Gastroesophageal Reflux Disease; LES = Lower Esophageal Sphincter; Nsaids = Nonsteroidal Anti-Inflammatory Drugs

Jennifer F. Wilson Science Writer David Goldmann,MD Christine Laine,MD,MPH Section Editors Reflux Disease Gastroesophageal in theclinic © 2008AmericanCollegeofPhysicians judgment. The informationcontainedhereinshouldneverbeusedasasubstituteforclinical resources referencedineachissueof primary resourcesformoredetailcanconsulthttp://pier.acponline.org andother MKSAP of sciencewritersandphysicianwriters.Editorialconsultantsfrom the ACP’s MedicalEducationandPublishing Divisionandwiththeassistance editors develop Knowledge andSelf-AssessmentProgram). PIER education resourcesofthe The contentof CME Questions Practice Improvement Treatment Diagnosis (Physicians’ InformationandEducationResource) provide expertreviewofthecontent.Readerswhoareinterestedinthese In theClinic In theClinic American CollegeofPhysicians is drawnfromtheclinicalinformationand from theseprimarysourcesincollaborationwith In theClinic Annals ofInternalMedicine . MKSAP (ACP), including page ITC2-16 page ITC2-13 page ITC2-5 page ITC2-2 PIER (Medical and 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 diagnosing 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 studies 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 characteristics. 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 Gastroen- atypical symptoms of GERD or in terol. 1985;7:477-81. • Bleeding [PMID: 4086742] those who have not responded to • Weight loss 10. Martinez SD, empirical therapy, clinicians should Malagon IB, Garewal • Early satiety HS, et al. Non-ero- consider alternative gastrointestinal • Choking (coughing, shortness of sive reflux disease breath, or hoarseness caused by acid) (NERD)—-acid reflux or biliary disease processes (Table 1). and symptom pat- • Anorexia terns. Aliment Phar- • Frequent vomiting macol Ther. 2003; When patients present with chest 17:537-45. [PMID: pain, clinicians should always 12622762]

5 August 2008 Annals of Internal Medicine In the Clinic ITC2-3 © 2008 American College of Physicians Table 1. Differential Diagnosis of GERD Disease Characteristics Notes Pill esophagitis Presents with dysphagia or odynophagia History of ingestion of the offending pill (e.g., potassium chloride, quinidine, tetracycline, doxycycline, NSAIDs, alendronate) Infectious esophagitis Presents with dysphagia or odynophagia Often in immunocompromised patients with candidal, cytomegalovirus, or herpes simplex virus esophagitis Esophageal motor disorders: Dysphagia for liquids and solids; also may be Nutcracker esophagus may be coincident with GERD; achalasia, diffuse esophageal associated with chest pain heartburn or chest pain in achalasia not due to spasm, hypertensive or spastic reflux but to fermentation of retained esophageal motility disorders (e.g., nutcracker contents or esophageal muscle spasm esophagus) Nonulcer dyspepsia Functional disorder, discomfort in midline of Usually does not respond to acid suppression upper abdomen with fullness, bloating, or nausea Eosinophilic esophagitis Allergic esophagitis; vomiting and abdominal pain Eosinophilis seen on esophageal biopsy that improve with removal of offending food Esophageal cancer Presents with dysphagia and weight loss, often Usually incurable by the time of clinical presentation in patients with longstanding GERD Coronary artery disease Chest pain that may be clinically indistinguishable In patients at high risk for cardiac disease, should rule from chest pain associated with GERD out cardiac disease before evaluating for GERD Conditions Associated with GERD Pregnancy Symptoms are experienced by 25%–50% of The frequency and severity of symptoms increase pregnant women throughout gestation Hypersecretory states (e.g., the 43% of patients with the Zollinger-Ellison Patients also may have associated peptic ulceration Zollinger-Ellison syndrome) syndrome have endoscopic esophagitis or diarrhea Connective tissue disorders Esophagus is involved in up to 90% of patients Characterized by low or absent LES pressure and poor (e.g., scleroderma) with scleroderma; often results in severe esophageal motor function esophagitis and stricture formation

GERD = gastroesophageal reflux disease; LES = lower esophageal sphincter; NSAIDs = nonsteroidal anti-inflammatory drugs.

