eMedicine Feature Series

Gastroesophageal Reflux Disease Newsletter _________ Series 1, Issue 5, 2007

CLINICAL MANIFESTATIONS AND DIAGNOSIS OF GERD

Xaralambos Zervos, DO
Mount Sinai Medical Center

Nikolaos Pyrsopoulos, MD, PhD
Florida Hospital

INTRODUCTION

Gastroesophageal reflux disease (GERD) is now widely accepted as the abnormal reflux of gastric contents into the esophagus, with the refluxed contents not limited to only acid. As a result of this definition, the term acid reflux is no longer accurate for patients who present with the cardinal symptoms of reflux disease (ie, heartburn, regurgitation, or dysphagia). In fact, patients may be appropriately diagnosed with GERD and treated for the condition even if they do not present with the cardinal symptoms.

Other symptoms of GERD may constitute an atypical presentation of the condition. Such symptoms include chest pain, recurrent sinusitis, chronic cough, hoarseness, asthma, laryngitis, and middle ear infections. Taken together, these "atypical" symptoms account for a significant number of primary care office visits. At times, identifying the underlying etiology and, thus, the effective treatment and management can be challenging for clinicians. When the accepted treatment for these symptoms fails or the usual workup does not reveal a cause for the symptoms, GERD should be considered as a possible underlying etiology. Thus, awareness of both the typical and atypical manifestations of GERD is important for the clinician. As diagnostic studies remain far from perfect, the clinical presentation of the patient remains vital in the guidance of management.

Therapy should be initiated early, with a targeted goal of improved quality of life and prevention of complications. Several trials of patients who were treated with proton pump inhibitor (PPI) therapy have demonstrated improvement of symptoms. Questionnaires administered by de Souza and colleagues demonstrated improved quality of life and decreased esophagitis in the patients.¹ The effectiveness of PPI therapy has also created a challenge in the diagnosis and treatment of patients who present for specialized evaluation, as suppressive therapy initiated by the primary care physician or the patient himself may affect the ability to make a definitive diagnosis.

TYPICAL MANIFESTATIONS

Heartburn and regurgitation

The cardinal symptom of GERD is heartburn. Heartburn due to GERD accounts for an estimated 2-5% of all primary care visits, with 40% of the population in the United States experiencing symptoms of GERD.

Heartburn commonly precedes the other manifestations and is the most common GERD-related symptom for which patients seek medical attention. It is often associated with other typical symptoms, such as regurgitation, dysphagia, and odynophagia. Heartburn, acid reflux, or both at least once weekly are reported by 20% of adults; 40% report having these symptoms at least once a month. A significant percentage of chest pain that is noncardiac in origin can be attributed to heartburn-related GERD. Therapy for patients with these symptoms should be initiated early with a targeted goal of improved quality of life. Many completed randomized trials have provided strong evidence that treatment, specifically with PPIs, offers significant resolution to GERD symptoms. Fass and colleagues demonstrated that patients with persistent heartburn may require doubling the dose of medication or changing to another PPI to obtain satisfactory symptom relief.²

Dysphagia and odynophagia

Patients with GERD may develop discomfort or pain with swallowing if the esophagus has been exposed to enough acid to allow for local irritation, inflammation, or even ulceration of the esophageal mucosa. Dysphagia is one of the alarm signs (along with recent weight loss and blood in the stool) of which physicians need to be aware when treating patients with GERD. Patients with dysphagia require immediate attention, and endoscopy should be performed for direct visualization of the mucosa and initiation of appropriate pharmacologic therapy. PPIs remain at the forefront when treating these patients. Clinical trials have shown that patients with dysphagia experience symptom relief as early as one day after initiation of treatment.³ Endoscopic findings on these patients after treatment with PPIs have demonstrated esophageal healing in 77% of patients at 4 weeks posttreatment and in 90% of patients at 8 weeks posttreatment.³

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ATYPICAL (EXTRAESOPHAGEAL) MANIFESTATIONS

The association of GERD with atypical clinical symptoms or manifestations is still being defined. However, when such symptoms are present in patients, the symptoms should be considered as possible evidence for the presence of reflux disease. These symptoms include but are not limited to chest pain, sialorrhea, hoarseness, globus sensation, chronic coughing, episodic bronchospasm, asthma, hiccup, eructations, throat clearing, laryngitis, and pharyngitis.

Globus and hoarseness

Efforts to prospectively evaluate this have been attempted by both Noordzij et al and El-Serag et al, using groups of 53 and 22 patients, respectively.^4,5 Both studies were randomized double-blind placebo trials. Noordzij found that treatment with omeprazole 40 mg twice a day versus placebo demonstrated statistical significance in improvement for hoarseness and throat clearing only.⁴ El-Serag did not achieve any statistical differences between treatment with lansoprazole 30 mg twice a day and treatment with placebo.⁵

Asthma

GERD has been reported to occur in 30-80% of patients with asthma. GERD may exacerbate or even be the cause of asthma, but no definite association between the two conditions has been effectively shown. El-Serag and Sonnenberg looked at over 100,000 cases in the Veterans Administration system.⁶ Their objective was to compare patients with esophagitis to a controlled group and account for symptoms of GERD in each group. Their analysis concluded that patients with esophagitis are more likely than those without esophagitis to have not only asthma but other pulmonary diseases as well.

