GI Consult: Dyspepsia

What do we know about the pathophysiology of functional dyspepsia and why it occurs? When does a patient with chronic epigastric symptoms need endoscopy to rule out more serious diseases? These and other questions are addressed.

By Christine L. Frissora, MD, Philip O. Katz, MD, and Kenneth L. Koch, MD

What is dyspepsia?

The term dyspepsia refers to the symptom of pain or discomfort in the epigastric region—the area of the abdomen between the umbilicus and the xiphoid process. It denotes abnormal or difficult digestion and is usually considered to be associated with gastroesophageal reflux disease (GERD), peptic ulcer, gallbladder disease, pancreatic disease, or use of nonsteroidal anti-inflammatory drugs (NSAIDs). Some clinicians have attributed it to gastritis caused by Helicobacter pylori, a hypothesis that remains controversial.

What is functional dyspepsia?

Functional dyspepsia is a disorder in which there is no gross mucosal or structural abnormality that would account for symptoms of discomfort and early satiety. These symptoms are thought to be due to abnormal gastric function, sensation, or motility.

The patient with early satiety and postprandial fullness may have impaired relaxation of the fundus or slow emptying of the stomach (gastroparesis). Still another possibility is that the stomach's electrical rhythms are abnormal (gastric dysrhythmia). The rhythm of a normal stomach measures three cycles per minute (cpm). Patients with dyspepsia may have tachygastrias (3.7 to 10 cpm), bradygastrias (1 to 2.5 cpm), or a combination of these (mixed dysrhythmia). Any of the gastric dysrhythmias may be associated with dyspepsia and nausea. These rhythms can be measured noninvasively using a process similar to electrocardiography that generates an electrogastrogram (EGG).

When does a patient with dyspepsia need endoscopy?

For the patient with persistent dyspepsia, a thorough history to screen for alarm symptoms and a physical examination with stool guaiac are essential. Any alarm symptom—hematemesis, weight loss, fever, persistent vomiting, anorexia, or dehydration—or occult blood loss indicates endoscopy. New-onset dyspepsia in patients over 45 also warrants endoscopy. Family history of gastric cancer is a further consideration.

If endoscopy is performed, the duodenum should be carefully examined for evidence of sprue (also called celiac disease), which is an intolerance to the grain proteins loosely termed "gluten." The duodenal mucosa may exhibit creases, fissures, decreased folds, and a scalloped or serrated appearance in patients with sprue. Sprue can present with atypical reflux symptoms. When sprue is suspected, it is important to take at least six biopsies to assess the crypt-to-villi ratio. In the United States, prevalence of sprue is estimated at one in 200, with patients of English, Irish, and German descent most often affected. No study has addressed the prevalence of sprue in patients with dyspepsia, but many believe it is underdiagnosed.

Many clinicians would biopsy the stomach of patients undergoing endoscopy to look for H. pylori gastritis. The difficulty with this practice is that research on treatment of H. pylori infection in patients with nonulcer dyspepsia has found no improvement in symptoms compared with a placebo group. Any decision to investigate for H. pylori should therefore be individualized.

It is important to exclude a structural cause of dyspepsia such as gastric cancer, gastric outlet obstruction, or other mucosal lesion. However, repeat endoscopies are usually not helpful or indicated in the absence of new alarm symptoms.

What other tests are necessary to evaluate dyspepsia?

Laboratory studies should be ordered as appropriate; consider testing for giardiasis, H. pylori, and other gastrointestinal infections based on the history. Certain patients may need to be tested for bacterial overgrowth (breath testing or duodenal culture), gastroparesis (gastric emptying study), and gastric dysrhythmias (EGG). Impedance planimetry, a technique being developed to study motility primarily in the esophagus, has not been used in dyspepsia evaluation.

Should H. pylori be treated in patients with dyspepsia?

Helicobacter pylori has been classified as a carcinogen by the World Health Organization. It can cause duodenal ulcer, gastric ulcer, MALT (mucosa-associated lymphoid tissue) lymphoma, and adenocarcinoma of the stomach. For those reasons our practice is to eradicate H. pylori, which is easily diagnosed by a stool antigen test or breath test. (Serology can be done, but it will not necessarily reflect active infection, since the IgG antibodies can remain for years in the absence of active infection.) First-line treatment is a proton pump inhibitor (PPI) plus two antibiotics for 10 days to two weeks. The PPI is generally given twice a day (or in the case of esomeprazole, a single 40-mg daily dose), usually with amoxicillin, 1 gm twice a day, and clarithromycin, 500 mg twice a day.

