Mucosal break >5 mm in the stomach or duodenum, most often due to H. pylori or NSAIDs.
Also known as: PUD, peptic ulcer, gastric ulcer, duodenal ulcer
Overview
Mucosal defect of the stomach or duodenum extending through the muscularis mucosae, typically ≥5 mm in diameter. Caused by an imbalance between mucosal aggressors (acid, pepsin, H. pylori, NSAIDs) and protective factors (mucus, bicarbonate, prostaglandins, blood flow).
Epidemiology
Lifetime prevalence 5-10%. Duodenal ulcers outnumber gastric ulcers ~4:1 historically, declining with H. pylori eradication. Incidence falling in developed countries; NSAID-related ulcers rising in elderly.
Try two board-style Peptic Ulcer Disease questions
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Question 1EndocrineMedium
A 38-year-old man presents with kidney stones, peptic ulcer disease unresponsive to PPI (proton pump inhibitor) therapy, and diarrhea. Fasting serum gastrin is markedly elevated at 1,800 pg/mL. Secretin stimulation test results in a paradoxical rise in gastrin. CT shows a 1.5 cm pancreatic head mass. What is the most likely diagnosis?
Paradoxical rise in gastrin with secretin stimulation is pathognomonic
Most gastrinomas are located in the gastrinoma triangle (duodenum, pancreatic head, porta hepatis)
25% of cases are associated with multiple endocrine neoplasia type 1 (MEN1)
Treatment: high-dose proton pump inhibitor (PPI) for symptom control plus surgical resection if localized
Why the others are wrong
Insulinoma — causes hypoglycemia with elevated insulin, not acid hypersecretion or elevated gastrin
VIPoma — vasoactive intestinal peptide-secreting tumor (VIPoma) causes secretory diarrhea, not peptic ulcers or elevated gastrin
Glucagonoma — presents with necrolytic migratory erythema, not the described triad
Somatostatinoma — another pancreatic neuroendocrine tumor that causes diarrhea (steatorrhea) and can arise in the pancreatic head, but somatostatin suppresses gastrin and gastric acid, producing hypochlorhydria, diabetes, and gallstones rather than refractory peptic ulcers with a markedly elevated gastrin
Question 2GastrointestinalMedium
A 61-year-old man with chronic NSAID use has burning epigastric pain. He becomes lightheaded on standing. Laboratory studies show a hemoglobin of 8.6 g/dL, decreased from 13.4 g/dL 3 months ago. Which of the following complications is this patient most likely experiencing?
APenetration into the pancreas
BGastric outlet obstruction from scarring
CMalignant change in a chronic ulcer
DUpper gastrointestinal hemorrhage
EFree perforation with peritonitis
Reveal answer & full explanation
Correct answer: D — Upper gastrointestinal hemorrhage
APenetration into the pancreas
BGastric outlet obstruction from scarring
CMalignant change in a chronic ulcer
DUpper gastrointestinal hemorrhage✓
EFree perforation with peritonitis
Why Upper gastrointestinal hemorrhage is correct
An NSAID-related peptic ulcer can erode into a submucosal vessel and cause upper GI bleeding.
The fall in hemoglobin from 13.4 to 8.6 g/dL, together with orthostatic lightheadedness, shows clinically significant ongoing blood loss.
Hemorrhage is the most common complication of peptic ulcer disease, and it is the complication these findings show. Ongoing loss puts him at risk of hypovolemic shock.
Why the others are wrong
Gastric outlet obstruction from scarring — Right-disease-wrong-complication trap: obstruction from chronic ulcer scarring causes vomiting and early satiety. It does not cause the ongoing blood loss seen here.
Free perforation with peritonitis — Plausible-but-not-shown trap: perforation has a higher case fatality than bleeding, but it presents with sudden severe pain and a rigid abdomen. This patient's anemia and orthostasis point to hemorrhage.
Penetration into the pancreas — Posterior-ulcer trap: a penetrating ulcer causes constant pain that bores through to the back, often with a raised amylase. It does not cause the progressive anemia and orthostatic symptoms of blood loss described here.
Malignant change in a chronic ulcer — alarm-feature trap: anemia and age over 60 do call for endoscopy, and gastric ulcers are biopsied because a cancer can look like an ulcer, but a benign NSAID ulcer is not a premalignant lesion, and a 4.8 g/dL fall in hemoglobin with orthostatic lightheadedness is the picture of ongoing ulcer bleeding.
