Peptic Ulcer Disease (PUD)

BASICS

Definition: Defects in the stomach and/or duodenal mucosa with inflammation and erosion by gastric acid and pepsin.
Types:
Esophageal ulcer: distal esophagus (often due to GERD or gastrinoma)
Duodenal ulcer: most common; usually in anterior duodenal bulb
Gastric ulcer: less common (unless NSAIDs used); along lesser curvature/antrum
Multiple/Distal ulcers: consider gastrinoma (Zollinger-Ellison syndrome)

Global prevalence declining due to H. pylori therapy and careful NSAID use
Incidence: Any age; duodenal (30–50 yrs, men); gastric (>60 yrs, women)
Annual cases: 500,000 new/year; 4 million recurrences/year
Lifetime risk: 5–10% general population; 10–20% in H. pylori-positive patients

Most common causes: H. pylori infection (gram-negative), NSAIDs/aspirin
Other medications: corticosteroids, bisphosphonates, KCl, clopidogrel, sirolimus
Hypersecretory syndromes: gastrinoma (ZES), systemic mastocytosis, CF, hyperparathyroidism
Other risk factors: tobacco, alcohol, stress, radiation, obesity, genetic/familial clustering
Ectopic ulcers: Meckel diverticulum (with ectopic gastric mucosa), embryonic esophagus remnant

Avoid NSAIDs/aspirin/alcohol/tobacco/caffeine when possible
Use acetaminophen or lowest NSAID dose with PPI or misoprostol if NSAID necessary
Test/eradicate H. pylori if at risk
Maintenance PPI/H2 blocker for prior complications, refractory ulcers, or persistent infection
Weight loss for obesity

Often asymptomatic (70%)
Midepigastric gnawing/burning, episodic pain
Duodenal ulcer: pain relieved by food/antacids; nocturnal pain
Gastric ulcer: pain worsened by food, relieved by antacids
Nausea, vomiting, loss of appetite, fullness
Red flags: Age >55, new symptoms, GI bleeding, anemia, persistent vomiting, weight loss, dysphagia, FHx gastric cancer
NSAID-induced ulcers often silent; may present with perforation/bleed

Functional dyspepsia, gastritis, GERD, biliary colic, pancreatitis, cholecystitis, Crohn, malignancy, MI, mesenteric ischemia

Labs: CBC, LFTs, amylase/lipase as needed
H. pylori tests:
Urea breath test (active infection, high accuracy)
Stool antigen (active infection)
Serology (for untreated only; not for eradication confirmation)
Hold antibiotics/bismuth 4wks, PPIs 2wks before testing
EGD (gold standard): All >50 with dyspepsia or alarm symptoms, or non-responders; biopsy for H. pylori and malignancy
Fasting gastrin: refractory/multiple ulcers (rule out ZES)
Imaging: Barium swallow if EGD not possible

Acid suppression: PPIs preferred
Omeprazole 20 mg/day, lansoprazole 30 mg/day, rabeprazole 20 mg/day, esomeprazole 40 mg/day, pantoprazole 40 mg/day
4–8 weeks (longer for NSAID-induced ulcers)
Precautions: bone density loss, risk of pneumonia/C. diff/hypomagnesemia
H2 blockers: Safer long-term, but less effective than PPIs
NSAID/aspirin-induced ulcers: stop NSAID; treat with PPI 6–8 weeks; maintenance if long-term NSAID/ASA required
H. pylori eradication: 14 days (see below)
Triple therapy: PPI BID + clarithromycin 500 mg BID + amoxicillin 1g BID (or metronidazole if allergic)
Quadruple therapy: PPI BID + bismuth + tetracycline + metronidazole
Concomitant therapy: PPI BID + clarithromycin 500 mg BID + amoxicillin 1g BID + nitroimidazole 500 mg BID
Confirm eradication 4 weeks post-therapy (urea breath/stool antigen)

If initial therapy fails: Levofloxacin triple/quadruple/sequential/hybrid therapy (see source)
Ulcer-healing agents: Sucralfate, antacids (symptomatic only)
Drug interactions: cimetidine (CYP450 inhibitor), omeprazole (prolongs diazepam/warfarin effects), sucralfate (impairs tetracycline/quinolone absorption)

Pregnancy: PPIs not associated with adverse outcomes
Breastfeeding: Ranitidine and esomeprazole excreted in low amounts—generally safe

EGD for red flags, new-onset symptoms >55, failed therapy, overt GI bleeding, anemia, weight loss

Indications: Refractory ulcers, high complication risk, bleeding not controlled by endoscopy, perforation
Duodenal ulcers: Truncal/selective/highly selective vagotomy ± drainage
Gastric ulcers: Partial gastrectomy (Billroth I/II)
Emerging: Vonoprazan (novel acid blocker)

Stop ulcerogenic agents
Bleeding ulcers: PPIs (oral = IV post-endoscopy), endoscopic intervention, emergent surgery for perforation

Lifestyle changes: smoking/alcohol/caffeine cessation, weight loss, NSAID reduction