American Gastroenterological Association Medical Position Statement: Evaluation of Dyspepsia

Differential Diagnosis of Dyspepsia 

Dyspepsia refers to chronic or recurrent pain or discomfort centered in the upper abdomen.3 Patients with predominant or frequent (occurring more than once a week) heartburn or acid regurgitation are considered to have gastroesophageal reflux disease (GERD) until proven otherwise and are not part of the definition of dyspepsia (Figure 1). It is, however, recognized that there is considerable symptom overlap and it is often difficult to distinguish between dyspepsia and GERD in the uninvestigated patient with upper gastrointestinal symptoms in primary care.4, 5 Further research into the most appropriate definition of dyspepsia in uninvestigated patients in primary and secondary care is recommended.

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Figure 1. Initial management of dyspepsia. COX, cyclooxygenase.

Peptic ulcer is responsible for approximately 10% of upper gastrointestinal symptoms; most patients with dyspepsia undergoing endoscopy are found to have functional dyspepsia.3, 6 More than 50% of patients with GERD will not have any evidence of esophagitis at upper gastrointestinal endoscopy, so this condition can be confused with functional dyspepsia.3 H pylori is the main cause of peptic ulcers not associated with nonsteroidal anti-inflammatory drugs (NSAIDs) and also causes functional dyspepsia in a small proportion of cases.7

Management Options for New-Onset Dyspepsia 

The main strategies for managing new-onset dyspepsia are (1) empirical H2-receptor antagonist therapy, (2) empirical proton pump inhibitor (PPI) therapy, (3) H pylori testing and treatment of positive cases (H pylori test and treat) followed by acid suppression if the patient remains symptomatic, (4) early endoscopy alone, (5) early endoscopy with biopsy for H pylori and treatment if positive, (6) acid suppression followed by endoscopy and biopsy if the patient remains symptomatic, or (7) H pylori test and treat with endoscopy if the patient remains symptomatic.

Management Recommendations 

Patients 55 years of age or younger without alarm features should receive H pylori test and treat followed by acid suppression if symptoms remain (Figure 2).3 H pylori testing is optimally performed by a 13C-urea breath test or stool antigen test. PPIs are the drug class of choice for acid suppression.3 Those who are H pylori negative should be prescribed an empirical trial of acid suppression with a PPI for 4–8 weeks. Empirical PPI therapy is the most cost-effective approach in populations with a low prevalence of H pylori (10% or less). The recommendation to test and treat is based on randomized controlled trials8 and the possible impact of eradication in preventing future gastric adenocarcinoma.3

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Figure 2. Management of dyspepsia based on age and alarm features. EGD, esophagogastroduodenoscopy.

Patients who respond to H pylori test and treat or PPI therapy can be managed without further investigation.3 Endoscopy usually adds little in young patients who continue to have upper gastrointestinal symptoms without alarm features despite H pylori test and treat and PPI therapy. There is a very low probability of finding relevant organic disease in this group of patients. Endoscopy may reassure some young patients with continued symptoms, but evidence suggests this is not the case in those who are most anxious9 and that many H pylori test-and-treat patients can be managed in the long term without further investigation.10 Endoscopy may be appropriate for some young patients who continue to have dyspepsia, but this should be considered in the wider context of reevaluating the symptoms and the diagnosis. Endoscopy appears not to be a cost-effective use of resources compared with alternatives such as screening for colorectal cancer11 (Figure 3).

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Figure 3. Endoscopy in patients who have failed empirical therapy. EGD, esophagogastroduodenoscopy.

The value of alarm symptoms in younger patients is controversial.12 A systematic review of alarm symptoms suggests that these are not very useful in diagnosing upper gastrointestinal malignancy.3 However, although the yield of endoscopy is low, it is recommended for patients older than 55 years of age and for younger patients with alarm features (eg, weight loss, progressive dysphagia, recurrent vomiting, evidence of gastrointestinal bleeding, or family history of cancer) presenting with new-onset dyspepsia. Upper gastrointestinal malignancy becomes more common after age 55 years.3 Biopsy specimens should be obtained for H pylori at the time of endoscopy and eradication therapy offered to those who are infected because this may reduce the risk of subsequent peptic ulcer disease and gastric malignancy.3 Endoscopy should be preferred over upper gastrointestinal radiography because it has greater diagnostic accuracy and biopsy specimens can be taken for H pylori infection. After endoscopy, and H pylori eradication therapy if positive, treatment should be targeted at the underlying diagnosis. Most patients will have functional dyspepsia and can be offered acid suppression therapy.13

Patients of any age who continue to have symptoms despite appropriate investigations, therapy, and reassurance are a difficult group to manage (Figure 4). Symptoms should be reassessed and prokinetic agents, antidepressant therapy, or psychological treatments considered, although the benefits of these approaches are not established.14, 15, 16

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Figure 4. Management of functional dyspepsia. IBS, irritable bowel syndrome.