• Causes of Peptic Ulcer Disease
• Symptoms of Peptic Ulcer Disease
• Diagnosis of Peptic Ulcer Disease
• Treatment of Peptic Ulcer Disease
• Prevention Of Peptic Ulcer 
• Complications Of Peptic Ulcer 

Peptic ulcer disease (PUD) is characterized by discontinuation in the inner lining of the gastrointestinal (GI) tract because of gastric acid secretion or pepsin. It extends into the muscularis propria layer of the gastric epithelium. It usually occurs in the stomach and proximal duodenum. It may involve the lower esophagus, distal duodenum, or jejunum. Epigastric pain usually occurs within 15-30 minutes following a meal in patients with a gastric ulcer; on the other hand, the pain with a duodenal ulcer tends to occur 2-3 hours after a meal. Today, testing for Helicobacter pylori is recommended in all patients with peptic ulcer disease. Endoscopy may be required in some patients to confirm the diagnosis, especially in those patients with sinister symptoms. Today, most patients can be managed with a proton pump inhibitor (PPI) based on triple-drug therapy.

A peptic ulcer (stomach ulcer) is a sore on the lining of your stomach or duodenum. People who take NSAIDs such as aspirin and ibuprofen long-term or are infected with the bacteria H. pylori are most likely to develop peptic ulcers.

Causes of Peptic Ulcer Disease

Peptic ulcer disease (PUD) has various causes; however, Helicobacter pylori-associated PUD and NSAID-associated PUD account for the majority of the disease etiology.[rx]

Causes of Peptic Ulcer Disease

Common

• H. pylori infection
• NSAIDs
• Medications
• Zollinger-Ellison syndrome
• Malignancy (gastric/lung cancer, lymphomas)
• Stress (Acute illness, burns, head injury)
• Viral infection
• Vascular insufficiency
• Radiation therapy
• Crohn disease
• Chemotherapy
• long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin  and ibuprofen
• an infection with the bacteria Helicobacter pylori (H. pylori)
• rare cancerous and noncancerous tumors in the stomach, duodenum, or pancreas—known as Zollinger-Ellison syndrome (ZES)
• unclean food
• unclean water
• unclean eating utensils
• contact with an infected person’s saliva and other bodily fluids, including kissing

Helicobacter Pylori-Associated PUD

• H. pylorus is a gram-negative bacillus that is found within the gastric epithelial cells. This bacterium is responsible for 90% of duodenal ulcers and 70% to 90% of gastric ulcers. H. pylori infection is more prevalent among those with lower socioeconomic status and is commonly acquired during childhood. The organism has a wide spectrum of virulence factors allowing it to adhere to and inflame the gastric mucosa. This results in hypochlorhydria or achlorhydria, leading to gastric ulceration.

 Virulence Factors of  Helicobacter pylori

• Urease – The secretion of urease breaks down urea into ammonia and protects the organism by neutralizing the acidic gastric environment.
• Toxins – CagA/VacA is associated with stomach mucosal inflammation and host tissue damage.
• Flagella – Provides motility and allows movement toward the gastric epithelium.

NSAID-associated PUD

• Nonsteroidal anti-inflammatory drugs use is the second most common cause of PUD after H. pylori infection.[rx][rx] The secretion of prostaglandin normally protects the gastric mucosa. NSAIDs block prostaglandin synthesis by inhibiting COX-1 enzyme resulting in a decrease in gastric mucus and bicarbonate production and a decrease in mucosal blood flow.

Medications

• Apart from NSAIDs, corticosteroids, bisphosphonates, potassium chloride, steroids, and fluorouracil have been implicated in the etiology of PUD.
• Smoking also appears to play a role in duodenal ulcers, but the correlation is not linear. Alcohol can irritate the gastric mucosa and induce acidity.

