Peptic ulcer disease

A gastric or duodenal ulcer is a breach in the epithelium of the gastric or duodenal mucosa that penetrates the muscularis mucosae, which is confirmed on endoscopy. Gastric and duodenal ulceration is collectively known as peptic ulcer disease.¹

Helicobacter pylori (H. pylori) infection is associated with about 95% of duodenal ulcers and 70% of gastric ulcers.²

How common is peptic ulcer disease? (Epidemiology)¹³

Dyspepsia occurs in 40% of the population annually and leads to a primary care consultation in 5% and endoscopy in 1%.

The lifetime prevalence of peptic ulcer disease in the general population is estimated to be approximately 5–10%. The incidence of peptic ulcer disease is about 0.1–0.3% per year. The incidence of gastric ulcers peaks in the 5th to 7th decades. The incidence of duodenal ulcers peaks in the 3rd to 5th decades.

Of those who undergo endoscopy:

• About 40% have functional or non-ulcer dyspepsia.

• 40% have gastro-oesophageal reflux disease (GORD).

• 13% have ulcer disease.

• 2% have gastric cancer.

• 1% have oesophageal cancer.

In the past, duodenal ulcer was 10 times as common in men as in women and gastric ulcer had a male preponderance of 3:2. Now the frequency is much less, largely because of H. pylori eradication and the sex incidence being more even.

Peptic ulcer disease prevalence is decreasing in the West, but there is ethnic variation.⁴ One systematic review reported that globally, the annual incidence rates of peptic ulcer disease were 0.10-0.19% for physician-diagnosed disease and 0.03-0.17% when based on hospitalisation data. Overall, incidence and prevalence were decreasing, thought to be due to a decrease in H. pylori-related peptic ulcer disease.⁵

Causes of peptic ulcer disease (aetiology)⁶

• H. pylori.

• NSAIDs.

• Pepsin.

• Smoking.

• Alcohol.

• Bile acids.

• Steroids.

• Stress.

• Changes in gastric mucin consistency (may be genetically determined).⁷

Defence mechanisms include mucus, bicarbonate, mucosal blood flow and prostaglandins.

Symptoms of peptic ulcer disease (presentation)⁸

Symptoms of peptic ulcer disease are sometimes very nonspecific and a diagnosis is unreliable on history alone:

• Epigastric pain, usually 1 to 3 hours postprandial - it may sometimes wake the patient in the night, and be relieved by food.

• Nausea.

• Oral flatulence, bloating, distension and intolerance of fatty food - the last is also associated with gallstones.

• Heartburn sometimes occurs although it is more typically associated with gastro-oesophageal reflux.

• A posterior ulcer may cause pain radiating to the back.

• Symptoms are relieved by antacids (very nonspecific).

Risk factors for silent or asymptomatic peptic ulcer include old age, male sex, current smoking, H. pylori infection, and absence of atrophic gastritis. It is higher in Korea than in Western countries. This is thought to be due to an increased incidence of H. pylori infection. Asymptomatic peptic ulcer can present with unheralded perforation or bleeding.⁹

Signs¹⁰

In uncomplicated cases there is very little to find on examination:

• There is often epigastric tenderness.

• If gastric emptying is slow, there may be a succussion splash.

Differential diagnosis

• Abdominal aortic aneurysm.

• GORD.

• Gastric cancer.

• Gallstones.

• Chronic pancreatitis.

• Crohn's disease.

• Diverticular disease.

• Irritable bowel syndrome.

• Drug-induced dyspepsia.

• Hepatitis.

• Acute ulceration (occur at times of severe physiological stress - eg, severe burns/head injury).

• Zollinger-Ellison syndrome (if H. pylori is negative, or has been eradicated and ulceration is refractory/recurrent).

• Coronary heart disease.

Diagnosing peptic ulcer disease (investigations)³

• FBC may show evidence of iron-deficiency anaemia.

