Last updated on: June 25th, 2021

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Peptic ulcer disease

Clinicals - History


A peptic ulcer is an ulcer in the lining of the stomach or duodenum that is caused by exposure to gastric acid.


Dyspepsia will usually have been present for at least one month. Dyspepsia is characterized by gnawing or burning epigastric pain that occurs two to five hours after meals, or on an empty stomach; and which may awaken the patient at night. Dyspepsia is relieved by food intake, antacids, or antisecretory agents—all of these counterbalance acid secretion by the stomach. Persistent pain may suggest complications such as bleeding, obstruction, or perforation.

Epigastric fullness

Epigastric fullness indicates abnormal gastric emptying. This is typically due to dysfunction of gastric motor function; mucosal inflammation, irritation, and spasm may contribute.

Nausea and vomiting

Nausea and vomiting may occur—particularly if there is gastric outlet obstruction.


Heartburn may occur if there is co-existing gastroesophageal reflux. This is due to irritation of the esophageal mucosa by contact with the acidic gastric contents.

Anorexia and weight loss

Anorexia and weight loss may be caused by fear of food intake; or where malignant transformation has occurred, due to gastric cancer.

Hematemesis and melena

Hematemesis and melena may occur following acute or subacute bleeding of a peptic ulcer.

No symptoms

Nearly one-third of older patients with peptic ulcers do not have abdominal pain or show only mild pain.

Helicobacter pylori infection

Helicobacter pylori infection is the major cause of PUD. All patients should be explicitly asked as to whether they were tested in the past in this regard; and if they tested positive, whether a full course of treatment was completed.

Other comorbidities

Risk factors for PUD include a past history of PUD, cirrhosis, chronic kidney disease, Crohn’s disease, sarcoidosis, gastric cancer, lung cancer, lymphomas, myeloproliferative disorders, tuberculosis, cytomegalovirus infection, critical illness, and rarely, hypersecretory states such as Zollinger-Ellison syndrome.

Nonsteroidal Anti-Inflammatory Drug (NSAID) use

NSAID use is the second most common cause of peptic ulcer disease. NSAIDs inhibit cyclo-oxygenase-1 (COX-1), an enzyme present in gastrointestinal epithelium that regulates prostaglandin secretion. Prostaglandins are mediators in mucosal protection; a decrease in their levels increases the risk of mucosal disruption and ulceration. Concomitant inhibition of cyclo-oxygenase-2 (COX-2), an isoenzyme induced by inflammation, may also play a role.

Other drugs

A detailed medication history should be obtained—especially in the elderly. Drugs to look for include antiplatelet drugs, warfarin, selective serotonin reuptake inhibitors, bisphosphonates, corticosteroids, potassium chloride and chemotherapeutic agents.

Social history

There is limited evidence of an association between PUD and alcohol, illegal drug use, stress, and social deprivation. Smoking appears to confer an increased risk of duodenal ulcers, in patients with Helicobacter pylori infection.

Clinicals - Examination

Patients without complications

In uncomplicated PUD, physical examination findings are scarce and unreliable.

Patients with complications

In complicated PUD, physical examination may reveal numerous findings. These include:

  1. Fever, hypotension, and oliguria due to sepsis.
  2. Tachycardia, orthostasis, or syncope due to bleeding or dehydration following vomiting.
  3. Abdominal tenderness or guarding and hypoactive bowel sounds due to perforation.
  4. A succussion splash or epigastric mass with visible peristalsis due to gastric outlet obstruction.

Nonetheless, it is important to appreciate that the elderly and immunosuppressed may only show nonspecific signs such as confusion or abdominal distension.

Differential Diagnoses

Functional dyspepsia

Functional dyspepsia (FD) is a set of upper gastrointestinal symptoms that occur in the absence of organic disease. As per the Rome IV criteria, at least one of the following four symptoms must have been present for at least six months, and become more bothersome over at least the last three months:

  1. bothersome early satiety for three or more days per week;
  2. bothersome postprandial fullness for three or more days per week;
  3. bothersome epigastric pain of or one or more days per week; or
  4. bothersome epigastric burning for one or more days per week.

In addition, there must be no evidence of organic, systemic, metabolic or structural disease likely to explain symptoms.

FD is a diagnosis of exclusion; differentiation from PUD is via upper gastrointestinal endoscopy.

Gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) can present similarly to PUD, with heartburn that is worse after meals or the Valsalva maneuver. GERD also shares risk factors with PUD—e.g., smoking and alcohol use.

The heartburn of GERD generally radiates to the throat (“water-brash”) and is usually less intense than that of PUD. Upper gastrointestinal endoscopy, distal esophageal pH monitoring, and Helicobacter pylori testing allow for differentiation.

Acute gastritis

Acute gastritis can present with heartburn, epigastric pain, early satiety, nausea, vomiting, anorexia, and weight loss; however, unlike in PUD, these symptoms appear relatively suddenly, are prominent, and then to resolve spontaneously after a few days.

Chronic gastritis

Chronic gastritis can present with dyspepsia, nausea, vomiting or epigastric fullness; and can also be related to Helicobacter pylori infection, NSAID consumption, and tobacco or alcohol use. However, symptoms generally milder than those of PUD. Upper gastrointestinal endoscopy and Helicobacter pylori testing aid in the differentiation.

Acute pancreatitis

Acute pancreatitis can present with epigastric pain aggravated by ingestions, epigastric fullness, nausea, and vomiting. However, symptom progression is rapid—from sudden isolated mild epigastric pain to a florid picture of intense and constant pain radiating to the chest or mid back, and accompanied by persistent nausea, and vomiting. Jaundice may also be present. Serum amylase and lipase levels, inflammatory marker levels, and imaging studies of the abdomen may allow for differentiation.

