Peptic Ulcer — Causes, Symptoms, Diagnosis & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Peptic ulcer disease (PUD) is a condition in which chronic ulcers — full-thickness mucosal defects penetrating through the muscularis mucosae — form in the mucosal lining of the stomach (gastric ulcer) or the first part of the small intestine (duodenal ulcer, the most common type — occurring 4x more frequently than gastric ulcers). The underlying mechanism is an imbalance between mucosal-damaging factors (hydrochloric acid, pepsin, Helicobacter pylori virulence factors, NSAIDs reducing prostaglandin-mediated mucosal defence) and mucosal-protective factors (mucus secretion, bicarbonate buffer, prostaglandin-mediated mucosal blood flow, rapid epithelial cell renewal). PUD has a lifetime prevalence of approximately 10% in Western populations and is declining in parallel with the decreasing prevalence of H. pylori infection following improved sanitation, antibiotic use, and eradication treatment. H. pylori infection is responsible for approximately 70% of duodenal ulcers and 50% of gastric ulcers. NSAID use (including low-dose aspirin) accounts for the majority of H. pylori-negative ulcers — particularly in elderly patients with cardiovascular or musculoskeletal disease on long-term anti-inflammatory therapy. Before the era of H. pylori discovery, PUD had a 70-80% recurrence rate, which has fallen to below 5% following eradication therapy — fundamentally altering its natural history and management.

Helicobacter pylori: a gram-negative, spiral-shaped bacterium colonising the gastric mucosa of approximately 50% of the global population (90%+ in low-income countries; 30-40% in high-income countries), transmitted via the faecal-oral route. H. pylori evades the hostile acid environment using urease to produce a locally alkaline ammonia cloud; it disrupts the mucosal barrier via vacuolating cytotoxin A (VacA) and the CagA pathogenicity island — triggering chronic active gastritis, which reduces somatostatin secretion, raises gastrin, and elevates acid output in duodenal ulcer disease. NSAIDs and aspirin: inhibition of COX-1-derived prostaglandins reduces gastric mucus secretion, bicarbonate production, and mucosal blood flow — the prostaglandin-mediated protective barrier — combined with direct topical epithelial injury from NSAID acidity. The combination of H. pylori infection and NSAID use is highly synergistic, elevating ulcer risk 17-fold compared to either alone. Risk factors: smoking (impairs mucosal prostaglandin synthesis, increases acid, and delays ulcer healing); alcohol (direct mucosal irritant); age above 65; prior PUD; corticosteroid use (minimal risk alone, synergistic with NSAIDs); and selective serotonin reuptake inhibitors (SSRIs — interfere with platelet aggregation, increasing GI bleeding risk). Less common causes: Zollinger-Ellison syndrome (gastrinoma in the duodenum or pancreas causing massive hypergastrinaemia and acid hypersecretion — multiple ulcers, severe GORD, diarrhoea, serum gastrin above 1000 pg/mL); stress ulcers (Curling's ulcer in burns, Cushing's ulcer in head injury) in critical illness.

Epigastric pain is the cardinal symptom — a gnawing, burning, aching, or cramping discomfort localised to the upper central abdomen, rated as moderate to severe in 30% but absent in a significant minority (particularly elderly patients and those on NSAIDs, who may present initially with bleeding or perforation). The classical pain pattern provides diagnostic clues: duodenal ulcer pain is characteristically postprandial (2-3 hours after meals — when food-stimulated acid secretion peaks with an empty duodenum), relieved by food and antacids (food and calcium buffer acid), and occurs at night waking the patient from sleep (circadian acid secretion peaks between 11pm and 2am); gastric ulcer pain tends to be precipitated or worsened by food rather than relieved by it. Nausea, vomiting, bloating, belching, early satiety, and anorexia are common accompanying symptoms; significant weight loss raises concern for underlying gastric malignancy. Many NSAID-related ulcers are asymptomatic ('silent ulcers') until a complication (bleeding, perforation) occurs — particularly in elderly patients whose pain perception is blunted and who may be taking analgesics masking pain. Alarming symptoms indicating complications: haematemesis (vomiting fresh red blood or coffee-ground material — upper GI bleeding from a bleeding ulcer); melaena (passage of black, tarry, foul-smelling stools — digested blood from an upper GI bleeding source, indicating bleeding above the ileocaecal valve); sudden severe, constant epigastric pain becoming generalised, associated with a rigid board-like abdomen and absent bowel sounds — perforation and peritonitis, requiring emergency surgery.

