Peptic ulcer disease (PUD) is an umbrella term for the development of two different ulcers: gastric ulcers and duodenal ulcers.
PUD is a relatively common condition that frequently presents with dyspepsia, abdominal discomfort and nausea. It can be complicated by perforation, haemorrhage and gastric outlet obstruction.
It is important to understand the difference between ulcers and erosions:
The most commonly identified aetiological factors are H.pylori infection and NSAID use. Upper GI endoscopy is used for diagnosis whilst management consists of H.pylori eradication therapy (when indicated), proton-pump inhibitors and lifestyle and risk-factor modification.
There is an estimated lifetime prevalence of 5-10%.
The annual incidence is thought to be around 0.1-0.3%. The epidemiological pattern varies based on the affected location:
The majority of peptic ulcers are related to H.pylori infection.
H.pylori is by far the most commonly implicated aetiological factor associated with approximately 95% of duodenal ulcers and 70-80% of gastric ulcers. Medications may predispose to PUD with NSAIDS the most important agents. Others include corticosteroids, bisphosphonates and SSRI's.
Smoking and alcohol are commonly discussed although their role is disputed. Ulcers may be seen following major physiological stressors - classically patients with significant burns.
Below we discuss some of the most important aetiological factors in more detail.
H. pylori is a gram negative spiral-shaped, flagellated, micro-aerophilic bacterium, which is thought to colonise up to 50% of the world’s population.
The infection is more common in the developing world and usually acquired during childhood. It is estimated that up to 95% of patients with PUD are infected with H. pylori, yet only 15% of patients with H. pylori will develop PUD. H. pylori predominantly colonise the antrum of the stomach, which is the least acidic. Colonisation of the gastric antrum can lead to persistent low-grade inflammation.
This may damage the epithelial lining leading to the destruction of the normal gastric mucosal barrier. This promotes the development of ulcerations and other complications (e.g. upper GI bleeding, malignancy, gastritis, gastric outlet obstruction).
The enzymes it produces, ability to adhere and virulence factors are key to their ability to cause gastritis and PUD:
H. pylori has been associated with a number of GI malignancies. The exact pathogenesis are yet to be understood but as many individuals will have H. pylori without any malignancy developing, individual pre-disposing factors are key. The infection has been associated with:
NSAIDS inhibition of COX-1 reduces the production of mucosal protective prostaglandins.
NSAIDs are a common cause of GI disturbance (e.g. PUD, gastritis) through their inhibition of cyclooxygenase-1 (COX-1). Most NSAIDs are non-selective inhibitors of cyclooxygenase (i.e. both COX-1 and COX-2) which are both important enzymes:
It is suspected that 50% of patients taking NSAIDs show mucosal damage, 30% of patients have ulcers seen on endoscopy and 5% of patients are symptomatic.
Some newer NSAIDs (e.g. Celecoxib) have been developed that selectively target COX-2. These drugs may be taken in rheumatic disease to help reduce the number of GI side-effects. However use is limited owing to the increased risk of cardiovascular complications.
Zollinger-Ellison syndrome occurs secondary to a hyper-secreting gastrinoma within the pancreas.
Hypergastrinaemia leads to the development of multiple peptic ulcers. Sporadic cases account for around 80% of cases of Zollinger-Ellison syndrome.
Approximately, 20% are part of multiple endocrine neoplasia type I (see notes on MEN syndromes).
The hallmark features of PUD are epigastric pain, dyspepsia and heartburn.
Patients with PUD may present acutely with features of an acute upper GI bleed (UGIB) or perforation.
Gastric outlet obstruction may occur in PUD secondary to stricturing and narrowing resulting from inflammation, ulcers and scarring.
Patients present with nausea, vomiting and typically upper abdominal pain. Tenderness, distention and a succussion splash may be found on examination.
The definitive diagnosis of PUD is made on endoscopic examination. However, only a small number of patients presenting with dyspepsia/heartburn require upper GI endoscopy.
H. pylori testing may be non-invasive or invasive.
Non-invasive tests offer good sensitivity and specificity when used in the correct setting. Invasive testing may be completed during an upper GI endoscopy.
13C Urea breath test: Is a useful screening test for the presence of H. pylori. The subject ingests 13C urea, which is converted to 13CO2 in the presence of urease. It is a highly sensitive 97.6% and specific (96%) test. The breath test can be used for both diagnosis and testing for eradication. Importantly, patients must be off PPI’s prior to testing.
Serological test: A blood test is taken which checks IgG antibodies against H. pylori. This is a useful test for diagnosis and epidemiological studies. In general, it is a good test (sensitivity 90% and specificity of 83%). However, it cannot be used to check for eradication owing to the persistence of antibodies within the serum.
Stool antigen test: The stool test assesses the faeces for the presence of H. pylori antigen. It is a reliable test (sensitivity 97.6% and specificity 96%), and can be used for both diagnosis and testing for the eradication of H. pylori. Like the breath test, patients must be off PPI's prior to testing.
Urease test: The urease test is also known as the CLO test (campylobacter-like organism test). Biopsies are taken from the mucosa during endoscopy and added to a medium containing phenol red and urea. The presence of urease leads to the splitting of urea, and the release of ammonium that leads to a pH colour change. The test may be falsely negative in the presence of PPI therapy.
Histology: A section of a biopsy taken during endoscopy can be examined under a microscope with a Giemsa stain looking for the organism.
Culture: A biopsy specimen taken at the time of endoscopy can be used for culture of the organism. This test is useful for assessment of antibiotic sensitivities.
Management of PUD involves lifestyle modifications, PPIs and antibiotics.
Patients who test positive for H. pylori should be offered eradication therapy. The length of treatment (and need for specialist intervention) is dependent on H. pylori status, NSAID involvement and symptomatic control.
Lifestyle modifications are key to the management of PUD. Patients should maintain a healthy diet avoiding foods and drinks that exacerbate their symptoms.
For details of H.pylori eradication therapies see the chapter below.
Patients who test negative for H.pylori are given 4-8 weeks of full-dose PPI.
Due to the possibility of underlying malignancy, gastric ulcers should be biopsied and reassessed after treatment. This means a follow-up endoscopy to ensure healing in 6-8 weeks. Duodenal ulcers do not not routinely require follow-up endoscopy.
H. pylori eradication therapy needs to take into account previous antibiotic therapy and patient allergies.
Patients are given a 7-day course of triple-therapy, which includes a PPI and dual antibiotic therapy.
If 1st line therapy fails patients are given a different antibiotics and an extended course. The choice of pharmacotherapy is dependent on allergy status and previous antibiotic exposure.
Specialist referral is warranted in patients with disease that has not responded to second-line therapy or with unexplained symptoms.
Peptic ulcer disease may be complicated by perforation, haemorrhage and gastric outlet obstruction.
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