- Clinical science
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.
- Peptic ulcer: a defect in the gastric or duodenal mucosa with a diameter of at least 0.5 cm and a depth that reaches the muscularis mucosae
- Gastric ulcer: a peptic ulcer of the gastric mucosa, typically located along the lesser curvature in the transitional portion between the corpus and antrum 
- Duodenal ulcer: a peptic ulcer of the duodenal mucosa, usually located on the anterior or posterior wall of the duodenal bulb
- Erosive gastritis: acute mucosal inflammation of the stomach that does not extend beyond the muscularis mucosae
- Chronic gastritis caused by H. pylori, a curved, flagellated gram-negative rod
- Chronic gastritis of other etiology
- Long-term use of NSAIDs (e.g., patients with rheumatoid arthritis, SLE, etc.)
- Long-term use of NSAIDs plus glucocorticoids: risk increases 10 to 15-fold!
- Chronic alcohol consumption
- Patients with blood type O have a higher risk for duodenal ulcers.
- Age > 65 years
- Stress (see “Subtypes and variants” below)
- Rare risk factors
- Parietal cells
- Mucosal cells
- Chief cells
- 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
Findings common to both
|Pain and eating|| |
|Nocturnal pain|| || |
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!
- Description: In this rare disease, minor mucosal trauma can lead to major bleeding. It is caused by an abnormal submucosal artery.
- Location: proximal stomach
- Clinical presentation: signs of acute upper GI bleeding
- Treatment: endoscopic hemostasis (injection therapy, hemoclips, etc.), excision of the susceptible mucosa
- Causes: polytrauma, major surgery, SIRS, kidney failure, etc.
- Curling ulcer: severe burns → decreased plasma volume → decreased gastric blood flow → hypoxic tissue injury of stomach surface epithelium → weakening of the normal mucosal barrier
- Cushing ulcer: In patients with brain injury, increased vagal stimulation leads to increased production of stomach acid via acetylcholine release.
- Nonulcer dyspepsia; : symptoms including bloating, nausea, and belching persisting ≥ 3 months without organic cause (synonym: functional dyspepsia)
Imagine a brain resting on a cushion to remember that patients with brain injury can develop Cushing ulcers.
|Diagnostic approach for suspected PUD |
|Initial evaluation|| || |
| || |
|Further evaluation|| |
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.
|Classic endoscopic appearance of peptic ulcers|
|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”)|
- Gastrinoma: multiple ulcers and thick gastric folds
- Bleeding ulcers: see “Gastrointestinal bleeding”
An atypical location is suspicious for carcinoma!
Gastric ulcers 
- Biopsies are recommended in most cases.
- Multiple biopsies are recommended.
- Duodenal ulcers: Obtain biopsies from ulcers with endoscopic features that suggest malignancy.
Specialized laboratory studies 
Consider testing for rare causes if the etiology remains unclear or the patient presents with recurrent ulcers.
Fasting serum gastrin and secretin stimulation test
- Measure baseline serum gastrin level and repeat after administration of secretin.
- High levels in gastrinoma ( )
- Serum intact PTH level (hyperparathyroidism is a rare cause of PUD)
- Specific testing for systemic inflammatory diseases (e.g., Behcet disease, Crohn disease)
|Therapeutic approach to PUD |
|All patients|| |
H. Pylori test-and-treat strategy
| || |
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  |
|Drug class||Important considerations|
|Acid suppression medications||PPIs (most effective)|| |
|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.
- Recommended duration of acid suppression for PUD 
Cytoprotective agents (gastrointestinal mucosal protection)
Sucralfate : a sucrose sulfate-aluminium complex that reacts with HCl in an acidic environment to create a protective barrier over the gastric/duodenal mucosa
- Acts as an acid buffer and promotes HCO3 production.
- Used to promote ulcer healing mostly in patients with duodenal ulcers
- Misoprostol: used for PUD prevention for frail/elderly patients taking NSAIDs that cannot be discontinued.
- Sucralfate : a sucrose sulfate-aluminium complex that reacts with HCl in an acidic environment to create a protective barrier over the gastric/duodenal mucosa
- Antibiotics: e.g., (combined with amoxicillin and a PPI). See “” for other treatment regimens.
- Nonpharmacological measures 
Elective surgical treatment 
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
- Vagotomy: surgical division of the anterior and posterior vagal trunk of the vagus nerve (truncal vagotomy), both located along the lower esophagus. Denervation through truncal vagotomy results in ∼ 70% reduction of acid production.
- Partial gastrectomy (Billroth) and reconstruction
- Total gastrectomy and reconstruction: Roux-en-Y
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.”
- Evaluate for underlying cause (e.g., NSAID use)
- Identify and treat any life-threatening complications, e.g., active bleeding, (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.
Bleeding (see “”)
- Most common complication of PUD
- Located posterior more commonly than anterior
- Perforated gastric ulcers of the lesser curvature may cause hemorrhage of the left gastric artery.
- Duodenal ulcers of the posterior wall are more likely to cause massive bleeding because of their proximity to the gastroduodenal artery.
- Gastric/duodenal perforation (see also “ ” and “ ”)
- Subhepatic abscess
Gastric outlet obstruction (GOO)
- Definition: mechanical obstruction of the pyloric channel or duodenum
- Postprandial, nonbilious vomiting
- Succussion splash
- Early satiety
- Progressive gastric dilation
- Weight loss
- Fistula formation
- Malignant transformation
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.
We list the most important complications. The selection is not exhaustive.
Endoscopic follow-up 
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
- Gastric ulcer in patients with ≥ 1 of the following:
- Surveillance method: Repeat endoscopy and obtain new biopsies.
H. pylori eradication confirmation 
- Indication: H. pylori-associated ulcer
- Performed 4 weeks or more after
- PPIs need to be paused at least 2 weeks prior to this test.
- Diagnostic tests
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. 
|Indications for stress ulcer prophylaxis in critically ill patients |
|GI bleeding risk||Indications|
- Prophylactic agents 
- Duration: Continue for as long as significant risk factors are present or until critical illness resolves.