DEFINITIONS

The definition of dyspepsia is controversial, with some authorities including reflux symptoms whereas others do not. An international committee of clinical investigators that meets in Rome have routinely excluded reflux symptoms.

Dyspepsia has historically been defined as pain or discomfort located in the upper abdomen (mainly in or around the midline as opposed to the right or left hypochondrium). Discomfort may include bloating, fullness, early satiety, postprandial fullness or nausea. Dyspepsia may be either organic, implying an organic, systemic or metabolic disease has been identified as the cause, or functional, where there is no identifiable explanation for the symptoms. Functional dyspepsia is also known as idiopathic or non-ulcer dyspepsia.

The Rome III committee has redefined functional dyspepsia and limited the term to refer to the four following symptoms: bothersome post-prandial fullness, early satiation, epigastric pain, or epigastric burning. The remaining symptoms of discomfort listed above have been allocated clinical entities of their own, and together they comprise the functional gastroduodenal disorders (Table 4.1). In addition, as shown in Table 4.2, there are two new diagnostic categories within functional dyspepsia; namely postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS).

TABLE 4.1 Functional gastroduodenal disorders

TABLE 4.2 Subtypes of functional dyspepsia

* Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis

There is some overlap between symptoms of gastro-oesophageal reflux disease (GORD) and dyspepsia. Heartburn is traditionally excluded from the Rome II and III criteria for dyspepsia, although in Rome III a burning sensation confined to the epigastrium is not considered to be heartburn unless it also radiates retrosternally. Despite the exclusion of heartburn, reflux oesophagitis is the most common structural finding when patients with dyspepsia are evaluated by upper endoscopy in Western nations. Heartburn more than twice weekly strongly suggests GORD in favour of dyspepsia.

Uninvestigated dyspepsia refers to new onset or recurrent dyspepsia for which no diagnostic investigations have yet been performed and subsequently a specific diagnosis has not been reached. This has implications for both diagnostic and management pathways.

EPIDEMIOLOGY

The prevalence of dyspepsia in the Western society is approximately 25%, although the true prevalence depends on the population being studied. The annual incidence is cited between 1% and 10%. As similar numbers of patients experience resolution of their symptoms, fairly constant prevalence rates occur. Women suffer marginally more than men and symptoms tend to improve slightly with age.

CAUSES

Adapted from Feldman M, Friedman LS, Sleisenger MH. Sleisenger and Fordtran’s gastrointestinal and liver disease. 7th edn. Philadelphia: WB Saunders; 2002.

Peptic ulcer disease is implicated in up to 10% of cases of dyspepsia. A chronic duodenal ulcer is most often associated with Helicobacter pylori infection, whereas chronic gastric ulcers are also associated commonly with aspirin or non-steroidal antiinflammatory drug (NSAID) use. There is poor correlation between symptoms and the presence of ulcers in NSAID users. COX 2 inhibitors produce fewer symptoms than traditional NSAIDs, but the risk of dyspepsia is still increased.

Endoscopic criteria for reflux oesophagitis are found in 15% of patients with dyspepsia. Non-erosive gastro-oesophageal reflux disease may be readily confused with functional dyspepsia, but it often still responds to acid suppression therapy.

Adenocarcinoma of the stomach or oesophagus is seen in fewer than 2% of patients referred for endoscopy, and the vast majority (98%) are over 45 years of age. Alarm symptoms that may suggest the possibility of malignancy include:

Functional gastroduodenal disorders

Functional gastroduodenal disorders account for around 60% of presentations but are a diagnosis of exclusion. Current criteria require the presence of symptoms during the last 3 months occurring at least several times per week, with symptom onset at least 6 months before diagnosis and no evidence of structural disease on endoscopy (Tables 4.1 and 4.2).

The underlying pathophysiology of functional gastroduodenal disorders is incompletely understood. Gastric motility is abnormal in around 60% of cases with observed changes including delayed (or less often accelerated) gastric emptying, impaired proximal stomach accommodation leading to antral distension, and variable myoelectrical activity. None of these changes convincingly correlate with symptoms. Use of a gastric barostat balloon has demonstrated visceral hypersensitivity in over 40% of patients with dyspepsia.

In addition to its role in peptic ulcer disease and stomach cancers, H. pylori infection may account for some cases of functional dyspepsia. A Cochrane review of eradication therapy showed a small but statistically significant difference in favour of H. pylori treatment after 12 months of follow-up.

Other

No foods have been causally implicated in dyspepsia, but coffee and foods with a high fat content may aggravate symptoms.

Acid secretion is normal in functional dyspepsia, but acid sensitivity may be relevant in a subset. A minority (one-third at most) respond to acid suppression over placebo.

Anxiety and depression may aggravate symptoms and may promote healthcare seeking for dyspepsia, but a causal link with functional dyspepsia is not established.

MANAGEMENT

Figure 4.1 shows an algorithm for the approach to the patient with uninvestigated dyspepsia. Taking a thorough history with appropriate physical examination to clarify whether the symptoms are pancreatic, biliary or colonic in origin is an essential first step. Once a specific diagnosis has been made, treatment should be directed towards the specific condition. If uncomplicated dyspepsia is a consideration, discontinuing use of aspirin/NSAIDs and, if present, treatment of symptoms of GORD with a proton pump inhibitor (PPI) should be instituted. It is critical to make an assessment of the presence of alarm symptoms and signs. Older age and/or presence of alarm features indicates the need for early endoscopy, whereas the remainder may be managed with a ‘test and treat’ strategy (referring to establishing the presence/absence of H. pylori).

