Diagnosis of Gastroesophageal Reflux Disease

Clinical presentation

The prevalence of heartburn, the most common clinical manifestation of Gastroesophageal reflux, is difficult to determine. Most people consider this sensation normal and do not seek medical attention. It is estimated that at least one third to one half of the U.S. population experience heartburn at least once a month and up to 20% of the population experience heartburn daily. The most common symptoms of Gastroesophageal reflux disease are as follows:

1. Heartburn (pyrosis). A substernal burning pain, radiating upward. Ingestion of antacids usually relieves this symptom within 5 minutes.
2. Regurgitation. Reflux of sour or bitter material into the mouth usually at night, while lying down, or when bending over. It suggests severe reflux.
3. Dysphagia. Difficulty in swallowing. Dysphagia usually indicates a narrowing or stricture of the esophagus; however, it may occur due to inflammation and edema, which may resolve with aggressive medical therapy of the Gastroesophageal reflux disease.
4. Odynophagia. Pain on swallowing, which sometimes accompanies severe esophagitis.
5. Waterbrash. Filling of the mouth suddenly with a clear, slightly salty fluid, which comes in large quantities. The fluid is not refluxed from the stomach but is secreted by the salivary glands in response to Gastroesophageal reflux.
6. Chest pain. Resembling angina of cardiac origin, chest pain is an atypical presentation of Gastroesophageal reflux disease. This pain may result from acid-induced irritation of the nerve endings in the elongated rete pegs protruding into the surface epithelium or from Gastroesophageal reflux-induced esophageal spasm or Gastroesophageal reflux-induced angina pectoris. In a study of the cardiovascular effect of reflux, esophageal acid perfusion produced an increase in cardiac workload in patients with angiographically proven coronary artery disease. Some patients had ischemic changes on electrocardiography during acid perfusion. This suggests that esophageal and cardiac disease not only may coexist, but also may interconnect. The standard clinical approach aimed at distinguishing between esophageal and cardiac pain may represent a serious oversimplification.
7. Hemorrhage may be the first clinical manifestation of esophagitis. It may be brisk, bright red, or slow and may result in iron-deficiency anemia.
8. Pulmonary symptoms may be the only manifestation of Gastroesophageal reflux and include chronic cough, hoarseness of voice, wheezing, hemoptysis, asthma, and recurrent aspiration pneumonia. Although it is often assumed by clinicians that pulmonary symptoms associated with reflux result from aspiration, reflux may increase airway resistance without aspiration, apparently through vagus-mediated neural reflexes.

Diagnostic studies

When a patient describes recurrent retrosternal burning or regurgitation that is worse after eating, lying down, or bending but is relieved with antacids, clinical diagnosis of Gastroesophageal reflux disease can easily be made. However, when the presentation is atypical and Gastroesophageal reflux disease is suspected, further testing may be required to establish the diagnosis and determine the severity and extent of the disease.

Usefulness of tests in Gastroesophageal reflux disease. The tests of Gastroesophageal reflux disease can be divided into three subgroups.

• Tests indicating possible Gastroesophageal reflux

1. Barium swallow, upper gastrointestinal series.
2. Endoscopy.
3. Manometry, measurement of lower esophageal sphincter pressure.

• Tests showing results of Gastroesophageal reflux

1. Bernstein test.
2. Endoscopy.
3. Mucosal biopsy.
4. Double-contrast barium esophagram.

• Tests measuring actual Gastroesophageal reflux

1. Barium swallow and esophagram.
2. Standard acid reflux test.
3. Prolonged pH monitoring of the esophagus.

GE scintiscan.

Barium esophagram and upper gastrointestinal series. Radiologic examination of the esophagus, stomach, and proximal duodenum is one of the first and most common tests ordered in patients with upper gastrointestinal complaints. The demonstration of barium reflux during this study is not specific, and many patients with Gastroesophageal reflux disease may not show reflux during the time of study.

Gastroesophageal reflux damage to the esophageal mucosa is usually not detected by single-contrast esophagrams. The double-contrast studies may not show mild degrees of inflammation but are more sensitive for severe grades of esophagitis. Positive signs include contour irregularity, erosions, ulcerations, longitudinal fold thickening, incomplete esophageal distensibility, and stricture formation. An upper gastrointestinal series will also help to rule out other upper gastrointestinal lesions, such as peptic ulcer disease. It is a poor test in assessing esophageal motor dysfunction but should be obtained in all patients with dysphagia to look for anatomic causes.

