Peptic ulcer disease

Peptic ulcer disease (PUD) is the presence of one or more ulcerative lesions in the stomach or duodenum. Etiologies include Helicobacter pylori infection (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 testing 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 as indicated, 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 ^[1]
• 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

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

• Incidence: ∼ 1 case/1,000 person-years ^[2]
• Prevalence
  • ∼ 6 million cases annually in the US ^[3]
  • The prevalence of PUD is decreasing (see “Etiology”). ^[4]
  • Duodenal ulcers occur on average 10–20 years earlier than gastric ulcers. ^[5]
• 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 H. pylori infection 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
  • Associated with 40–70% of duodenal ulcers and 25–50% of gastric ulcers ^[6][7]
  • The rate of H. pylori infection (and, therefore, the development of PUD) is decreasing. ^[8]
• Chronic NSAID use
  • Associated with a fourfold risk of developing PUD ^[9]
  • Increases the risk for complications of PUD (see “Complications of peptic ulcer disease”)

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:

• Shared risk factors for PUD, GERD and gastritis (i.e., smoking, heavy alcohol use, glucocorticoids, caffeine)
• Diet ^[11]
• Psychological factors (e.g., anxiety, stress, PTSD)
• Genetic factors ^[12]

Rare causes of PUD

• Acid hypersecretory states
  • Zollinger-Ellison syndrome (gastrinoma)
  • Systemic mastocytosis
  • Hyperparathyroidism
• Non-NSAID medications
  • Acetaminophen
  • Bisphosphonates
  • Sirolimus
  • Mycophenolate
  • SSRIs
  • Chemotherapeutics (e.g., 5-FU)
• Infections
  • CMV
  • HSV-1
  • EBV
  • Helicobacter heilmannii
• Others
  • Radiation
  • Illicit drug use (e.g., cocaine, methamphetamine)
  • Systemic inflammatory diseases (e.g., Crohn disease, sarcoidosis)
  • Mechanical (e.g., foreign body, GI tract obstruction, postsurgical anatomy)

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]

• Parietal cells
  • Secrete hydrochloric acid (HCl) and intrinsic factor
  • Stimulated by acetylcholine, histamine, and gastrin
  • Inhibited by prostaglandins and somatostatin
• Mucosal cells
  • Secrete protective mucus
  • Stimulated by acetylcholine, prostaglandins (which inhibit HCl secretion), and secretin
• Chief cells
  • Secrete pepsinogen
  • Stimulated by acetylcholine, gastrin, secretin, and vasoactive intestinal polypeptide (VIP)

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

Mechanisms of physiological disruption ^[13]

• H. pylori
  • Gastric ulcers
    • 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
    • H. pylori inhibits somatostatin secretion → ↑ gastrin secretion → ↑ H⁺ secretion → excess H⁺ delivery to the duodenum
    • Direct spread of H. pylori to the duodenum → inhibition of duodenal HCO₃^- secretion→ acidification and insufficient neutralization of duodenal contents
• NSAIDs
  • Inhibit COX-1 and COX-2 → decrease in prostaglandin; production → erosion of the gastric mucosa
  • Decrease mucosal blood flow
  • Inhibit mucosal cell proliferation
• 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.

Asymptomatic PUD

• Up to 70% of patients with peptic ulcers do not experience symptoms. ^[14][15]
• Patients who take NSAIDs are more likely to have asymptomatic ulcers and present with complications of PUD.

Symptomatic PUD

• Abdominal pain
  • The most common symptom of PUD ^[16]
  • Commonly located in the epigastrium
  • Often described as “gnawing” or “burning”
  • Can be related to meal intake depending on the location of the ulcer (see “Clinical symptoms of gastric and duodenal ulcers”)
• Other associated symptoms
  • Belching
  • Indigestion
  • Gastrointestinal reflux
  • Nausea and/or vomiting
  • Bloating/abdominal fullness

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

Approach ^{[19][20][21][22]}

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:

• 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 ^[24]

• Gastrinoma: multiple ulcers and thick gastric folds
• Bleeding ulcers: See “Gastrointestinal bleeding.”

An atypical location is suspicious for carcinoma!

Indications for biopsy

• Gastric ulcers ^[20]
  • 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.
  • Duodenal ulcers are usually benign and do not require routine 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.

• Fasting serum gastrin and secretin stimulation test
  • Measure baseline serum gastrin level and repeat after administration of secretin.
  • High levels in gastrinoma (Zollinger-Ellison syndrome)
• Serum intact PTH level
• Specific testing for systemic inflammatory diseases (e.g., Behcet disease, Crohn disease)

Differential diagnosis of gastric and duodenal ulcers

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.