Kiljander and colleagues recently performed a randomized double-blind study to evaluate the effect of esomeprazole 40 mg twice a day in patients with asthma and GERD.⁷ Their findings were that patients’ peak expiratory flow rates statistically improved in the morning and evening when compared to the placebo group.

Chronic cough

GERD is considered to account for about 40% of patients who present with chronic cough. The American College of Chest Physicians guidelines on cough associated with GERD, as outlined by Irwin, caution that even after empiric trials of PPIs, GERD cannot adequately be ruled out as the cause of persistent cough.⁸ Acid is not the only cause of GERD; other gastric contents, such as alkaline pH, pancreatic enzymes, and bile, can also stimulate cough.

Many trials have been performed to evaluate the treatment of GERD, and its implicated role on cough, with empiric medical interventions. The variation in reported results is, in large part, because of the differences in dosage and scheduling of medication. One year after antireflux surgery on patients whose GERD has not responded to medical intervention, more than 80% of patients achieve relief from cough.⁹

Chronic sinusitis

Chronic sinusitis is a common clinical condition. Increasing data from observational studies indicate that both pediatric and adult patients with chronic sinusitis frequently have associated GERD. GERD might contribute to the pathogenesis of chronic sinusitis by causing sinonasal congestion, compromised sinus drainage, and inflammation. This association of chronic sinusitis with GERD remains relatively unproven, and additional randomized trials need to be performed before any further conclusions can be drawn.

Otitis media

Otitis media with effusion is a prevalent condition commonly associated with hearing loss in childhood. Tasker and colleagues reported high concentrations of pepsin/pepsinogen in 59 of 65 middle ear effusion samples from children with otitis media.¹⁰ Further testing is required, as Tasker concluded a possibility of gastric contents from reflux being the cause of otitis media with effusions.

Poelmans and colleagues looked at the association of GERD with patients who have chronic otitis media with effusions.¹¹ Of the patients studied, 5 had chronic secretory effusions and 16 had chronic refractory sensation of pressure in the ears. These patients were treated with omeprazole twice a day. More than 80% of patients experienced complete resolution of symptoms.

DIAGNOSTIC TESTING

Barium evaluation

Barium esophagrams remain a staple in the initial evaluation of patients with upper GI symptoms. However, the utility of this test in diagnosing GERD is limited because the test is only useful in the presence of abnormal structural pathology such as hiatal hernias, peptic esophageal strictures, or dysfunction of the opening of the lower esophageal sphincter.

Upper GI endoscopy

The benefit of esophagogastroduodenoscopy (EGD) for evaluation of patients with GERD lies in the test’s ability not only to directly visualize the esophagus and the other associated structures but also to obtain biopsies and eliminate other potential etiologies of symptoms that are suggestive of reflux disease. The direct visualization also allows clinicians to quantify the degree of erosive esophagitis present using standard scales like the Savary-Miller classification and the Los Angeles classification.

Savary-Miller classification

Grade I - Single or multiple erosions on a single fold
Grade II - Multiple erosions on multiple folds
Grade III - Multiple circumferential erosions
Grade IV - Ulcer, stricture, and esophageal shortening
Grade V - Barrett epithelium

Los Angeles classification

Grade A - Mucosal break shorter than 5 mm
Grade B - Mucosal break longer than 5 mm
Grade C - Mucosal break in at least 2 continuous gastric folds
Grade D - Mucosal break in at least 75% of the circumference of the esophagus

Patients with atypical symptoms of GERD seem to have a low incidence of endoscopic findings that are suggestive of esophagitis. Esophagitis has been reported in about 10-30% of patients with atypical GERD, while patients with typical GERD present with esophagitis 50% of the time.

The use of EGD in the diagnosis of GERD is losing favor primarily because more and more patients are being started on acid suppressive therapy prior to visiting a gastroenterologist, which is when an EGD would be performed. Because PPIs heal the erosive esophagitis present in up to 90% of patients, endoscopy procedures performed after acid suppressive therapy is started tend to reveal mucosa with a normal or improved appearance.

pH monitoring

Esophageal pH monitoring is considered by many investigators as the criterion standard in diagnosing GERD. Measuring esophageal acid exposure in the distal esophagus allows clinicians to diagnose GERD even in the absence of endoscopic visible lesions. Newer wireless tools like the Bravo pH Monitoring System (Medtronic, Minneapolis, Minn) are available and increase the testing time tolerated by patients. Gillies and colleagues found that patients who were tested with the catheter-free Bravo system experienced significantly less discomfort during placement of the device, monitoring, eating, sleeping, and work and experienced less interference with daily activities than patients who used the nasoesophageal catheter.¹² They also concluded an advantage with the Bravo system to the ability to appropriately diagnose GERD.

