Peptic ulcer disease

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

The gastroduodenal mucosa normally resists acid through mucus, bicarbonate, epithelial integrity, blood flow and prostaglandin-dependent repair. H. pylori disrupts regulation and generates chronic inflammation; NSAIDs impair cyclo-oxygenase-dependent defence. These factors can coexist, making combined infection and NSAID exposure particularly important. Smoking slows healing, while physiological stress in critical illness and rare gastrinoma syndromes belong to different clinical contexts.

Uncomplicated ulcer may produce burning or gnawing epigastric pain, nausea and nocturnal symptoms, yet some ulcers are silent until they bleed. Dyspepsia is a low-specificity syndrome and should be separated from alarm features and from an acute abdomen. Endoscopy is indicated when cancer referral criteria, bleeding, recurrent vomiting, anaemia, diagnostic uncertainty or treatment failure changes the risk–benefit balance; non-invasive H. pylori testing is appropriate only when endoscopy is not otherwise needed.

Management removes the cause and allows mucosal healing. H. pylori-positive disease receives combination eradication; NSAID-related disease receives acid suppression and medicine modification. A gastric ulcer is followed to documented healing and adequate histology. Failure to heal should trigger a systematic check of adherence, ongoing NSAID use, persistent H. pylori, smoking, malignancy, Crohn's disease, infection in an immunocompromised host and acid hypersecretion rather than indefinite empirical PPI escalation.

Key points

Peptic ulcer is a mucosal break extending beyond the muscularis mucosae, most commonly driven by H. pylori infection or exposure to NSAIDs and aspirin.
Epigastric pain patterns around meals are not sufficiently accurate to distinguish gastric from duodenal ulcer or to exclude cancer.
Ask about prescribed and non-prescribed ibuprofen, naproxen, aspirin and combination remedies; corticosteroids, anticoagulants and antiplatelets amplify bleeding risk in combination.
Test for active H. pylori with valid preparation and eradicate confirmed infection using the current resistance-aware regimen, then demonstrate cure when an ulcer was present.
Stop the NSAID where possible; if it must continue after healing, reassess indication and dose and co-prescribe appropriate gastroprotection according to risk.
Gastric ulcers require adequate biopsy and planned repeat endoscopy, commonly at 6–8 weeks, because benign appearance and symptom improvement do not reliably exclude malignancy.
Duodenal ulcers are very rarely malignant, but persistent or recurrent disease still requires confirmation of eradication, medicine review and consideration of hypersecretory or inflammatory causes.
Major complications are upper-GI bleeding, free or contained perforation, penetration into an adjacent organ and chronic scarring that produces gastric outlet obstruction.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Helicobacter pylori

Chronic H. pylori gastritis alters acid regulation and mucosal defence, causing most non-NSAID duodenal and many gastric ulcers.

NSAIDs and aspirin

Cyclo-oxygenase inhibition reduces protective prostaglandins, mucus, bicarbonate and mucosal blood flow, with antithrombotics and corticosteroids amplifying bleeding risk.

Other mucosal stress

Smoking, severe physiological illness and uncommon hypersecretory states modify ulcer risk, while gastric ulcers warrant careful consideration of underlying malignancy.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Defence-acid imbalance
Reduced epithelial protection or excessive acid-pepsin exposure causes focal mucosal necrosis extending beyond the muscularis mucosae.
2
Deepening ulcer crater
Ongoing inflammation and digestion penetrate submucosa, exposing vessels and muscular or serosal layers as mucosal defence fails.
3
Healing or structural failure
Fibrotic repair may narrow the outlet, while uncontrolled depth causes arterial haemorrhage or free perforation into the peritoneum.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Uncomplicated epigastric syndrome

Localised upper abdominal discomfort, nausea or nocturnal pain may fit ulcer disease, but examination can be normal and the relationship to eating cannot determine site or histology.

Occult blood loss

Fatigue, exertional dyspnoea or iron-deficiency anaemia may reflect chronic ulcer bleeding. Search for an upper and lower GI cause as appropriate rather than attributing anaemia to dyspepsia alone.

Acute haemorrhageRed flag

Haematemesis, coffee-ground vomit, melaena, postural symptoms or shock requires acute upper-GI bleeding assessment. Bright rectal blood can occur with a brisk proximal bleed.

