A peptic ulcer is a break in the lining of the gastrointestinal tract, extending through to the muscular layer (muscularis mucosae) of the bowel wall. It is an endoscopic diagnosis.
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 (in Western countries). Duodenal ulcers classically present 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.
Peptic ulcer disease occurs when there is an imbalance between factors that protect the mucosa of the stomach and duodenum, and factors that cause damage to it.
Most commonly, this is through the presence of Helicobacter pylori (H. pylori) or Non-Steroidal Anti-Inflammatory Drug* (NSAID) use.
*NSAIDs can cause peptic ulcer formation by their action in inhibiting prostaglandin synthesis, resulting in a reduced secretion of glycoprotein, mucous, and phospholipids by the gastric epithelial cells, which would otherwise normally protect the gastric mucosa
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
The two main risk factors for peptic ulcers are H. pylori infection and prolonged NSAID use. Other risk factors include corticosteroid use (when used with NSAIDs), previous gastric bypass surgery, physiological stress (such as severe burns (Curling’s ulcer) or head trauma (Cushing’s ulcer)), or Zollinger-Ellison syndrome (rare).
Up to 70% of peptic ulcers can be asymptomatic. For symptomatic patients, peptic ulcers can present with epigastric or retrosternal pain*, nausea, bloating, post-prandial discomfort, or early satiety.
Less commonly, patients may present with complications of their peptic ulcer disease, such as bleeding, perforation, or gastric outlet obstruction.
NICE guidelines suggest that a referral for urgent upper Oesophago-Gastro-Duodenoscopy (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
*Classically, any pain from a gastric ulcer is exacerbated by eating, whilst duodenal ulcers are worse 2-4 hours after eating or even alleviated by eating
Any condition that causes dyspepsia, chest pain, or epigastric pain can be considered a differential for peptic ulcer disease.
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.
Many patients may not require an OGD initially and can be treated empirically initially. A full blood count may be warranted however to assess for any potential anaemia.
Most patients, especially younger patients, should undergo non-invasive H. pylori testing*, which will be either as:
- Carbon-13 urea breath test
- Serum antibodies to H. pylori
- Stool antigen test
In older patients, those with red flag symptoms, or those with ongoing symptoms despite empirical treatment, an OGD is required.
At endoscopy, any peptic ulceration seen (Fig. 2) can be biopsied, which will be sent for histology (if looks suspicious for malignancy) and for rapid urease test (the CLO test, giving an rapid result for determining presence of H. pylori).
NICE guidance recommends that all identified gastric ulcers are biopsied, due to malignant potential, and that a repeat endoscopy is performed towards the end of PPI therapy to check for resolution.
*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
Any patient with suspected or confirmed peptic ulcer disease should be given lifestyle advice to reduce symptoms, such as smoking cessation, weight loss, and reduction in alcohol consumption. There should also be an avoidance / cessation of NSAIDs where possible.
Patients with suspected or confirmed ulcers can be started on a Proton Pump Inhibitor for 4-8 weeks to reduce acid production. They should be reassessed after this period for resolution of symptoms (“Test and Treat”). Those patients with a positive H. pylori test should be started on triple therapy*.
Persistence of symptoms post-PPI +/- eradication therapy warrants further work-up, with first line being an urgent OGD to exclude any malignancy. Following this, other causes of treatment failure can be considered, such as failure of H. pylori eradication or 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.
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
- 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