Author: Craig Walker, Rajesh Chatha / Editor: Janet Skinner, Frances Balmer / Codes: GC8, SLO1 / Published: 04/05/2022


  • The Nobel Prize for Medicine and Physiology was awarded to Warren and Marshall in 2005 for discovering and establishing the role of Campylobacter pyloridis (later renamed Helicobacter pylori) in peptic ulcer disease (PUD) in 1982 [1]. Their discovery changed the perception of PUD from being a primarily acid-driven entity to an infectious disease.
  • Antibiotic treatment of H. pylori and the widespread use of potent anti-secretory drugs means PUD is now less prevalent than it was two decades ago. The lifetime prevalence in the general population is currently estimated at 5-10%, with an incidence of 0.1-0.3% a year [2].
  • However, complications from PUD remain constant. An ageing population with multiple co-morbidities, and more frequently used ulcerogenic medication may be contributing to this [3].

Learning Bite

1 in 10 people in the UK will develop PUD at some stage in their lives.


A peptic ulcer is a peptic acid injury of the digestive tract resulting in a mucosal break greater than 3-5mm which reaches the submucosa [2].

Common sites:

  • Stomach
  • Proximal duodenum

Less common sites:

  • Lower oesophagus (e.g. a Cameron ulcer within a sliding hiatus hernia)
  • Distal duodenum
  • Ileum (e.g. Meckel’s diverticulum, ectopic gastric mucosa)

Learning Bite

Peptic ulcers result from peptic acid injury of the digestive tract.

Helicobacter Pylori

  • H. pylori is a gram-negative, motile, spiral-shaped bacterium.
  • The prevalence of H. pylori infection is decreasing.
  • Previous studies suggested that 90% of duodenal ulcers and 70% of gastric ulcers are associated with H. pylori infection. This is also thought to be falling [3].

H. pylori pathophysiology

  • H. pylori lives in the mucous layer above the gastric epithelial cells.
  • H. pylori multiplies optimally at a pH of 6.0 to 8.0. To survive in the acidic stomach, H. pylori produces a urease enzyme. This converts the urea produced by gastric epithelial cells into ammonia and bicarbonate, thereby buffering gastric acid and allowing survival.
  • In health, a low antral pH stimulates the release of somatostatin from D cells. This inhibits gastrin release from adjacent G cells, and so increases pH.
  • The ammonia produced by H. pylori prevents the D cells from sensing the true pH. The negative feedback loop is lost, causing ongoing inappropriate gastrin release and excess acid production.
  • H. pylori also impairs neural pathways which would otherwise down-regulate acid production.
  • H. pylori can only colonise gastric epithelial cells. However, excess acid secretion can provoke gastric metaplasia of duodenal cells, allowing colonisation.
  • Infected cells become more susceptible to erosion and ulceration [11].
  • In addition to acid hypersecretion, the immune response provoked by H. pylori impairs mucosal defences and can lead to ulceration through a complex interplay between epithelial-derived cytokines, neutrophils, macrophages, leukotrienes, and B- and T-lymphocytes.

Learning Bite

The urease enzyme produced by H. pylori allows its survival and leads to inappropriate gastrin release and excess acid production.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

  • NSAIDs cause 10% of peptic ulcers [5].
  • The annual risk of a life-threatening ulcer-related complication is 1-4% in patients who use NSAIDs long-term [8].
  • Ulcers and ulcer-related complications increase with older age, concurrent steroid or anticoagulant use, prior ulcer or bleeding, and in those with major organ impairment [8][13].
  • The use of NSAIDs in patients with active H. pylori infection increases the risk of PUD and of bleeding [20].

NSAID pathophysiology

  • NSAIDs cause mucosal injury through multiple mechanisms.
  • The most well-known of these is through inhibition of prostaglandin synthesis by inhibiting cyclo-oxygenase(COX)-1. This reduces mucous and bicarbonate secretion, reduces mucosal blood flow and impairs platelet aggregation, all of which reduce host defences to injury [14].
  • NSAIDs also exert a direct local toxic effect to gastric cells through a variety of mechanisms [14].

Learning Bite

NSAIDs cause mucosal damage through local and systemic mechanisms.