Chronic pancreatitis

Chronic pancreatitis can present with epigastric pain— sudden bouts of acute pain that eventually progress to constant pain. The pain may radiate to the mid-back and is often worsened by the ingestion of food or leaning forward. Steatorrhea and diabetes mellitus may also occur. The gold standard for the diagnosis is endoscopic ultrasonography; but contrast-enhanced computerized tomography or magnetic resonance imaging will also allow for differentiation.

Crohn's disease

Crohn’s disease with gastroduodenal involvement may present with epigastric pain that is worse after meals; and may occur in the context of NSAID consumption and smoking. However, Crohn's disease is also accompanied by other findings such as chronic diarrhea, fatigue, right-lower quadrant abdominal pain, and vitamin deficiencies. Endoscopy and biopsy with histological studies will allow for diagnosis.


Malignancies such as gastric cancer, pancreatic cancer, and Helicobacter pylori associated MALT lymphomas can present with dyspepsia and other upper gastrointestinal symptoms. This possibility should be suspected in the presence of red flag features such as unintended significant weight loss, progressive dysphagia, evidence of blood loss, iron deficiency anemia, jaundice, or a family history of cancer. Upper gastrointestinal endoscopy will allow for differentiation.

Acute coronary syndromes

Acute coronary syndromes (ACS) may atypically present with epigastric pain—particularly when the inferior wall of the heart is involved. A careful clinical history may allow for differentiation from PUD. ECGs and serum troponin, myoglobin, or creatine kinase myocardial band levels will allow for confirmation.

Investigations - Diagnosis

Helicobacter pylori infection

Testing for Helicobacter pylori infection can be performed if symptoms persists despite the use of proton pump inhibitors for two weeks or longer. The test to use depends on the duration of PPI use and prior antibiotic use. Options include urea breath tests and stool monoclonal antigen tests. Antisecretory therapy should be withheld for at least for two weeks prior to testing.

Upper gastrointestinal endoscopy

Upper gastrointestinal endoscopy allows for direct visualization of any peptic ulcers and biopsy sampling. This is recommended in patients older than 55 years; or if red flag symptoms and signs are present.

Barium swallow

A barium swallow can be ordered in patients unsuitable for endoscopy; or if perforation or gastric outlet obstruction is suspected. The sensitivity and specificity is less than that of endoscopy.

Management - Supportive

Managing risk factors

Patients should stop smoking and reduce alcohol consumption. Medications conferring an increased risk for PUD should also be omitted. As per the American College of Gastroenterology (ACG), where prescribed, NSAIDs should be combined with PPI therapy or misoprostol.

Proton-pump inhibitors

Proton-pump inhibitors (PPI) include omeprazole, pantoprazole, lansoprazole, esomeprazole, and rabeprazole. These agents inhibit gastric acid secretion. Long-term PPI use is associated with numerous adverse effects; treatment should be for the least duration required. H2-blocker antihistamines such as ranitidine, cimetidine, famotidine are alternatives, but are less effective.

Cytoprotective agents

Sucralfate binds selectively to ulcer sites and via several mechanisms protects the gastric mucosa and promotes healing. Bismuth-containing compounds are effective against H pylori and also promote ulcer healing by an unclear mechanism. Misoprostol, a prostaglandin E1 analogue, has similar efficacy to PPI, but a higher incidence of adverse effects.

Management - Specific

Helicobacter pylori eradication

All patients who test positive to Helicobacter pylori should be treated. The relevant regimen should be based on regional bacterial resistance patterns and patient factors such as past antibiotic use and the presence of allergies. Common first-line regimens include clarithromycin triple therapy—PPI, clarithromycin, and amoxicillin or metronidazole; or bismuth quadruple therapy—PPI, bismuth subcitrate or subsalicylate, tetracycline, and metronidazole. Salvage regimens are used if first-line therapy fails. These include bismuth quadruple therapy (as above) and the levofloxacin salvage regimen—PPI, levofloxacin, and amoxicillin.

Eradication should be confirmed via a urea breath test, fecal antigen test or biopsy-based testing; this should be performed at least four weeks after completion of the relevant regimen. PPI therapy should be stopped for one to two weeks prior.

Ulcer bleeding

Bleeding is the most common complication of PUD, occurring in 15-20% of patients. It is also the main cause of surgery and death. Treatment should aim to achieve hemostasis and prevent cardiovascular deterioration and multiorgan failure.

In patients who are stable, all medications with ulcerogenic potential should be stopped and PPI should be commenced. Upper gastrointestinal endoscopy should then be performed to determine the risk of rebleeding. Unstable patients should receive fluid or packed red blood cell resuscitation followed by emergency upper gastrointestinal endoscopy with direct treatment of the bleeding sites. Massive or recurrent bleeding may require angiographic embolization. Failure to achieve hemostasis by other means may require surgery.


Perforation is uncommon, but has a high mortality if not treated promptly. Management is via urgent laparoscopy or open surgery.

Gastric outlet obstruction

Gastric outlet obstruction (GOO) is another rare but serious complication. Upper gastrointestinal endoscopy should be performed to assess the site, cause, and degree of obstruction. Acute episodes of inflammation and edema respond well nasogastric decompression, H2-blocker or PPI therapy, and Helicobacter pylori eradication. Chronic obstruction by scaring and fibrosis can be treated via endoscopic dilation or surgery. The possibility of a malignancy should be excluded.

Gastric cancer

Gastric cancer should be considered in patients with recurring or persistent ulcers. Treatment should be as per current protocols; this often includes surgical resection along with chemotherapy or chemoradiation.

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