Peptic ulcer disease

Description

Mucosal break >5 mm penetrating the muscularis mucosae in stomach or duodenum
Result of an imbalance: aggressive factors (acid, pepsin) vs mucosal defence (mucus-bicarbonate, prostaglandins, blood flow)

	Duodenal ulcer	Gastric ulcer
Site	Duodenal bulb	Antrum / lesser curve
*H. pylori*	Stronger association	Present, but less consistently
Acid output	Normal or high	Normal or low
Pain	Classically relieved by food, wakes at night, 2-3 h post-prandial	Worse with food -> weight loss
Malignancy	Essentially never	Must biopsy and confirm healing

**H. pylori is most strongly associated with duodenal ulcers**

Epidemiology

Lifetime prevalence ~5-10%; incidence falling with H. pylori eradication and PPI use
**H. pylori prevalence in Australia ~15-20%**, much higher in people born overseas in high-prevalence regions and in Aboriginal and Torres Strait Islander communities
NSAID- and aspirin-related ulcers now a rising proportion as H. pylori declines
*Idiopathic (H. pylori-negative, NSAID-negative) ulcers ~10-20% and rising - worse prognosis, higher rebleeding*

Aetiopathogenesis

Causes

*H. pylori* - urease -> ammonia -> local neutralisation; CagA/VacA virulence factors
- Antral-predominant gastritis -> inc gastrin -> inc acid -> duodenal ulcer
- Corpus/pangastritis -> atrophy -> dec acid -> gastric ulcer and gastric cancer
NSAIDs and aspirin - COX-1 inhibition -> dec prostaglandin -> dec mucus, bicarbonate and mucosal blood flow
- Systemic, not just topical - enteric-coated aspirin does not remove the risk
Zollinger-Ellison syndrome - a gastrin-secreting tumour (gastrinoma) causing severe, treatment-refractory, often multiple and distal ulcers
Stress ulceration (Curling - burns; Cushing - head injury), critical illness
Crohn disease, vasculitis, CMV/HSV (immunocompromised), radiation, cocaine/methamphetamine, bisphosphonates, corticosteroids (only with NSAIDs), SSRIs, mastocytosis

Antibiotic resistance drives eradication failure

Clarithromycin resistance is the leading cause of failure - now well over 10% of isolates and rising
Metronidazole resistance >30%
Amoxicillin resistance <10% (which is why amoxicillin stays in almost every regimen)

Diagnosis

Presentation

Epigastric pain, dyspepsia, nausea, early satiety
Complication as first presentation is common - bleeding, perforation, obstruction - especially in NSAID users and the elderly, who may have no pain at all

Alarm features -> gastroscopy

Dysphagia, odynophagia, vomiting
Weight loss, iron deficiency anaemia, GI bleeding, mass
New dyspepsia age >50-55; family history of gastric cancer

Testing for H. pylori

Test	Notes
Urea breath test	Active infection; used for confirming eradication
Faecal antigen	Active infection; equally good for confirming eradication
Rapid urease (CLO) test at endoscopy	Fast, cheap
Histology	Also stages gastritis/atrophy
Serology (IgG)	Stays positive after eradication - cannot confirm cure. Largely abandoned
Culture / molecular susceptibility testing	For resistance-guided therapy after failure

**Stop PPI 2 weeks and antibiotics/bismuth 4 weeks before testing - false negatives otherwise**
Also falsely negative during acute GI bleeding - retest after

At endoscopy

Every gastric ulcer must be biopsied (malignancy) and re-scoped at 6-8 weeks to confirm healing
Duodenal ulcers do not require biopsy or repeat endoscopy unless atypical or non-healing
Forrest classification stratifies rebleeding risk (see GI bleeding note)

Consider Zollinger-Ellison if

*Multiple ulcers, distal to the duodenal bulb, refractory to therapy, recurrent after eradication, with diarrhoea, or H. pylori-negative and NSAID-negative*
Fasting serum gastrin off PPI (2 weeks) + gastric pH; secretin stimulation test; then localisation (Ga-68 DOTATATE PET, EUS)
Check for MEN1 - hyperparathyroidism, pituitary

Management

1. H. pylori eradication - the regimen has changed

Verified 2026: empirical clarithromycin triple therapy is no longer first line. Rising clarithromycin resistance has moved international and Australian guidance to bismuth quadruple therapy or an amoxicillin-based non-bismuth quadruple regimen for 14 days, with clarithromycin reserved for known-susceptible infection.