FIGURE 4.1 Management of dyspepsia.

EGD = endoscopic gastroduodenoscopy; FD = functional dyspepsia; GORD = gastro-oesophageal reflux disease; IBS = irritable bowel syndrome; NSAIDs = non-steroidal antiinflammatory drugs; PPI = proton pump inhibitor.

Non-invasive testing for H. pylori utilising either a urea breath test or a stool antigen immunoassay is appropriate in most patients. Serology is less accurate and is generally not recommended unless there is no alternative. Those who are already undergoing endoscopy should have a biopsy routinely obtained based on current guidelines. In these patients, rapid urease testing (e.g. CLOtest) with or without histology is usually performed.

The most accurate non-invasive test is the urease breath test with a sensitivity and specificity of 88%–95% and 95%–100%, respectively, however PPI or H₂-receptor antagonist use, recent upper gastrointestinal bleeding or antibiotics or bismuth use may induce false negative results. In these situations, alternative strategies should be considered. Similarly, endoscopic diagnosis with a biopsy urease test is highly sensitive and specific with the same caveats. Biopsies taken for histology may be examined in the event of a negative test.

First-line treatment for H. pylori is triple therapy with combinations of two antibiotics and one adjunctive agent over 7–14 days; a meta-analysis has demonstrated slight superiority with a two-week treatment period. The most common regimen includes a PPI (e.g. omeprazole 20 mg twice daily) with amoxicillin 1 g twice daily and clarithromycin 500 mg twice daily. Metronidazole may be substituted for amoxicillin in penicillin-sensitive patients, although the levels of metronidazole resistance are increasing significantly. Success rates of over 80% have been achieved in most trials.

Response to therapy may be assessed most effectively with a urea breath test performed at least 4 weeks after completing antibiotic therapy, and at least one week after stopping PPI therapy. Treatment failures are most commonly treated with a second-line regimen of quadruple therapy utilising bismuth, a PPI and alternative antibiotics such as metronidazole and tetracycline for a further 2 weeks. Rescue therapy for subsequent treatment failures involves changing the antibiotics to levofloxacin or rifabutin along with a PPI. If symptoms persist despite eradication of H. pylori, a trial of PPI should be undertaken. Alternative diagnoses should be considered if there is a continued lack of response and consideration also given to gastric emptying studies and psychological assessment (Figure 4.1).

When an organic diagnosis cannot be made and the presumptive diagnosis is a functional gastroduodenal disorder, the first step involves reassuring the patient of the benign nature of the condition. Next, despite the lack of convincing evidence, recommendations usually include smoking cessation and stopping or reducing consumption of coffee and alcohol, in addition to advice to eat several small low-fat meals per day.

PPIs and H₂-receptor antagonists are superior to placebo in the treatment of functional dyspepsia. Prokinetic agents, such as metoclopramide or domperidone, also appear to be modestly effective. Domperidone has the advantage of limited crossing of the blood–brain barrier and, consequently, exhibits fewer centrally-mediated side effects compared with metoclopramide.

One small study demonstrated some symptom improvement with amitriptyline. Unfortunately, most trials evaluating antidepressants in functional gastrointestinal disorders have not investigated dyspepsia independently of other disorders such as irritable bowel syndrome, so firm conclusions specifically related to their effects in dyspepsia cannot be drawn. Finally, studies have shown that patients with functional dyspepsia have higher scores on a variety of psychological parameters including anxiety, depression and neuroticism when compared with the community controls. A recent study of patients who had failed to respond to conventional pharmacologic treatments showed that psychotherapy or hypnotherapy may have both short- and long-term beneficial effects.

SUMMARY

Dyspepsia refers to pain or discomfort in the epigastric area. Most patients with dyspepsia have functional dyspepsia but aspirin or non-steroidal antiinflammatory drugs can often cause similar symptoms. Gastro-oesophageal reflux disease can present with epigastric pain or burning rather than typical heartburn. Endoscopy is indicated to rule out serious disease for patients who are older or who have alarm symptoms or signs. In younger patients without alarm features, a trial of empiric therapy is generally appropriate. Currently, testing for H. pylori using the urea breath test or stool antigen test is recommended. If the patient is positive, treatment for H. pylori is indicated. If the patient does not have H. pylori infection, a trial of acid suppression with a PPI for 4–8 weeks is usual first-line empiric therapy. If the patient has a negative endoscopy and documented functional dyspepsia, treatment options include antidepressants, prokinetic agents and psychological treatments if acid suppression or H. pylori eradication fails.

H. pylori causes gastritis, peptic ulcer disease and gastric adenocarcinoma. A minority of patients with functional dyspepsia and H. pylori infection will respond to anti-H. pylori therapy. False negative test results for H. pylori can occur in the setting of recent acid suppression. Ideally, patients should be off acid suppression therapy for 1–2 weeks prior to testing to avoid false-negative results. If standard triple therapy with a PPI, amoxicillin and clarithromycin fails to eradicate the infection, then the usual next management approach is to use quadruple therapy combining a PPI, bismuth, metronidazole and tetracycline for 2 weeks.