**** Dyspepsia *****

Dyspepsia

Dyspepsia refers to acute, chronic, or recurrent pain or discomfort centered in the upper abdomen. The discomfort may be characterized by or associated with upper abdominal fullness, early satiety, burning, bloating, belching, nausea, retching, or vomiting. Heartburn (retrosternal burning) should be distinguished from dyspepsia. Patients with dyspepsia often have heartburn as an additional symptom. When heartburn is the dominant complaint, gastroesophageal reflux is nearly always present. Dyspepsia occurs in 25% of the adult population and accounts for 3% of general medical office visits.

Etiology

Food or Drug Intolerance

Acute, self-limited "indigestion" may be caused by overeating, eating too quickly, eating high-fat foods, eating during stressful situations, or drinking too much alcohol or coffee. Many medications cause dyspepsia, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics (metronidazole, macrolides), various diabetes drugs (metformin, alpha-glucosidase inhibitors, amylin analogs, GLP-1 receptor antagonists), cholinesterase inhibitors (donepezil, rivastigmine), corticosteroids, digoxin, iron, and opioids.

Luminal Gastrointestinal Tract Dysfunction

Peptic ulcer disease is present in 5–15% of patients with dyspepsia. Gastroesophageal reflux disease is present in up to 20% of patients with dyspepsia, even without significant heartburn. Gastric cancer is identified in 1% but is rare in persons under age 45 years. Other causes include gastroparesis (especially in diabetes mellitus), lactose intolerance or malabsorptive conditions, and parasitic infection (Giardia, Strongyloides).

Helicobacter pylori Infection

Chronic gastric infection with H pylori as a cause of dyspepsia remains controversial. The prevalence of H pylori-associated chronic gastritis in patients with dyspepsia without peptic ulcer disease is 20–50%, the same as in the general population.

Pancreatic Disease

Pancreatic carcinoma, chronic pancreatitis.

Biliary Tract Disease

The abrupt onset of epigastric or right upper quadrant pain due to cholelithiasis or choledocholithiasis should be readily distinguished from dyspepsia.

Other Conditions

Diabetes, thyroid disease, renal insufficiency, myocardial ischemia, intra-abdominal malignancy, gastric volvulus or paraesophageal hernia, and pregnancy are sometimes accompanied by dyspepsia.

Functional Dyspepsia

This is the most common cause of chronic dyspepsia. Up to two-thirds of patients have no obvious organic cause for their symptoms after evaluation. Symptoms may arise from a complex interaction of increased visceral afferent sensitivity, gastric delayed emptying or impaired accommodation to food, or psychosocial stressors. Although benign, these symptoms may be chronic and difficult to treat.

Clinical Findings

Symptoms and Signs

Given the nonspecific nature of dyspeptic symptoms, the history has limited diagnostic utility. It should clarify the chronicity, location, and quality of the discomfort, its relationship to meals, and whether it is relieved by antacids. Concomitant weight loss, persistent vomiting, constant or severe pain, dysphagia, hematemesis, or melena warrants endoscopy or abdominal imaging. Potentially offending medications and excessive alcohol use should be identified and discontinued if possible. The patient's reason for seeking care should be determined. Recent changes in employment, marital discord, physical and sexual abuse, anxiety, depression, and fear of serious disease may all contribute to the development and reporting of symptoms. Patients with functional dyspepsia often are younger, report a variety of abdominal and extragastrointestinal complaints, show signs of anxiety or depression, or have a history of use of psychotropic medications.

The symptom profile alone does not differentiate between functional dyspepsia and organic gastrointestinal disorders. Based on the clinical history alone, primary care physicians misdiagnose nearly half of patients with peptic ulcers or gastroesophageal reflux and have < 25% accuracy in diagnosing functional dyspepsia.

The physical examination is rarely helpful. Signs of serious organic disease such as weight loss, organomegaly, abdominal mass, or fecal occult blood are further evaluated. In patients over age 45 years, initial laboratory work should include a blood count, electrolytes, liver enzymes, calcium, and thyroid function tests.

Special Examinations

Upper Endoscopy

Upper endoscopy is the study of choice to diagnose gastroduodenal ulcers, erosive esophagitis, and upper gastrointestinal malignancy. Upper gastrointestinal barium radiography is inferior to endoscopy for the evaluation of dyspepsia. Upper endoscopy is indicated to look for gastric cancer or other serious organic disease in all patients over age 55 years with new-onset dyspepsia and in all patients with "alarm" features such as weight loss, dysphagia, recurrent vomiting, evidence of bleeding, or anemia. It is also helpful for patients who are concerned about serious underlying disease. For patients born in regions in which there is a higher incidence of gastric cancer, an age threshold of 45 years may be appropriate.

