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Severe GERD: Effective treatment prevents potentially serious complicationsWhen left untreated—or when treated inadequately—severe gastroesophageal reflux disease can progress to esophagitis, ulcers, laryngeal disease, chronic cough, Barrett's esophagus, and esophageal adenocarcinoma.Elizabeth A. Featherstone, MMS, PA-CThe author works in an internal medicine practice with William Grubbs, MD, in Naples, Fla. She has indicated no relationships to disclose relating to the content of this article.
An estimated 44% of the 61 million adults living in the United States have heartburn, the hallmark of acid regurgitation, at least once a month.1 In most cases, no serious or permanent damage results; but in some people, chronic heartburn, known as gastroesophageal reflux disease (GERD), may cause serious complications such as esophagitis, peptic strictures, ulcers, laryngeal disease, chronic cough, asthma, Barrett’s esophagus, and adenocarcinoma. GERD is usually caused by an abnormality of function or a mechanical problem in the relaxation of the lower esophageal sphincter (LES), which allows the stomach contents to reflux into the esophagus. Severe GERD is a common, chronic, relapsing condition in which a patient continues to have acid breakthrough even while taking acid suppression therapy or redevelops GERD symptoms after cessation of therapy. Severe GERD is associated with a risk of significant morbidity and the possibility of mortality from complications. Complications of severe GERDEsophagitis, an inflammation of the lining of the esophagus, affects up to 50% of patients with reflux. It can cause bleeding and ulcers, and it occurs with repeated and prolonged acid exposure. Esophagitis is classified into four grades based on severity: grade I—erythema; grade II—linear nonconfluent erosions; grade III—circular confluent erosions; and grade IV—stricture or Barrett's esophagus. Grade IV or Barrett's esophagus can progress to adenocarcinoma with chronic reflux.2 Esophageal stricture is a narrowing of the inner part of the esophagus, caused by scar tissue located mainly in the distal esophagus. Repeated damage to the esophageal epithelium caused by acid reflux forms the scar tissue. Symptoms of dysphagia may develop as strictures form in the esophagus, thus making it difficult for a patient to swallow solids and eventually liquids. Strictures rarely form without other GERD complications. Barrett's esophagus occurs when the injured squamous lining of the esophagus is replaced by Barrett's metaplasia, a precancerous tissue in which adenocarcinoma can develop.36 The chances of a patient developing esophageal adenocarcinoma are even greater if high-grade dysplasia is present. Barrett's esophagus without dysplasia progresses to high-grade dysplasia in 5% of patients at 5 years. In contrast, low-grade dysplasia progresses to high-grade dysplasia in 25% of patients at 5 years.7 Barrett's esophagus does not always progress to esophageal adenocarcinoma.8 Esophageal adenocarcinoma is a rare condition that arises from Barrett’s esophagus. Lack of symptoms is one characteristic that distinguishes this disease from GERD. Usually esophageal adenocarcinoma is not detected until the patient presents complaining of dysphagia and weight loss. Esophageal cancer in patients presenting with these symptoms is usually incurable. Median survival is 2 years, and fewer than 10% of patients survive for 5 years.9 History and differential diagnosisThe practitioner should usually base the diagnosis of GERD on clinical findings and confirm it by the patient’s response to therapy. Further evaluation will be necessary if symptoms are chronic or refractory to therapy or if complications develop. Warning signs and symptoms that may suggest severe GERD or its complications include iron deficiency anemia, dysphagia, early satiety, GI bleeding, odynophagia, vomiting, unexplained weight loss, choking, and chest pain.10 A careful history and physical examination are needed to help establish the diagnosis in a patient with severe GERD, with the knowledge that most of the information will be obtained from the history. When a patient has a history of chronic GERD or has been taking medication longterm for acid suppression, the clinician should inquire about any break-through acid reflux and whether the patient uses any OTC medication for acid suppression. The history should include questions about heartburn, acid regurgitation, difficulty swallowing, cough, hoarseness, sore throat, sinusitis, or chest pain.
Unexplained chest pain should be evaluated for cardiac causes; if the patient has a burning feeling that is relieved by nitroglycerin, the cause could be cardiac instead of GERD. Esophageal spasm can cause chest pain, as can costochondritis. A patient with achalasia may present with heartburn. When proton pump inhibitor (PPI) therapy fails to relieve symptoms, GERD may be the wrong diagnosis. Certain medications (calcium channel blockers, nitrates, and ß-blockers), foods (coffee, chocolate, nicotine, and alcohol), or hormones (progesterone) can decrease LES pressure. Obesity increases intra-abdominal pressure and is often a contributory factor in decreased LES pressure as well.11 Some of the reasons that acid suppression therapy may not be working include poor adherence and, in some cases, inability to metabolize the drug given.12
If the patient has been taking medications long-term, be sure to ask about severe GERD symptoms (see Table 2). While performing the physical examination, make sure to check in the mouth for dental erosion. Diagnostic testingDiagnostic testing for GERD should be reserved for patients who do not respond to medication; who have unexplained GI bleeding, dysphagia, or weight loss; or who are at risk for complications such as adenocarcinoma, Barrett’s esophagus, esophageal stricture formation, or esophagitis. Barium esophagography is the initial test to evaluate for dysphagia because it will show an ulcer, stricture, or tumor (see Figure 1). Esophagogastroduodenoscopy (EGD) with biopsy might be the next step to help identify esophagitis or Barrett’s esophagus; this is the only test that can confirm Barrett’s esophagus (see Figure 2). Although EGD is the gold standard for assessing esophageal complications of GERD, it is not the most costeffective test. Indications for upper endoscopy are shown in Table 3.