Upper gastrointestinal endoscopy (OGD — oesophagogastroduodenoscopy) is the gold standard diagnostic procedure: directly visualises the ulcer, characterises its appearance (benign vs malignant features: rolled edges, irregular base, friable tissue), obtains biopsies for histology, performs rapid urease test (CLO test) from antral and corpus biopsies for H. pylori detection, and crucially allows therapeutic intervention for bleeding ulcers (adrenaline injection, thermal coagulation, through-the-scope clips, or haemostatic powder). Biopsy of all gastric ulcers is mandatory to exclude gastric malignancy — 3-5% of gastric ulcers harbour early gastric cancer. H. pylori testing: urea breath test (UBT — 13C or 14C labelled urea test — the most accurate non-invasive test for active infection and the preferred method for confirming eradication; requires 2-week PPI washout before testing); stool antigen test (HpSA — monoclonal antibody-based test, accurate alternative to UBT); serology (IgG — detects past or current infection, cannot confirm eradication — poor specificity and only useful when other tests not available). Alarm features requiring urgent 2-week wait upper GI endoscopy: dysphagia, progressive weight loss, haematemesis, melaena, iron deficiency anaemia, persistent vomiting, and new dyspepsia in patients over 55 years. Blood tests: FBC (iron deficiency anaemia from chronic occult bleeding), CRP, liver function (exclude biliary pathology). Helicobacter pylori testing should be performed before endoscopy where possible using the UBT or stool antigen test, stopping PPI 2 weeks beforehand.

H. pylori eradication is the most important therapeutic goal in H. pylori-positive PUD — achieving cure in over 90% when successfully eradicated. Standard first-line 14-day bismuth quadruple therapy (BQDT — PPI [omeprazole 20mg BD] + bismuth subcitrate [120mg QDS] + metronidazole [400mg TDS] + tetracycline [500mg QDS]) is preferred as first-line globally given increasing clarithromycin resistance (above 15-20% in many countries); non-bismuth quadruple (concomitant) therapy: PPI + amoxicillin + clarithromycin + metronidazole simultaneously for 14 days. Clarithromycin triple therapy (PPI + amoxicillin + clarithromycin for 14 days) remains appropriate only where local clarithromycin resistance is confirmed below 15% and the patient has no prior macrolide exposure. Confirm eradication by urea breath test (13C-UBT) at least 4 weeks after completing antibiotics and 2 weeks after stopping PPIs — failure to confirm eradication misses treatment failures and recurrent ulcer risk. Second-line rescue therapy: levofloxacin-based triple therapy or rifabutin-based therapy guided by sensitivity testing from biopsy culture. Proton pump inhibitors (omeprazole 20-40mg BD, lansoprazole, pantoprazole, esomeprazole): heal peptic ulcers by profoundly suppressing gastric acid secretion; standard course is 4-8 weeks for duodenal ulcers and 8-12 weeks for gastric ulcers; use at full dose (BD) during concurrent H. pylori eradication. NSAID ulcers: stop the offending NSAID if possible; if continued essential, prescribe a PPI (omeprazole 20mg daily) for the entire duration of NSAID therapy; switch to COX-2 selective inhibitor (celecoxib, etoricoxib) with PPI in very high-risk patients; consider paracetamol as an alternative analgesic. Management of bleeding peptic ulcer (acute haemorrhage): immediate resuscitation with IV access, group and crossmatch, IV fluids/blood transfusion; urgent upper GI endoscopy (within 24 hours — or within 12 hours for haemodynamic instability); endoscopic haemostasis with combination therapy (adrenaline injection plus thermal coagulation or mechanical clip); high-dose IV omeprazole infusion (80mg bolus then 8mg/hour for 72 hours) after successful endoscopic haemostasis significantly reduces re-bleeding; repeat endoscopy at 72 hours for high-risk stigmata; interventional radiology (transcatheter arterial embolisation) or emergency surgery (gastroduodenotomy with oversewing of the bleeding vessel) for endoscopic failure or re-bleeding.

