Peptic Ulcer Disease
NICE CKS Dyspepsia – proven peptic ulcer. Last revised: May 2024.
NICE clinical guideline [CG184] Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. Last updated: Oct 2019.
Background Information
Definition
Peptic ulcer disease is defined as a mucosal defect of the gastric or duodenal mucosa that extends through the muscularis mucosa into the submucosa or deeper layers
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This is an endoscopic diagnosis, as ulcers must be directly visualised on endoscopy to confirm the condition
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Clinically, patients with peptic ulcer disease typically present with dyspepsia (a spectrum of upper GI symptoms, see the Dyspepsia article for more information)
Erosion is the term most often confused with peptic ulcer disease.
- Erosions are superficial breaks in the gastric or duodenal mucosa that do NOT penetrate the muscularis mucosae
- Peptic ulcers penetrate through the muscularis mucosae
Aetiology
Common Causes
There are 2 major contributing factors:
| Aetiology | Pathophysiology |
|---|---|
| Helicobacter pylori infection | H. pylori secretes urease to convert urea into ammonia (a base) to survive in the low pH of gastric acid
|
| Chronic NSAID use | NSAIDs inhibit COX enzyme (→ ↓ prostaglandin levels)
|
Duodenal ulcers are strongly associated with H. pylori infection; gastric ulcers are strongly associated with NSAID use.
However, both H. pylori and NSAIDs can cause either ulcer type, and their effects are synergistic. Patients with both risk factors have a substantially increased risk of developing ulcers and complications.
Physiology of gastric acid secretion
| Main involved cells |
|
| Stimulators of acid secretion | Major stimulators:
|
| Inhibitors of acid secretion | Major inhibitor:
|
Other cells:
- Chief cells secrete pepsinogen
- Mucosal cells secrete protective mucus (stimulated by acetylcholine and prostaglandins)
Less Common Causes
Other associated risk factors (both gastric and duodenal ulcers):
- Smoking
- Alcohol use
- Caffeine
- Diet
- Psychological factors (e.g. anxiety, stress)
Rarer causes of peptic ulcer diseases:
- Zollinger-Ellison syndrome (gastrinoma)
- Secretes excess gastrin → excess gastric acid secretion
- Typically causes multiple / recurrent / refractory duodenal ulcers
- Curling’s ulcer (stress ulcer)
- Severe physiological stress (e.g. sepsis, severe burns, trauma) → mucosal ischaemia → ↓ protective barrier
- Cushing ulcers: if they occur in the context of raised ICP
- Mainly causes duodenal ulcers
- Gastric carcinoma (may mimic or cause ulceration)
- Other medications (exam-high yield)
- Aspirin
- Oral steroids
- SSRIs
- Bisphosphonates
- Recreational drugs (e.g. cocaine)
H. pylori infection or NSAIDs use alone do not typically cause peptic ulcer disease. There are often additional risk factors present, which together contribute to the development of an ulcer.
Diagnosis
Clinical Features
Most common symptom (in ~80% patients): dyspepsia (a spectrum of upper GI symptoms, including epigastric pain, discomfort, bloating) [Ref]
- Dyspepsia is highly non-specific
- In clinical practice, clinical features alone do NOT reliably differentiate gastric from duodenal ulcers (the only way to do so is by endoscopy)
However, it is important to learn the textbook clinical presentations that differentiate between gastric and duodenal ulcers (exam high-yield):
| Gastric ulcer |
|
| Duodenal ulcer |
|
Red Flags for Upper GI Malignancy
Offer urgent upper gastrointestinal endoscopy if:
- Dysphagia alone, or
- ≥55 y/o with weight loss and any of the following:
- Upper abdominal pain
- Reflux
- Dyspepsia
Other less commonly examined red flags:
- Consider a suspected cancer pathway referral for people with an upper abdominal mass consistent with stomach cancer
- Consider non-urgent direct access upper gastrointestinal endoscopy in people with haematemesis
- Consider non-urgent direct access upper gastrointestinal endoscopy in ≥55 y/o with:
- Treatment-resistant dyspepsia, or
- Upper abdominal pain with low haemoglobin levels, or
- Raised platelet count with any of the following:
- Nausea
- Vomiting
- Weight loss
- Reflux
- Dyspepsia
- Upper abdominal pain, or
- Nausea or vomiting with any of the following:
- Weight loss
- Reflux
- Dyspepsia
- Upper abdominal pain
Investigation and Diagnosis
Definitive test: upper GI endoscopy
- Endoscopy should NOT be routinely performed in patients with suspected peptic ulcer disease
- Only perform upper GI endoscopy if there are red flags (see above)
Direct visualisation on endoscopy is the only way to diagnose peptic ulcer disease, and to differentiate between gastric and duodenal ulcers
Management
Conservative / General Management
For all patients:
| Medication review | Important drugs to look out for:
|
| General lifestyle advice |
|
| Prevent triggers / attacks |