Perforation or penetrationRed flag

Abrupt severe pain with guarding suggests free perforation; pain radiating to the back or persistent focal pain may reflect posterior penetration. Both require urgent imaging and surgical review.

Outlet scarring

Early satiety, succussion splash, weight loss and recurrent non-bilious vomiting of stale food suggest pyloric or duodenal narrowing and commonly produce chloride, potassium and volume depletion.

Possible gastric cancer

Progressive weight loss, early satiety, persistent vomiting, dysphagia, a mass or unexplained anaemia changes the pathway. A gastric ulcer is a lesion requiring histology and healing confirmation, not a symptom label.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Upper-GI endoscopyFirst step
Why
Confirm ulcer site, describe bleeding stigmata and obtain appropriate tissue.
Interpretation and limitations
Document size, depth, location and surrounding mucosa. Biopsy gastric ulcers adequately unless immediate haemostasis makes this unsafe, with a defined early repeat plan; routine biopsy of a typical duodenal ulcer is not required for malignancy exclusion.
02
Active H. pylori testing
Why
Find a causal infection that changes recurrence risk and treatment.
Interpretation and limitations
Use biopsy testing during indicated endoscopy or a correctly prepared breath or stool antigen test. PPI, antibiotics, bismuth and acute bleeding can suppress detection, so a negative result may need repeating.
03
FBC and iron profile
Why
Detect acute or chronic blood loss and establish a replacement baseline.
Interpretation and limitations
A falling haemoglobin, microcytosis or low ferritin supports bleeding but does not locate it. Early haemoglobin can remain normal in acute haemorrhage before fluid redistribution.
04
Urea, electrolytes and creatinine
Why
Assess dehydration, renal safety and clues to upper-GI bleeding or obstruction.
Interpretation and limitations
A disproportionate urea rise can accompany digested blood. Vomiting can cause hypochloraemic, hypokalaemic metabolic alkalosis; renal impairment affects contrast, drug and resuscitation decisions.
05
Cross-sectional imaging
Why
Investigate perforation, penetration, obstruction or an alternative diagnosis.
Interpretation and limitations
Contrast CT is preferred for suspected perforation or complicated anatomy in a stable enough patient. Free air may be absent in a sealed leak; clinical peritonitis still requires urgent surgical judgement.
06
Fasting gastrin under specialist conditions
Why
Investigate a rare hypersecretory state when the phenotype is convincing.
Interpretation and limitations
Multiple, distal, recurrent or refractory ulcers with diarrhoea may suggest gastrinoma, but PPIs themselves raise gastrin. Stopping acid suppression can be dangerous and must follow a specialist protocol.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Functional dyspepsia

A compatible symptom pattern with no ulcer or other structural explanation supports functional disease; meal timing alone cannot distinguish it.

Gastric cancer

Weight loss, anaemia, irregular margins or non-healing gastric ulcer requires multiple biopsies and documented reassessment to exclude malignancy.

Biliary or pancreatic disease

Right-upper-quadrant attacks, jaundice, back-radiating pain or abnormal pancreatic and biliary imaging suggests a non-peptic source of symptoms.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01HealTreat an uncomplicated ulcerFirst stepEndoscopy demonstrates a peptic ulcer without active major bleeding, perforation or fixed outlet obstruction.

1Identify active H. pylori and every ulcerogenic medicine, including over-the-counter NSAIDs, low-dose aspirin, steroids, anticoagulants and antiplatelets, then assess tobacco exposure and cancer features.
2Eradicate confirmed H. pylori and prescribe a defined acid-suppression course appropriate to ulcer site and cause; discontinue the offending NSAID where clinically possible.
3Arrange proof of eradication and, for a gastric ulcer, repeat endoscopy at the planned healing interval with review of biopsy adequacy and any residual lesion.

02ProtectManage unavoidable NSAID exposureThe patient has healed ulcer disease but still has a compelling anti-inflammatory or antithrombotic indication.

1Discuss whether the medicine can be stopped, substituted or reduced, involving cardiology or another prescriber before withdrawing aspirin used for secondary cardiovascular prevention.
2Use the lowest effective NSAID strategy and co-prescribe a current formulary gastroprotective option according to age, ulcer history, interacting medicines and renal or cardiovascular risk.
3Educate about hidden non-prescription products and urgent bleeding symptoms, then review continued need rather than allowing gastroprotection to legitimise indefinite high-risk exposure.