Currently, the most accepted criterion to identify an episode of GERD during pH monitoring is a sudden change in intraesophageal pH level from above 4.0 to below 4.0. In the 1970s, Johnson and DeMeester published a set of normal values for pH monitoring that included criteria to separate normal from pathologic esophageal acid exposure.¹³ This set of values, still widely accepted by many centers, includes the following:

Percentage of total time that pH level is less than 4
Percentage of upright time that pH level is less than 4
Percentage of recumbent time that pH level is less than 4
Number of reflux episodes
Number of reflux episodes with pH level less than 4 for longer than 5 minutes
Duration of the longest single acid exposure episode

Of course, pH monitoring has limitations in making a firm diagnosis that excludes GERD. Increasing evidence indicates that gastric material other than acid may also be responsible for GERD, so the absence of a sudden decrease in intraesophageal pH level may not exclude GERD. In addition, the recent advances in public knowledge of acid suppressive therapy, specifically with OTC omeprazole, bring new challenges to the gastroenterologist in making a diagnosis of GERD. The power of a diagnostic study aimed at detecting acid is diminished if the patient is self-treating with acid suppressive therapy.

CONCLUSION

Much remains to be learned about GERD and its numerous manifestations. Diagnosing patients with GERD is a challenging and evolving process. The communication and patience of both practitioner and patient are vital to the success of treatment. Adequate control and resolution of symptoms vary from patient to patient and may require multiple pharmacologic changes in regimen and dosing. The amount of time needed to achieve satisfactory results varies, which makes GERD a formidable entity for practitioners to manage. Twice-daily dosing of PPIs has been widely accepted as treatment, and trials of this treatment have shown benefit for both the symptoms of GERD and the treatment of esophagitis. The role of antireflux surgery in this patient population has not yet been fully elucidated.

REFERENCES

1. De Souza CM, Ferrari AP, Ciconelli R, et al. Evaluation of health-related quality of life in gastroesophageal reflux disease patients before and after treatment with pantoprazole. Dis Esophagus. 2006;19(4):289-93.

2. Fass R, Sontag SJ, Traxler B, Sostek M. Treatment of patients with persistent heartburn symptoms: a double-blind, randomized trial. Clin Gastroenterol Hepatol. 2006;4(1):50-6.

3. Archimandritis AJ, Nikolopoulou V, Kouklakis G, et al. Effects of rabeprazole on early symptom relief in gastro-oesophageal reflux disease: the Hellenic Rabeprazole Study Group surveillance study. Curr Med Res Opin. 2005;21(4):603-10.

4. Noordzij JP, Khidr A, Evans BA, et al. Evaluation of omeprazole in the treatment of reflux laryngitis: a prospective, placebo-controlled, randomized, double-blind study. Laryngoscope. 2001;111:2147-51.

5. El-Serag HB, Lee P, Buchner A, et al. Lansoprazole treatment of patients with chronic idiopathic laryngitis: a placebo-controlled trial. Am J Gastroenterol. 2001;96(4):979-83.

6. El-Serag HB, Sonnenberg A. Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in United States military veterans. Gastroenterology. 1997;113(3):755-60.

7. Kiljander TO, Harding SM, Field SK, et al. Effects of esomeprazole 40 mg twice daily on asthma: a randomized placebo-controlled trial. Am J Resp Crit Care Med. 2006;173(10):1091-97.

8. Irwin RS. Chronic cough due to gastroesophageal reflux disease: ACCP evidence-based clinical practice guidelines. Chest. 2006; 129(1 Supp):80S-94S.

9. Novitsky YW, Zawacki JK, Irwin RS, et al. Chronic cough due to gastroesophageal reflux disease: efficacy of antireflux surgery. Surg Endosc. 2002;16:567-71.

10. Tasker A, Dettmar PW, Panetti M, et al. Is gastric reflux a cause of otitis media with effusion in children? Laryngoscope. 2002;112:1930-4.

11. Poelmans J, Tack J, Feenstra L. Prospective study on the incidence of chronic ear complaints related to gastroesophageal reflux and on the outcome of antireflux therapy. Ann Otol Rhinol Laryngol. 2002;111:933-8.

12. Gillies RS, Stratford JM, Booth MI, Dehn TC. Oesophageal pH monitoring using the Bravo catheter-free radio capsule. Eur J Gastroenetrol Hepatol. 2007;19(1):57-63.

13. Johnson LF, Demeester TR. Twenty-four-hour pH monitoring of the distal esophagus. A quantitative measure of gastroesophageal reflux. Am J Gastroenterol. 1974;62:325-32.