Symptoms of

Acid reflux

disease [GERD]

The symptom complex of GERD ranges from

typical anginal pain to almost classic asthmatic attacks

Typical symptoms of acid reflux are heartburn, dysphagia, water brash (heartburn with regurgitation of sour fluid or almost tasteless saliva into the mouth), and regurgitation. Examples of atypical, extraesophageal symptoms, which occur in 10% to 20% of patients with GERD, are cough, asthma, hoarseness, and sore throat. Acid reflux is also associated with noncardiac chest pain, as determined by 24-hour pH monitoring that shows changes in pH directly related to reflux episodes. Effective acid reflux relief treatment will resolve the chest pain.

"While in the past it was understood that the lower esophageal sphincter was not doing its job properly in patients with acid reflux," said Dr. Brazer, " we also believed that the upper esophageal sphincter (UES) acted as a barrier to further entry of acid into the airway. But we now know there is no upper esophageal sphincter tone when a person sleeps, and that the UES relaxes when acid is placed in the esophagus or the esophagus is abruptly dilated."

Thus, the UES doesn't function well when gastric contents reflux into the esophagus, and this sets the stage for damage to the larynx and airway structures. While the esophagus can tolerate intermittent attacks of acid, even a very brief exposure of acid on the larynx or in the trachea is extremely damaging.

Recent studies have shown that in patients with both asthma and GERI), approximately 80% improved with Nissen fundoplication surgery compared to about 4% to 8% treated with ranitidine and antacid alone. "A big advance that has occurred in the last 2 or 3 years is laparoscopic Nissen fundoplication," said Dr. Brazer.

Dr. Brazer recommended that physicians consider a diagnosis of acid reflux in patients with asthma, hoarseness, or chest pain who have been unresponsive to medication. At the same time, physicians must be very careful to differentiate the patient in whom acid reflux is the true cause of their symptoms versus only an association.

"You start with the history," said Dr. Brazer. "You'd like to see the cough or chest pain worsen after meals or when they lay down, and you'd like to see them get better with medical treatment for GERD. And pH testing is very helpful. "
Diagnostic Testing in acid reflux: When Is It Needed?

Stephen A. McClave, MD, Associate Professor at the University of Louisville School of Medicine in Louisville, Ky, began by pointing out that among the tests used to make a diagnosis of acid reflux, "some have more value than others-some are worthless, some are great."

Whether or not the physician embarks on a diagnostic workup depends on how the patient presents, his or her age, and the presence or absence of complications. Dr. McClave went on to discuss factors requiring an immediate diagnostic workup: increased age, atypical symptoms, and complications such as dysphasia, weight loss, or evidence of gastrointestinal (GI) bleeding.

Available diagnostic tests for acid reflux, provide different levels of information. "An upper GI series has only limited value, and a radioisotope scintiscan shouldn't be ordered," said Dr. McClave. Any time a patient swallows during an upper GI series, the LES will relax, allowing barium to pass up into the esophagus. And a radioisotope scintiscan does not differentiate a patient with reflux disease from a patient having a normal amount of physiologic reflux." However, an upper GI series can document complications of reflux disease such as stricture, esophageal ulcer, or adenocarcinoma arising in a Barrett esophagus.

Endoscopy is not as helpful as one would think, since half of the patients with severe symptoms of acid reflux will have a normal endoscopy. However, an abnormal endoscopy identifies patients who may respond somewhat better to acid-reducing medication.

Where reflux disease is suspected in patients with normal endoscopy, it is helpful to biopsy the distal esophagus for evidence of inflammatory infiltrate, increase in the length of the rete pegs, and an increase in the basal cell layer of the squamous epithelium. However, 20% of the normal population will also show these changes.

Dr. McClave then discussed the value of esophageal motility testing, particularly in patients whose endoscopy is negative. This test is helpful in determining those patients who may be at risk for acid reflux (based on low-amplitude contractions or hypointensive lower esophageal sphincter) as well as those patients whose noncardiac chest pain may be related to an esophageal dysmotility syndrome. Provocative tests designed to reproduce the patient's symptoms can also be done at the end of motility testing.

"The test that comes as close to the 'gold standard' as we're going to get is ambulatory 24-hour pH monitoring," said Dr. McClave. Alterations in pH patterns are analyzed by computer and compared to symptoms described in a patient diary. Also valuable is simultaneous monitoring of 24-hour pH and esophageal motility.

Dr. McClave warned that if coronary artery disease is suspected, a cardiologist should first clear the patient before the physician embarks on diagnostic testing for acid reflux.
Promotility Approach to acid reflux Therapy

"Acid reflux results from an impairment of both motility of the esophagus, either of the esophageal body or its sphincters, and an overlapping impairment of motility in the stomach, either of peristalsis or dysrhythmias," said Richard W. McCallum, MD, Professor of Internal Medicine at the University of Virginia Health Sciences Center at Charlottesville, Va. "This combination leads to reflux of gastric contents, particularly acid and pepsin." In addition, the motility component is often linked to, and can overlap, diffuse motility abnormalities ranging from gastroparesis to small bowel and colon involvement.

Dr. McCallum described acid reflux as a multifactorial disorder. Possible factors include impairment of transient LES relaxation, impaired LES tone, slow gastric emptying, impaired peristalsis or salivation in the esophagus, and compromised mucosal integrity. "But the problem is rarely by , persecretion of acid; the acid is just being exposed to a susceptible esophagus for too long," said Dr. McCallum.