Hypersecretory environments

• Zollinger Ellison syndrome
• Systemic mastocytosis
• Cystic fibrosis
• Hyperparathyroidism
• Antral G cell hyperplasia

Symptoms of Peptic Ulcer Disease

Signs and symptoms of peptic ulcer disease may vary depending upon the location of the disease and age. Gastric and duodenal ulcers can be differentiated from the timing of their symptoms in relation to meals. Nocturnal pain is common with duodenal ulcers. Those with gastric outlet obstruction commonly report a history of abdomen bloating and or fullness.

Common signs and symptoms include

• Epigastric abdominal pain
• Bloating
• Abdominal fullness
• Nausea and vomiting
• Weight loss/weight gain
• Hematemesis
• Melena[rx]
• Unintentional weight loss
• Progressive dysphagia
• Overt gastrointestinal bleeding
• Iron deficiency anemia
• Recurrent emesis
• Family history of upper gastrointestinal malignancy
• happens when your stomach is empty—such as between meals or during the night
• stops briefly if you eat or if you take antacids
• lasts for minutes to hours
• comes and goes for several days, weeks, or months

Diagnosis of Peptic Ulcer Disease

Diagnosis of PUD requires history taking, physical examination, and invasive/noninvasive medical tests.

History

• A careful history should be obtained and noted for the presence of any complications. Patient reporting of epigastric abdominal pain, early satiety, and fullness following a meal raise suspicion of PUD. The pain of gastric ulcers increases 2 to 3 hours after a meal and may result in weight loss, whereas the pain of duodenal ulcers decreases with a meal which can result in weight gain. Any patient presenting with anemia, melena, hematemesis, or weight loss should be further investigated for complications of PUD, predominantly bleeding, perforation, or cancer.

Physical Exam

• A physical exam may reveal epigastric abdominal tenderness and signs of anemia. A physical exam may help a doctor diagnose a peptic ulcer. During a physical exam, a doctor most often
  • checks for bloating in your abdomen
  • listens to sounds within your abdomen using a stethoscope
  • taps on your abdomen checking for tenderness or pain

Investigations

• Esophagogastroduodenoscopy (EGD) – Gold standard and most accurate diagnostic test with sensitivity and specificity up to 90% in diagnosing gastric and duodenal ulcers. The American Society of Gastrointestinal Endoscopy has published guidelines on the role of endoscopy in patients presenting with upper abdominal pain or dyspeptic symptoms suggestive of PUD[rx]. Patients over 50 years of age and new onset of dyspeptic symptoms should get evaluated by an EGD. Anyone with the presence of alarm symptoms should undergo EGD irrespective of age.
• Barium swallow – It is indicated when EGD is contraindicated.
• Complete blood work – liver function, and levels of amylase and lipase
• Serum gastric – is ordered if Zollinger Ellison syndrome is suspected

