Section 1: Aetiology and epidemiology
Peptic ulcer disease (PUD) is a common problem in the UK and has a wide spectrum of severity and complications.
The term 'peptic ulceration' refers to defects in the gastric or duodenal mucosa that extend through the muscularis mucosa. To understand the development and risk factors for PUD it is helpful to consider the two main pathogenic systems: increased acid secretion and loss of normal barriers.
Helicobacter pylori infection, the main cause of PUD, results in chronic inflammation and increased gastric acid secretion.
The prevalence of H pylori varies according to country, socio-economic group and age. Although many of those infected will not develop PUD, 60 per cent of gastric and up to 90 per cent of duodenal ulcers are due to this infection.
It is clear other risk factors work with H pylori infection in the development of ulceration. Such risk factors include alcohol consumption and smoking.
Another major independent risk factor is chronic use of NSAIDs. These drugs block the function of cyclo-oxygenase 1, which is essential for the production of prostaglandins to protect gastric mucosa.
As the prevalence of ulceration caused by H pylori declines in the western world, due to falling childhood incidence and more medical treatment, a greater proportion of ulcers will be due to the chronic use of NSAIDs.
Other risk factors
Risk factors, such as spice consumption and blood type, have been shown to be of relatively minor importance in the development of peptic ulcers.1
Severe physiological stress, particularly burns and head trauma, can also lead to PUD by deregulation of acid production and redundancy of the GI tract. This can develop over a surprisingly short period of time and represent a severe complication of the original illness.
There is debate as to the clinical significance of psychological stress in the development of peptic ulcers, although it is clear that chronic stress increases gastric acid production and that when combined with irregular mealtimes this may be risk factor for PUD.2
A rare cause of PUD is gastrin-secreting tumours called gastrinomas (as seen in Zollinger-Ellison syndrome). The resulting increase in acid secretion causes multiple ulcers that are resistant to treatment.
The lifetime risk for developing a peptic ulcer is around 10 per cent.3 The incidence of complications of PUD has decreased dramatically over the past two decades since the introduction of antibiotics and PPIs in the management.
Section 2: Presentation and diagnosis
Uncomplicated PUD classically presents with epigastric pain that may have been present for a number of weeks or months. This may be associated with a burning sensation and be temporally associated with mealtimes (either relieved by a meal or occurring two to three hours after eating).
Patients may report mild relief using OTC antacid preparations. Some patients describe worsening of pain at night and radiation to the back.
Belching, bloating, anorexia and nausea are commonly ass-ociated symptoms but these are of little use in discriminating between gallstone disease, gastritis, pancreatic disorders and gastric cancer, which are the main differential diagnoses in this situation. Because of this diagnostic difficulty, it is estimated that only a quarter of patients with clinically suspected PUD have this diagnosis confirmed on further investigation.
Despite this statistic, it is vital to continue to consider this diagnosis in such presentations in order to institute appropriate treatment and avoid the serious complications of this condition.
If there are no other features of systemic disease or suggestion of malignancy an outpatient oesophagogastroduodenoscopy (OGD), should be arranged.
If there are concerns of an underlying malignant cause, or if the symptom complex is new in a patient over 55 years, then this investigation may be expedited under the two-week wait referral system. At the time of OGD, it is practice to perform H pylori testing if ulceration or severe gastritis is found. Biopsies are taken from all gastric ulcers to exclude malignancy.
Perforation occurs when the whole thickness of the stomach or duodenal wall has been breached. This allows air and gastrointestinal contents to leak into the abdomen, presenting clinically as a sudden worsening of the patient's pain and change in nature to a constant, severe upper abdominal pain that may radiate to the back.
Vomiting is a prominent feature in this situation. Due to the resulting peritonism the pain is classically worse with movement and patients will chose to lie flat and still. On examination, upper abdominal rebound and guarding are expected and patients may be tachycardic and febrile.
Perforation is a life-threatening complication that requires urgent surgical attention. The diagnosis is confirmed by the finding of free air under the diaphragm on an erect chest radiograph.
It is noteworthy that a pro-portion of patients (estimated 10 per cent) with perforated ulcers have normal plain films at presentation, and if clinical suspicion is high further investigation is required.
A less common presentation of perforated PUD is localised intra-abdominal sepsis that presents days to weeks after a perforation.
This situation arises when a small full thickness defect is sealed off by the omentum and patients do not seek medical attention. The key to making this diagnosis is in the history of chronic upper abdominal pain that suddenly worsens and then eases off before the symptoms of systemic upset develop.
This complication requires prompt investigation and management in secondary care.
Bleeding from PUD may be slow and chronic or profuse and life threatening. Chronic or intermittent bleeding presents as an iron-deficiency anaemia or melaena in a cardiovascularly stable patient.