11. Sharma N, Agrawal resistance and pH, so it can be research protocols or to evaluate A, Freeman J, et al. helpful to distinguish nonacid from esophageal function before anti- An analysis of persistent symptoms in acid reflux (11). These tests may be reflux surgery. There are no specific acid-suppressed patients undergoing helpful in evaluating patients with manometric findings sensitive and impedendance-ph symptoms that are atypical or specific for the clinical diagnosis monitoring. Clin Gastroenterol Hepa- refractory to empirical therapy of GERD. tol. 2008; 6: 521-4. with PPIs. [PMID: 18356117] 12. Johnston BT, Is there any connection between Troshinsky MB, Barium radiography GERD and Helicobacter pylori Castell JA, et al. Comparison of bar- Barium radiography, the most sen- infection? ium radiology with sitive test for detecting esophageal esophageal pH There is controversy over the role monitoring in the strictures, may be useful for evalu- diagnosis of gastro- of Helicobacter pylori in GERD esophageal reflux ating patients who present with (13). Concomitant H. pylori gastric disease. Am J Gas- dysphagia. Barium radiography has troenterol. 1996;91: infection and GERD may reduce 1181-5. [PMID: limited usefulness in most patients, the effects of GERD by causing 8651167] however, and should not be used in 13. O’Connor HJ. Review gastric atrophy and decreased gas- article: Helicobacter routine diagnosis (1). Reflux of bar- tric acid production, so eradication pylori and gastro- ium during radiographic examina- oesophageal reflux of H. pylori may worsen GERD by disease-clinical tion is positive in only 25% to 75% implications and increasing gastric acid production. management. Ali- of patients with known GERD and Furthermore, ammonia produced ment Pharmacol is falsely positive in up to 20% of Ther. 1999;13:117-27. by H. pylori infection could buffer [PMID: 10102940] control participants (12). 14. Goldblum JR, Vicari the gastric fluid refluxing into the JJ, Falk GW, et al. Inflammation and Esophageal manometry esophagus, an effect that would be intestinal metaplasia of the gastric cardia: Esophageal manometry measures lost after H. pylori eradication (14). the role of gastroe- muscle pressure in the lower esoph- Conversely, one prospective study sophageal reflux and H. pylori infection. agus and has a very limited role in demonstrated that eradication of H. Gastroenterology. 1998;114:633-9. GERD diagnosis. Use of this tech- pylori actually improved the endo- [PMID: 9516382] nique is generally limited to scopic appearance of reflux

© 2008 American College of Physicians ITC2-4 In the Clinic Annals of Internal Medicine 5 August 2008 esophagitis in patients with duode- GERD, especially Barrett’s esopha- 15. Ishiki K, Mizuno M, Take S, et al. Heli- nal ulcer (15). gus and its associated dysplasia and cobacter pylori eradication improves adenocarcinoma (18). pre-existing reflux In theory, patients who are receiv- esophagitis in When should clinicians consider patients with duo- ing prolonged PPI therapy and denal ulcer disease. who are also infected with H. pylori gastroenterology consultation Clin Gastroenterol Hepatol. 2004;2:474- may be at risk for atrophic gastritis, during the evaluation of GERD? 9. [PMID: 15181615] but studies have found no evidence Consultation may be helpful when 16. Lundell L, Miettinen P, Myrvold HE, et al. of accelerated development of a patient does not respond to an Lack of effect of acid suppression therapy atrophic gastritis in patients with empirical 4- to 8-week trial of acid on gastric atrophy. H. pylori who are on long-term suppression with a standard-dose Nordic Gerd Study Group. Gastroen- omeprazole (16, 17). Currently, PPI. It is also indicated when a terology. 1999;117: 319-26. [PMID: H. pylori eradication in GERD patient has pulmonary or otolaryn- 10419912] patients who require long-term PPI geal symptoms, such as wheezing, 17. Gillen D, Wirz AA, Neithercut WD, et al. therapy is not considered necessary shortness of breath, chronic cough or Helicobacter pylori hoarseness, unexplained chest pain, infection potentiates to prevent the development of the inhibition of gas- atrophic gastritis. globus, choking, halitosis, and sore tric acid secretion by omeprazole. Gut. throat, that do not respond to an 1999;44:468-75. Finally, some research suggests that empirical therapy of at least double- [PMID: 10075952] 18. Vaezi MF, Falk GW, the type of H. pylori strain infecting dose PPI for 2 to 3 months. The Peek RM, et al. CagA- a patient might be relevant to positive strains of presence of certain warning signs Helicobacter pylori GERD. One study found that also warrants further diagnostic may protect against Barrett’s esophagus. patients carrying cagA-positive evaluation because these symptoms Am J Gastroenterol. strains of H. pylori may be pro- may signal a complication, such as 2000;95:2206-11. [PMID: 11007219] tected against the complications of cancer, stricture, or ulceration (1).

