® in the clinic Gastroesophageal Reflux Disease Diagnosis page ITC2-2 Treatment page ITC2-5 Practice Improvement page ITC2-13 CME Questions page ITC2-16 Section Editors The content of In the Clinic is drawn from the clinical information and Christine Laine, MD, MPH education resources of the American College of Physicians (ACP), including David Goldmann, MD PIER (Physicians’ Information and Education Resource) and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine Science Writer editors develop In the Clinic from these primary sources in collaboration with Jennifer F. Wilson the ACP’s Medical Education and Publishing Division and with the assistance of science writers and physician writers. Editorial consultants from PIER and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://pier.acponline.org and other resources referenced in each issue of In the Clinic. The information contained herein should never be used as a substitute for clinical judgment. © 2008 American College of Physicians in the clinic astroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders in Western industrialized countries. Men G and women develop GERD with equal frequency, but complicated GERD occurs more frequently in men and with advanced age. It is typically the result of prolonged exposure of the esophagus to gastric acid due to impaired esophageal motility, defects in the lower esophageal sphincter, and impairments in the antireflux barrier at the gastroesophageal junction. The acid exposure can damage the esophageal mucosa, potentially leading to Barrett’s esophagus and esophageal cancer. GERD is a chronic disease, and many patients require lifelong therapy. Treatment helps to reduce symptoms, promote esophageal healing, and reduce the risk for cancer. Diagnosis What symptoms and signs should When should clinicians consider prompt clinicians to consider an empirical therapeutic trial of Consider GERD in Patients with GERD? acid-suppression therapy to the Following Symptoms Typical GERD symptoms include support a preliminary diagnosis of • Heartburn or regurgitation chest discomfort (heartburn) and GERD? • Wheezing or dyspnea regurgitation. Symptoms occur Performing diagnostic tests for all • Chronic cough patients presenting with symptoms most often after meals, especially • Chronic hoarseness or sore throat that might indicate GERD would fatty meals. Lying down, bending, • Globus be costly and is not necessary to • Throat clearing or physical exertion often aggravate arrive at a sufficiently accurate • Chest pain symptoms, and antacids provide diagnosis. Response to an empirical • Halitosis relief. Patients with classic symp- trial of acid-suppression therapy is toms rarely require testing to con- considered a sufficiently sensitive firm the diagnosis because of the and specific method for establishing high positive predictive value of a GERD diagnosis among patients classic symptoms (1). When heart- with classic symptoms of heartburn burn (89% specificity, 81% positive or regurgitation. Although proton pump inhibitors (PPIs) are more 1. DeVault KR, Castell predictive value) and regurgitation DO. Updated guide- (95% specificity, 57% positive pre- expensive than H2-receptor blockers, lines for the diagnosis and treatment of gas- dictive value) occur together, a PPIs are considered the drug of troesophageal reflux choice for an empirical therapeutic disease. Am J Gas- physician can diagnose GERD with troenterol. 2005; trial because they block acid more 100:190-200. greater than 90% accuracy (2). [PMID: 15654800] effectively than H2-receptor blockers. 2. Klauser AG, Schindl- An empirical trial typically consists beck NE, Müller- GERD can also cause extra- Lissner SA. Symptoms esophageal symptoms, including of a double-dose of a PPI (such as in gastro-oesophageal omeprazole 20 to 40 mg twice reflux disease. Lancet. wheezing, chronic cough, shortness 1990;335:205-8. daily) for 1 week or a standard-dose [PMID: 1967675] of breath, hoarseness, unexplained 3. Fass R, Ofman JJ, PPI (such as omeprazole 20 to 40 Sampliner RE, et al. chest pain, globus (choking sensa- The omeprazole test mg once daily) for 2 weeks. is as sensitive as 24-h tion), halitosis, and sore throat or a oesophageal pH sense of needing to clear one’s A study that compared 24-hour pH moni- monitoring in diag- nosing gastro- throat. Up to 80% of patients have toring with a 2-week course of high-dose oesophageal reflux omeprazole in 35 patients with erosive disease in sympto- at least one extraesophageal matic patients with esophagitis found that the omeprazole test erosive oesophagitis. symptom. It is worth noting that was at least as sensitive as 24-hour pH Aliment Pharmacol Ther. 2000;14:389-96. although these symptoms are asso- monitoring in diagnosing GERD (3). [PMID: 10759617] ciated with GERD, establishing a 4. Schenk BE, Kuipers EJ, A study randomly assigned 85 patients who Klinkenberg-Knol EC, definitive causal relationship et al. Omeprazole as had ambulatory pH monitoring and grade a diagnostic tool in between GERD and extra- gastroesophageal 0 or 1 esophagitis by upper endoscopy to reflux disease. Am J esophageal symptoms is difficult either omeprazole 40 mg/d or placebo for Gastroenterol. because GERD may be one of 1997;92:1997-2000. 