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Peptic Ulcer Disease

By Michael C. DiMarino, MD, Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University

A peptic ulcer is a round or oval sore where the lining of the stomach or duodenum has been eaten away by stomach acid and digestive juices.

  • Peptic ulcers can result from Helicobacter pylori infection or from drugs that weaken the lining of the stomach or duodenum.

  • Discomfort caused by ulcers tends to come and go.

  • The diagnosis of peptic ulcer disease is based on symptoms of stomach pain and on the results of an examination of the stomach with a flexible viewing tube (upper endoscopy).

  • Antacids and other drugs are given to reduce acid in the stomach, and antibiotics are given to eliminate Helicobacter pylori.

Ulcers penetrate into the lining of the stomach or duodenum (the first part of the small intestine). Ulcers may range in size from several millimeters to several centimeters. Ulcers can occur at any age, including infancy and childhood, but are most common among middle-aged adults. Gastritis may develop into ulcers.

The names given to specific ulcers identify their anatomic locations or the circumstances under which they developed. Duodenal ulcers, the most common type of peptic ulcer, occur in the first few inches of the duodenum. Gastric (stomach) ulcers, which are less common, usually occur along the upper curve of the stomach. Marginal ulcers can develop when part of the stomach has been removed surgically, at the point where the remaining stomach has been reconnected to the intestine. Stress ulcers, like those that form in acute stress gastritis, can occur as a result of the stress of severe illness, skin burns, or injury. Stress ulcers occur in the stomach and the duodenum.


Ulcers develop when the normal defense and repair mechanisms of the lining of the stomach or duodenum are weakened, making the lining more likely to be damaged by stomach acid.

By far, the two most common causes of peptic ulcers are

H. pylori infection is present in 50 to 70% of people with duodenal ulcers and in 30 to 50% of people with stomach ulcers. NSAID use causes more than 50% of peptic ulcers. However, most people who take NSAIDs do not develop peptic ulcers.

People who smoke are more likely to develop a peptic ulcer than people who do not smoke, and their ulcers heal more slowly and are likely to recur. Although alcohol increases stomach acid production, drinking moderate amounts of alcohol does not seem to cause ulcers or delay their healing. Although psychologic stress can increase acid production, no link has been found between psychologic stress and peptic ulcers.

A rare cause of peptic ulcers is a type of cancer that releases a hormone called gastrin that causes excess acid production (see Zollinger-Ellison Syndrome: An Acid-Stimulating Cancer). The symptoms of cancerous ulcers are very similar to those of noncancerous ulcers. However, cancerous ulcers usually do not respond to the treatments used for noncancerous ulcers.

About 50 to 60% of children who have duodenal ulcers have a family history of peptic ulcer disease.


Symptoms can vary with the location of the ulcer and the person's age. For example, children and older people may not have the usual symptoms or may have no symptoms at all. In these instances, ulcers are discovered only when complications develop.

The most common symptom of a peptic ulcer is mild to moderately severe pain. The pain is typically described as gnawing, burning, aching, or soreness or sometimes as a sensation of hunger and is usually located just below the breastbone. It is usually relieved by food or antacids. The typical ulcer tends to heal and recur. Thus, pain may occur for days or weeks, then wane or disappear, and then return again when the ulcer returns. Only about half of people have typical symptoms.

Duodenal ulcer symptoms tend to follow a pattern. Pain is usually absent when the person awakens but appears by mid-morning. Drinking milk or eating (which buffers stomach acid) or taking antacids generally relieves the pain, but it usually returns 2 or 3 hours later. Pain that awakens the person during the night is common. Frequently, the pain erupts once or more a day over a period of one to several weeks and then may disappear without treatment. However, pain usually recurs, often within the first 2 years and occasionally after several years. People generally develop patterns and often learn by experience when a recurrence is likely (commonly in spring and fall and during periods of stress).

The symptoms of gastric ulcers, marginal ulcers, and stress ulcers, unlike those of duodenal ulcers, do not follow any pattern. Eating may relieve pain temporarily or may cause pain rather than relieve it. Gastric ulcers sometimes cause scarring and swelling of the tissues (edema) that lead into the small intestine, which may prevent food from easily passing out of the stomach. This blockage may cause bloating, nausea, or vomiting after eating.