Approach ^[23]

• General measures
  • Nonpharmacological measures: e.g., avoid NSAIDs, restrict alcohol.
  • Follow-up to confirm treatment success; possibly endoscopic surveillance
• H. pylori diagnostics
  • Positive
    • H. pylori eradication therapy with antibiotics and a PPI
    • Continue acid suppression medication (i.e., PPIs) for 4–8 weeks. ^[22]
  • Negative: Trial of acid suppression medication (i.e., PPIs) for 4–8 weeks, followed by reevaluation
• Failure of medical treatment : Consider elective surgery.
• Management of critical complications of PUD
  • Acute stabilization: airway management for massive hematemesis, immediate hemodynamic support for shock
  • Initial management of overt GI bleeding
  • Management of gastrointestinal perforation

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:
  • Complications of PUD
  • Insufficient pain control
  • Need for further workup
• Consider ICU admission or direct transfer to the OR for:
  • Hemodynamic instability
  • Peritonitis and/or sepsis

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.

• Acid suppression medications and antacids are covered in detail in “Treatment of dyspepsia.”
• Recommended duration of acid suppression for PUD ^[1][22]
  • Duodenal ulcers: ≥ 4 weeks
  • Gastric ulcers: ≥ 8 weeks
  • Unknown location: Consider 8 weeks of empiric treatment.
  • Select patients (e.g., those with idiopathic ulcers) may benefit from maintenance acid suppression therapy to prevent recurrence.
• 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
    • Acts as an acid buffer and promotes HCO₃ production
    • Mostly used to promote ulcer healing in patients with duodenal ulcers
    • Should not be taken simultaneously with a PPI or H₂ blocker
  • 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). ^[10][28][29]
• Antibiotics: e.g., optimized bismuth quadruple therapy (metronidazole, tetracycline, bismuth, and a PPI). ^[30] See “H. pylori eradication therapy” for other treatment regimens.
• Nonpharmacological measures ^[1]
  • Restrict alcohol, smoking, and caffeine, and avoid stress.
  • Avoid medications that may cause or worsen PUD (e.g., discontinue NSAIDs, reduce or stop corticosteroids if possible).
  • Avoid eating before bedtime.

Elective surgical treatment ^[31]

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
• Surgical procedures
  • 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.
    • Complications include delayed gastric emptying, postvagotomy diarrhea , postvagotomy hypergastrinemia, and dumping syndrome.
    • To improve results, truncal vagotomy is combined with one of the following drainage procedures:
      • Pyloroplasty
      • Antrectomy
      • Subtotal gastrectomy
  • Partial gastrectomy (Billroth) and reconstruction
    • Billroth I: distal gastrectomy with end-to-end or side-to-end gastroduodenostomy
    • Billroth II: resection of the distal two-thirds of the stomach with a blind-ending duodenal stump and end-to-side gastrojejunostomy
  • 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).
• Perform noninvasive tests for H. pylori infection 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 ^[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.

Perform H. pylori eradication confirmation ≥ 4 weeks after completion of H. pylori eradication therapy. ^[19]

Bleeding peptic ulcer

Overview

• The most common complication of PUD
• Can be a chronic, slow bleed or an overt, rapid, life-threatening hemorrhage

Etiology

• Posterior duodenal ulcers are more likely to bleed than anterior duodenal ulcers.
• Gastric ulcers of the lesser curvature may cause bleeding from the left gastric artery.
• Duodenal ulcers of the posterior wall may cause bleeding from the gastroduodenal artery.

Clinical features

• Hematemesis (coffee-grounds emesis)
• Melena
• Clinical features of anemia
• Hematochezia (less common; only seen in massive bleeding)
• Orthostatic hypotension

Diagnostics

• Consult gastroenterology for EGD.
• Management strategy is determined by endoscopic risk stratification, e.g., Forrest classification.
• See “Diagnostic approach to overt GI bleeding.”

Management

• General measures ^[33]
  • NPO
  • Volume resuscitation, transfusion as needed
  • See “Initial management of an overt GI bleed” for details.
• Ulcer with high-risk stigmata ^[34]
  • Endoscopic hemostasis is indicated.
    • Thermocoagulation, sclerosant injection, clips
    • Epinephrine injection hemostatic power spray can be used in combination with other methods.
  • Requires inpatient care
  • After after index endoscopy
    • Start 3 days of high-dose PPI, e.g., esomeprazole . ^[34]
    • Continue PPI treatment on days 4–14, e.g., esomeprazole (off-label) . ^[34]
• Ulcer with unclear risk: Controversial; PPI therapy alone or endoscopic hemostasis may be considered. ^[34][35][36]
• Ulcer with low-risk stigmata
  • Endoscopic hemostasis is not recommended.
  • Can usually be managed as outpatients with PPI therapy

