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 (NSAID-induced ulcer), 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.
- Peptic ulcer: a defect in the gastric or duodenal mucosa with a diameter of at least 0.5 cm and a depth that penetrates through 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
- Incidence: ∼ 1 case/1,000 person-years 
- Age: The median age of diagnosis is 18–30 years.
- Sex: ♂ = ♀
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.
- Helicobacter pylori infection
Chronic NSAID use
- Associated with a fourfold risk of developing PUD 
- Increases the risk for complications of PUD (see “ ”)
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:
- Shared risk factors for PUD, GERD and gastritis (i.e., smoking, heavy alcohol use, glucocorticoids, caffeine)
- Diet 
- Psychological factors (e.g., anxiety, stress, PTSD)
- Genetic factors 
Rare causes of PUD
- Acid hypersecretory states
- Non-NSAID medications
- Helicobacter heilmannii
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 
- Parietal cells
- Mucosal cells
- Chief cells
See “” in “ ” for more details on typical physiological secretions.
Mechanisms of physiological disruption 
- H. pylori secretes urease → conversion of urea to NH3 → alkalinization of acidic environment → survival of bacteria in gastric lumen
- Bacterial colonization and attachment to epithelial cells → release of cytotoxins (e.g., cagA toxin) → disruption of the mucosal barrier and damage to underlying cells
- Duodenal ulcers
- Gastric ulcers
- Acid hypersecretion: : acid hypersecretion (e.g., Zollinger-Ellison syndrome) and increased gastrin production → ↑ H+ secretion and parietal cell mass → delivery of excessive acid to the duodenum
PUD may be asymptomatic or manifest with a variety of clinical features, e.g., general dyspepsia or complications such as perforation or bleeding.
- Up to 70% of patients with peptic ulcers do not experience symptoms. 
- Patients who take NSAIDs are more likely to have asymptomatic ulcers and present with .
- Abdominal pain
- Other associated symptoms
|Clinical symptoms of gastric and duodenal ulcers|
Findings common to both
|Pain and eating|| |
|Nocturnal pain|| || |
|Diagnostic approach for suspected PUD |
|Patient group||Testing strategy|
|Initial evaluation|| |
| || |
|Further evaluation|| |
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) 
The 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
Endoscopic findings 
|Differentiating between benign and malignant gastroduodenal ulcers|
(classic endoscopic appearance of peptic ulcers)
|Base|| || |
|Edges|| || |
|Surrounding mucosa|| || |
An atypical location is suspicious for carcinoma!
Indications for biopsy
Gastric ulcers 
- Biopsies are recommended in most cases.
- Multiple biopsies are recommended.
- Duodenal ulcers
Specialized laboratory studies 
Consider testing for rare causes if the etiology remains unclear or the patient presents with recurrent ulcers.
|Differential diagnosis of gastric and duodenal ulcers|
H. pylori infection
| || |
|Other causes|| |
|Pathophysiology||H. pylori infection|
|Pain and eating|| |
|Nocturnal pain || || |
|Carcinoma risk|| || |
Differential diagnoses based on clinical presentation
For differential diagnoses based on the initial clinical presentation, see:
- “Differential diagnoses of acute abdominal pain”
- “Differential diagnoses of dyspepsia”
- “Differential diagnoses of nausea and vomiting”
- “Differential diagnoses of upper GI bleeding”
- “Differential diagnoses of chest pain”
The differential diagnoses listed here are not exhaustive.
- General measures
- H. pylori test-and-treat strategy
- Failure of medical treatment : Consider elective surgery.
- Management of critical
A is a surgical emergency.
- Outpatient management is usually appropriate for patients without complications.
- Obtain GI consult for patients with .
- 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.
- are covered in detail in “Treatment of dyspepsia.”
- Recommended duration of acid suppression for PUD 
Cytoprotective agents (gastrointestinal mucosal protection)
- Sucralfate : a sucrose sulfate-aluminum complex that reacts with HCl in an acidic environment to create a protective barrier over the gastric/duodenal mucosa
- Misoprostol : Consider as an alternative to PPIs for ulcer prophylaxis in patients at high risk of developing NSAID-induced GI toxicity (e.g., older individuals, those with a history of complicated peptic ulcer). 
- 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 evaluation)
- Refractory symptoms or recurrence of disease despite appropriate medical treatment
- Diseases that require the continuation of NSAIDs
- 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.”