Gastric bypass surgery

A marginal ulcer is seen in approximately 5% of patients who have undergone gastric bypass surgery for obesity. The incidence can be as high as 27-36% in patients with upper gastrointestinal symptoms following upper GI Surgery [26,27].

Cigarette smoking

Cigarette smokers are twice as likely as non-smokers to develop PUD. Smoking increases gastric acid secretion and reflux, and decreases gastroduodenal prostaglandin production and pancreaticoduodenal bicarbonate production [13][19].

Medications and alcohol

Alcohol, steroids, potassium chloride, bisphosphonates, chemotherapy agents (e.g. 5-fluorouracil) and selective serotonin reuptake inhibitors (e.g. SSRIs) are all linked to PUD.

Zollinger-Ellison syndrome

A gastrin-secreting tumour can cause increased gastric acid secretion and parietal cell hyperplasia resulting in PUD.

Meckel’s diverticulum

Meckel’s diverticulum is the most common congenital abnormality of the small intestine. It is caused by incomplete obliteration of the vitelline duct. This can leave ectopic gastric mucosa present in the distal ileum and can lead to ulceration.


Other factors linked to the development of PUD include:

  • Neoplastic lesions – primary or secondary
  • Autoimmune diseases – e.g. vasculitis, sarcoidosis and Crohn’s disease
  • Viral infections – especially if immunocompromised
  • Radiation damage
  • Physiological Stress associated with trauma and critical illness
  • Psychological Stress – accommodation in a refugee shelter was a risk factor peptic ulcer disease after a large scale disaster [30]

Learning bite

At least 20% of cases are not linked to H. Pylori, aspirin or NSAID use [28].

Key points in the history

  • Symptoms of PUD are non-specific and have limited predictive value.
  • Elderly patients with PUD are frequently asymptomatic or have minor symptoms [6].
  • NSAID-induced ulcers are more likely to be asymptomatic [13].
  • Patients with gastric ulcers may have postprandial abdominal pain, nausea and weight loss.
  • Patients with duodenal ulcers typically feel hungry or have nocturnal abdominal pain.
  • Patients may present with complications such as bleeding, perforation or gastric outlet obstruction.
  • Patients should be specifically asked whether there has been a change in bowel habit, melaena or rectal bleeding, and whether there has been any coffee-ground or fresh haematemesis. Patients may not always volunteer such information due to fear or embarrassment.
  • Ask about features suggesting malignancy:
    • dysphagia
    • unintentional weight loss
    • persistent vomiting
    • epigastric mass
    • altered stools

Red-Flag Features

  • Signs of acute bleeding
    • Melaena
    • Haematemesis
    • Tachycardia or hypotension
    • Signs of severe anaemia
  • Signs of perforation
    • Severe abdominal pain
    • Peritonitis
  • Symptoms suggesting malignancy
    • New dyspepsia and > 60 years
    • Dysphagia
    • Unexplained weight loss
    • Loss of appetite
    • Recurrent vomiting
  • Symptoms persist despite successful eradication
  • Second line eradication therapy fails

Learning Bite

Patients with NSAID-induced ulcers are the most likely to have minimal preceding symptoms and present with complications.


  • Physical examination is poorly predictive in patients with PUD [4].
  • Pronounced tenderness on abdominal examination may suggest perforation or penetration.
  • A palpable mass may suggest malignancy.
  • Digital rectal examination may detect melaena.

Learning Bite

Physical examination is of limited value in predicting patients with PUD.

  • Baseline observations.
  • Urinalysis and ßhCG in all females of child-bearing age to exclude an ectopic pregnancy.
  • Bloods including FBC, U&Es, LFTs and amylase.
    • A low Hb (especially if microchromic microcytic anaemia) and raised urea may suggest bleeding.
    • LFTs may point to differential diagnoses including biliary colic, acute cholecystitis or acute pancreatitis.
  • Group & Save or cross-match if suspicion of gastrointestinal bleeding.
  • 12-lead ECG to exclude acute coronary syndromes.
  • Erect chest x-ray looking for pneumoperitoneum (air under the diaphragm) if perforation is suspected. This may also be appropriate if there are risk factors for malignancy.
  • Consider a bedside USS for older patients with epigastric pain radiating to the back to assess for abdominal aortic aneurysm.