Complications of peptic ulcers, such as bleeding or rupture, are accompanied by symptoms of low blood pressure, such as dizziness and fainting.


Most peptic ulcers can be cured without complications. However, in some cases, peptic ulcers can develop potentially life-threatening complications, such as

  • Penetration

  • Perforation

  • Bleeding (hemorrhage)

  • Obstruction (blockage)

  • Cancer


An ulcer can go through (penetrate) the muscular wall of the stomach or duodenum (the first segment of the small intestine) and continue into an adjacent organ, such as the liver or pancreas. This penetration causes intense, piercing, persistent pain, which may be felt in another area of the body other than the area involved. For example, the back may hurt when a duodenal ulcer penetrates the pancreas. The pain may intensify when the person changes position. Doctors use imaging tests such as computed tomography (CT) and magnetic resonance imaging (MRI) to diagnose penetrations. If drugs do not heal the ulcer, surgery may be needed.


Ulcers on the front surface of the duodenum, or less commonly the stomach, can go through the wall, creating an opening (perforation) to the free space in the abdominal cavity. The resulting pain is sudden, intense, and steady. The pain rapidly spreads throughout the abdomen. The person may feel pain in one or both shoulders. Breathing deeply and changing position worsen the pain, so the person often tries to lie very still. The abdomen is tender when touched, and the tenderness worsens if a doctor presses deeply and then suddenly releases the pressure. (Doctors call this rebound tenderness.)

Symptoms may be less intense in older people, in people taking corticosteroids or immunosuppressants, or in very ill people. A fever indicates an infection in the abdominal cavity. If the condition is not treated, shock may develop. Doctors do x-rays or CT to aid the diagnosis. This emergency situation (called an acute abdomen) requires immediate surgery and antibiotics given by vein.


Bleeding (hemorrhage) is a common complication of ulcers even when they are not painful. Vomiting bright red blood or reddish brown clumps of partially digested blood that look like coffee grounds (hematemesis) and passing black tarry stools (melena) or obviously bloody stools (hematochezia) can be symptoms of a bleeding ulcer. Blood loss may also cause weakness, a decrease in blood pressure when a person stands up, sweating, thirst, and fainting. However, small amounts of blood in the stool may not be noticeable but, if persistent, can still lead to anemia.

Bleeding may result from other digestive conditions as well, but doctors begin their investigation by looking for the source of bleeding in the stomach and duodenum. Unless bleeding is massive, a doctor uses a flexible viewing tube (endoscope) to do an upper endoscopy. If a bleeding ulcer is seen, the endoscope can be used to cauterize it (that is, destroy it with heat). A doctor may also use the endoscope to inject a material that causes a bleeding ulcer to clot.

If the source cannot be found and the bleeding is not severe, treatments include taking drugs that suppress the production of acid, such as histamine-2 (H2) blockers or proton pump inhibitors. The person also receives fluids by vein and takes nothing by mouth, so the digestive tract can rest. If these measures fail, surgery is needed.


Swelling of inflamed tissues around an ulcer or scarring from previous ulcer flare-ups can narrow the outlet from the stomach or narrow the duodenum. A person with this type of obstruction may vomit repeatedly—often regurgitating large volumes of food eaten hours earlier. A feeling of being unusually full after eating, bloating, and a lack of appetite are symptoms of obstruction. Over time, vomiting can cause weight loss, dehydration, and an imbalance in body chemicals (electrolytes). Doctors base the diagnosis on the results of x-rays. Treating the ulcers and swelling relieves the obstruction in most cases, but severe obstructions caused by scarring may require endoscopy or surgery.


People with ulcers caused by Helicobacter pylori are 3 to 6 times more likely to develop stomach cancer later in life. There is no increased risk of developing cancer from ulcers that have other causes.


  • Upper endoscopy

  • Sometimes blood tests

A doctor suspects an ulcer when a person has characteristic stomach pain. Sometimes the doctor simply treats the person for an ulcer to see whether the symptoms resolve (called empiric therapy). If the symptoms resolve, the person most likely had an ulcer.

