Part of the TeachMe Series

Peptic Ulcer Disease

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Original Author(s): Michael John
Last updated: October 6, 2019
Revisions: 50

Original Author(s): Michael John
Last updated: October 6, 2019
Revisions: 50

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peptic ulcer is a break in the lining of the gastointestinal tract, extending through to the muscular layer (muscularis mucosae) of the bowel wall.

Figure 1 – The greater and lesser curvatures of the stomach

Whilst they may technically appear anywhere in the gastrointestinal tract, they are most often located on the lesser curvature of the proximal stomach or the first part of the duodenum.

The incidence of peptic ulcers is estimated to be around 0.1-0.2% of the population per annum, with duodenal ulcers typically presenting earlier than gastric ulcers by around 20 years.

In this article, we shall look at the clinical features, investigations and management of peptic ulcer disease.


The normal gastrointestinal mucosa is protected by numerous defensive mechanisms, such as surface mucous secretion and HCO3- ion release. Ulceration occurs when there is an overwhelming presence of a noxious substance or when these natural barriers are impaired.

Most commonly, this is through the presence of Helicobacter pylori (H. pylori) or Non-Steroidal Anti-Inflammatory Drug* (NSAID) use, however less common causes include high alcohol intake, steroid use, foreign body ingestion e.g batteries, or Zollinger-Ellison syndrome (rare).

*NSAIDs can cause peptic ulcer formation by their action in inhibiting prostaglandin synthesis. This results in a reduced secretion of glycoprotein, mucous, and phospholipids by the gastric epithelial cells, which would otherwise normally contribute to the barrier protecting the gastric mucosa.

Helicobacter Pylori

H. pylori is a Gram negative spiral-shaped bacillus, found in the mucous layer of those with duodenal ulcers (90%) or gastric ulcers (70%). It survives in the stomach by producing an alkaline micro-environment and induces an inflammatory response in the mucosa, leading to eventual ulceration, by:

  • Invoking an cytokine and interleukin-driven inflammatory response
  • Increasing gastric acid secretion in both the acute and chronic phases of infection, by inducing the release of histamine which acts on parietal cells
  • Damaging host mucous secretion by degrading surface glycoproteins and down-regulating bicarbonate production

Risk Factors

The two main risk factors for peptic ulcers are H. pylori infection and prolonged NSAID use. Other risk factors include alcohol excess, smoking, chemotherapy or radiotherapy, and steroid use.

Clinical Features

Up to 70% of peptic ulcers are asymptomatic, however the main symptoms symptomatic patients typically present with are discussed below.

Less commonly, patients may present with complications of their peptic ulcer disease, such as bleeding, perforation, or gastric outlet obstruction.

The ALARMS mnemonic (Anaemia / Lost weight / Anorexia / Recent rapid onset / Melaena / Swallowing difficulties) has historically been used as a basis for referral for urgent endoscopy to assess for any malignancy.

However NICE guidelines now suggest that a referral for urgent OGD should be done for patients presenting with either:

  • New-onset dysphagia
  • Aged >55 years with weight loss and either upper abdominal pain, reflux, or dyspepsia
  • New onset dyspepsia not responding to PPI treatment

Gastric Ulcer

  • Epigastric pain, typically exacerbated by eating
  • Nausea and anorexia
  • Weight loss, secondary to the anorexia

Duodenal Ulcer

  • Epigastric pain
    • Worse around 2-5 hours after consuming after a meal
    • Often can be alleviated by eating

Differential Diagnoses

Any condition that causes dyspepsia, chest pain, or epigastric pain can be considered a differential for peptic ulcer disease. However, those most important to rule out include gastric malignancy, pancreatitis, acute coronary syndrome, gastro-oesphageal reflux, and gallstone disease.

Zollinger-Ellison Syndrome

Zollinger-Ellison Syndrome refers to a triad of (i) severe peptic ulcer disease (ii) gastric acid hypersecretion and (iii) gastrinoma. The characteristic finding is a fasting gastrin level of >1000 pg/ml.

A third of these cases are discovered as part of Multiple Endocrine Neoplasia Type 1 syndrome (Pancreas / Pituitary / Parathyroid tumours), so further investigations for MEN syndrome are often warranted.


Patients with any red-flag symptoms should be referred for upper GI endoscopy (OGD).

An OGD that identifies peptic ulceration (Fig. 2) will also allow for biopsies to be taken, which will be sent for histology and rapid urease “CLO” test (histological test used for determining presence of H. pylori). A full blood count may be warranted to assess for anaemia present.

For those patients who do not need an OGD but are not responding to initial conservative management (as discussed below), non-invasive H. pylori testing* is required, which will be either as:

  • Carbon-13 urea breath test
  • Serum antibodies to H. pylori
  • Stool antigen test

*Importantly, prior to any H. pylori test, patients should stop any current medical therapy for 2 weeks prior to investigation to reduce the risk of false negatives; once H. pylori is identified, no further investigations are warranted prior to starting eradication therapy

Fig 2 - Features of peptic ulcers on endoscopy (A) peptic ulcer located in the gastric antrum (B) haemorrhaging gastric ulcer

Figure 2 – Features of peptic ulcers on OGD (A) peptic ulcer located in the gastric antrum (B) haemorrhaging gastric ulcer



Any patient with dyspepsia should be given lifestyle advice to reduce symptoms, such as smoking cessationweight loss, and reduction in alcohol consumption. There should also be an avoidance/cessation of NSAIDs where possible.

Any patient who fails initial conservative management and has a negative H. pylori testing can be started on a Proton Pump Inhibitor (such as omeprazole or lansoprazole) for 8 weeks to reduce acid production. Those patients with a positive H. pylori test should be started on triple therapy*.

NICE guidance recommends gastric ulcers to be biopsied at presentation due to malignant potential and a repeat endoscopy performed towards the end of PPI therapy to check for resolution. Persistence of symptoms post-PPI therapy should lead the clinician to suspect failure of H. pylori eradication, malignancy, or rare causes such as Zollinger-Ellison Syndrome.

*Any patient with positive H. pylori testing requires eradication therapy (also termed triple therapy), which commonly consists of a PPI with oral amoxicllin and clarithromycin or metronidazole for 7 days.

Fig 3 - Suggested initial investigation and treatment algorithm for dyspepsia

Figure 3 – Algorithm for suggested initial investigation and treatment for dyspepsia

Surgical Management

Surgery for peptic ulcer disease is rare, except in emergencies (such as perforation) or in the management of Zollinger-Ellison Syndrome. However, in severe or relapsing disease, either partial gastrectomy or selective vagotomy may be considered


The main complications of peptic ulcer disease are perforation, haemorrhage, and pyloric stenosis (rare).

Key Points

  • H. pylori and NSAIDs are the most common causes for peptic ulcer disease
  • Conservative management, through lifestyle changes and PPI therapy, is the mainstay of treatment in most cases
  • Any patient with red-flag symptoms or not responding to conservative management should be referred for urgent upper GI endscopy
  • Surgical management of uncomplicated peptic ulcer disease is rare