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The GI battlefield  

Although the number of people with peptic ulcer disease has fallen in recent years, it can have potentially serious complications if left untreated, as Steve Titmarsh explains…
 


Peptic ulcer disease is a term that encompasses both gastric and duodenal ulcers. Around 13 per cent of people with dyspepsia, which describes a range of upper gastrointestinal tract symptoms often referred to by patients as indigestion, have an ulcer.1

In the past, ten times as many men as women suffered from duodenal ulcer, while gastric ulcer was seen in around three men for every two women. Nowadays the frequency in men and women is similar.1

The prevalence of peptic ulcer disease is decreasing in western countries, possibly due to a fall in peptic ulcer disease associated with Helicobacter pylori infection. Annual incidence is estimated to range from 0.10 to 0.19 per cent based on physician-diagnosed peptic ulcer disease and from 0.03 to 0.17 per cent based on hospital data.2

Casus belli
Peptic ulcers develop when gastric acid and pepsin damage the mechanisms, such as mucus and bicarbonate secretion, which protect the gastrointestinal mucosa.2

Peptic ulcers mainly occur in the stomach where they are called gastric ulcers, or in the proximal duodenum, known as duodenal ulcers. They are defined as a break in the mucosal lining of the stomach or duodenum larger than 5mm that penetrates down to the submucosa,3 confirmed by endoscopy.4

Originally H. pylori infection was discovered to be the main cause of peptic ulcer disease, but as the prevalence of H. pylori infection has fallen in western countries non-steroidal anti-inflammatory drugs (NSAID) and acetylsalicylic acid use has become the main cause of gastric ulcers.2 Alcohol, smoking and stress have also been associated with peptic ulcer disease.5

Peptic ulcer disease brings with it the risk of developing complications such as gastroduodenal haemorrhage, perforation and obstruction, which in turn are associated with a high mortality risk. The risk of complications is higher among older people, those with comorbidities and people taking drugs such as NSAIDs. About 1 in 10 people with a bleeding peptic ulcer will die, as will around a quarter of people with a perforated peptic ulcer.4
Patients at high risk of developing gastrointestinal complications with an NSAID include those with a history of complicated peptic ulcer, or those with more than two of the following risk factors:6


•      Over 65 years of age
•      Taking high-dose NSAIDs
•      Taking other drugs that increase the risk of gastrointestinal adverse effects (eg anticoagulants, corticosteroids, selective serotonin reuptake inhibitors)
•      Serious comorbidity (eg cardiovascular disease, hypertension, diabetes, renal or hepatic impairment)
•      Heavy smoker
•      Excessive alcohol consumption
•      Previous adverse reaction to NSAIDs
•      Needing to take NSAIDs for a prolonged time.


The symptoms
Symptoms of peptic ulcer disease are typically present for four or more weeks.4 They vary and can include:1,7
•      Upper abdominal pain or discomfort
•      Nausea, vomiting
•      Feeling full after eating
•      Heartburn occasionally although it is more typically associated with gastro-oesophageal reflux


When to refer…
Patients whose symptoms persist despite treatment should see their doctor. Those experiencing weight loss or sudden sharp pain that becomes worse should be referred for immediate medical attention. Bleeding or perforation with complicated disease is a medical emergency that needs immediate treatment.8

Gastric ulcer symptoms are inconsistent – eating can sometimes make pain worse rather than relieve it. Pain associated with a duodenal ulcer tends to be more consistent, perhaps starting mid-morning, relieved by food but then returning two to three hours later. If a patient wakes in the night with pain that suggests they have a duodenal ulcer.9

Treatment
Peptic and duodenal ulcer can be treated with acid-suppressing drugs - eight weeks’ treatment with full dose proton pump inhibitors (PPI) or H2 receptor agonists. H. pylori eradication can be offered to people who test positive for the bacterium.
Lifestyle changes can also help manage the condition, such as stopping smoking, reducing alcohol consumption, losing weight if appropriate, and eating healthily.10

Long-term regular use of antacids and/or alginates should be discouraged.6 People taking NSAIDs should stop doing so if possible. If not, their use should be reviewed at least six-monthly. ‘As needed’ usage could be tried or a lower dosage. Switching to paracetamol, low-dose ibuprofen or an alternative analgesic could be considered. People who have had an ulcer before, and are therefore considered high risk, should be considered for a cyclo-oxygenase (COX)-2-selective NSAID rather than a standard NSAID.10
 