Helicobacter pylori testing

• Serologic testing – Serological test, also called serology test or antibody test, any of several laboratory procedures carried out on a sample of blood serum (the clear liquid that separates from the blood when it is allowed to clot) for the purpose of detecting antibodies or antibody-like substances that appear specifically in association with certain diseases. There are different types of serological tests—for example, flocculation tests, neutralization tests, hemagglutinin-inhibition tests, enzyme-linked immunosorbent assays (ELISAs), and chemiluminescence immunoassays.
• Urea breath test – High sensitivity and specificity. It may be used to confirm eradication after 4 to 6 weeks of stopping treatment. In the presence of urease, an enzyme produced by H.pylori, the radiolabeled carbon dioxide produced by the stomach is exhaled by the lungs.
• Blood test – A blood test involves drawing a sample of your blood at your doctor’s office or a commercial facility. A health care professional tests the blood sample to see if the results fall within the normal range for different disorders or infections.
• Stool test – Doctors use a stool test to study a sample of your stool. A doctor will give you a container for catching and storing your stool at home. You return the sample to the doctor or a commercial facility, who then sends it to a lab for analysis. Stool tests can show the presence of H. pylori.
• Antibodies – to H.pylori can also be measured
• Stool antigen test – Stool antigen tests (SATs) are relatively inexpensive noninvasive tests. Several guidelines on Helicobacter pylori (H. pylori) infection from around the world indicates that SATs using monoclonal antibodies are useful for primary diagnosis as well as for assessing the results of eradication therapy.
• Urine-based ELISA and rapid urine test – A rapid urine test is the quickest way to test urine. This involves dipping a test strip with small square-colored fields on it into the urine sample for a few seconds. After that, you have to wait for a little for the result to appear.
• Endoscopic biopsy – Culture is not generally recommended as it is expensive, time-consuming, and invasive. It is indicated if eradication treatment fails or there is suspicion about antibiotic resistance. Biopsies from at least 4-6 sites are necessary to increase sensitivity. Gastric ulcers are commonly located on the lesser curvature between the antrum and fundus. The majority of duodenal ulcers are located in the first part of the duodenum.
• Upper gastrointestinal (GI) endoscopy and biopsy – In an upper GI endoscopy, a gastroenterologist, surgeon, or other trained health care professional uses an endoscope to see inside your upper GI tract. This procedure takes place at a hospital or an outpatient center.
• Upper GI series – An upper GI series looks at the shape of your upper GI tract. An x-ray technician performs this test at a hospital or an outpatient center. A radiologist reads and reports on the x-ray images. You don’t need anesthesia. A health care professional will tell you how to prepare for the procedure, including when to stop eating and drinking.
• Computerized tomography – A CT scan uses a combination of x-rays and computer technology to create images. For a CT scan, a health care professional may give you a solution to drink and an injection of a special dye, which doctors call contrast medium. You’ll lie on a table that slides into a tunnel-shaped device that takes the x-rays. An x-ray technician performs the procedure in an outpatient center or a hospital, and a radiologist interprets the images. You don’t need anesthesia of the abdomen with contrast is of limited value in the diagnosis of PUD itself but is helpful in the diagnosis of its complications like perforation and gastric outlet obstruction.

Treatment of Peptic Ulcer Disease

Medical treatment

Antisecretory drugs used for PUD include H2-receptor antagonists and the proton pump inhibitor (PPIs). PPIs have largely replaced H2 receptor blockers due to their superior healing and efficacy. PPIs block acid production in the stomach, providing relief of symptoms and promote healing.

• Corticosteroids, bisphosphonates, and anticoagulants should also be discontinued if possible. Prostaglandin analogs (misoprostol) are sometimes used as prophylaxis for NSAID-induced peptic ulcers.
• The first-line treatment for H. pylori-induced PUD is a triple regimen comprising two antibiotics and a proton pump inhibitor. Pantoprazole, clarithromycin, and metronidazole or amoxicillin are used for 7 to 14 days.[rx]
• Antibiotics and PPIs work synergistically to eradicate H. pylori.[rx] The antibiotic selected should take into consideration the presence of antibiotic resistance in the environment.
• If first-line therapy fails, quadruple therapy with bismuth and different antibiotics is used.

NSAIDs induced PUD can be treated by stopping the use of NSAIDs or switching to a lower dose. If NSAIDs are causing your peptic ulcer and you don’t have an H. pylori infection, your doctor may tell you to

• stop taking the NSAID
• to reduce how much of the NSAID you take
• a switch to another medicine that won’t cause a peptic ulcer

Your doctor may also prescribe medicines to reduce stomach acid and coat and protect your peptic ulcer. Proton pump inhibitors (PPIs), histamine receptor blockers, and protectants can help relieve pain and help your ulcer heal.

PPIs

PPIs reduce stomach acid and protect the lining of your stomach and duodenum. While PPIs can’t kill H. pylori, they do help fight the H. pylori infection.

