Clinical Review

Managing Dyspepsia

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A range of disorders included in the differential

Symptom severity is a poor predictor of the seriousness of dyspepsia; more intense symptoms are no more likely than milder cases to have an organic cause.

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’s 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 of uncomplicated PUD estimated to be 17.5 times higher among those who test positive for H pylori and take NSAIDs vs a 3- to 4-fold increase in ulcer incidence among those with either of these risk factors alone.22

The work-up starts with a search for red flags

Symptom severity is a poor predictor of the seriousness of dyspepsia; more intense symptoms are no more likely than milder cases to have an organic cause.

Evaluation of a patient with dyspepsia begins with a thorough history. Start by determining whether the patient has any red flags, or alarm features, that may be associated with a more serious condition—particularly an underlying malignancy. One or more of the following is an indication for an esophagogastroduodenoscopy (EGD):5,8,12
• family and/or personal history of upper GI cancer
• unintended weight loss
• GI bleeding
• progressive dysphagia
• unexplained iron-deficiency anemia
• persistent vomiting
• palpable mass or lymphadenopathy
• jaundice.

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.

While it is important to rule out these red flags, they are poor predictors of malignancy.23,24 With the exception of a single study, their positive predictive value was a mere 1%.8 Their usefulness lies in their ability to exclude malignancy, however; when none of these features is present, the negative predictive value for malignancy is >97%.8

Age is also a risk factor. In addition to red flags, EGD is recommended by the American Gastroenterological Association (AGA) for patients with new-onset dyspepsia who are 55 years or older—an age at which upper GI malignancy becomes more common. A repeat EGD is rarely indicated, unless Barrett’s esophagus or severe erosive esophagitis is found on the initial EGD.25

Physical exam, H pylori evaluation follow

A physical examination of all patients presenting with symptoms suggestive of dyspepsia is crucial. While the exam is usually normal, it may reveal epigastric tenderness on abdominal palpation. Rebound tenderness, guarding, or evidence of other abnormalities should raise the prospect of alternative diagnoses. GERD, for example, has many symptoms in common with dyspepsia, but is a more likely diagnosis in a patient who has retrosternal burning discomfort and regurgitation and reports that symptoms worsen at night and when lying down.

Lab work has limited value. Although laboratory work is not specifically addressed in the AGA guidelines (except for H pylori testing), a complete blood count is a reasonable part of an initial evaluation of dyspepsia to check for anemia. Other routine blood work is not needed, but further lab testing may be warranted based on the history, exam, and differential diagnosis.

H pylori risk. Because of the association between dyspepsia and H pylori, evaluating the patient’s risk for infection with this bacterium, based primarily on his or her current and previous living conditions (TABLE 1),9 is the next step. Although a test for H pylori could be included in the initial work-up of all patients with dyspepsia, a better—and more cost-effective—strategy is to initially test only those at high risk. (More on testing and treating H pylori in a bit.)

Initiate acid suppression therapy for low-risk patients

First-line treatment for patients with dyspepsia who have no red flags for malignancy or other serious conditions and either are not at high risk for H pylori or are at high risk but have been tested for it and had negative results is a 4- to 8-week course of acid suppression therapy. Patients at low risk for H pylori should be tested for the bacterium only if therapy fails to alleviate their symptoms.9

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