• Clinical science
  • Clinician

Peptic ulcer disease (PUD)

Summary

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, some 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.

Definition

Epidemiology

References:[2][3][4][5][6]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[3][7][8][9][10][11][12]

Pathophysiology

Gastric secretions

Disturbances

  • H. pylori gastritis: increased acid secretion, decreased protective factors/mucus production
  • NSAIDs inhibit COX-1 and COX-2 decrease in PGE2 (normally decreases gastric acid secretion and increases HCO3- and mucus secretion) → gastric mucosa erosions

Clinical features

Gastric ulcer

Duodenal ulcer

Findings common to both

Pain and eating
  • Pain increases shortly after eating → weight loss
  • Pain increases 2–5 hours after eating
  • Pain on an empty stomach (hunger pain) that is relieved with food intake weight gain
Nocturnal pain
  • 30–40% of patients
  • 50–80% of patients

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

Taking NSAIDs can often mask PUD symptoms until complications such as hemorrhage and perforation occur!

References:[13][14][15][16]

Subtypes and variants

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.

References:[17][18][19]

Diagnostics

Approach [20][21][22][23]

Diagnostic approach for suspected PUD [24]
Indications 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 of occult bleeding:
    • CBC, BMP
    • Fecal occult blood test
  • Patients ≤ 60 years of age without red flags for dyspepsia
Further evaluation
  • Patients with persistently uncertain etiology

EGD [24]

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

  • Malignancy screening: to differentiate PUD from gastric cancer
    • Visualization of the lesions
    • Biopsy sampling
  • Invasive H. Pylori testing
  • Simultaneous therapeutic measures, e.g., hemostasis treatment with electrocautery for active bleeding

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.

Findings [25]

Classic endoscopic appearance of peptic ulcers
Benign Malignant
Base Smooth Ulcerated mass protruding into the lumen
Edges Rounded, regular Irregular, overhanging
Surrounding mucosa Regular Nodular, irregular
Location Typical (see “Definitions”) Atypical
Histopathology Chronic inflammatory changes and active granulation Dysplasia, invasion of deeper layers (see also “Gastric cancer”)

An atypical location is suspicious for carcinoma!

Biopsies

  • Gastric ulcers [21]
    • Biopsies are recommended in most cases.
    • Multiple biopsies are recommended.
      • From the edge and base of the ulcer (essential to rule out malignancy, which is not uncommon in gastric ulcers)
      • Multiple biopsies from different areas of the stomach lining, including those not surrounding the ulcer (to test for H. pylori)
  • Duodenal ulcers: Obtain biopsies from ulcers with endoscopic features that suggest malignancy.

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.

Treatment

Approach

Therapeutic approach to PUD [24]
Clinical scenario Management
All patients
  • Nonpharmacological measures: e.g., avoid NSAIDs, restrict alcohol
  • Follow-up to confirm treatment success and possibly endoscopic surveillance (see “Follow-up” for more details)

H. Pylori test-and-treat strategy

Positive
Negative
  • Medically refractory symptoms
  • Inability to tolerate or adhere to medical treatment
  • Confirmed upper GI malignancy
  • Consider elective surgery.
Complications

Medical treatment of PUD

Pharmacologic therapies for uncomplicated PUD include a trial of acid suppression and, if detected, H. pylori 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.

Antacids and acid suppression medications [26] [1]
Drug class Important considerations
Acid suppression medications PPIs (most effective)
  • Omeprazole
  • Esomeprazole
  • Pantoprazole
  • Lansoprazole
  • Dexlansoprazole
  • Rabeprazole
H2 antagonists (mostly for maintenance or in combination with PPIs if needed)
Antacids
(acid neutralization, mainly used alongside acid suppression for rapid symptom relief)

“Eat with aluminum CHOPSticKs”: The most important side effects of aluminum hydroxide are Constipation, Hypophosphatemia, Osteodystrophy, Proximal muscle weakness, Seizures, and hypoKalemia.

Elective surgical treatment [30]

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.

  • Indications (consider after thorough individual evaluation)
    • Refractory symptoms or recurrence of disease despite appropriate medical treatment
    • NSAIDs need to be continued
    • Inability to tolerate medical treatment
  • Surgical procedures

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.”

Acute management checklist

  • Evaluate for underlying cause (e.g., NSAID use)
  • Identify and treat any life-threatening complications, e.g., active bleeding, intestinal perforation (see “GI bleeding” and “Secondary peritonitis”).
  • Consider evaluation for occult bleeding (e.g., CBC, BMP, FOBT)
  • Apply H. Pylori test-and-treat strategy in patients < 60 years of age without red flags for dyspepsia (see “H. Pylori eradication therapy”).
  • Refer directly to EGD if any red flags for dyspepsia, age > 60 years, or unsuccessful empiric medical therapy.
  • Provide trial of acid suppression therapy with PPI.
  • Discontinue underlying triggers (e.g., NSAIDs, alcohol, tobacco, caffeine) and counsel on lifestyle modification.
  • Consider specialized diagnostic studies if etiology remains unclear.
  • Ensure appropriate follow-up (e.g., EGD, H. Pylori eradication confirmation).
  • Consider referral for elective surgery for refractory or complicated cases.

Complications

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.

References:[31][32][33][34][35][36][37][38][39][40]

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

Follow-up

Endoscopic follow-up [21]

  • 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 [20]

  • Indication: H. pylori-associated ulcer
  • Considerations
  • Diagnostic tests
    • Urea breath testing
    • Stool antigen assay
    • Endoscopic biopsies with rapid urea testing (only if endoscopy is indicated; see indications above)

Stress ulcer prophylaxis

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. [41][42][43][44]

Indications for stress ulcer prophylaxis in critically ill patients [44]
GI bleeding risk Indications
High
Moderate
Low
  • Prophylactic agents [44]
  • Duration: Continue for as long as significant risk factors are present or until critical illness resolves. [45]

Both PPIs and H2RA may increase the risk of pneumonia in critically ill patients. [44]

Stress ulcer prophylaxis likely has little effect on mortality, length of admission, length of stay in critical care units, and duration of mechanical ventilation. [44]