- Identify and treat critical complications, e.g., GI bleeding, gastrointestinal perforation, secondary peritonitis.
- Evaluate for underlying cause (e.g., NSAID use).
- 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.
- Consider referral to EGD if the patient has red flags for dyspepsia, is > 60 years of age, or has had 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 modifications.
- Consider specialized diagnostic studies if the etiology remains unclear.
- Ensure appropriate follow-up (e.g., EGD, H. pylori eradication confirmation).
- Consider referral for elective surgery for refractory or complicated cases.
Endoscopic follow-up 
- Gastric ulcer in patients with ≥ 1 of the following :
- 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 
Bleeding (see “”)
Definition: the bleeding and/or hemorrhage of a peptic ulcer (either duodenal or gastric)
- The most common complication of PUD
- Can be a chronic, slow bleed or an overt, rapid, life-threatening hemorrhage
- Clinical features
- Treatment 
Peptic ulcer perforation (see also “ ” and “ ”)
Definition: full-thickness injury and loss of bowel wall integrity that results in leakage of gastrointestinal contents
- The second most common complication of PUD
- PUD is the most common cause of GI perforation.
- Clinical features
- Treatment 
Ulcer penetration and fistula formation
- Definition: Penetration of a peptic ulcer through the gastric/duodenal wall into adjacent organs (e.g., pancreas, biliary tree, colon) without leaking of gastric contents into the peritoneal cavity
- Etiology: Duodenal ulcers are the most common cause of penetration.
Clinical features: a change in clinical symptoms that are related to the affected neighboring organs
- Colon: Gastrocolic or duodenocolic fistulas may manifest with copremesis and postprandial diarrhea.
- Liver, spleen, or diaphragm: Penetration may result in visceral abscesses (fever, abdominal tenderness, and sepsis).
- Gastroduodenal artery or aorta: Vascular fistulas may result in severe hemorrhage.
- Biliary tree: Choledochoduodenal fistulas may manifest with biliary tract obstruction (fever, jaundice, RUQ pain).
- Pancreas: increased epigastric pain and peritonitis
- Clinical features
- Gastric ulcers 
- Usually benign
- Routine biopsy is not required.
We list the most important complications. The selection is not exhaustive.
Subtypes and variants
- Critical illness, such as:
- Major surgery
- 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: brain injury → increased vagal stimulation → increased production of stomach acid via acetylcholine release
Stress ulcer prophylaxis 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 
- PPIs (preferred for patients with moderate-to-high risk factors): e.g., pantoprazole
- H2 receptor blockers (may be used as an alternative): e.g., famotidine
- Continue stress ulcer prophylaxis for as long as significant risk factors are present or until critical illness resolves. 
NSAID-induced ulcers 
- NSAIDs are widely used for their antiinflammatory, analgesic, and antiplatelet properties.
- NSAIDs act by inhibiting cyclooxygenase, an enzyme required for the synthesis of prostaglandins that protect the gastric mucosal barrier.
- Chronic use of NSAIDs can result in gastrointestinal toxicity, including peptic ulcer disease and its complications (e.g., GI hemorrhage, perforation).
Risk factors for NSAID-induced GI toxicity 
- Age > 60 years 
- Concurrent H. pylori infection
- Concurrent use of corticosteroids, aspirin (including low-dose), or SSRIs ,
- Higher doses or use of higher-risk NSAIDs 
- Prior peptic ulcer disease
- Dyspepsia 
- Comorbidities 
Prevention of NSAID-induced GI toxicity 
- Consider switching NSAID to an alternative agent (e.g., an ), if appropriate.
- Modify where possible, e.g.:
- Select an NSAID based on the patient's . 
- Determine the need for gastric mucosal protection based on the presence of .
- In general, PPIs are preferred; ; see “PPIs” in “Acid suppression medications” for dosages.
- Misoprostol can be given as an alternative, but its use is limited because of associated adverse effects (especially at higher doses). 
- Reassess indications for gastric mucosal protection periodically; discontinue when no longer indicated. 
|Risk-based strategies to prevent NSAID-induced GI toxicity |
|Risk of GI toxicity||Criteria ||Management |
|High risk |
|Moderate risk|| |
|Low risk|| |
In patients with a recent, complicated ulcer, NSAIDS should be avoided or used with extreme caution. 
Always use the lowest possible effective dose of an NSAID.