What is acid reflux?

Endoscopy

Upper endoscopy is the current standard for documenting the type and extent of mucosal injury to the esophagus. It identifies the presence of esophagitis and excludes other causes of the patient’s complaints. However, only 40% to 60% of patients with abnormal esophageal reflux by pH testing have endoscopic evidence of esophagitis. Thus, the sensitivity of endoscopy for GERD is 60% at best, but it has excellent specificity, at 90% to 95%.

The earliest endoscopic signs of acid reflux include edema and erythema. Neither finding is specific for GERD, and both are very dependent on the quality of endoscopic visual images. More reliable are the findings of friability, granularity, and red streaks. Friability (easy bleeding), occurring with gentle pressure on the mucosa, results from the development of enlarged capillaries near the mucosal surface in response to acid. Red streaks may extend upward from the esophagogastric junction along the ridges of the esophageal folds. In studies evaluating these stigmata, nearly all patients had GERD. With progressive acid injury, erosions develop. These are characterized by shallow thinning of the mucosa associated with a white or yellow exudate surrounded by erythema. Commonly located just above the esophagogastric junction, erosions may be either single lesions or coalesced regions. Typically, they occur along the tops of mucosal folds, areas most prone to acid exposure. Erosions may also be caused by nonsteroidal antiinflammatory drug use, heavy smoking, and infectious esophagitis. Ulcers reflect more severe esophageal damage. They penetrate the mucosa, tend to have either a white or yellow discolored base, and may be seen either isolated along a fold or surrounding the esophagogastric junction.

Endoscopic grading of GERD depends on the endoscopist’s interpretation of these visual images. Unfortunately, there exists no standard classification scheme for endoscopic findings. Instead, several grading systems are available, but none are completely satisfactory. In Europe, the most popular scheme is the Savary-Miller classification, which is based on degree of mucosal erosions. In the United States, the Hetzel and Los Angeles systems are most popular. The Hetzel system grades severity not by the number of erosions but by the area of mucosal injury. In the Los Angeles system, the number, length, and location of mucosal breaks determine the degree of esophagitis. These different classification systems diverge the most when defining the subtlest degree of injury. When erythema, edema, and an indistinct Z-line are included, the sensitivity of diagnosing GERD rises at the expense of specificity.

Most patients with GERD are treated initially without endoscopy. The important exception is the patient experiencing alarm symptoms: dysphagia, odynophagia, weight loss, and gastrointestinal bleeding. With such symptoms, endoscopy should be performed early to rule out other entities such as infections, ulcers, cancer, or varices.

The role of endoscopy in GERD in the absence of alarm symptoms is more controversial and is evolving in the era of PPI therapy. Initially, endoscopy was used to place patients into two groups—those with nonerosive or mild disease and those with severe erosive disease—and to direct their treatment more precisely. However, this practice is now less popular with the use of PPIs as the first line of therapy for GERD. Because these drugs treat both groups equally well, early endoscopy has less impact on the choice of therapy. Currently, the most important reason for performing endoscopy in patients with GERD is to identify peptic strictures or Barrett esophagus. Using this rationale, most patients with chronic GERD need only one endoscopic examination while they are receiving therapy.

Esophageal Biopsy

The ability to obtain tissue during endoscopy is very important. Biopsies of the esophagus help to identify reflux injury, exclude other esophageal diseases, and confirm the presence of complications, especially Barrett esophagus. Microscopic changes indicative of reflux may occur even when the mucosa appears normal endoscopically. In patients with classical esophagitis, biopsies are usually not taken unless they are needed to exclude other diagnoses such as neoplasm, infection, pill injury, or bullous disease. When Barrett esophagus is suspected, biopsies are mandatory and are best done when esophagitis is healed.

The most sensitive histological markers of GERD are reactive epithelial changes characterized by an increase in the basal cell layer greater than 15% of the epithelium thickness or papilla elongation into the upper third of the epithelium. These changes represent increased epithelial turnover of the squamous mucosa. Papilla, or rete peg, height increases as a result of loss of surface cells from acid injury, whereas basal cell hyperplasia is indicative of mucosal repair. Unfortunately, these changes are also noted in up to 50% of healthy persons when biopsies are taken from the distal 2 to 3 cm of the esophagus. Hence, the changes are sensitive markers for GERD but have poor specificity.

Acute inflammation characterized by the presence of neutrophils and eosinophils is very specific for esophagitis. Acid reflux injury to the vascular bed of the esophagus releases vasoactive substances that promote edema and migration of neutrophils and eosinophils into the area. Neutrophils are specific for acute esophagitis but are an insensitive marker, being present in only 15% to 40% of patients with GERD. Eosinophils are found more often on biopsy (19% to 63% of subjects) but are less specific, present in up to 33% of healthy adults. Interestingly, the sensitivity and specificity of eosinophils in children are much stronger, reflecting the lack of eosinophils in the juvenile inflammatory response.