Key Facts

Peptic ulcer disease (PUD) refers to ulceration of the gastric or duodenal mucosa, extending through the muscularis mucosae. It remains a significant cause of morbidity despite declining incidence due to H. pylori eradication and PPI use.

Epidemiology

Lifetime prevalence is approximately 5-10%. Incidence has declined significantly over the past 30 years due to H. pylori eradication and reduced NSAID use. However, PUD remains the commonest cause of upper GI bleeding. Duodenal ulcers are 4x more common than gastric ulcers. Male predominance (2:1). Peak incidence is 30-50 years for duodenal ulcers and 50-70 years for gastric ulcers.

Aetiology

• H. pylori infection: ~60% of gastric ulcers, ~90% of duodenal ulcers
• NSAIDs/aspirin: ~20% of gastric ulcers; inhibit COX-1 → reduced prostaglandin → reduced mucosal protection
• Smoking: 2x risk, impairs ulcer healing
• Physiological stress: Curling ulcer (burns), Cushing ulcer (raised ICP)
• Zollinger-Ellison syndrome: gastrinoma → massive acid hypersecretion
• Other: corticosteroids (synergistic with NSAIDs), alcohol, crack cocaine

Pathophysiology

PUD results from an imbalance between mucosal defence factors (mucus-bicarbonate barrier, prostaglandins, mucosal blood flow, epithelial cell renewal) and aggressive factors (gastric acid, pepsin, H. pylori, NSAIDs). H. pylori colonises the gastric antrum, producing urease (generates ammonia → alkaline microenvironment), CagA, and VacA toxins that cause chronic inflammation and disrupt the mucosal barrier. NSAIDs inhibit COX-1, reducing mucosal prostaglandin synthesis and compromising the mucus-bicarbonate barrier.

Duodenal Ulcer

• Epigastric pain relieved by food and antacids ("hunger pain")
• Pain worse at night/early morning (empty stomach)
• May have periods of remission and relapse

Gastric Ulcer

• Epigastric pain worsened by eating
• Nausea, early satiety
• Weight loss (may occur due to food avoidance)

Complications

• Bleeding: haematemesis, melaena, iron deficiency anaemia
• Perforation: sudden severe epigastric pain → peritonitis; free air on erect CXR
• Gastric outlet obstruction: persistent vomiting, succussion splash, metabolic alkalosis

Red Flags

• Haematemesis/melaena (bleeding ulcer)
• Acute severe abdominal pain with peritonism (perforation)
• Persistent vomiting with weight loss (outlet obstruction or malignancy)
• Age ≥55 with new dyspepsia (exclude malignancy — NICE NG12)
• Symptoms not responding to PPI + H. pylori eradication

Bedside

• H. pylori testing: urea breath test (¹³C-UBT) — first-line; OR stool antigen test. Stop PPI ≥2 weeks and antibiotics ≥4 weeks before testing
• Observations: if GI bleeding suspected

Bloods

• FBC: iron deficiency anaemia (chronic blood loss)
• U&Es: urea disproportionately raised with upper GI bleed
• LFTs, amylase/lipase: exclude biliary/pancreatic cause
• Group and save/crossmatch: if bleeding
• Fasting gastrin: if Zollinger-Ellison suspected (multiple/refractory ulcers)

Imaging

• OGD: gold standard — visualise ulcer, take biopsies (ALL gastric ulcers must be biopsied to exclude malignancy; duodenal ulcers rarely malignant), CLO test for H. pylori
• Erect CXR: free air under diaphragm if perforation suspected
• CT abdomen: if perforation suspected and CXR equivocal; staging if malignancy found

Special Tests

• CLO test (rapid urease test): biopsy placed in urea medium — colour change if H. pylori present
• Histology: Sydney protocol biopsies for H. pylori and dysplasia
• Repeat OGD: all gastric ulcers should have repeat OGD at 6-8 weeks to confirm healing and exclude malignancy

Non-pharmacological

• Stop NSAIDs/aspirin if possible; if essential, co-prescribe PPI
• Smoking cessation: impairs ulcer healing
• Dietary: no specific diet proven effective; avoid foods that worsen symptoms
• Reduce alcohol intake

Pharmacological

• H. pylori eradication (if positive):
  • First-line: PPI (omeprazole 20 mg BD or lansoprazole 30 mg BD) + amoxicillin 1 g BD + clarithromycin 500 mg BD for 7 days
  • Penicillin allergy: PPI + metronidazole 400 mg BD + clarithromycin 500 mg BD for 7 days
  • Second-line (if first-line fails): PPI + amoxicillin 1 g BD + metronidazole 400 mg BD for 7 days; or bismuth quadruple therapy
  • Confirm eradication: UBT or stool antigen ≥4 weeks after completing treatment
• PPI for ulcer healing: omeprazole 20 mg OD (duodenal — 4 weeks) or 20-40 mg OD (gastric — 8 weeks)
• Gastroprotection with NSAID use: PPI co-prescription (omeprazole 20 mg OD); consider switching to COX-2 inhibitor (celecoxib)

Surgical/Interventional

• Endoscopic haemostasis: for bleeding ulcers — adrenaline injection (1:10,000) + thermal coagulation or clips; repeat OGD if rebleed
• Interventional radiology: selective arterial embolisation for failed endoscopic haemostasis
• Surgery: for perforation (omental patch/Graham patch repair), uncontrolled bleeding (under-running of ulcer), and gastric outlet obstruction
• Highly selective vagotomy: historical; rarely performed now

Referral Criteria

• Urgent 2WW OGD: alarm features or age ≥55 with new dyspepsia (NICE NG12)
• Urgent surgical referral: perforation, uncontrolled bleeding
• Gastroenterology: refractory ulcers, suspected Zollinger-Ellison syndrome

H. pylori eradication cures >95% of H. pylori-associated duodenal ulcers and >80% of gastric ulcers. Reinfection rate in UK is <1% per year after successful eradication. NSAID-associated ulcers heal in >90% with PPI if NSAID stopped. Upper GI bleeding from peptic ulcers has an overall mortality of 5-10%. Perforation mortality is 5-10% with prompt surgical treatment (higher in elderly/delayed presentation). Rockall score >8 is associated with >40% mortality.

Rockall Score (Post-OGD)

Glasgow-Blatchford Score (Pre-OGD)

• Uses Hb, urea, SBP, pulse, melaena, syncope, liver disease, heart failure
• Score 0 = very low risk — may be suitable for outpatient management
• Score ≥6 = high risk — requires inpatient management + urgent OGD