Peptic Ulcer Disease (PUD)
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.
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Risk factors
- Helicobacter pylori infection (responsible for ~70% of duodenal and ~40% of gastric ulcers)
- NSAID and aspirin use (dose-dependent; risk amplified in elderly, prior ulcer, concurrent steroid or anticoagulant)
- Smoking, heavy alcohol use
- Physiologic stress (ICU, mechanical ventilation >48 h, burns — Curling ulcer; head injury — Cushing ulcer)
- Zollinger-Ellison syndrome (gastrinoma) — multiple ulcers, refractory, distal duodenum/jejunum
- Chronic kidney disease, cirrhosis, COPD
- 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 |
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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