What is the pathophysiology of functional dyspepsia?

The etiology of functional dyspepsia is not known. Current thoughts are that it involves abnormal stomach motility and increased visceral sensitivity. There may be decreased emptying and impaired relaxation of the fundus after eating. In addition, patients with functional dyspepsia have increased sensitivity to distension. Experimentally this can be demonstrated by inflating gastric balloons in patients' stomachs. Patients with functional dyspepsia have more discomfort at lower volumes of distension than normal patients do. This can be determined by a response to a water load during a standard, noninvasive EGG test. Clinically, patients with functional dyspepsia often experience epigastric discomfort and nausea after eating a large meal.

What causes functional dyspepsia?

The cause is not known. One possibility is that an episode of viral gastroenteritis can leave the enteric nervous system of the stomach hypersensitized. Decreased motility may occur as a result of damage to the neuronal plexus in the stomach. Hormonal factors linked with dyspepsia include pregnancy, oral contraceptives, and hormone replacement therapy. Other drugs associated with dyspepsia include alendronate, atorvastatin and other HMG-CoA reductase inhibitors, and the NSAIDs. Some of the PPIs can cause abdominal discomfort in a few patients, so it may be necessary to decrease the dose or change to another PPI if symptoms seem to be aggravated.

What is the treatment for dyspepsia?

The first step is to educate the patient about functional dyspepsia. Reassure the patient that there is no cancer or ulcer. Explain to the patient the idea of motility and sensitivity disorders in combination. Establishing a diagnosis such as gastric dysrhythmia or gastroparesis helps to educate the patient and provides a pathophysiological basis for treatment. Symptoms can improve slowly over time if they were caused by a gastroenteritis or medication. If the dyspeptic symptoms seem acid-related and the discomfort is described as a burning sensation, or in other terms characteristic of acid reflux, it is appropriate to begin with a trial of antisecretory therapy for six to eight weeks. A high-dose PPI regimen is not needed in these patients; those that will respond will do so with single daily doses. All dyspeptic patients should be advised to avoid smoking, alcohol, fatty foods, caffeine, and carbonated beverages.

What is the role of motility drugs in treating functional dyspepsia?

Cisapride was removed from the market in the United States due to concerns about cardiac arrythmias in patients with cardiac diseases and in certain other patient groups. It is available through a limited access program if the appropriate paperwork is completed. Metoclo-pramide, which was the first promotility drug, can also be used for dyspepsia symptoms. Both drugs improve gastric emptying and may correct gastric dysrhythmias. Typical dosage for either drug is 10 mg four times a day. Metoclopramide should be given for no more than three or four weeks at a time, since more prolonged treatment is likely to produce adverse central nervous system effects such as depression and extrapyramidal symptoms.

Tegaserod, 6 mg twice a day, was recently approved by the U.S. Food and Drug Administration for the treatment of irritable bowel syndrome (IBS) in women whose primary symptom is constipation. Investigations of tegaserod for functional dyspepsia are being conducted. Also approved recently was alosetron, 1 mg daily, for women with severe diarrhea-predominant IBS. Earlier studies showed that alosetron increased fundal relaxation and may be of use in functional dyspepsia, possibly at a lower dose (0.5 mg). To date no studies are available. Constipation is the main side effect; rarely, ischemic colitis has been reported.

None of these drugs is established as safe in pregnancy or lactation. For the treatment of nausea and vomiting in pregnancy, see "GI Consult: GI Disorders During Pregnancy" in the August 2002 issue of EMERGENCY MEDICINE.

Are antidepressants or anticholinergics useful in treating functional dyspepsia?

Patients whose description of symptoms suggests spasm may be helped by an antispasmodic. In our experience, hyoscyamine sulfate, 0.125 mg twice a day as needed, can relieve pain and nausea in some patients.

In a thin patient who is anxious, not sleeping well, and has persistent epigastric discomfort, citalopram, 10 mg daily at bedtime, can be given. This antidepressant modulates pain in low doses and helps patients sleep. Citalopram usually causes weight gain, so the patient's current weight is an important consideration in prescribing.

Bupropion is useful for smokers to aid in smoking cessation and is generally well tolerated. Its action is mildly amphetamine-like, so it should be taken during the early part of the day to prevent insomnia.

Tricyclic antidepressants such as desipramine, 10 mg daily at bedtime, may help patients with abdominal pain but may also provoke constipation, sedation, dry mouth, weight gain, or sexual dysfunction. Prolongation of the QT interval is also possible.

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