Upper gastrointestinal haemorrhage is the most common and serious complication of peptic ulcer disease — occurring in 15-20% of ulcer patients, causing haematemesis (vomiting bright red blood or 'coffee grounds' — digested blood), melaena (black tarry foul-smelling stools from digested blood), or chronic occult blood loss presenting as iron deficiency anaemia. The Rockall score (pre-endoscopy: age, shock, comorbidity; post-endoscopy: + diagnosis, stigmata of recent haemorrhage) stratifies 30-day re-bleeding and mortality risk; 30-day mortality from acute upper GI haemorrhage is approximately 10% overall, rising to 25-30% in elderly patients with haemodynamic compromise and high Rockall scores. Peptic ulcer perforation: occurs in approximately 5% of ulcer patients — predominantly men, anterior duodenal ulcers, NSAID users — causing sudden explosive abdominal pain with board-like rigidity; erect chest X-ray shows free subdiaphragmatic air in 70-80%; requires emergency laparoscopic or open surgical repair (Graham patch closure) within hours; mortality is 5-10% overall, rising substantially with delayed diagnosis. Gastric outlet obstruction from fibrosis and scarring at the pyloric channel: presents with early satiety, projectile non-bilious vomiting (food ingested hours previously), weight loss, and hypochloraemic hypokalaemic metabolic alkalosis from loss of hydrochloric acid (saline and potassium replacement needed); managed endoscopically (balloon dilatation) or surgically. Gastric cancer risk: chronic H. pylori infection (particularly cagA-positive strains) increases gastric cancer risk 2-4x through progression from atrophic gastritis to intestinal metaplasia (Correa cascade); H. pylori eradication reduces gastric cancer risk by 35-40% (meta-analyses).

Test and treat H. pylori in all patients commencing long-term NSAID or low-dose aspirin therapy — H. pylori eradication before NSAID initiation halves the subsequent GI ulcer complication risk. PPI gastroprotection (omeprazole 20mg daily or equivalent) co-prescribed throughout the duration of long-term NSAID use — mandatory for all patients over 65, those with prior peptic ulcer, and those on concurrent anticoagulants, corticosteroids, or SSRIs; reduces GI complication risk by 60-70%. Prescribe the lowest effective NSAID dose for the shortest necessary duration; paracetamol is the preferred first-line analgesic for musculoskeletal pain in high-GI-risk patients. Avoid smoking (delays ulcer healing, doubles recurrence risk) and excessive alcohol (direct mucosal irritant; synergistic with H. pylori and NSAIDs). Gastric ulcer surveillance: repeat upper GI endoscopy at 6-8 weeks after completing PPI therapy to confirm complete ulcer healing and obtain further biopsies from the ulcer site to exclude an underlying gastric cancer — mandatory for all gastric ulcers (duodenal ulcers do not require routine follow-up endoscopy in the absence of alarm features). H. pylori eradication is the single most important intervention for long-term ulcer prevention — reducing 1-year recurrence from 70-80% to below 5% (well-established from multiple RCTs).

Seek emergency care at A&E immediately for: vomiting blood (red blood or coffee-ground material — haematemesis), passing black tarry stools (melaena), sudden severe knife-like abdominal pain with a rigid board-like abdomen (perforation — peritonitis — requires emergency surgery within hours). Call 999 if you faint, are pale, or have a very rapid weak pulse alongside abdominal pain or bleeding — haemodynamic compromise from major GI haemorrhage is life-threatening. See your GP urgently (within 48 hours) for: persistent upper abdominal pain lasting more than 2-3 weeks not responding to antacids, epigastric pain occurring at night or relieved by food, or any unexplained iron deficiency anaemia in a man or post-menopausal woman (requires upper GI investigation to exclude a bleeding source). Alarm features warranting urgent 2-week wait gastroscopy referral include: any of the above plus dysphagia, progressive unintentional weight loss, persistent vomiting, new onset dyspepsia in a patient over 55, or family history of gastric cancer. Do not take NSAIDs for epigastric pain — they will worsen the underlying ulcer.