More brisk or continuous bleeds may cause cardiovascular instability with haematemesis or melaena. If the passage of blood through the GI tract is rapid then profuse fresh red PR bleeding may be seen. More significant bleeding is often due to posterior duodenal ulcers that erode into the gastroduodenal artery. Patients presenting in general practice with these symptoms require immediate referral to secondary care.
A late complication of healed PUD is duodenal stenosis or gastric outlet obstruction. These occur when fibrotic scar tissue contracts. These complications may present months to years after healing of previous PUD and symptoms may be a vague collection of upper abdominal complaints that follow meals.
When stenosis or outlet obstruction is severe the predominant feature is pain that is relieved by large volume vomit. The differential diagnosis in this situation is recurrent ulceration. Both diagnoses can be made at endoscopy.
Section 3: Management
When dealing with the acute complications of PUD immediate hospital referral and, if needed, resuscitation are key. Traditionally surgical teams will receive patients with suspected perforation, while medical firms are better equipped to manage patients with melaena or haematemesis.
Once the diagnosis of PUD has been made by endoscopic visualisation of the affected mucosa (or at laparotomy in the case of perforated PUD) the management is multimodal.
All acute bleeding complications are treated in the hospital setting by endoscopic diathermy, clipping, injection or laser therapy.
With modern techniques the need for surgical management of bleeding PUD is uncommon. All patients with perforated PUD require surgical treatment to wash out gastric contents from the abdomen and enable closure of the defect.
This operation is commonly performed as an open procedure however there is a trend for the laparoscopic approach in this situation.
After the acute phase, management is focused on facilitating healing of the ulcer and preventing recurrence. This is achieved using 'triple therapy'. This term refers to the combination of a PPI to reduce the production of gastric acid, and two antibiotics (chosen according to local sensitivities) to eradicate H pylori.
For patients who have uncomplicated PUD that has been diagnosed at outpatient endoscopy, management follows the same principle of healing and risk reduction.
NICE guidelines on dyspepsia (2004) recommend testing for H pylori prior to initiating treatment. H pylori testing can be performed on biopsies taken at endoscopy or by non-invasive methods including stool antigen testing and the urea breath test.
Recently it has been suggested that all patients with PUD require 'triple therapy' eradication and current practice varies. NICE plan to review these guidelines in 2011.
Good communication of findings and management plans between primary and secondary care is vital.
All patients with PUD require two months of full-dose PPI and good education about lifestyle choices to reduce risk factors. Patients should stop smoking, reduce their alcohol intake and avoid NSAIDs.
Ongoing PPI treatment should be low dose, possibly on an as-required basis. Annual review provides an opportunity to promote stepwise withdrawal of therapy where appropriate and also check patient understanding of the rationale for treatment and check the patient's compliance with medication and lifestyle advice.
Section 4: Prognosis and follow up
The prognosis of PUD depends on the presence of complications and the patient's compliance with subsequent eradication and acid reduction treatments.
Mortality from bleeding of PUD is difficult to quantify, as it is heavily dependent on the comorbidity and physiological reserve of the patient. Patients with pre-existing cardiovascular disease are in a higher risk group.
Mortality from perforated ulcers is similarly difficult to predict as it depends on the physiological state of the pati- ent and the degree of chemical and bacterial peritonitis.
The extent of the patient's systemic inflammatory response may also contribute to the development of post-operative organ failure and mortality.
For patients with uncomplicated PUD that receive triple therapy, infection is cured and healing achieved in 85-90 per cent of cases.4
Re-infection is rare but possible and patients may require repeat courses of therapy. For NSAID-associated ulceration prognosis depends on compliance with PPI medication and avoidance of the offending drug.
The longer term prognosis of both complicated and uncomplicated PUD depends on the presence of complications and the compliance with subsequent eradication and acid reduction treatments.
One complication that occurs in the late phase is the development of duodenal stricture. This situation presents with postprandial epigastric pain and vomiting and the diagnosis is made with upper GI endoscopy.
Clearly, any patients with malignant gastric ulcers have a different post-operative mortality due to the neoplastic disease process.
1. Salih B, Abasiyanik F, Bayyurt N et al. H pylori infection and other risk factors associated with peptic ulcers in Turkish patients: A retrospective study. World J Gastroenterol 2007; 13 (23): 3245-8.
2. Wachirawat W, Hanucharurnkul S, Suriyawongpaisal P et al. Stress, but not Helicobacter pylori, is associated with peptic ulcer disease in a Thai population. J Med Assoc Thai 2003; 86 (7): 672-85. PMID 12948263.
3. Snowden FM. Emerging and reemerging diseases: a historical perspective. Immunol Rev 2008; 225: 9-26.
4. Javid G, Zargar SA, U-Saif R et al. Comparison of p.o. or i.v. proton pump inhibitors on 72-h intragastric pH in bleeding peptic ulcer. J Gastroenterol Hepatol 2009; 24(7): 1236-43.
NICE guideline: CG17 Dyspepsia NICE, London, 2004.