrolled bleeding
- Death within 48 hours after endoscopy
- Death from surgical complications or within 1 month following surgery
- Endoscopic-related mortality
- Non-bleeding–related mortality
- Death from cardiac causes
- Death from pulmonary causes
- Death from cerebrovascular disease
- Death from multiorgan failure
- Death from terminal malignancy
The investigators determined that among patients suffering from peptic ulcer bleeding, deaths from non-bleeding–related causes (79.7%) were significantly higher than those from bleeding-related causes (18.4%). Terminal malignancy (33.7%), multiorgan failure (23.9%), and pulmonary conditions (23.5%) were the most frequent non-bleeding–related causes of mortality.
Most bleeding-related deaths in the study resulted when attempts at immediate bleeding control failed (29.2%) or occurred in patients who died within 48 hours after endoscopic therapy (25.5%). The mean age of patients who suffered bleeding-related mortality (75.4 years) was found to be greater than that of patients who died from the other listed causes (71.7 years; P = 0.010).
According to the study's authors, clinicians can attempt to optimize the management of patients with peptic ulcer bleeding by concentrating not only on achieving hemostasis, but also on reducing the patients' risks for multiorgan failure and cardiopulmonary death.
Sex
- Prevalence has shifted from predominance in males to similar occurrences for both sexes.
- Lifetime prevalence is approximately 11-14% for men and 8-11% for women.
Age
- Age trends for ulcer occurrence reveal declining rates in younger men, particularly for duodenal ulcer, and increasing rates in older women.
- Trends reflect complex changes in risk factors for PUD, including age-cohort phenomena with the prevalence of H pylori infection and the use of NSAIDs in older populations.
Clinical
History
- Epigastric pain (the most common symptom)
- Gnawing or burning sensation
- Occurs 2-3 hours after meals
- Relieved by food or antacids
- Patient awakens with pain at night.
- May radiate to the back (consider penetration)
- Nausea
- Vomiting, which might be related to partial or complete gastric outlet obstruction
- Dyspepsia, including belching, bloating, distention, and fatty food intolerance
- Heartburn
- Chest discomfort
- Anorexia, weight loss
- Hematemesis or melena resulting from gastrointestinal bleeding
- Dyspeptic symptoms that might suggest PUD are not specific because only 20-25% of patients with symptoms suggestive of peptic ulceration are found on investigation to have a peptic ulcer.
Physical
- In uncomplicated PUD, clinical findings are few and nonspecific.
- Epigastric tenderness
- Guaiac-positive stool resulting from occult blood loss
- Melena resulting from acute or subacute gastrointestinal bleeding
- Succussion splash resulting from partial or complete gastric outlet obstruction
Causes
- H pylori infection
- H pylori infection and NSAID use account for most cases of PUD.
- The rate of H pylori infection for duodenal ulcers in the United States is less than 75% for patients who do not use NSAIDs. Excluding patients who use NSAIDs, 61% of duodenal ulcers and 63% of gastric ulcers are positive for H pylori in one study. This rate also depends on the demographic, which appears to be less frequent in whites as compared to nonwhites.
- Prevalence in complicated ulcers (ie, bleeding, perforation) is significantly lower than that found in uncomplicated ulcer disease.
- Nonsteroidal anti-inflammatory drugs
- Similar to H pylori infection, NSAID use is a common cause for PUD.
- Corticosteroids alone do not increase the risk for PUD; however, they can potentiate the ulcer risk in patients who use NSAIDs concurrently.
- Severe physiologic stress
- Burns
- CNS trauma
- Surgery
- Severe medical illness
- Hypersecretory states (uncommon)
- Gastrinoma (Zollinger-Ellison syndrome) or multiple endocrine neoplasia (MEN-I)
- Antral G cell hyperplasia
- Systemic mastocytosis
- Basophilic leukemias
- Diseases associated with an increased risk of PUD include cirrhosis, chronic obstructive pulmonary disease, renal failure, and organ transplantation.
- Additional rare, miscellaneous causes include radiation-induced or chemotherapy-induced ulcers, vascular insufficiency (crack cocaine), and duodenal obstruction.
More on Peptic Ulcer Disease |
 Overview: Peptic Ulcer Disease |
| Differential Diagnoses & Workup: Peptic Ulcer Disease |
| Treatment & Medication: Peptic Ulcer Disease |
| Follow-up: Peptic Ulcer Disease |
| References |
| Further Reading |
| Next Page » |
References
Cai S, García Rodríguez LA, Massó-González EL, Hernández-Díaz S. Uncomplicated peptic ulcer in the UK: trends from 1997 - 2005. Aliment Pharmacol Ther. Aug 26 2009;[Medline].