Tests may be needed to confirm the diagnosis, especially when symptoms do not resolve after a few weeks of treatment, or when they first appear in a person who is over age 45 or who has other symptoms such as weight loss, because stomach cancer can cause similar symptoms. Also, when severe ulcers resist treatment, particularly if a person has several ulcers or the ulcers are in unusual places, a doctor may suspect an underlying condition that causes the stomach to overproduce acid.

To help diagnose ulcers and determine their cause, the doctor does upper endoscopy (a procedure done using a flexible viewing tube called an endoscope).

During endoscopy, a doctor can do a biopsy (removal of a tissue sample for examination under a microscope) to determine if a gastric ulcer is cancerous and to help identify the presence of H. pylori bacteria. An endoscope also can be used to stop active bleeding and decrease the likelihood of recurring bleeding from an ulcer.

Blood tests to measure gastrin levels are done in people who may have Zollinger-Ellison syndrome.


If Helicobacter pylori infection is successfully treated, peptic ulcer disease comes back in less than 10% of people. However, peptic ulcer disease comes back in more than 50% of infected people who are treated only with drugs that suppress the production of acid.


  • Antibiotics

  • Acid-reducing drugs

  • Antacids

  • Sometimes surgery

Because infection with H. pylori bacteria is a major cause of ulcers, antibiotics are often used. Sometimes bismuth subsalicylate is used in combination with antibiotics. Neutralizing or reducing stomach acid by taking drugs that directly inhibit the stomach's production of acid promotes healing of peptic ulcers regardless of the cause (see Table: Drugs Used to Treat Peptic Ulcer Disease). In most people, treatment is continued for 4 to 8 weeks. Although bland diets may help reduce acid, no evidence supports the belief that such diets speed healing or keep ulcers from recurring. Nevertheless, it makes sense for people to avoid foods that seem to make pain and bloating worse. Eliminating possible stomach irritants, such as NSAIDs, alcohol, and nicotine, is also important.

Acid-reducing drugs

Proton pump inhibitors are the most potent of the drugs that reduce acid production. Proton pump inhibitors promote healing of ulcers in a greater percentage of people in a shorter period of time than do histamine-2 (H2) blockers. They are also very useful in treating conditions that cause excessive stomach acid secretion, such as Zollinger-Ellison syndrome.

Histamine-2 (H2) blockers, such as cimetidine, famotidine, nizatidine, and ranitidine, relieve symptoms and promote ulcer healing by reducing the production of stomach acid. These highly effective drugs are taken once or twice a day. H2 blockers usually do not cause serious side effects. However, all H2 blockers may cause diarrhea, rash, fever, muscle pains, and confusion. Cimetidine may cause breast enlargement and erectile dysfunction in men. In addition, cimetidine and, to a lesser extent, the other H2 blockers may interfere with the body's elimination of certain drugs, such as theophylline for asthma, warfarin for excessive blood clotting, and phenytoin for seizures.


Antacids do not effectively heal ulcers but they do relieve symptoms of ulcers by neutralizing stomach acid and thereby raising the pH level in the stomach. Their effectiveness varies with the amount of antacid taken and the amount of acid a person produces. Almost all antacids can be purchased without a doctor's prescription and are available in tablet or liquid form. However, antacids can interfere with the absorption of many different drugs, so a pharmacist should be consulted about possible drug-drug interactions before antacids are taken.

Sodium bicarbonate (baking soda) and calcium carbonate, the strongest antacids, may be taken occasionally for fast, short-term relief. However, because they are absorbed by the bloodstream, continual use of these drugs may make the blood too alkaline (alkalosis), resulting in nausea, headache, and weakness. Therefore, these antacids generally should not be used in large amounts for more than a few days. These products also contain a lot of salt and should not be used by people who need to follow a low-sodium diet or who have heart failure or high blood pressure.

Aluminum hydroxide is a relatively safe, commonly used antacid. However, aluminum may bind with phosphate in the digestive tract, thereby depleting the body of calcium, reducing phosphate levels in the blood, and causing weakness and a loss of appetite. The risk of these side effects is greater in people who have alcoholism, who are undernourished, and who have kidney disease, including those receiving dialysis. Aluminum hydroxide may also cause constipation.