Risk stratification

Risk stratify patients with PUD into one of the following groups:

  1. Life-threatening complications or haemodynamic instability requiring immediate resuscitation in the emergency department.
  2. Stable but requiring admission.
  3. Stable and can be safely discharged from the emergency department and managed on an outpatient basis. Arrange appropriate follow-up for those patients who are discharged.

Management Flow-Chart

Learning Bite

It is essential to assess for red flag features when assessing any patient with epigastric pain.

Management of complicated PUD


Patients who are haemodynamic unstable need urgent resuscitation and gastroenterology or surgical review.

  • Move to Resus area
  • Oxygen via 15L NRB mask
  • Insert 2 x large bore cannula
  • Take bloods including cross-match and coagulation screen
  • Consider intravenous fluids or blood products and regularly reassess
  • Catheterise to monitor input/output
  • Urgent referral to gastroenterology or surgical team.
  • Consider Critical Care


Bleeding peptic ulcers account for 40-60% of acute upper gastrointestinal bleeds (UGIB). UGIBs range from small bleeds in haemodynamically stable patients, to large exsanguinating bleeds that require urgent endoscopic treatment. 10% of patients will require urgent angiography and embolization or surgery for bleeding despite endoscopic intervention [32].

Clinical features

  • Haematemesis or coffee ground vomiting
  • Maleana
  • Postural hypotension or collapse
  • Anaemia
  • Raised urea

Initial Management of Unstable Upper Gastrointestinal Bleed

  • Resuscitation with crystalloid solution, aiming for a heart rate < 100 bpm and a systolic blood pressure > 100mmHg to avoid dislodging a developing clot.
  • Transfusion should be limited, with a target haemoglobin of > 70g/L (or > 90g/L in unstable coronary artery disease) as this is associated with reduced mortality [33].
  • Correct coagulopathy:
    • Transfuse platelets if actively bleeding and platelet count < 50 x 109/L. ◦ Fresh frozen plasma (FFP) if actively bleeding and INR > 1.5.
    • If fibrinogen remains < 1.5g/L despite FFP, offer cryoprecipitate.
    • If taking Warfarin and actively bleeding offer vitamin K and FFP or prothrombin complex concentrate (PCC) according to local policy.
    • If taking a DOAC and actively bleeding, discuss with Haematology and consider PCC. If taking Dabigatran, discuss the use of Idarucizumab.
  • Urgent endoscopy

The Halt-It trial showed tranexamic acid did not reduce mortality in patients with UGIB but recorded an increased incidence of venous thromboembolic events and seizures in the treatment group compared to controls [30].

Initial management of stable Upper Gastrointestinal Bleed

For stable patients several risk stratification tools are available to assess disease severity, risk of complications, and mortality. The most commonly used are:

  • Rockall score. A full Rockall score requires endoscopy findings, but a modified pre-endoscopy score can be used as a marker for severity in the UK. A pre-endoscopy Rockall score of 0 equates with a mortality of 0.2%, a score of 3 with a mortality of 11% and a score of 7 with a 50% mortality.
  • Glasgow-Blatchford score. The Glasgow-Blatchford score can be calculated in the emergency department and does not require endoscopy findings.
  • A Rockall or Glasgow-Blatchford score of 0 accurately identifies low-risk patients who can be managed on an out-patient basis.

Many stable patients with an UGIB will also be taking anti-platelet or anti-thrombotic medication. Current data on how best to manage these patients is limited and decisions often need to be tailored to individual patients, based on the severity of bleeding and the risk of thromboembolism. This may require discussion with Cardiology or Stroke Teams.

  • Continuing aspirin after an UGIB doubles the risk of recurrent bleeding
  • Patients receiving dual anti-platelet therapy for drug-eluting stent should avoid stopping both anti-platelet drugs even for a brief period due to the high risk of stent thrombosis

The use of intravenous proton pump inhibitors (PPIs) is common but controversial. Maintaining a neutral gastric pH seems to improve clot stability. There is some evidence that when PPIs are given before endoscopy, they reduce the need for treatment during endoscopy [2]. However, there is no evidence they improve mortality or re-bleeding rates, so NICE advises against giving PPIs before endoscopy. PPIs are recommended post-endoscopy [20].

