Each year, an estimated 25% to 30% of the US population experiences dyspepsia.1 Most self-treat with home remedies and OTC products, while others seek medical care. Dyspepsia accounts for an estimated 2% to 5% of primary care visits annually,2 mostly by patients who are found to have no organic, or structural, cause for their symptoms.1,3
Such patients are said to have functional dyspepsia (FD), a category that applies to about two-thirds of those with dyspepsia.1 A small number of cases are categorized as organic dyspepsia, indicating the presence of a clear structural or anatomic cause, such as an ulcer or mass. The remainder are said to have undifferentiated dyspepsia, which simply means that their signs and symptoms do not rise to the level for which further investigation is warranted, and thus it is not known whether the dyspepsia is functional or organic.
There are many possible causes of FD—ranging from medications3,4 to abnormal gastroduodenal motility5,6 to Helicobacter pylori infection7—and a comprehensive differential diagnosis. The first step in an investigation is to rule out red flags suggestive of gastrointestinal (GI) cancer or other serious disorders.
Patients with FD, like the vast majority of those treated in a primary care setting, experience significant morbidity. Most have chronic symptoms, with intermittent flare-ups interspersed with periods of remission.8 This article and the dyspepsia treatment algorithm5,7-12 describe an evidence-based patient management approach.
SYMPTOMS AND CAUSES: WHAT TO LOOK FOR
The primary symptoms of dyspepsia include bothersome postprandial fullness, early satiety, and epigastric pain and burning. To meet the Rome criteria for dyspepsia, these symptoms must have been present for the last three months and have had an onset ≥ 6 months prior to diagnosis.2 Recurrent belching and nausea are also common but are not included in the Rome diagnostic criteria.
Symptom severity is a poor predictor of the seriousness of the condition, however, and more intense symptoms are no more likely than milder cases to have an organic cause.13,14 Indeed, anxiety is a common comorbidity in patients with FD and a risk factor for the diagnosis. Compared with the general public, patients with FD have been found to have higher levels of anxiety, chronic tension, hostility, and hypochondriasis, as well as a tendency to be more pessimistic.15
Possible causes of FD While the etiology of organic dyspepsia is clear, the cause of FD is often far more difficult to determine.
Medication use should always be considered, as many types of drugs—including bisphosphonates, antibiotics, narcotics, steroids, iron, metformin, and NSAIDs—are associated with dyspepsia.3,4
Gastroduodenal motility and accommodation, which has been found in numerous studies of patients with FD, is a proposed etiology.5,6
Visceral hypersensitivity also appears to play a role. In one study of patients with severe dyspepsia, 87% of those with FD had a reduced or altered GI pain threshold, compared with 20% of those with organic dyspepsia.16
H pylori, commonly linked to peptic ulcer disease (PUD), is also associated with both organic dyspepsia and FD.17,18 The gram-negative rod-shaped bacterium is present in approximately half of the population worldwide but is more common in developing nations.7H pylori immunoglobulin G (IgG) is more prevalent in patients with dyspepsia, particularly in those younger than 30. The exact mechanism by which H pylori causes nonulcerative dyspepsia is not clear, but inflammation, dysmotility, visceral hypersensitivity, and alteration of acid secretion have all been proposed.17
Dysfunctional intestinal epithelium is increasingly being considered in the pathophysiology of dyspepsia, among other conditions. Researchers theorize that certain foods, toxins, infections, and/or other stressors lead to changes in the structure and function of tight junctions, resulting in increased intestinal permeability.19 This in turn is thought to allow the outflow of antigens through the leaky epithelium and to stimulate an immune response—a process that may play a role in the increased GI inflammation or hypersensitivity associated with dyspepsia.
The “leaky gut” theory may eventually lead to new ways to treat dyspepsia. But thus far, high-quality evidence of the efficacy of treatments aimed at this mechanism is lacking.
A range of disorders included in the differential
The primary differential diagnosis for dyspepsia includes gastroesophageal reflux disease (GERD), esophagitis, chronic PUD (including both gastric and duodenal ulcers), and malignancy. The differential may also include biliary disorder, pancreatitis, hepatitis, or other liver disease; chronic abdominal wall pain, irritable bowel syndrome, motility disorders, or infiltrative diseases of the stomach (eosinophilic gastritis, Crohn disease, sarcoidosis); celiac disease and food sensitivities/allergies, including gluten, lactose, and other intolerances; cardiac disease, including acute coronary syndrome, myocardial infarction, and arrhythmias; intestinal angina; small intestine bacterial overgrowth; heavy metal toxicity; and hypercalcemia.8
Ulcers are found in approximately 10% of patients undergoing evaluation for dyspepsia.8 Previously, PUD was almost exclusively due to H pylori infection. In developed countries, however, chronic use of NSAIDs, including aspirin, has increased and is now responsible for most ulcer diseases.20,21
The combination of H pylori infection and NSAID usage appears to be synergistic, with the risk for uncomplicated PUD estimated to be 17.5 times higher among those who test positive for H pylori and take NSAIDs versus a three- to four-fold increase in ulcer incidence among those with just one of these risk factors.22
Continue for the workup starts with a search for red flags >>