Magnesium hydroxide is a more effective antacid than aluminum hydroxide. This antacid acts fast and neutralizes acids effectively. Bowel movements usually remain regular if only a few tablespoons a day are taken. More than four doses a day may cause diarrhea. Because small amounts of magnesium are absorbed into the bloodstream, people with kidney damage should take magnesium hydroxide only in small doses. To limit diarrhea, many antacids contain both magnesium hydroxide and aluminum hydroxide.

Anyone who has heart disease, high blood pressure, or a kidney disorder should consult a doctor before selecting an antacid.

Miscellaneous drugs

Sucralfate may work by forming a protective coating in the base of an ulcer to promote healing. It works well on peptic ulcers and is a reasonable alternative to antacids. Sucralfate is taken 2 to 4 times a day and is not absorbed into the bloodstream, so it causes few side effects. It may, however, cause constipation, and in some cases it reduces the effectiveness of other drugs.

Misoprostol may be used to reduce the likelihood of developing stomach and duodenal ulcers caused by NSAIDs. Misoprostol may work by reducing production of stomach acid and by making the stomach lining more resistant to acid. Older people, people taking corticosteroids, and people who have a history of ulcers or of complications resulting from ulcers are at higher risk of developing an ulcer when they take NSAIDs. These people can take misoprostol with food and their NSAID. However, misoprostol causes diarrhea and other digestive problems in 30% of people who take it. In addition, this drug can cause spontaneous abortions in pregnant women. Alternatives to misoprostol are available for people taking aspirin, NSAIDs, or corticosteroids. These alternatives, such as proton pump inhibitors, are just as effective for reducing the likelihood of developing an ulcer and cause fewer side effects.

Drugs Used to Treat Peptic Ulcer Disease

Drug Type

Some Side Effects



  • Aluminum hydroxide

  • Calcium carbonate

  • Magnesium hydroxide

  • Sodium bicarbonate

Aluminum hydroxide: Nausea, headache, weakness, loss of appetite, and constipation

Magnesium hydroxide: Diarrhea

These drugs are used mainly to relieve symptoms, not as a cure.

Histamine-2 blockers

  • Cimetidine

  • Famotidine

  • Nizatidine

  • Ranitidine

Rash, fever, diarrhea, muscle pains, and confusion

Cimetidine: May cause breast enlargement and erectile dysfunction in men and may interfere with elimination of certain drugs

The once-daily dose is taken in the evening or at bedtime. Doses taken in the morning are less effective.

Proton pump inhibitors

  • Esomeprazole


  • Omeprazole

  • Pantoprazole

  • Rabeprazole

Diarrhea, constipation, and headache

These drugs are usually well tolerated and are most effective means of reducing stomach acid.


  • Amoxicillin

  • Clarithromycin

  • Metronidazole

  • Tetracycline

Altered taste and nausea

Amoxicillin, clarithromycin, or tetracycline: Diarrhea

These drugs are effective for treating peptic ulcers caused by Helicobacter pylori infection.


  • Bismuth subsalicylate

  • Misoprostol

  • Sucralfate


Bismuth subsalicylate: Darkening of the tongue and stool, constipation

Misoprostol: Abdominal cramping, spontaneous abortion

Sucralfate: May reduce absorption of other drugs, constipation

Bismuth subsalicylate is used in combination with antibiotics to cure H. pylori infection.


Surgery for ulcers is now seldom needed because drugs so effectively heal peptic ulcers and endoscopy so effectively stops active bleeding. Surgery is used primarily to deal with complications of a peptic ulcer, such as

  • A perforation

  • An obstruction that fails to respond to drug therapy or that recurs

  • Two or more major episodes of bleeding ulcers

  • A gastric ulcer suspected of being cancerous

  • Severe and frequent recurrences of peptic ulcers

A number of different surgical procedures may be done to treat these complications. Surgery can also be done to reduce the production of acid and ensure the stomach can drain properly. However, ulcers may recur after surgery, and each procedure may cause problems of its own, such as weight loss, poor digestion, frequent bowel movements (dumping syndrome), and anemia.

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