TreatmentThe goal in managing severe GERD is to relieve symptoms and heal any lesions. Even during treatment for severe GERD, the patient should work on modifying contributing factors such as diet and obesity. Protonpump inhibitors have become the cornerstone of treatment for erosive esophagitis. Meta-analyses have documented their superiority to H2-receptor antagonists for healing erosive esophagitis.15 The clinician may find, after reviewing how the patient is taking the medication, that directions are not being followed. Patients should take PPIs 30 to 60 minutes before the first meal of the day. An H2 blocker can be added 30 minutes before the evening meal if the PPI has begun to wear off. If patients complain that they are still having acid reflux, the practitioner can increase the PPI therapy to twice a day for 3 months or consider switching to a different PPI. For patients with chronic or severe GERD, the potential benefit of long-term PPI therapy generally outweighs the risk of adverse events. The most common side effects include headache and diarrhea. Rarely, cobalamin absorption is slightly decreased, but a clinically significant decline in serum levels is unusual. The profound reduction in gastric acid secretion induced by PPIs leads to increased gastrin production by antral G cells. Since their release more than 16 years ago, PPIs have not been linked to gastric cancer or carcinoid tumors.16 Metoclopramide (Reglan) is a promotility agent that is used to increase LES strength, which in turn decreases reflux. Motility agents can be used with PPIs, although adverse events may limit the use of metoclopramide. One side effect to consider is tardive dyskinesia, which can be permanent.17 GERDTegaserod (Zelnorm)—a medication that stimulates the 5HT4 receptors, thereby releasing acetylcholine—increases GI motility and is now being studied for possible use in the treatment of GERD.18 A pilot study evaluated the efficacy of four different twice-a-day regimens of tegaserod compared to placebo for reducing esophageal acid exposure by measuring LES pressure and distal esophageal pH. Tegaserod in a dosage of 1 mg/d caused a significant decrease in postprandial esophageal acid exposure. Nonsurgical treatments are available for esophageal stricture, a possible cause of dysphagia and a complication of severe GERD. In one approach, an uninflated balloon is inserted endoscopically into the opening of the stricture. The balloon is then inflated to open the stricture. Surgical dilation through the mouth is another method used to open strictures. A small dilator is used to start, followed by increasingly larger ones, until the stricture is opened. Occasionally, surgery may be necessary to open the stricture. Surgery may be considered when a hiatal hernia must be reduced back into the abdomen, a diaphragmatic hiatus must be repaired, or LES function requires improvement. Indications for surgery may also include Barrett’s esophagus or incomplete symptom control with a PPI. Surgery alleviates heartburn and regurgitation in 75% to 90% of patients but is less effective in relieving extraesophageal symptoms such as cough, asthma, or laryngitis.19 Patients contemplating surgery should be evaluated thoroughly, and procedures should be performed only by an experienced surgeon on a patient with well-documented GERD. Preoperative testing should include barium esophagography, esophageal manometry, 24-hour pH testing, and often, gastric function tests. Esophageal manometry may alter the surgical decision in as many as 10% of cases and should be a routine preoperative procedure.20 The clinician should advise patients that not everyone responds to antireflux surgery and those who do respond may have complications.21 The operation requires a minimal hospital stay, with patients usually returning to work in 5 to 10 days. Antireflux surgery may not be possible in some patients who have had previous upper abdominal surgery and may be less effective in extremely obese patients.22,23 Approximately 20% of patients develop postsurgical complications; some of the more common are solid food dysphagia, gas bloating, diarrhea, nausea, and early satiety. Comparisons of antireflux surgery and antacid therapy in patients with erosive esophagitis have demonstrated marginal superiority for surgery as measured by heartburn relief, esophagitis healing, and improved quality of life. However, longterm followup studies have found that within 3 to 5 years of surgery, 52% of patients are taking antireflux medications again.24 Newer endoscopic modalities, including the Stretta and EndoCinch procedures, are less invasive and have fewer complications than antireflux surgery, but response rates are lower.25 ConclusionPatients who have severe GERD must weigh the benefits and risks of prolonged medical therapy and antireflux surgery. Clinicians should screen for severe GERD in those patients who have been receiving long-term antireflux therapy or who have severe GERD symptoms. The practitioner should advise these patients of warning symptoms for severe GERD. Medical treatments, especially PPIs, are effective for all forms of GERD, although patients will require daily medication for life. PPI treatment is the mainstay of GERD therapy and works in controlling most symptoms. A careful history may reveal that some of those patients who develop severe GERD are not taking their medicine as directed or that they may need to work on losing weight or altering their diet. Chronic severe GERD can lead to serious complications such as esophagitis, peptic strictures, ulcers, and Barrett’s esophagus, which can eventually progress to esophageal adenocarcinoma. To ascertain which treatment would be most beneficial, the clinician should discuss pharmacologic therapy versus surgery with the patient, the gastroenterologist, and possibly a surgeon. REFERENCES
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When a patient presents with refractory or severe heartburn, the differential diagnosis should include those conditions listed in Table 1. If the presenting complaint is a retrosternal burning sensation aggravated by bending and relieved by antacids, the diagnosis is most likely GERD. 
Twenty-four-hour pH monitoring (pH probe) is the accepted standard for establishing or excluding GERD. The probe has a sensitivity of 70% to 96%, but false-positive or false-negative results are possible.13
This test is helpful when the clinician wants to quantify the reflux since it allows the symptoms and the reflux episodes to be associated.14
It is important that pH monitoring be performed when patients are considering antireflux surgery. 