PPIs include

• esomeprazole (Nexium)
• dexlansoprazole (Dexilant)
• lansoprazole (Prevacid)
• omeprazole (Prilosec, Zegerid)
• pantoprazole (Protonix)
• rabeprazole (AcipHex)

Histamine receptor blockers

Histamine receptor blockers work by blocking histamine, a chemical in your body that signals your stomach to produce acid. Histamine receptor blockers include

• cimetidine (Tagamet)
• famotidine (Pepcid)
• ranitidine (Zantac)
• nizatidine (Axid) Protectants

Protectants

• Protectants coat ulcers and protect them against acid and enzymes so that healing can occur. Doctors only prescribe one protectant—sucralfate (Carafate) NIH external link—for peptic ulcer disease.
• Tell your doctor if the medicines make you feel sick or dizzy or cause diarrhea or headaches. Your doctor can change your medicines. If you smoke, quit. You also should avoid alcohol. Drinking alcohol and smoking slowly the healing of a peptic ulcer and can make it worse.

Histamine receptor blockers

Histamine receptor blockers work by blocking histamine, a chemical in your body that signals your stomach to produce acid. Histamine receptor blockers include

• cimetidine (Tagamet)
• famotidine (Pepcid)
• ranitidine (Zantac)
• nizatidine (Axid)

Antibiotics

• A doctor will prescribe antibiotics to kill H. pylori. How doctors prescribe antibiotics may differ throughout the world. Over time, some types of antibiotics can no longer destroy certain types of H. pylori.
• Antibiotics can cure most peptic ulcers caused by H. pylori or H. pylori-induced peptic ulcers. However, getting rid of the bacteria can be difficult. Take all doses of your antibiotics exactly as your doctor prescribes, even if the pain from a peptic ulcer is gone.

Bismuth subsalicylates

• Medicines containing bismuth subsalicylate NIH external link, such as Pepto-Bismol, coat a peptic ulcer and protect it from stomach acid. Although bismuth subsalicylate can kill H. pylori, doctors sometimes prescribe it with antibiotics, not in place of antibiotics.

Antacids

• An antacid may make the pain from a peptic ulcer go away temporarily, yet it will not kill H. pylori. If you receive treatment for an H. pylori-induced peptic ulcer, check with your doctor before taking antacids. Some of the antibiotics may not work as well if you take them with an antacid.

Triple therapy

For triple therapy, your doctor will prescribe that you take the following for 7 to 14 days:

• the antibiotic clarithromycin
• the antibiotic metronidazole or the antibiotic amoxicillin
• a PPI

Quadruple therapy

For quadruple therapy, your doctor will prescribe that you take the following for 14 days:

• a PPI
• bismuth subsalicylate
• the antibiotics tetracycline NIH external link and metronidazole

Doctors prescribe quadruple therapy to treat patients who

• can’t take amoxicillin because of an allergy to penicillin NIH external link. Penicillin and amoxicillin are similar.
• have previously received a macrolide antibiotic, such as clarithromycin.
• are still infected with H. pylori after triple therapy treatment.

Doctors prescribe quadruple therapy after the first treatment has failed. In the second round of treatment, the doctor may prescribe different antibiotics than those that he or she prescribed the first time.

Sequential therapy

For sequential therapy, your doctor will prescribe that you take the following for 5 days:

• a PPI
• amoxicillin

Then the doctor will prescribe you the following for another 5 days:

• a PPI
• clarithromycin
• the antibiotic tinidazole

Triple therapy, quadruple therapy, and sequential therapy may cause nausea and other side effects, including

• an altered sense of taste
• darkened stools
• a darkened tongue
• diarrhea
• headaches
• temporary reddening of the skin when drinking alcohol
• vaginal yeast infections

Talk with your doctor about any side effects that bother you. He or she may prescribe you other medicines.

Refractory disease and Surgical treatment

• Surgical treatment is indicated if the patient is unresponsive to medical treatment, noncompliant, or at high risk of complications.
• A refractory peptic ulcer is one over 5 mm in diameter that does not heal despite 8-12 weeks of PPI therapy. The common causes are persistent H/pylori infection, continued use of NSAIDs or significant comorbidities that impair ulcer healing or other conditions like gastrinoma or gastric cancer.
• If the ulcer persists despite addressing the above risk factors, patients can be candidates for surgical treatment. Surgical options include vagotomy or partial gastrectomy[rx].