H. pylori testing and eradication
A carbon-13 urea breath test or stool antigen test can be offered to test for H pylori. Another option is laboratory-based serology if the lab’s performance has been locally validated.10

Only carbon-13 urea breath testing is recommended for re-testing as there is not enough evidence to support the use of the stool antigen test.10 There should be a two-week washout period after taking PPIs before a test for H. pylori is done.10

For people who test positive for H. pylori first-line eradication treatment is a seven-day course of twice daily PPI and amoxicillin, and either clarithromycin or metronidazole. People who are allergic to penicillin can be offered a PPI and clarithromycin and metronidazole.

Those who are allergic to penicillin and who have taken clarithromycin previously should be offered a seven-day course of a PPI and bismuth and metronidazole and tetracycline.10 Treatment adherence is paramount and should be discussed with patients. If the treatment does not work a second-line option should be offered, such as a PPI and amoxicillin, and either clarithromycin or metronidazole (whichever was not used the first time). For those who previously took clarithromycin and metronidazole, offer seven days’ treatment with a PPI and amoxicillin and tetracycline (or levofloxacin if tetracycline cannot be used).

Those who are allergic to penicillin and have not been treated with a fluoroquinolone antibiotic before should be offered a seven-day twice daily course of a PPI and metronidazole and levofloxacin. Individuals allergic to penicillin who have received a fluoroquinolone antibiotic before should receive a seven-day course of a PPI and bismuth and metronidazole and tetracycline.10

If H. pylori infection persists after second-line therapy patients should be referred to a gastroenterologist.10 For people in whom H. pylori has been eradicated there is 5 per cent lifetime risk of recurrence of ulcers. However, that risk level rises to 60 per cent for gastric ulcers and 80 per cent for duodenal ulcers if they remain H. pyloripositive.4
 

References

1. patient.info. Peptic ulcer disease (https://patient.info/doctor/peptic-ulcer-disease; accessed 5 November 2021).
2. Sung JJ, Kuipers EJ, El-Serag HB. Systematic review: the global incidence and prevalence of peptic ulcer disease. Aliment Pharmacol Ther 2009;29(9):938–46.
3. BMJ Best Practice. Peptic ulcer disease (https://bestpractice.bmj.com/topics/en-gb/3000205?utm_source=Google&utm_medium=cpc&utm_campaign=usage&utm_term=inst_hee&gclid=Cj0KCQjw5oiMBhDtARIsAJi0qk0gUUVX9i_zNGRg1fQOy8v0lR0CTCE-kCFHeSi6GWUR1GbNEjG7sN4aAqpOEALw_wcB; accessed 5 November 2021).
4. Clinical Knowledge Summaries. Dyspepsia – proven peptic ulcer (https://cks.nice.org.uk/topics/dyspepsia-proven-peptic-ulcer; accessed 5 November 2021).
5. Prabhu V, Shivani A. An overview of history, pathogenesis and treatment of perforated peptic ulcer disease with evaluation of prognostic scoring in adults. Ann Med Health Sci Res 2014;4(1):22–9.
6. British National Formulary. Peptic ulcer disease (https://bnf.nice.org.uk/treatment-summary/peptic-ulcer-disease.html; accessed 8 November 2021).
7. Narayanan M, Reddy KM, Marsicano E. Peptic Ulcer Disease and Helicobacter pylori infection. Mo Med 2018;115(3):219–24.
8. NHS.UK. Stomach ulcer (www.nhs.uk/conditions/stomach-ulcer/symptoms; accessed 8 November 2021).
9. MSD Manual Professional Version. Peptic Ulcer Disease (https://www.msdmanuals.com/en-gb/professional/gastrointestinal-disorders/gastritis-and-peptic-ulcer-disease/peptic-ulcer-disease; accessed 5 November 2021).
10. National Institute for Health and Care Excellence (NICE). Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. Clinical guideline [CG184] (www.nice.org.uk/guidance/cg184/chapter/1-Recommendations; accessed 5 November 2021).
 




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