|
Management Pathways
Remember, patients do NOT present as peptic ulcer disease (peptic ulcer disease is an endoscopic diagnosis). So there would be 2 cohorts of patients:
- Proven peptic ulcer disease: these patients have undergone an endoscopy due to red flags or other reasons
- Uninvestigated dyspepsia: peptic ulcer disease is suspected (based on clinical features) but not proven endoscopically
Proven Peptic Ulcer Disease
1st line: H. pylori infection testing (1st line: urea breath test or stool antigen test, see the Helicobacter Pylori Infection article for more information)
Following H. pylori testing, there are 3 scenarios:
| Scenarior | Management |
|---|---|
| +ve H. pylori AND associated with NSAID use |
|
| +ve H. pylori but NOT associated with NSAID use |
|
| -ve H. pylori |
|
Regarding long-term treatment with PPI, advise:
- Long-term PPI is not routinely recommended
- Use the lowest effective dose to control symptoms
- If possible, step down or stop treatment
- Consider self-treatment with antacid and/or alginate therapy, although not recommended for long-term or continuous use
Key long-term complications of PPI use:
- Risk of infections – C. difficile infection, pneumonia
- Electrolyte deficiencies – hyponatraemia, hypomagnesaemia
- Malabsorption – iron deficiency, risk of osteoporosis (from impaired calcium absorption)
- GI effects – rebound acid hypersecretion when stopped suddenly, hypergastrinaemia → fundic gland polyps
Uninvestigated Dyspepsia
These patients should be managed in line with the dyspepsia guidelines (see the Dyspepsia article for more information).
Step up if symptoms persist (this is the same as what is outlined in the dyspepsia article – uninvestigated dyspepsia management section):
| Step 1 | Offer one of the following approaches
|
| Step 2 | Attempt the alternative approach (as listed in step 1) |
| Step 3 | Consider H2-receptor antagonist (e.g. ranitidine, famotidine, nizatidine) |
Regarding long-term treatment with PPI, advise:
- Long-term PPI is not routinely recommended
- Use the lowest effective dose to control symptoms
- If possible, step down or stop treatment
- Consider self-treatment with antacid and/or alginate therapy, although not recommended for long-term or continuous use
Key long-term complications of PPI use:
- Risk of infections – C. difficile infection, pneumonia
- Electrolyte deficiencies – hyponatraemia, hypomagnesaemia
- Malabsorption – iron deficiency, risk of osteoporosis (from impaired calcium absorption)
- GI effects – rebound acid hypersecretion when stopped suddenly, hypergastrinaemia → fundic gland polyps
Follow-up
All patients with a proven gastric ulcer need follow-up with:
- Repeat endoscopy to confirm healing
- H. pylori re-testing (at 6-8 weeks after starting eradication therapy and/or PPI)
- 1st line: carbon-13 urea breath test
- 2nd line: stool antigen test
- Since endoscopy is being performed anyway, H. pylori re-testing can be done via the invasive method (biopsy for CLO testing)
Rationale:
- Gastric ulcers are more dangerous, as they can be malignant or hide underlying gastric adenocarcinoma
- Duodenal ulcers are safer, as they are almost always benign and malignancy is extremely rare in the duodenum
Complications and Management
There are 2 main complications, and an important trend to be aware of is:
- Anterior duodenal ulcers usually perforate (not bleed)
- Posterior duodenal ulcers usually bleed (not perforate)
Bleeding Peptic Ulcer – Most Common
Most commonly bleeding vessel:
- Gastric ulcers of the lesser curvature → left gastric artery
- Posterior duodenal ulcers → gastroduodenal artery
Clinically presents as upper GI bleed:
- Haematemesis (coffee-ground vomit)
- Melaena (black tarry stools)
- Features of anaemia
- Postural hypotension
Assessment and management:
- Definitive: upper GI endoscopy (for both diagnosis and management)
- Perform Glasgow-Blatchford score (pre-endoscopy) and Rockall score (post-endoscopy)
- Offer post-endoscopy PPI if there are signs of recent or active bleeding at endoscopy (reduces risk of re-bleeding and need for surgery)
- See the Upper Gastrointestinal Bleeding article for more information
Perforated Peptic Ulcer
Clinically presents as GI perforation
- Diffuse peritonitis → sepsis
- Diffuse guarding and rigidity + percussion tenderness
Diagnosis: [Ref]
- An upright chest X-ray or abdominal X-ray may detect free air under the diaphragm (pneumoperitoneum)
- Gold standard: CT abdomen
Management: [Ref]
- Initial resuscitation
- Sepsis 6 (importantly, antibiotics and fluids)
- IV PPIs
- NBM and NG decompression
- Definitive: surgical management
- Most patients require surgery
- Standard management for small (<2 cm) perforation: simple closure +/- omental patch
- Tailored approach for large (≥ 2 cm) perforation (typically resection is necessary, esp. large gastric ulcers that raise the suspicion of malignancy)