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 1GastrointestinalMedium
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 is the most serious potential complication?
AGastric outlet obstruction from scarring
BPenetration into the pancreas
CFree perforation with peritonitis
DUpper gastrointestinal hemorrhage
Reveal answer & full explanation
Correct answer: D — Upper gastrointestinal hemorrhage
AGastric outlet obstruction from scarring
BPenetration into the pancreas
CFree perforation with peritonitis
DUpper gastrointestinal hemorrhage✓
Why Upper gastrointestinal hemorrhage is correct
An NSAID-related peptic ulcer can erode into a submucosal artery and produce brisk upper GI bleeding.
The falling hemoglobin plus orthostatic lightheadedness already signals clinically significant, ongoing blood loss in this patient.
It is the most immediately life-threatening of the ulcer complications because of hypovolemic shock risk.
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, not the ongoing blood loss evident here.
Free perforation with peritonitis — Plausible-but-not-shown trap: perforation is grave but presents with sudden rigid abdomen, whereas this patient's anemia and orthostasis point to hemorrhage.
Penetration into the pancreas — Posterior-ulcer trap: a penetrating ulcer causes constant pain boring through to the back with a raised amylase, not the progressive anemia and orthostatic symptoms of blood loss described here.
Question 2GastrointestinalMedium
A 47-year-old man with heavy NSAID use has epigastric pain and melena. Which of the following complications is most likely?
AUpper gastrointestinal hemorrhage
BLower gastrointestinal hemorrhage
CGastric outlet obstruction
DFree perforation with peritonitis
Reveal answer & full explanation
Correct answer: A — Upper gastrointestinal hemorrhage
AUpper gastrointestinal hemorrhage✓
BLower gastrointestinal hemorrhage
CGastric outlet obstruction
DFree perforation with peritonitis
Why Upper gastrointestinal hemorrhage is correct
NSAIDs impair prostaglandin-mediated mucosal defense, causing peptic ulcers that erode into submucosal vessels.
Melena (black, tarry stool) signals a bleeding source proximal to the ligament of Treitz, classic for a bleeding duodenal or gastric ulcer.
Why the others are wrong
Lower gastrointestinal hemorrhage — A lower-tract source typically produces hematochezia, not melena; the black tarry stool points upstream (anchoring on the word bleeding).
Gastric outlet obstruction — Chronic ulcer scarring can obstruct, but that causes early satiety and succussion-splash vomiting, not melena (right-disease-wrong-complication).
Free perforation with peritonitis — Perforation produces sudden rigid abdomen and pneumoperitoneum, not melena; bleeding and perforation are distinct ulcer complications (premature closure on severity).
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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 elevated gastric pH
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 if local clarithromycin resistance <15%
Bismuth quadruple therapy (PREFERRED in most US regions): PPI BID + bismuth subsalicylate QID + tetracycline QID + metronidazole QID × 14 days
Or clarithromycin triple therapy: PPI BID + clarithromycin BID + amoxicillin BID (or metronidazole if PCN-allergic) × 14 days — only if no prior macrolide exposure and local resistance low
H. pylori — second-line / salvage
Levofloxacin triple: PPI BID + levofloxacin daily + amoxicillin BID × 14 days
Rifabutin triple (PPI + rifabutin + amoxicillin) for refractory cases
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)
IV PPI bolus + infusion (or intermittent high-dose IV PPI)
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 2017 — Chey WD et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol 2017;112:212-239
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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