• Highlights
• Introduction
• Causes
• Symptoms
• Complications
• Risk Factors
• Diagnosis
• Treatment
• Treatment for NSAID-Induced Ulcers
• Medications
• Treatment for Bleeding Ulcers
• Lifestyle Changes
• Resources
• References

Peptic ulcers

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of stomach and GI ulcers.

Alternative Names

Duodenal ulcers; Gastric ulcers; H. pylori

Causes

Before the discovery of the bacterium Helicobacter (H.) pylori , the stomach was believed to be a sterile environment. However, in 1982, two Australian scientists identified Helicobacter pylori (H. pylori) as the main cause of stomach ulcers. This discovery showed that inflammation of the stomach and stomach ulcers result from an infection of the stomach caused by the H. pylori bacterium. This discovery was so important that the two researchers received the Nobel Price in Medicine in 2005. The bacterium appears to trigger ulcers in the following way:

• H. pylori's corkscrew shape enables it to penetrate the mucous layer of the stomach or duodenum so that it can attach itself to the lining.
• It survives its highly acidic environment by producing urease, an enzyme that generates ammonia and neutralizes the acid.
• H. pylori then produces a number of toxins and factors that in certain individuals cause inflammation and damage to the lining, leading to ulcers.
• It also alters certain immune factors that allow it to evade detection and cause persistent inflammation for a person's lifetime -- even without invading the mucous membrane.

Even if ulcers do not develop, the bacterium is now considered to be a major cause of active chronic inflammation in the stomach ( gastritis ) and in the upper part of the small intestine ( duodenitis ).

It is also strongly linked to stomach (gastric) cancer and possibly other non-intestinal problems.

Factors That Trigger Ulcers in H. pylori Carriers. It should be noted that H. pylori is found in about 25% of people who do not have peptic ulcers. The magnitude of H. pylori infection, particularly in older people, may not always predict the presence or absence of peptic ulcers. Other variables, then, need to be present to actually trigger ulcers. They may include the following:

• Genetic Factors. Some people harbor genetic strains of H. pylori that may make the bacteria more dangerous and increase the risk for ulcers in infected individuals. The most intensively investigated genetic factor is cytotoxin-associated gene A (CagA), which has been associated with both gastric and duodenal ulcers as will as with stomach cancer. Other genetic types that may also increase bacterial severity are called vacuolating cytotoxin (vacA) and antigen-binding adhesin (BabA) genotypes. Some of these genetic factors may be more or less important for development of ulcers depending on ethnicity.
• Immune Abnormalities. Some experts suggest that certain individuals have abnormalities in the immune response in the intestine that allow the bacteria to become injurious to the lining.
• Lifestyle Factors. Although lifestyle factors such as chronic stress, drinking coffee, and smoking were long believed to be the primary cause of ulcers, it is now thought they only increase susceptibility to ulcers in some H. pylori carriers.

When H. pylori was first identified as the major cause of peptic ulcers, it was found in 90% of people with duodenal ulcers and in about 80% of people with gastric ulcers. As more people are being tested and treated for the bacteria, however, the rate of H. pylori associated ulcers has declined. For example, a 2001 study suggested that about half of ulcers are not caused by H. pylori . Instead, they tend to be due to regular use of nonsteroidal anti-inflammatory drugs (NSAIDs), which include aspirin and other common pain relievers. Genetic factors, or, rarely, Crohn's disease or Zollinger-Ellison syndrome also cause ulcers.

A 2006 study published in the Journal of Biological Chemistry, indicates that a protein called decay-accelerating factor (DAF) acts as receptor for H. pylori. Animal studies show that blocking this interaction makes H. pylori harmless to the stomach. Researchers hope the discovery leads to new drugs that can reduce the risk of peptic ulcer.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Long-term use of NSAIDs is the second most common cause of ulcers and the rate of NSAID-caused ulcers is increasing. About 20 million people take prescription NSAIDs regularly, and over 25 billion tablets of over-the-counter brands are sold each year in America. The most common NSAIDs are aspirin, ibuprofen (Advil), and naproxen (Aleve, Naprosyn), although many others are available. Patients who have an ulcer caused by NSAIDs should stop taking these drugs.

NSAIDs definitely increase the risk for ulcers and gastrointestinal (GI) bleeding. The risk for bleeding is continuous for as long as a patient is on these drugs and may even persist for about a year after taking them. Taking short courses of NSAIDs for temporary pain relief should not cause major problems because the stomach has time to recover and repair any damage that has occurred.

Specific NSAIDs pose greater or lesser risks for ulcers and bleeding. No NSAIDs, however, even over-the-counter brands, should be used long-term except under a doctor's direction.

Ulcer Risk by Specific NSAIDs
Lowest Risk	Medium Risk	Highest Risk
Nabumetone (Relafen) Etodolac (Lodine) Salsalate Sulindac (Clinoril)	Aspirin. Even low-dose aspirin (81 mg) used to protect the heart may pose some risk (although lower than standard doses). Ibuprofen (Motrin, Advil, Nuprin, Rufen) Naproxen (Aleve, Naprosyn, Naprelan, Anaprox) Diclofenac (Voltaren) Tolmetin (Tolectin) NOTE: Drugs within the medium risk group vary in risk. For example, studies show that use of naproxen is twice as likely as ibuprofen to be associated with hospitalization from GI bleeding.	Flurbiprofen (Ansaid) Piroxicam (Feldene) Fenoprofen Indomethacin (Indocin) Meclofenamate (Meclomen) Ketoprofen (Actron, Orudis KT) NOTE: Ketoprofen is often considered a medium-risk drug, but one study reported that taking the drug even one week at low doses causes significant GI injury.

Other Causes

The least common major cause of peptic ulcer disease is the Zollinger-Ellison syndrome (ZES).

Rarely, certain conditions may cause ulceration in the stomach or intestine, including:

• Radiation treatments.
• Bacterial or viral infections.
• Alcohol abuse.
• Physical injury.
• Burns.

Zollinger-Ellison Syndrome (ZES) What is ZES? The least common major cause of peptic ulcer disease is the Zollinger-Ellison syndrome (ZES). In this condition, gastrinomas (tumors in the pancreas and the duodenum) produce excessive amounts of gastrin, a hormone that stimulates gastric acid formation. These tumors are usually malignant, so proper and prompt management of the disease is essential.

Who Gets ZES? The incidence of ZES in the United States is estimated at one case per million people per year, and at 0.1% to 1% among patients with peptic ulcers. The mean age at onset is 45 to 50 years, and men are affected more often than women. How Is ZES Diagnosed? ZES should be suspected in patients with ulcers who are not infected with H. pylori and have no history of NSAID use. Diarrhea may precede ulcer symptoms. Ulcers occurring in the second, third, or fourth portions of the duodenum or the jejunum (the middle section of the small intestine) are signs of the syndrome. Gastroesophageal reflux disease (backflow of the stomach's contents into the esophagus) is more prevalent and often more severe in patients with ZES, and can be complicated by ulcerations and strictures of the esophagus. How Is ZES Treated? Peptic ulcers associated with ZES are typically persistent and difficult to treat. Treatment consists of removing the tumors and suppressing acid with intravenous proton-pump inhibitors (Protonix). Proton-pump inhibitors block acid production and are a major advance for these patients. Previously, removing the stomach was the only option.

• Review Date: 7/14/2006
• Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

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