Management of acid reflux is based on addressing some of the pathophysiologic abnormalities. Strategies include lifestyle reordering, symptom relief by self-medicating, acid suppression, prokinetic drugs, and, finally, surgery. Dr. McCallum pointed out that lifestyle reordering is of vital importance. "Unless patients actually lose weight, stop smoking, and reassess the timing and volume of meals, as well as their fat content, they can sabotage the efficacy of any drug therapy."

The newest advance in treatment is prokinetic therapy. Metoclopramide is an efficacious drug, but for potentially life long therapy, its use has been limited by its extrapyramidal side effect profile and its central nervous system (CNS) effects such as drowsiness and lassitude, which occur in approximately 30% of patients. While erythromycin is also a prokinetic, it is not that efficacious, according to Dr. McCallum, and is not indicated for the treatment of acid reflux.

The introduction in 1993 of cisapride following FDA approval for the treatment of nocturnal heartburn due to acid reflux has revived interest in the use of prokinetics in addressing the cause of reflux disease. Cisapride improves LES sphincter pressure, stimulates esophageal motility, enhances salivation, and enhances gastric emptying of liquids and solids.

It has a unique site-specific mechanism of action, producing targeted effects on GI motor function-restoring and facilitating motility and transit throughout the GI tract, while decreasing esophageal mucosa contact time with acid, pepsin, and bile. And it does so without causing unwanted cholinergic effects elsewhere in the body and without any dopamine-mediated sequela.

Cisapride has no CNS side effects and does not increase acid secretion. Its only side effects are a slight headache, some initial increase in stool frequency, and increased secretion of saliva.

"Cisapride may be the optimal therapy for phase 2 treatment of acid reflux, where patients are being treated in the primary care setting," stated Dr. McCallum. It is particularly helpful for patients who experience nocturnal heartburn, regurgitation, and postprandial satiety, bloating, fullness, nausea, and indigestion,

Dr. McCallum suggested that for patients with stage 3 acid reflux who show only modest improvement, combination therapy with cisapride and an H,, blocker may prove helpful until control of'symptom relief has occurred. In patients refractory to this approach when the endoscopy shows grade III changes (severe erosions, ulceration, and/or stricture, and/or Barrett), oineprazole is indicated for short-term (up to 2 months) symptom control and healing. Then tapering the dose or alternating omeprazole and cisapride on different days is recommended. In patients with severe reflux where bile reflux may also be occur ring, omeprazole does not prevent regurgitation of bile and other gastric contents.

Dr. McCallum emphasized that acid reflux is a lifelong disease that requires long-term therapy. The term maintenance therapy is misleading, since the dose for long-term efficacy may often be the same dose used initially for symptom control and/or healing. This means continuing to use the same dose it took to control the original symptoms. Dr. McCallum concluded by saying, "Cisapride makes sense as a medication for GERD initially and for long-term use, since it addresses the pathophysiology of acid reflux in a physiologic and very safe manner."
The Difficult Patient With acid reflux

Management of the difficult patient-the one with atypical manifestations of acid reflux who is not responding to therapy-was discussed by Jeffrey B. Raskin, MD, Professor of Medicine at the University of Miami School of Medicine at Miami, Fla. He suggested that physicians begin by evaluating patient compliance with recommended lifestyle changes such as diet, weight loss, and smoking, as well as compliance with medication therapy.

"It's difficult for people to make changes in lifestyle when it comes to diet. But chocolate, peppermint, and foods with high fat content really have to be eliminated, since they reduce LES pressure. And foods that directly irritate the esophageal lining should be eliminated, such as coffee, tomato-based products, and citrus fruits. Sometimes that's all that's necessary."

Another management strategy is to use higher and more frequent dosing of H2 antagonists than are traditionally used for peptic ulcer disease. Some studies with ranitidine suggest that qid dosing may be required to get adequate esophageal healing and symptom relief The combination of highdose H2 blockers, plus a Prokinetic agent, may be beneficial in some individuals.

Patients should be questioned about other medications they are taking, since a number of drugs have been known to interfere with the management of acid reflux. Examples are quinidine, tetracycline, birth control pills, theophylline, and especially the nonsteroidal antiinflammatory agents. When any of these are present, an attempt should be made to discontinue them if possible.

In conclusion, Dr. Raskin pointed out that the diagnosis may require re-evaluation through further testing, such as endoscopy in the difficult-to-manage patient, to rule out a variety of conditions. Some of these conditions are scleroderma, periesophageal hernia, cardiac disease, emotional problems with pain syndromes, motility disturbance of the esophagus, Barrett's epithelium, esophageal cytomegalovirus infections, and adenocarcinoma.

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  Acid reflux Symptoms and Signs

  TYPICAL SYMPTOMS
   Heartburn
   Dysphagia
   Water brash
   Regurgitation

ATYPICAL (EXTRAESOPHIGEAL) SYMPTOMS

Pulmonary
Cough
Asthma
Bronchitis
Pneumonia
Interstitial lung disease

Head and neck
Hoarseness
Sore throat
Pharyngitis
Loss of dental enamel
Chest pain

Last updated Jan 4/07