Definitive management

Endoscopy within 24 hours provides prognostic information and effective therapy, usually by direct injection of adrenaline 1:10,000. If there are high-risk stigmata (i.e. blood in lumen or visible vessel), dual- or triple-therapy may be considered, which consists of adrenaline, mechanically clipping the vessel +/- heat application (either by heater probe, Argon plasma coagulator or multipolar probe). In a meta-analysis of randomised controlled trials, endoscopic treatment reduced re-bleeding, surgery and mortality. Endoscopy also identified low-risk patients suitable for early hospital discharge [2].

A full discussion of the assessment and management of UGIB is available on the RCEM Learning Session Upper Gastrointestinal Haemorrhage.

Learning Bite

Patients with upper gastrointestinal bleeding and haemodynamic instability require urgent resuscitation and endoscopy.

Learning Bite

Patients with upper gastrointestinal bleeding who are haemodynamically stable should be assessed using a risk stratification score.


Perforation occurs in 2-10% of patients with PUD [23]. It normally involves the anterior wall of the duodenum (60%) but may also affect the gastric antrum (20%) and lesser curvature (20%). Perforation and the resultant bacterial peritonitis have a mortality rate of 30-50% in older patients [4].

Clinical features:

  • Acute-onset, severe abdominal pain which rapidly worsens
  • Pain may radiate to the back or either shoulder
  • Generalised abdominal tenderness with guarding, rebound tenderness or rigidity with hypoactive bowel sounds
  • Tachycardia, hypotension, fever and oliguria

An erect chest x-ray may show free subdiaphragmatic air but can not rule out a perforation. If there is a strong clinical suspicion, further investigation with CT Abdomen is indicated.

Initial Management

  • Resuscitation as above
  • Broad-spectrum intravenous antibiotics (normally a 3rd generation cephalosporin and metronidazole or tazocin)

Definitive Management

  • Surgical intervention traditionally consists of laparotomy, placing an omental patch and washout of peritoneal contents.
  • Perforated gastric ulcers are treated with an omental patch, wedge resection of the ulcer, or a partial gastrectomy and re-anastomosis [4].
  • Laparoscopic repair is now becoming more common. One meta-analysis showed better outcomes compared to laparotomy [35].

Gastric Outlet Obstruction

PUD accounts for 5-8% of cases. Differentials include pyloric stenosis in paediatric populations, and neoplastic lesions (especially pancreatic malignancies) in older populations.

Clinical features:

  • Persistent large-volume vomiting containing undigested food
  • Dehydration
  • Distended, tympanic abdomen
  • There may be a palpable epigastric mass or visible peristalsis
  • Weight loss, lethargy, and malaise
  • There may be a hypochloraemic, hypokalaemic metabolic alkalosis

Initial Management

  • Resuscitation.
  • Chest x-ray and abdominal x-ray.
  • NG tube insertion and aspiration of gastric contents.

Definitive Management

  • Upper GI Endoscopy is performed to assess the site, severity and nature of the disease.
  • Surgical removal of the obstructive lesion may be possible.
  • Obstruction caused by inflammation and oedema due to PUD usually responds to H. pylori eradication and proton-pump inhibitors (PPIs).


Patients who are > 60 or with alarm features in the history should be discussed with gastroenterology and have inpatient or outpatient endoscopy within 2 weeks.

Management of uncomplicated PUD

In patients with uncomplicated dyspepsia and no red flag features, the initial approach is to offer lifestyle advice:

  • Stop NSAIDs
  • Decrease or stop smoking
  • Reduce or stop alcohol and illicit drug use
  • Weight reduction
  • Healthy eating advice

If this fails to resolve symptoms, the patient should be offered a four week trial of a proton pump inhibitor (PPI), or a H. pyloriTest and Treat” strategy as per NICE guidelines [20]. A trial of a H2-receptor antagonist (HRA) can be offered if there is inadequate response to a PPI.