Esophageal manometry has limited usefulness in the routine evaluation of patients with Gastroesophageal reflux disease. It is helpful in evaluating the atypical patient with chest pain, patients in whom medical therapy has failed, and those being considered for antireflux surgery. It is a poor test in predicting Gastroesophageal reflux unless the lower esophageal sphincter pressure is less than 6 mm Hg.

GE scintiscan. In this test, 300 mL of normal saline containing technetium 99m-sulfur colloid is placed into the stomach, and counts over the stomach and esophagus are measured at 30-second intervals while abdominal pressure is increased incrementally using an abdominal pressure cuff. A reflux index is calculated as the number of counts over the esophagus for given 30-second intervals as a percentage of the number of counts initially present over the stomach. The sensitivity and specificity are considered to be 90%. Because external pressure is applied to the abdomen, however, it is not certain that this technique approximates the physiologic situation.

Prolonged pH monitoring. In recent years, prolonged esophageal pH monitoring has become the gold standard for measurement of acid Gastroesophageal reflux. This test provides the most physiologic measurement of acid reflux over 12 to 24 hours in relation to meals, body position, activity, and sleep.

A pH electrode is placed 5 cm above the lower esophageal sphincter, and the pH is charted electronically by a system similar to the Holter monitoring of cardiac rhythm. Patients follow a normal diet with the exception of foods with pH below 5.0. Patients are asked to write down their symptoms and their body position (upright or supine) during the test period. Reflux is defined as the point at which the pH drops to less than 4.0. Each patient’s reflux status is assessed by a composite score that incorporates six components:

• Percent of time of total acid exposure of the esophagus.
• Percent of acid exposure in upright and recumbent positions.
• Presence of reflux episodes.
• Total number of reflux episodes.
• Number of reflux episodes longer than 5 minutes.

The longest reflux (time). This test is excellent in identifying acid Gastroesophageal reflux but does not detect «alkaline» reflux. Prolonged pH monitoring has also been helpful in documenting the suspected association between Gastroesophageal reflux and pulmonary disease.

Esophagogastroduodenoscopy and mucosal biopsy. Flexible fiberoptic endoscopy has become the most widely used method to examine the mucosal surface of the esophagus for evidence of esophagitis. Endoscopic forceps biopsies are adequate for evaluating histologic changes of Gastroesophageal reflux disease. Even when endoscopic appearance of the esophagus is normal, histologic examination of the biopsies may confirm the presence of Gastroesophageal reflux disease.

Findings of esophagitis by endoscopy are as follows:

• Mild. Erythema; edema of the mucosa with obliteration of small, linear blood vessel; mild friability; and increased irregularity of the Z line.
• Moderate-severe. Round and longitudinal superficial ulcers or erosions, diffusely hemorrhagic mucosa with exudates, and deep, punched-out esophageal ulcers and strictures.
• Histology. In patients with Gastroesophageal reflux disease, there is a hyperplasia of the basal cell layer of the squamous epithelium. This layer constitutes more than 15% of the epithelial thickness. The dermal papilla extends more than 65% of the distance to the epithelial surface. Polymorphonuclear leukocytes and eosinophils may be seen in the lamina propria and may invade the epithelium. Ingrowth of capillaries is also seen in the lamina propria.

In about 10% to 20% of the patients with chronic Gastroesophageal reflux disease, a specialized columnar metaplastic epithelium (Barrett’s epithelium) is present. Endoscopic examination of the stomach and the duodenum can rule out other possible lesions in these areas.

Summary

For the diagnosis of Gastroesophageal reflux disease, most patients with the classic symptoms of Gastroesophageal reflux disease of heartburn or regurgitation are given an empiric trial of medical therapy without further investigation. Endoscopy and mucosal biopsies are recommended in patients with refractory symptoms, odynophagia, dysphagia, and atypical symptoms and in patients when Barrett’s esophagus is suspected (e.g., those patients with Gastroesophageal reflux symptoms for more than 5 years). Prolonged pH monitoring and manometry are reserved for patients with atypical symptoms and pulmonary complaints.

Jennifer Bowles

Jennifer is a clinical pharmacologist. She helps doctors of all medical specialties choose medications. Jennifer consults about drug dosage, interactions, and side effects.