03ReconsiderInvestigate non-healing diseaseSymptoms, ulceration or anaemia persist despite an apparently adequate initial course.

1Check adherence, actual PPI administration, continued NSAID or smoking exposure and whether H. pylori testing or test-of-cure occurred under valid conditions.
2Repeat high-quality endoscopy with adequate gastric sampling and review pathology for cancer, lymphoma, Crohn's disease, cytomegalovirus or another unusual cause where the context supports it.
3Seek specialist evaluation before altering PPI around gastrin testing or pursuing rare hypersecretory syndromes, and manage any complication through its dedicated pathway.

Key medicines and prescribing safety2 treatments · regimens, roles and cautions

Suppresses acid to permit gastric or duodenal mucosal healing and provides gastroprotection when ulcerogenic treatment must continue.

Proton-pump inhibitor for ulcer healing

A licensed example is omeprazole 20 mg once daily for 4–8 weeks; NICE uses a full-dose PPI for eight weeks in NSAID-associated ulcer, with product and duration adjusted to cause and response.

Use a named formulary product and review long-term need. Check interactions, renal and hepatic context, magnesium and B12 risk when prolonged, enteric infection risk and rebound symptoms; PPI use can invalidate H. pylori testing.

Removes the principal infectious cause of ulcer recurrence and should accompany an ulcer-healing and test-of-cure plan.

H. pylori eradication treatment when infection is confirmed

Use the current seven-day NICE and local antimicrobial combination, selected for penicillin allergy and previous antibiotic exposure; do not copy a historical regimen without checking current strengths and resistance advice.

Reconcile the full combination, pregnancy, allergy, QT and CYP interactions, renal and liver function and previous macrolide, nitroimidazole or fluoroquinolone use. Persistent symptoms alone do not justify repeated antibiotics.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Upper-GI haemorrhage

Arterial erosion causes haematemesis or melaena, shock and rebleeding risk, while chronic oozing produces iron-deficiency anaemia.

Perforation

Full-thickness penetration releases gastroduodenal contents into the peritoneum, causing abrupt pain, sepsis and urgent source-control need.

Gastric outlet obstruction

Acute oedema or chronic pyloroduodenal scarring retains food, causing vomiting, dehydration, alkalosis and nutritional decline from retained contents.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Review pain, oral intake, weight, vomiting and any overt or occult bleeding during the planned healing interval.
Repeat FBC and iron indices when anaemia or bleeding was present, while investigating another source if recovery is incomplete.
Document active-infection cure after H. pylori-associated ulcer using a valid breath or stool test with appropriate medicine washout.
Ensure every gastric ulcer has a named owner for histology review and repeat endoscopy, usually 6–8 weeks after treatment begins according to size.
For continued NSAID, aspirin, anticoagulant or antiplatelet therapy, reassess indication, dose, interactions and gastroprotection at each relevant review.
Escalate non-healing, recurrent, multiple or distal ulceration for diagnostic reassessment rather than continuing unexamined acid suppression.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Pain timing is weak

The traditional meal relationship of gastric and duodenal pain is insufficiently reliable for site diagnosis; investigation and causal assessment matter more.

Two causes can coexist

Finding H. pylori does not make regular ibuprofen irrelevant, and identifying NSAID exposure does not remove the need to seek infection.

Haemoglobin can lag

Acute whole-blood loss initially removes plasma and cells together, so the first concentration may look deceptively preserved despite shock.

Gastric means recheck

Repeat examination of a gastric ulcer verifies healing and revisits sampling because infiltrative cancer can initially mimic benign inflammation.

Gastrin needs planning

PPI withdrawal before gastrin assessment can provoke dangerous acid rebound in genuine hypersecretion, so this is not a casual primary-care test.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing ulcer site from whether food relieves or worsens the pain.
02
Failing to ask about over-the-counter NSAIDs and combination cold or analgesic products.
03
Assuming a gastric ulcer is benign because its edges look smooth at the first endoscopy.
04
Stopping secondary-prevention aspirin without weighing cardiovascular harm or involving the responsible team.
05
Using a negative H. pylori test obtained during PPI treatment as definitive exclusion.
06
Ordering fasting gastrin while continuing a PPI and interpreting the predictable elevation as gastrinoma.