PPI Full/Standard Dose

20mg once a day


30mg once a day


20mg once a day


40mg once a day


20mg once a day

“Test and Treat” involves a non-invasive H. pylori test, eradication of infection in those who test positive, and 4-8 weeks of PPI or HRA for those who test negative. The non-invasive “Test and Treat” strategy is as effective as endoscopy in the management of patients with uncomplicated dyspepsia who are less than 55 years old [20].

Endoscopy is indicated in patients whose symptoms do not resolve following 4-8 weeks of PPI or HRA or eradication therapy.

If symptoms subsequently return, NICE recommend continuing PPI therapy at the  lowest dose required to control symptoms [20].

Learning Bite

Patients who present with uncomplicated dyspepsia, should be given lifestyle advice and advised to attend their GP for further investigation. If symptoms are severe, a PPI or HRA may be prescribed in the interim, although this could delay H. Pylori testing.

H. Pylori Testing

Validated tests for H. pylori include:

  • 13C-urea breath test (CUBT)
  • Faecal antigen tests
  • Serum ELISA tests
  • Campylobactor-like organism (CLO) testing of biopsy specimens

CUBT and faecal antigen tests confirm active infection, so are also useful for confirming H. pylori eradication after treatment. Serum ELISA tests cannot distinguish between active and previous infection [4]. CLO testing can be performed on biopsies taken at endoscopy and give a result within 30 minutes.

CUBT should not be performed within two weeks of PPI therapy or four weeks of antibiotic therapy as false negative results may occur [18].

Learning Bite

CUBT and faecal antigen tests are the non-invasive tests of choice for active H. pylori infection.

H. pylori positive patients

Antibiotic choice is determined by regional sensitivities. Adherence can be an issue and patient education is key. NICE recommend the following H. pylori eradication regimes, twice-daily for seven days [20]:

Fine line If penicillin allergy  Penicillin allergy and previous Clarithromycin
Amoxicillin Clarithromycin Metronidazole
or Metronidazole
Metronidazole Tetracycline


Second line Penicillin allergy and no previous fluoroquinolone Penicillin allergy and previous fluoroquinolone use
Amoxicillin Metronidazole Metronidazole

Either Clarithromycin or Metronidazole (whichever was not used first line).


If previous exposure to Clarithromycin and Metronidazole, offer Tetracycline or Levofloxacin

Levofloxacin Tetracycline

H. pylori negative patients

Patients who test negative for H. pylori should be offered 4-8 weeks of a PPI or HRA.

If the patient is taking regular NSAIDs, these should be discontinued if possible. The much-publicised COX-2 inhibitors were developed in an attempt to increase gastrointestinal tolerance. COX-2 inhibitors reduce but do not eliminate ulcers or their complications [15], and multiple studies have shown they increase cardiovascular mortality. Many have been withdrawn from the market [16, 17, 18]. Some patients will require long term acid-suppression, especially those over 65 years of age, with a history of PUD, or taking other ulcerogenic medications including aspirin, steroids, SSRIs or anticoagulants.

If symptoms do not resolve after PPI or HRA, patients should be referred for endoscopy. Other therapies can be considered in the interim including prostaglandins (misoprostol), a PGE1 analogue which decreases cAMP generation in parietal cells and enhances mucosal defences.

There is no high-level evidence base for the treatment of marginal ulcers (ulcers occurring in patients who have undergone gastric bypass surgery); they are often difficult to treat.

Endoscopy in PUD


  1. Haemorrhage control in patients with upper GI bleeding.
  2. Confirmation of PUD in patients with persistent dyspepsia.
  3. Biopsy for confirmation of H. pylori infection and/or neoplasia.
  4. Reassessment in patients with ongoing symptoms despite H. pylori-eradication or withdrawal of NSAIDs.
  • NSAID-induced PUD is often asymptomatic until patients present with complications.
  • Failure to assess for red flag features in patients presenting with dyspepsia may result in delays in diagnosing malignancy or miss those with serious complications such as UGIB.
  • Signs and symptoms of UGIB may be subtle. A thorough history, examination including DRE and review of bloods is required.
  • Consider marginal ulcers as a possible cause of dyspepsia in patients who have undergone obesity surgery.
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