First line - one of:

Bismuth quadruple, 14 days: PPI BD + bismuth subcitrate + tetracycline 500 mg QID + metronidazole 400 mg TDS
- Eradication ~85-90%, and unaffected by clarithromycin resistance
Non-bismuth (concomitant) quadruple, 14 days: PPI + amoxicillin 1 g + clarithromycin 500 mg + metronidazole 400 mg, all BD
Clarithromycin triple therapy only where susceptibility is known, or local resistance is documented to be low and there has been no prior macrolide exposure

Salvage

Levofloxacin-based: PPI + amoxicillin 1 g + levofloxacin 500 mg, 10-14 days
Rifabutin-based triple therapy for multiply refractory infection
Susceptibility-guided therapy after two failures
Never reuse a macrolide or a quinolone the patient has already failed - resistance is acquired

Always

Confirm eradication with urea breath test or faecal antigen >=4 weeks after finishing antibiotics and >=2 weeks off PPI
Test and treat family/household members in high-prevalence settings

2. Acid suppression

PPI for 4-8 weeks to heal the ulcer (longer for a large or complicated ulcer)
Continue PPI long-term if: ongoing NSAID/aspirin, prior bleeding ulcer, H. pylori-negative idiopathic ulcer, high-dose or dual antiplatelet therapy
Otherwise stop after healing and eradication

3. Remove the aggressor

Stop the NSAID if at all possible
If it must continue: PPI co-therapy, lowest effective dose, or switch to a COX-2 selective agent plus PPI
Review corticosteroids, SSRIs, anticoagulants, bisphosphonates
Smoking cessation; alcohol reduction

4. Prophylaxis for NSAID users - who gets a PPI

Prior peptic ulcer or ulcer bleeding
Age >65
Concurrent corticosteroid, anticoagulant, antiplatelet or SSRI
High-dose or multiple NSAIDs
Significant comorbidity
Test and eradicate H. pylori before starting long-term NSAID or aspirin in patients with an ulcer history

5. Complications

Bleeding - resuscitate, high-dose PPI, endoscopic dual-modality haemostasis (see GI bleeding note); embolisation then surgery if refractory
Perforation - erect CXR/CT; resuscitation, IV antibiotics, PPI, urgent surgery (omental patch repair)
Gastric outlet obstruction - NG decompression, PPI, correct hypochloraemic hypokalaemic metabolic alkalosis, then endoscopic dilatation or surgery
Zollinger-Ellison - high-dose PPI, localise and resect the gastrinoma, screen for MEN1

Associations

**H. pylori -> gastric adenocarcinoma and gastric MALT lymphoma**
- MALT lymphoma regresses with eradication alone in ~70-80% if t(11;18)-negative
Zollinger-Ellison syndrome and MEN1
NSAID/aspirin use; corticosteroids with NSAIDs
Cirrhosis, chronic kidney disease, COPD
Systemic mastocytosis, basophilia (myeloproliferative neoplasms) - inc histamine
Hyperparathyroidism
Smoking, alcohol
Critical illness - Curling ulcer (burns), Cushing ulcer (raised ICP)

Natural history & complications

*Eradication of H. pylori essentially cures the disease* - recurrence falls from ~60-80%/yr to <5%/yr
Ulcers recur if H. pylori persists, NSAIDs continue, or the ulcer is idiopathic
Idiopathic ulcers have the worst prognosis - higher rebleeding, higher mortality

Complications and their numbers

Bleeding ~15% of ulcers - the commonest complication; rebleeding after endoscopic therapy ~10%
Perforation ~5% - mortality up to 20% in the elderly
Gastric outlet obstruction ~2%
Ulcer bleed mortality overall ~5-10%, driven by comorbidity rather than exsanguination

Follow-up

Gastric ulcer: repeat endoscopy at 6-8 weeks to confirm healing and re-biopsy if unhealed
*Confirm H. pylori eradication in everyone treated*
A non-healing gastric ulcer is malignant until proven otherwise

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