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

• 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.
• Etiology
  • Prepyloric gastric ulcers are the most common cause of perforation.
  • Duodenal ulcers of the anterior wall are more likely to perforate than ulcers of the posterior wall.
• Clinical features
  • Sudden, diffuse abdominal pain and rigidity
  • Fever, tachycardia, tachypnea, hypotension
  • Pneumoperitoneum
  • Shoulder pain (irritation of the phrenic nerve)
• Treatment ^[33]
  • NPO, volume resuscitation, supportive care
  • Graham patch: surgical repair of a small, (generally < 5 mm) perforated duodenal ulcer using a piece of omentum to close the perforation
  • See “Treatment” in “Gastrointestinal perforation” for more details.

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

• 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
• Treatment
  • Conservative management: indicated in all patients, as most fistulas close spontaneously
  • Surgical resection: in patients unresponsive to conservative management

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).

• Pathophysiology
  • Acute PUD → inflammation and edema
  • Chronic PUD → scarring and fibrosis
• Clinical features
  • Postprandial, nonbilious vomiting
  • Succussion splash
  • Early satiety
  • Progressive gastric dilation
  • Weight loss
• Diagnostics
  • Imaging (e.g., barium swallow, CT abdomen)
  • EGD (confirmatory test)
  • Laboratory studies may show hypokalemic hypochloremic metabolic alkalosis.
• Management
  • Symptomatic: nasogastric suction, electrolyte and fluid replacement, and parenteral nutrition
  • Definitive: surgery or endoscopic dilation

Malignant transformation

• Gastric ulcers ^[20]
  • High malignant potential (progression to cancer in 5–10% of cases)
  • Malignancy should be ruled out with biopsy.
• Duodenal ulcers
  • Usually benign
  • Routine biopsy is not required.

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

Stress ulcers

Stress ulcers are ulcers associated with erosive gastritis, i.e., acute damage to the gastric mucosa resulting from increased levels of endogenous glucocorticoids and decreased blood flow to the stomach.

Etiology ^[37]

• Critical illness, such as:
  • Respiratory failure requiring ventilation for > 48 hours
  • SIRS
  • Renal failure
  • Hepatic failure
  • Severe head or spinal cord injury
  • Burns affecting a surface area > 35% of the body surface area.
• Major surgery

Types

• 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

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.

Management ^{[38][39][40][41]}

Indications

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.

Prophylactic agents ^[41]

• 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. ^[42]

Both PPIs and H₂ receptor antagonists may increase the risk of pneumonia in critically ill patients. ^[41]

Stress ulcer prophylaxis likely has little effect on mortality, length of admission, length of stay in critical care units, and duration of mechanical ventilation. ^[41]

NSAID-induced ulcers ^[10][43]

• 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 ^[10][44]

• Age > 60 years ^[45][46]
• Concurrent H. pylori infection
• Concurrent use of antithrombotics, corticosteroids, aspirin (including low-dose), or SSRIs
• Higher doses or use of higher-risk NSAIDs ^[10]
• Prior peptic ulcer disease
• Dyspepsia ^[47]
• Comorbidities ^[47]

Prevention of NSAID-induced GI toxicity ^[10][44]

• Consider switching NSAID to an alternative agent (e.g., an oral analgesic), if appropriate.
• Modify risk factors for NSAID-induced GI toxicity where possible, e.g.:
  • Decrease NSAID dose to the lowest effective dose.
  • In patients requiring long-term NSAID therapy consider testing for H. pylori, followed by H. pylori eradication if positive. ^{[10][44][45][47]}
• Select an NSAID based on the patient's ASCVD risk. ^[10][44]
  • Celecoxib is preferred in patients with low cardiovascular risk.
  • Naproxen is preferred in patients with high cardiovascular risk.
• Determine the need for gastric mucosal protection based on the presence of risk factors for NSAID-induced GI toxicity.
  • 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). ^[10][28][29]
  • Reassess indications for gastric mucosal protection periodically; discontinue when no longer indicated. ^[46][48]

In patients with a recent, complicated ulcer, NSAIDS should be avoided or used with extreme caution. ^[10]

Always use the lowest possible effective dose of an NSAID. ^[10][48]

Generally, prescribe a PPI for patients on low-dose aspirin who have at least one other risk factor for NSAID-induced GI toxicity (e.g., currently taking another NSAID or antithrombotic). ^[10][46]

Management of NSAID-induced GI toxicity ^[44][45][46]

• See “Treatment of peptic ulcer disease.”
• Patients with a GI bleed on antithrombotics: Consult specialists to decide when and how to withhold, adjust, or resume antithrombotics.
• For secondary prevention, see “Prevention of NSAID-induced GI toxicity.”