Additional high-yield points
Frequency and lethality are different questions. Bleeding is the most common ulcer complication, while perforation is less common but more often fatal. A patient with anemia and orthostasis is bleeding, whichever complication is deadliest.
ACG 2021 guideline on upper GI and ulcer bleeding (Laine et al., Am J Gastroenterol 2021): transfuse red cells at a hemoglobin threshold of 7 g/dL, perform endoscopy within 24 hours of presentation, and give endoscopic therapy for active bleeding or a nonbleeding visible vessel.
After successful endoscopic hemostasis, ACG 2021 recommends high-dose PPI (continuous or intermittent) for 3 days, then oral PPI twice daily through 2 weeks.
Stop the NSAID and test for H. pylori. If positive, treat per ACG 2024, where bismuth quadruple therapy is preferred when susceptibility is unknown.
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Glucocorticoids — risk amplifier when combined with NSAIDs (independent risk weak)
Pathophysiology
H. pylori produces urease, ammonia, cytotoxin-associated antigen (CagA), and vacuolating toxin (VacA), inducing chronic gastritis. Antral-predominant infection increases acid secretion → duodenal ulcer. Corpus-predominant atrophic gastritis decreases acid → gastric ulcer and cancer risk. NSAIDs inhibit COX-1, reducing prostaglandin-mediated mucus, bicarbonate, and mucosal blood flow.
Clinical presentation
Symptoms
Epigastric pain — burning, gnawing, or hunger-like
Duodenal ulcer: pain 2-3 h after meals, relieved by food or antacids, nocturnal awakening
Gastric ulcer: pain worsened by food, weight loss
Nausea, early satiety, bloating, belching
Hematemesis, melena, or hematochezia if bleeding
Signs / physical exam
Epigastric tenderness on palpation
Signs of GI bleeding: pallor, tachycardia, orthostasis
Peritoneal signs (rigid abdomen, rebound) if perforated — surgical emergency
Succussion splash if gastric outlet obstruction
Classic findings
Duodenal: pain relieved by eating. Gastric: pain provoked by eating.
Differential diagnosis
GERD — Retrosternal burning rather than epigastric pain; relieved by antacids; normal mucosa or esophagitis on EGD
Functional dyspepsia — Symptoms identical to PUD but normal EGD; Rome IV criteria; treat with PPI ± prokinetic
Gastric cancer — Weight loss, anemia, persistent ulcer despite therapy, age >55; biopsy all gastric ulcers
Acute pancreatitis — Epigastric pain radiating to back, lipase >3× ULN; alcohol or gallstones
Cholelithiasis / biliary colic — RUQ or epigastric pain after fatty meals, lasting hours; gallstones on ultrasound
Mesenteric ischemia — Postprandial pain out of proportion, weight loss, atherosclerotic risk factors; CT angiography
Acute coronary syndrome (inferior MI) — Epigastric pain with diaphoresis, dyspnea; ECG and troponin in older patients or with cardiac risk factors
Zollinger-Ellison syndrome — Multiple, refractory, or distal ulcers; diarrhea; fasting gastrin >1000 pg/mL with gastric pH <2 (acid hypersecretion); secretin stimulation test if equivocal; high gastrin with a high gastric pH instead suggests PPI use or atrophic gastritis
Diagnostic workup
Labs
CBC (anemia from chronic blood loss)
BMP, LFTs
Type and screen / crossmatch if acute bleed
H. pylori testing: urea breath test or stool antigen (preferred non-invasive); biopsy-based rapid urease test or histology if EGD performed
Fasting gastrin level if Zollinger-Ellison suspected
Imaging
Upper endoscopy (EGD) — gold standard; visualizes ulcer, allows biopsy and therapeutic intervention; biopsy ALL gastric ulcers to exclude malignancy
Upright CXR — free air under diaphragm in perforation
CT abdomen with contrast if perforation or complication suspected
Other studies
Withhold PPI 2 weeks and antibiotics 4 weeks before H. pylori testing to avoid false negatives
Repeat EGD in 8-12 weeks to confirm gastric ulcer healing and re-biopsy if not healed
Diagnostic algorithm
Feature
Duodenal Ulcer
Gastric Ulcer
Pain timing
2-3 h after meals, nocturnal
Soon after eating
Effect of food
Relieved
Worsened
Typical age
30-55
55-70
Acid secretion
Increased or normal
Normal or decreased
H. pylori prevalence
~70%
~40%
Malignancy risk
Negligible
4% — biopsy all
Bleeding risk
Higher (posterior — gastroduodenal artery)
Lower
Repeat EGD
Not routine
8-12 weeks to confirm healing
Duodenal vs gastric ulcer — distinguishing features.