• Testing for H. pylori. Test using a carbon-13 urea breath test or a stool antigen test, or laboratory-based serology where its performance has been locally validated. If re-testing is required, a carbon-13 urea breath test is the chosen test. There is currently insufficient evidence to recommend the stool antigen test as a test of eradication. Office-based serological testing is not currently recommended because of its inadequate performance.

• Endoscopy:
  

  • National Institute for Health and Care Excellence (NICE) guidelines state that endoscopy is not required unless the patient is presenting warning signs (as below).

  • For people presenting with dyspepsia together with significant acute gastrointestinal bleeding, refer them immediately (on the same day) to a specialist.

The NICE guideline for suspected cancer states for stomach cancer:¹¹

• Consider a suspected cancer pathway referral for people with an upper abdominal mass consistent with stomach cancer.

• Offer urgent, direct access upper gastrointestinal endoscopy (to be done within 2 weeks) to assess for stomach cancer in people with dysphagia, or aged 55 and over with weight loss and any of the following: upper abdominal pain, reflux, or dyspepsia.

• Consider non-urgent, direct access upper gastrointestinal endoscopy to assess for stomach cancer in people with haematemesis.

• Consider non-urgent, direct access upper gastrointestinal endoscopy to assess for stomach cancer in people aged 55 or over with:

  • Treatment-resistant dyspepsia or

  • Upper abdominal pain with low haemoglobin levels or

  • Raised platelet count with any of the following: nausea, vomiting, weight loss, reflux, dyspepsia, upper abdominal pain, or

  • Nausea or vomiting with any of the following: weight loss, reflux, dyspepsia, upper abdominal pain.

Management of peptic ulcer disease

Modification of behaviour¹

• If drugs are the cause then they should be stopped or replaced but this may not be possible. Being more meticulous about the instructions for taking alendronate or taking NSAIDs including aspirin after food may be required.

• Cessation of smoking should be advised if applicable. Smoking increases the risk of peptic ulcer and delays healing as well as opposing the action of H₂-receptor antagonists. It has many effects on other parts of the gut, including facilitating gastro-oesophageal reflux.

Healing ulcers - H. pylori-positive¹²

Treatment for H. pylori-associated ulcer disease is mainly directed at eradication of infection. See the separate Helicobacter Pylori article.

Healing ulcers - H. pylori-negative, NSAID-induced

The NSAID should be stopped. Studies suggest that whilst H₂-receptor antagonists will heal NSAID-induced ulcers, PPIs are more effective.¹³

A large, randomised trial has not shown any difference in gastric ulcer healing between groups receiving esomeprazole 40 mg, esomeprazole 20 mg and ranitidine.¹⁴ NICE recommends full-dose PPI for two months.³ Of note, ranitidine is no longer available globally due to links with cancer risk.

PPIs are better than standard-dose H₂-receptor antagonists and misoprostol for prevention of duodenal ulcers.¹⁵ Patients with high cardiovascular risk should continue to receive prophylactic low-dose aspirin and full-dose naproxen is the preferred NSAID. Co-therapy with a PPI or misoprostol is recommended for these groups. If patients are unable to tolerate PPI treatment, a systematic review of randomised trials found that double-dose H₂-receptor antagonists reduce risk of both gastric and duodenal ulcers.

H. pylori-negative NSAID-negative ulcer⁷

Ulceration of the gastric or duodenal mucosa in the absence of H. pylori infection and NSAID or aspirin usage is rare. A careful history of the use of NSAIDs and aspirin is very important in any patient presenting with gastroduodenal ulceration in the absence of H. pylori infection. The patient might be unaware that several drugs obtainable over the counter as well as some herbal medications contain NSAIDs or aspirin.

To exclude the rare conditions that may cause this, such as Zollinger-Ellison syndrome, samples should be taken from the ulcer and surrounding mucosa.

