Peptic ulcer disease

Last updated: August 5, 2022

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Peptic ulcer disease (PUD) is the presence of one or more ulcerative lesions in the stomach or duodenum. Etiologies include infection with Helicobacter pylori (most common), prolonged NSAID use (possibly in combination with glucocorticoids), conditions associated with an overproduction of stomach acid (hypersecretory states), and stress. Epigastric pain is a typical symptom of PUD; however, many patients remain asymptomatic. Usually, patients younger than 60 years of age can be managed with a test-and-treat strategy for H. pylori infection or with empirical acid suppression therapy. Older patients and those with high-risk clinical features benefit from an esophagogastroduodenoscopy (EGD) and biopsies to confirm the diagnosis or rule out differential diagnoses (especially gastric cancer). First-line treatment for most peptic ulcers involves symptom control (e.g., acid-lowering medication), H. pylori eradication therapy, and withdrawal of causative agents. Antisecretory drugs (e.g., proton-pump inhibitors), which reduce stomach acid production, are continued for 4–8 weeks after eradication therapy and may be considered for maintenance therapy if symptoms recur. Surgical intervention may be considered in rare cases. Some patients benefit from endoscopic surveillance, especially if symptoms persist or there is clinical suspicion for malignancy.

Erosions are more superficial than ulcers. Ulcers involve damage to the gastric mucosa extending beyond the muscularis mucosa layer into the submucosa.

Epidemiological data refers to the US, unless otherwise specified.

Common causes of PUD

The two major contributing factors to the development of PUD are gastrointestinal infection with H. pylori and nonsteroidal anti-inflammatory drug (NSAID) use. Both factors contribute to the development of PUD and interact with other risk factors to promote ulcer formation.

For patients requiring chronic NSAID therapy, consider acid suppression medication for ulcer prevention. [10]

Associated risk factors

H. pylori infection or NSAID use alone do not typically cause ulcer formation. There are often additional risk factors present, such as the following, that increase the probability of developing an ulcer:

Rare causes of PUD

Under typical physiological conditions, the cells of the gastric mucosa secrete a gastric juice (an acidic fluid composed of HCl, pepsinogen, intrinsic factor, and mucus), which may damage the native cells of the GI tract. Protective mechanisms (e.g., secretion of mucus and HCO3- to form a protective barrier) prevent the gastric juices from digesting and eroding the gastric epithelial cells. Ulcer formation occurs when either the protective mechanisms are disrupted and/or excessive acids or pepsin are secreted.

Physiological gastric secretions [13]

See “Secretory and regulatory products of the gastrointestinal tract” in “Gastrointestinal tract” for more details on typical physiological secretions.

Mechanisms of physiological disruption [13]

PUD may be asymptomatic or manifest with a variety of clinical features, e.g., general dyspepsia or complications such as perforation or bleeding.

Asymptomatic PUD

Symptomatic PUD

  • Abdominal pain
  • Other associated symptoms
    • Belching
    • Indigestion
    • Gastrointestinal reflux
    • Nausea and/or vomiting
    • Bloating/abdominal fullness
Clinical symptoms of gastric and duodenal ulcers

Gastric ulcer

Duodenal ulcer

Findings common to both

Pain and eating
  • Pain increases shortly after eating → weight loss
  • Pain is relieved with food intake weight gain
  • Pain increases 2–5 hours after eating. [17]
Nocturnal pain
  • Less common [18]
  • More common [18]

Gastric ulcer is associated with pain after light (weight loss) Gorging. Duodenal ulcer is associated with relief after massive (weight gain) Desserts.

Stress ulcer

Imagine a hot curling iron to remember that Curling ulcers occur in patients with severe burns.

Imagine a brain resting on a cushion to remember that patients with brain injury can develop Cushing ulcers.

Approach [19][20][21][22]

Diagnostic approach for suspected PUD [23]
Patient group Testing strategy
Initial evaluation
  • All patients
  • Screen for common etiologies on history, e.g., NSAID use (see “Etiology”)
  • Consider the following if there is suspicion for occult bleeding:
Further evaluation
  • All patients with persistently uncertain etiology

Alarm features warranting an EGD in younger patients include progressive dysphagia, odynophagia, rapid weight loss, persistent vomiting, suspected GI bleeding, and a family history of upper GI malignancy.

Esophagogastroduodenoscopy (EGD) [23]

The most accurate test to confirm the diagnosis. Other clinical applications include:

Endoscopic findings [24]

Differentiating between benign and malignant gastroduodenal ulcers


(classic endoscopic appearance of peptic ulcers)

  • Smooth
  • Ulcerated mass protruding into the lumen
  • Rounded, regular
  • Irregular, overhanging
Surrounding mucosa
  • Regular
  • Nodular, irregular
  • Atypical
  • Chronic inflammatory changes and active granulation

An atypical location is suspicious for carcinoma!