Prevention Of Peptic Ulcer 

There are a lot of things you can do to prevent the symptoms of GERD. Some simple lifestyle changes include

• Elevate the head of your bed at least six inches. If possible, put wooden blocks under the legs at the head of the bed. Or, use a solid foam wedge under the head portion of the mattress. Simply using extra pillows may not help.
• Avoid foods that cause the esophageal sphincter to relax during their digestion. These include:
  • Coffee
  • Chocolate
  • Fatty foods
  • Whole milk
  • Peppermint
  • Spearmint
• Limit acidic foods that make the irritation worse when they are regurgitated. These include citrus fruits and tomatoes.
• Excess pounds put pressure on your abdomen, pushing up your stomach and causing acid to reflux into your esophagus.
• Smoking decreases the lower esophageal sphincter’s ability to function properly.
• If you regularly experience heartburn while trying to sleep, place wood or cement blocks under the feet of your bed so that the head end is raised by 6 to 9 inches. If you can’t elevate your bed, you can insert a wedge between your mattress and box spring to elevate your body from the waist up. Raising your head with additional pillows isn’t effective.
• Wait at least three hours after eating before lying down or going to bed.
• Put down your fork after every bite and pick it up again once you have chewed and swallowed that bite.
• Common triggers include fatty or fried foods, tomato sauce, alcohol, chocolate, mint, garlic, onion, and caffeine.
• Clothes that fit tightly around your waist put pressure on your abdomen and the lower esophageal sphincter.
• Avoid carbonated beverages. Burps of gas force the esophageal sphincter to open and can promote reflux.
• Eat smaller, more frequent meals.
• Do not eat during the three to four hours before you go to bed.
• Avoid drinking alcohol. It loosens the esophageal sphincter.
• Lose weight if you are obese. Obesity can make it harder for the esophageal sphincter to stay closed.
• Avoid wearing tight-fitting garments. Increased pressure on the abdomen can open the esophageal sphincter.
• Use lozenges or gum to keep producing saliva.
• Do not lie down after eating.

Complications Of Peptic Ulcer 

• Perforation – A hole develops in the lining of the stomach or small intestine and causes an infection. A sign of a perforated ulcer is sudden, severe abdominal pain.
• Internal bleeding – Bleeding ulcers can result in significant blood loss and thus require hospitalization. Signs of a bleeding ulcer include lightheadedness, dizziness, and black stools.
• Scar tissue – This is thick tissue that develops after an injury. This tissue makes it difficult for food to pass through your digestive tract. Signs of scar tissue include vomiting and weight loss.
• Gastrointestinal bleeding is the most common complication. Sudden large bleeding can be life-threatening. It occurs when the ulcer erodes one of the blood vessels, such as the gastroduodenal artery.
• Perforation (a hole in the wall of the gastrointestinal tract) often leads to catastrophic consequences if left untreated. Erosion of the gastro-intestinal wall by the ulcer leads to spillage of the stomach or intestinal content into the abdominal cavity. Perforation at the anterior surface of the stomach leads to acute peritonitis, initially chemical and later bacterial peritonitis. The first sign is often sudden intense abdominal pain; an example is Valentino’s syndrome, named after the silent-film actor who experienced this pain before his death. Posterior wall perforation leads to bleeding due to the involvement of the gastroduodenal artery that lies posterior to the first part of the duodenum.
• Penetration is a form of perforation in which the hole leads to and the ulcer continues into adjacent organs such as the liver and pancreas.
• Gastric outlet obstruction is a narrowing of the pyloric canal by scarring and swelling of the gastric antrum and duodenum due to peptic ulcers. The person often presents with severe vomiting without bile.
• Cancer is included in the differential diagnosis (elucidated by biopsy), Helicobacter pylori as the etiological factor making it 3 to 6 times more likely to develop stomach cancer from the ulcer.

References