Bleeding ulcers¹⁶

Early endoscopic intervention with ablative or mechanical treatment to the bleeding vessels is the treatment of choice. For more information see the separate Upper gastrointestinal bleeding (includes Rockall score) article.

Management of recurrence and its prevention³

• For gastric ulcer with H. pylori infection, NICE recommends eradication therapy followed by proof of eradication and repeat endoscopy. This is a consensus statement. If eradication is successful but the ulcer unhealed then malignancy needs to be considered.

• Serology tests are applicable only for initial diagnosis, as they remain positive for a long while.

• The situation concerning H. pylori eradication in patients who require long-term NSAIDs is still being researched.¹⁷ Currently, several guidelines recommend that any patient who has had a peptic ulcer bleed (PUB) or who is put on long-term NSAIDs should be checked for H. pylori infection.⁸

• For patients who have relapses, intermittent therapy and annual review are recommended.

Monitoring

Patients should be reviewed at the end of a course of treatment, especially H. pylori eradication, to confirm a satisfactory outcome.

Effectiveness of interventions³

The NICE guidelines give the following data on the effectiveness of interventions based on a number of sources:

• In duodenal ulcer, acid suppression for 4 to 8 weeks produces healing of the ulcer in 69%. This rises by an extra 5.4% with eradication therapy too. Number needed to treat (NNT) = 18.

• In duodenal ulcer, relapse at 3 to 12 months after treatment is 39% after short-term acid suppression alone but eradication increases this by 52% to 91%. NNT = 2.

• In gastric ulcer, supplementation of acid suppression with eradication therapy does not improve healing rates but it does reduce relapse so that 3 to 12 months later 45% are free of ulcers after just acid suppression but eradication raises this by 32% to 77%. NNT = 3.

• In patients taking NSAIDs, eradication did not improve the ulcer healing rate but it did halve the number of endoscopically proven ulcers six months later from 18% to 9%.

Complications of peptic ulcer disease¹⁸

• Haematemesis or melaena is associated with erosion of a large blood vessel and significant haemorrhage. Urgent admission to hospital is required. In patients whose ulcers have bled, eradication of H. pylori is more effective than even long-term acid suppression without eradication.¹⁸

• Perforation of a peptic ulcer causes an acute abdomen with epigastric pain that may progress to generalised rigidity. In the presence of steroids the symptoms of perforation may be suppressed or absent.

• Scarring of the duodenum may lead to pyloric stenosis with vomiting and weight loss but this is rare these days with effective treatment. The classical feature is that the vomit shows food such as tomato skins that were eaten 12 to 24 hours ago.

• Gastric malignancy (increased risk in Helicobacter pylori positive gastric ulcer disease).

• Adverse reactions to PPIs and H₂-receptor antagonists are usually rare and mild but severe problems can arise. Rare but not serious problems may include taste disturbance, peripheral oedema, photosensitivity, fever, arthralgia, myalgia and sweating. Serious problems include liver dysfunction, hypersensitivity reactions (including urticaria, angio-oedema, bronchospasm, anaphylaxis), depression, interstitial nephritis, blood disorders (including leukopenia, leukocytosis, pancytopenia, thrombocytopenia) and skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous eruption).¹⁹

• Misoprostol often causes diarrhoea and abdominal pain, especially at higher doses.

Prognosis¹

• With PPI therapy, duodenal ulcers typically heal within 4 weeks and gastric ulcers within 8 weeks.

• With peptic ulcer disease associated with Helicobacter pylori infection, eradication markedly reduces the risk of recurrent ulceration and may cure duodenal ulcers.

• Lifetime risk of recurrence for gastric ulcers is 60% if the person remains H. pylori positive, but 5% following eradication of H. pylori.

• Lifetime risk of recurrence for duodenal ulcers is 80% if the person remains H. pylori positive, but 5% following eradication of H. pylori.

• About 10% of people with a bleeding peptic ulcer will die, and 25% of people with a perforated peptic ulcer will die.