Indications for biopsy

To rule out gastric cancer, patients with suspicious gastric ulcers should undergo follow-up EGD and histology until the ulcer has healed completely!

Specialized laboratory studies [1]

Consider testing for rare causes if the etiology remains unclear or the patient presents with recurrent ulcers.

Differential diagnosis of gastric and duodenal ulcers

Differential diagnosis of gastric and duodenal ulcers

Gastric ulcers

Duodenal ulcers


H. pylori infection

  • 25–50%
  • 40–70%
Other causes
Pathophysiology H. pylori infection
  • H. pylori secretes urease alkalinization of acidic environment → survival of bacteria in gastric lumen
  • Release of cytotoxins (e.g., cagA toxin) → disruption of the mucosal barrier and damage to underlying cells
Other causes
  • Acid hypersecretion
  • Mucosal protection

Clinical features
Pain and eating
  • Pain increases shortly after eating weight loss
  • Pain is relieved with food intake weight gain
  • Pain increases 2–5 hours after eating. [17]
Nocturnal pain [18]
  • Less common
  • More common
Diagnostics General
  • Multiple biopsies are recommended in most cases and should be taken:
    • From the edge and base of the ulcer
    • From different areas of the stomach lining, including those not surrounding the ulcer (to test for H. pylori)
Carcinoma risk
  • Increased

Differential diagnoses based on clinical presentation

For differential diagnoses based on the initial clinical presentation, see:

The differential diagnoses listed here are not exhaustive.

Approach [23]

A perforated peptic ulcer is a surgical emergency.

In patients with hemorrhagic shock, consider ulcer penetration into a major artery as the underlying cause. [25]

Disposition [26][27]

  • Outpatient management is usually appropriate for patients without complications.
  • Obtain GI consult for patients with alarm features of PUD.
  • Consider hospital admission for patients with:
  • Consider ICU admission or direct transfer to the OR for:

Medical treatment of PUD

Pharmacologic therapies for uncomplicated PUD include a trial of acid suppression therapy and, if H. pylori is detected, eradication therapy. These may be complemented with antacids for rapid symptom relief, and in some cases with cytoprotective agents for mucosal protection. All patients should also be counseled on lifestyle and risk factor modification.

Elective surgical treatment [28]

Surgical management of uncomplicated peptic ulcers is rarely necessary because they usually respond well to medical treatment. When malignancy is confirmed or complications such as massive bleeding or gastrointestinal perforation occur, surgery specific to these complications must be performed.

The anterior and posterior branches of the vagus nerve (CN X) are also known as nerves of Latarjet, which divide into terminal branches that innervate the stomach and the pylorus. The terminal branches on the antropyloric area are sometimes referred to as “crow's foot.”

Bleeding (see “Gastrointestinal bleeding”)

Peptic ulcer perforation (see also “Secondary peritonitis” and “Gastrointestinal perforation”)

Posterior ulcers are more likely to bleed and anterior ulcers are more likely to perforate: Postal workers wear Blue collars and should not have an Antisocial Personality.

Ulcer penetration and fistula formation

Gastric outlet obstruction (GOO)

GOO is more commonly due to malignancy in regions where the treatment of PUD and H. Pylori is prevalent (see “Gastric cancer” for details).

Malignant transformation

We list the most important complications. The selection is not exhaustive.

Endoscopic follow-up [20]

  • Indications
    • Gastric ulcer in patients with ≥ 1 of the following :
      • Refractory symptoms
      • Ulcer of unknown etiology
      • Ulcer that appears malignant in initial EGD (even if biopsies are negative)
      • No biopsies taken in initial EGD (e.g., due to active bleeding)
      • Ulcer diagnosed via radiological imaging
    • Duodenal ulcer: if symptoms persist after an appropriate course of antisecretory treatment
    • Bleeding peptic ulcer requiring initial emergency endoscopy: endoscopic control on the following day
    • Dysplasia: endoscopy every 6–12 months depending on the degree of dysplasia
    • Refractory ulcer: Consider repeated EGD until the ulcer heals or etiology is identified.
    • New onset of symptoms after successful H. pylori eradication
  • Surveillance method: Repeat endoscopy and obtain new biopsies.

H. pylori eradication confirmation [19]

Prophylaxis for stress ulcer disease should be considered in any critically ill patient with a risk of GI bleeding. Prophylaxis was formerly recommended for all ICU patients, but evidence suggests that risks (e.g., for pneumonia) outweigh the benefits in patients with low bleeding risk. [30][31][32][33]

Indications for stress ulcer prophylaxis in critically ill patients [33]
GI bleeding risk Indications

Both PPIs and H2 receptor antagonists may increase the risk of pneumonia in critically ill patients. [33]

Stress ulcer prophylaxis likely has little effect on mortality, length of admission, length of stay in critical care units, and duration of mechanical ventilation. [33]

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