Empiric Management

In patients younger than 55 years with uncomplicated dyspepsia (in whom gastric cancer is rare), initial noninvasive management strategies should be pursued. In most clinical settings, a noninvasive test for H pylori (IgG serology, fecal antigen test, or urea breath test) should be performed first. Although serologic tests are inexpensive, performance characteristics are poor in low-prevalence populations. If test results are negative in a patient not taking NSAIDs, peptic ulcer disease is virtually excluded. Most of these H pylori-negative patients have functional dyspepsia or atypical gastroesophageal reflux disease and can be treated with an antisecretory agent (proton pump inhibitor) for 4 weeks. For patients who have symptom relapse after discontinuation of the proton pump inhibitor, intermittent or long-term proton pump inhibitor therapy may be considered.

For patients in whom test results are positive for H pylori, antibiotic therapy proves definitive for over 90% of peptic ulcers and may improve symptoms in a small subset (< 10%) of infected patients with functional dyspepsia. Patients with persistent dyspepsia after H pylori eradication can be given a trial of proton pump inhibitor therapy. In clinical settings in which the prevalence of H pylori infection in the population is low (< 10%), it may be more cost-effective to initially treat all young patients with uncomplicated dyspepsia with a 4-week trial of a proton pump inhibitor. Patients who have symptom relapse after discontinuation of the proton pump inhibitor should be tested for H pylori and treated if positive.

Abdominal imaging (ultrasonography or CT scanning) is performed only when pancreatic or biliary tract disease is suspected. Gastric emptying studies are valuable only in patients with recurrent vomiting. Ambulatory esophageal pH testing may be of value when atypical gastroesophageal reflux is suspected.

Treatment of Functional Dyspepsia

Regardless of the initial strategy undertaken for patients with dyspepsia, a significant proportion will have persistent or recurrent symptoms requiring evaluation with endoscopy. Most patients will have no significant findings and will be given a diagnosis of functional dyspepsia.

General Measures

Most patients have mild, intermittent symptoms that respond to reassurance and lifestyle changes. Alcohol, caffeine, and fatty foods should be reduced or discontinued. A food diary, in which patients record their food intake, symptoms, and daily events, may reveal dietary or psychosocial precipitants of pain.

Pharmacologic Agents

Drugs have demonstrated limited efficacy in the treatment of functional dyspepsia. One-third of patients derive relief from placebo. Antisecretory therapy for 2–4 weeks with either H2-receptor antagonists (ranitidine or nizatidine, 150 mg twice daily; famotidine, 20 mg twice daily; or cimetidine, 400–800 mg twice daily) or proton pump inhibitors (omeprazole, esomeprazole, or rabeprazole 20 mg, lansoprazole 30 mg, or pantoprazole 40 mg) may benefit 10–15% of patients, particularly those with dyspepsia and heartburn ("reflux-like dyspepsia"). Superiority of proton pump inhibitors to H2-antagonists has not been established. Low doses of antidepressants (eg, desipramine or nortriptyline, 10–50 mg at bedtime) are believed to benefit some patients, possibly by moderating visceral afferent sensitivity. However, side effects are common and response is patient specific. Doses should be increased slowly. The prokinetic agent metoclopramide (5–10 mg three times daily) may improve symptoms, but improvement does not correlate with the presence or absence of gastric emptying delay. Long-term metoclopramide use is associated with a high incidence of neuropsychiatric side effects and cannot be recommended. Limited studies to date have not demonstrated efficacy for the prokinetic agent tegaserod.

Anti-H pylori Treatment

A meta-analysis has suggested that a small number of patients (<10%) derive benefit from H pylori eradication therapy.

Alternative Therapies

Psychotherapy and hypnotherapy may be of benefit in selected motivated patients. Herbal therapies (peppermint, caraway) may offer benefit with little risk of adverse effects.

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Talley NJ et al; American Gastroenterological Association: American Gastroenterological Association Medical Position Statement: Evaluation of dyspepsia. Gastroenterology 2005;129:1753. [PMID: 16285970]


Talley NJ et al; Practice Parameters Committee of the American College of Gastroenterology: Guidelines for the management of dyspepsia. Am J Gastroenterol 2005;100:2324. [PMID: 16181387]


Timmons S et al: Functional dyspepsia: motor abnormalities, sensory dysfunction, and therapeutic options. Am J Gastroenterol 2004;99:739. [PMID: 15089910]