14 days and concluded that a symptomatic [PMID: 9362179] many causes of these symptoms. response to omeprazole had a sensitivity © 2008 American College of Physicians ITC2-2 In the Clinic Annals of Internal Medicine 5 August 2008 and specificity similar to ambulatory 24- consider coronary artery disease hour pH monitoring (4). before concluding that GERD is the cause of the chest pain. According to one meta-analysis of 15 stud- ies that compared the clinical response to Symptoms can be unreliable for PPI with objective measures, such as 24- differentiating GERD from a car- hour pH monitoring, endoscopy, and diac source of chest pain (1). symptom questionnaires, testing may be GERD is present in approximately necessary to definitively diagnose GERD in 50% of unexplained chest pain some patients even though many patients cases after coronary artery disease with uncomplicated GERD respond to has been excluded, and although empirical PPI therapy (5). classic symptoms are present in many cases where GERD is the When should clinicians consider cause of chest pain, they are not upper endoscopy in evaluating always present (8, 9). patients with possible GERD? If patients respond to empirical Which other laboratory tests therapy, endoscopy is not necessary should clinicians consider in to confirm the diagnosis. Although evaluating patients when the the specificity of esophagitis on diagnosis of GERD is uncertain? 5. Numans ME, Lau J, endoscopy is 90% to 100%, approx- When patients present with de Wit NJ, Bonis PA. Short-term treat- imately 50% to 70% of patients atypical symptoms, testing with ment with proton- with classic GERD symptoms have esophageal manometry, pH pump inhibitors as a test for gastro- no esophagitis on endoscopy (6). If monitoring, and barium swallow esophageal reflux may help to differentiate GERD disease: a meta- endoscopy is done, then histologic analysis of diagnos- evaluation of seemingly normal from other diagnoses. tic test characteris- tics. Ann Intern Med. squamous mucosa has little power 2004;140:518-27. Ambulatory pH monitoring to detect pathologic acid reflux (7). [PMID: 15068979] Ambulatory pH monitoring detects 6. Tefera L, Fein M, Rit- However, the American College of ter MP, et al. Can the the presence or absence of reflux of combination of Gastroenterology recommends that symptoms and acidic gastric contents and is the clinicians consider upper endoscopy endoscopy confirm best way to measure the actual the presence of gas- to rule out Barrett’s esophagus in troesophageal reflux amount of time reflux is present disease? Am Surg. patients with chronic symptoms; to and to correlate symptoms with 1997;63:933-6. evaluate patients who do not [PMID: 9322676] reflux episodes. However, up to 7. Schindlbeck NE, respond to empirical therapy; and Wiebecke B, Klauser 25% of patients with documented AG, et al. Diagnostic to investigate symptoms, such as esophagitis may have normal results value of histology in dysphagia or weight loss, that sug- non-erosive gastro- on pH monitoring (10). Tradition- oesophageal reflux gest stricture, ulceration, or malig- disease. Gut. ally, pH monitoring is performed 1996;39:151-4. nancy (1). with catheter-based probes. A [PMID: 8977332] 8. Hewson EG, Sinclair What other diagnoses should wireless pH capsule probe is a new JW, Dalton CB, technique that may be more tolera- Richter JE. Twenty- clinicians consider in patients with four-hour ble and may allow for longer assess- esophageal pH suspected GERD and atypical monitoring: the symptoms? ment of esophageal pH. Impedence- most useful test for pH monitoring is another emerging evaluating noncar- Clinicians should be aware that, in diac chest pain. Am technique that evaluates intraluminal J Med. 1991;90:576- some patients, the cause of GERD- 83. [PMID: 2029015] 9. Davies HA, Jones DB, like symptoms or endoscopic Rhodes J, New- esophagitis is not reflux but rather combe RG. Angina- Warning Symptoms for Stricture, like esophageal pain: infection, pill-induced injury, or Ulceration, or Malignancy differentiation from radiation. In patients who have cardiac pain by his- • Dysphagia or odynophagia tory. J Clin