Sung JJ, Tsoi KK, Ma TK, et al. Causes of mortality in patients with peptic ulcer bleeding: a prospective cohort study of 10,428 cases. Am J Gastroenterol. Sep 15 2009;[Medline].
Javid G, Zargar SA, U-Saif R, Khan BA, Yatoo GN, Shah AH, et al. Comparison of p.o. or i.v. proton pump inhibitors on 72-h intragastric pH in bleeding peptic ulcer. J Gastroenterol Hepatol. Jul 2009;24(7):1236-43. [Medline].
Singh V, Mishra S, Maurya P, et al. Drug resistance pattern and clonality in H. pylori strains. J Infect Dev Ctries. Mar 1 2009;3(2):130-6. [Medline]. [Full Text].
Chan FK, Graham DY. Review article: prevention of non-steroidal anti-inflammatory drug gastrointestinal complications--review and recommendations based on risk assessment. Aliment Pharmacol Ther. May 15 2004;19(10):1051-61. [Medline].
Conn HO, Poynard T. Corticosteroids and peptic ulcer: Meta-analysis of adverse events during steroid therapy. J Intern Med. 1994;236:619. [Medline].
Ford AC, Delaney BC, Forman D, Moayyedi P. Eradication therapy in Helicobacter pylori positive peptic ulcer disease: systematic review and economic analysis. Am J Gastroenterol. Sep 2004;99(9):1833-55. [Medline].
Gisbert JP, Khorrami S, Carballo F, et al. Meta-analysis: Helicobacter pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer. Aliment Pharmacol Ther. Mar 15 2004;19(6):617-29. [Medline].
Hawkey CJ, Karrasch JA, Szczepanski L, et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal anti-inflammatory drugs. Omeprazole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) Study Group. N Engl J Med. 338(11):727-34. [Medline].
Jyotheeswaran S, Shah AN, Jin HO, et al. Prevalence of Helicobacter pylori in peptic ulcer patients in greater Rochester, NY: is empirical triple therapy justified?. Am J Gastroenterol. Apr 1998;93(4):574-8. [Medline].
Piper JM, Ray WA, Daugherty JR, Griffin MR. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med. May 1 1991;114(9):735-40. [Medline].
Quan C, Talley NJ. Management of peptic ulcer disease not related to Helicobacter pylori or NSAIDs. Am J Gastroenterol. Dec 2002;97(12):2950-61. [Medline].
Rautelin H, Lehours P, Megraud F. Diagnosis of Helicobacter pylori infection. Helicobacter. 2003;8 Suppl 1:13-20. [Medline].
Salcedo JA, Al-Kawas F. Treatment of Helicobacter pylori infection. Arch Intern Med. Apr 27 1998;158(8):842-51. [Medline].
Silverstein FE, Graham DY, Senior JR, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 123(4):241-9. [Medline].
Soll AH. Consensus conference. Medical treatment of peptic ulcer disease. Practice guidelines. Practice Parameters Committee of the American College of Gastroenterology. JAMA. Feb 28 1996;275(8):622-9. [Medline].
Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. Jun 17 1999;340(24):1888-99. [Medline].
Yeomans ND, Tulassay Z, Juhasz L, et al. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal anti-inflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group. N Engl J Med. 338(11):719-26. [Medline].
Further Reading
Clinical guidelines
Peptic ulcer disease.
University of Michigan Health System - Academic Institution. 1996 Oct (revised 2005 May). 9 pages. NGC:004376
ASGE guideline: the role of endoscopy in acute non-variceal upper-GI hemorrhage.
American Society for Gastrointestinal Endoscopy - Medical Specialty Society. 2004 Oct. 8 pages. NGC:004062
Clinical trials
Peptic Ulcer Perforation Study (PULP)
Surveillance of Bleeding Peptic Ulcer Using Wireless Capsule Endoscopy
Importance of Cytokines in Peptic Ulcer Disease: Implications for Treatment
Related eMedicine topics
Peptic Ulcer Disease
Peptic Ulcer, Surgical Treatment
Gastritis and Peptic Ulcer Disease
Perforated Peptic Ulcer
Gastric Ulcers
Keywords
peptic ulcer disease, ulcer symptoms, peptic ulcer, stomach ulcer, duodenal ulcer, gastric ulcer, , treatment, infection, infection, gastrointestinal bleeding, gastrinoma, Zollinger-Ellison syndrome