Treatment
First-line
PPI — omeprazole, pantoprazole, esomeprazole — 4-8 weeks (8-12 weeks for gastric ulcer)
H. pylori eradication if positive (see by_subtype)
Discontinue NSAIDs and aspirin if possible; switch to acetaminophen
Lifestyle: smoking cessation, limit alcohol
H. pylori positive — first-line (ACG 2024)
Bismuth quadruple therapy (PREFERRED when susceptibility is unknown, and with penicillin allergy): PPI BID + bismuth subsalicylate QID + tetracycline QID + metronidazole QID × 14 days
Alternatives if no penicillin allergy: rifabutin triple (omeprazole 40 mg + amoxicillin 1 g + rifabutin 50 mg, each q8h) or vonoprazan 20 mg BID + amoxicillin 1 g TID, each × 14 days; clarithromycin triple (PPI BID + clarithromycin + amoxicillin × 14 days) only if the strain is documented clarithromycin-susceptible
H. pylori — second-line / salvage
Bismuth quadruple × 14 days if not previously used; rifabutin triple × 14 days if bismuth quadruple already used
Levofloxacin- or clarithromycin-containing salvage only if susceptibility is documented (resistance now high)
Confirm eradication 4 weeks after therapy with urea breath test or stool antigen
NSAID-induced
Stop NSAID; if continuation necessary, use lowest dose plus PPI co-therapy
Misoprostol QID as alternative gastroprotective agent (contraindicated in pregnancy)
Consider COX-2 selective inhibitor (celecoxib) with PPI in high-risk patients balanced against CV risk
Bleeding ulcer (Forrest classification)
After endoscopic hemostasis of high-risk stigmata (active bleeding, visible vessel, adherent clot): high-dose PPI (80 mg IV bolus then 8 mg/h, or intermittent high-dose) × 3 days, then oral PPI BID through the first 2 weeks after endoscopy; keeping gastric pH >6 stops acid and pepsin from lysing the clot. Low-risk ulcers (Forrest IIc/III): oral PPI and early feeding
Endoscopic hemostasis for active bleeding, visible vessel, or adherent clot (combination injection plus thermal or clip)
Transfuse to Hgb ≥7 (≥8 if cardiovascular disease)
IR embolization or surgery if endoscopic failure
Complications
Upper GI bleeding (most common complication)
Perforation — sudden severe epigastric pain, peritonitis, free air on imaging; surgical repair (Graham patch)
Penetration — into pancreas, biliary tree, or adjacent organ
Gastric outlet obstruction — early satiety, vomiting of undigested food, succussion splash
Gastric malignancy — especially long-standing H. pylori; MALT lymphoma can regress with eradication
PANCE pearls
Biopsy ALL gastric ulcers — 4% harbor malignancy; duodenal ulcers virtually never malignant.
Confirm H. pylori eradication 4 weeks post-treatment in all patients (especially complicated PUD, MALT lymphoma, refractory dyspepsia).
Withhold PPI 2 weeks before urea breath test or stool antigen; serology unaffected but cannot confirm active infection.
Forrest IIc (flat pigmented spot) and III (clean base) do not require endoscopic therapy — early PPI and feeding.
Recurrent or refractory ulcer, multiple ulcers, or ulcers distal to duodenal bulb — check fasting gastrin for Zollinger-Ellison.
Curling ulcer (burn patient) and Cushing ulcer (head injury) are stress ulcers — prophylax high-risk ICU patients with PPI or H2RA.
References
ACG 2024 — Chey WD, Howden CW, Moss SF, et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol 2024;119:1730-1753
ACG 2021 — Laine L et al. ACG Clinical Guideline: Upper Gastrointestinal and Ulcer Bleeding. Am J Gastroenterol 2021;116:899-917
Maastricht VI/Florence — Malfertheiner P et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence Consensus Report. Gut 2022;71:1724-1762
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