Diagnosis... Common symptoms of GERD include heartburn and regurgitation, especially when the patient is lying down. Other symptoms include dysphagia, chronic cough or hoarseness, shortness of breath or wheezing, sore throat, throat clearing, globus, and halitosis. Always consider and exclude coronary artery disease in patients with chest pain even when it is suspected to be a symptom of GERD. In most uncomplicated cases, clinicians can accurately diagnose GERD on the basis of symptoms. Relief of classic symptoms with high-dose acid suppression is sufficiently sensitive and specific to confirm the diagnosis. In patients with atypical symptoms or who are unresponsive to empirical therapy, consider alternative disease processes. Upper endoscopy is usually reserved for patients with atypical symptoms or to evaluate for Barrett’s esophagus in patients with chronic GERD. CLINICAL BOTTOM LINE

Treatment

What is the role of dietary avoid large, fatty meals and foods modification in the treatment and beverages that contribute to of GERD? Foods and Beverages That May GERD symptoms (see Box). Contribute to GERD Symptoms Dietary modifications may reduce • Chocolate GERD symptoms, but they have Dietary modifications that lead to weight loss might also reduce • Peppermint not been rigorously tested in clini- • Onions GERD symptoms and complica- cal trials and their benefits are mod- • Garlic est at best. In particular, patients tions. However, various studies that • Alcohol may benefit from avoiding certain examined a possible link between • Carbonated beverages foods that decrease lower esophageal obesity and GERD had inconclu- • Citrus juices sphincter (LES) pressure, delay gas- sive findings. There is some obser- • Tomato products tric emptying, or provoke reflux vational evidence that obesity is • Large, fatty meals symptoms. Counsel patients to associated with an elevated risk for

5 August 2008 Annals of Internal Medicine In the Clinic ITC2-5 © 2008 American College of Physicians adenocarcinoma of the esophagus Patients with GERD-related stric- Behaviors to Decrease GERD Symptoms and Distal Acid in patients with GERD. tures may also need to avoid pills Exposure that could lodge proximal to A cross-sectional study based on data strictures and result in esophagitis, • Elevate the head of the bed from 80110 members of the Kaiser Perma- ulcers, and recurrent or refractory while sleeping nente multiphasic health check-up cohort • Avoid recumbency for 3 hours strictures. Nonsteroidal anti- found the presence of reflux-type symp- after meals inflammatory drugs, alendronate, • Sleep in the left lateral position toms in 11% of the population, with an association between obesity and an potassium preparations, quinidine, • Stop smoking iron supplements, and multiple • Avoid alcohol increase in GERD-like symptoms in white male patients but not in other ethnic antibiotics have been implicated in groups (19). pill-induced esophagitis. 19. Corley DA, Kubo A, Zhao W. Abdominal obesity, ethnicity A population-based study of 820 middle- Which nonprescription and gastro- medications are effective in the oesophageal reflux aged or elderly persons in Sweden in 1995 symptoms. Gut. to 1997 found no association between management of GERD? 2007;56:756-62. [PMID: 17047097] normal body mass index versus >25 kg/mL The goals of drug therapy are 20. Lagergren J, and GERD symptoms (odds ratio, 0.99 elimination of symptoms, Bergström R, Nyrén O. No relation [95% CI, 0.66 to 1.100]) (20). healing of existing esophagitis, between body mass prevention of complications, and and gastro- A recent Australian study compared oesophageal reflux maintenance of remission. Many symptoms in a almost 800 patients with adenocarcinoma Swedish population patients with mild GERD have based study. Gut. of the esophagus with 1580 adults without 2000;47:26-9. [PMID: cancer and found that obesity in combi- adequate relief of symptoms with 10861260] antacids and over-the-counter H - 21. Australian Cancer nation with ongoing GERD symptoms 2 Study. Combined increased the risk for adenocarcinoma of receptor antagonists or PPIs. Two effects of obesity, acid reflux and the lower esophagus to nearly 17 times the older studies that predate availabil- smoking on the risk risk in nonobese adults without GERD ity of over-the-counter H -receptor of adenocarcinomas 2 of the oesophagus. symptoms (21). antagonists and PPIs in the United Gut. 2008;57:173-80. [PMID: 17932103] States suggest that effective symp- 22. Lagergren J, Are behavioral interventions tom relief occurs in 20% of patients Bergström R, Adami HO, Nyrén O. Associ- effective in the treatment of GERD? using over-the-counter agents ation between med- Behavioral modifications, such as ications that relax (Table 2) (23, 24). the lower not lying down immediately after esophageal sphincter Antacids and risk for eating or elevating the head of the esophageal adeno- bed can help decrease symptoms of Antacids are commonly used to carcinoma. Ann Intern Med. 2000; reflux and distal acid exposure (see temporarily relieve heartburn. They 133:165-75. [PMID: work within the esophageal lumen 10906830] Box). Although observations sug- 23. Behar J, Sheahan to rapidly elevate esophageal pH DG, Biancani P, et al. gest that these lifestyle changes Medical and surgical decrease reflux symptoms and and neutralize esophageal acid management of within 15 to 30 minutes, typically reflux esophagitis. A esophageal acid exposure, the true 38-month report of efficacy of these maneuvers in producing modest relief lasting up a prospective clinical to 90 minutes. Although inexpen- trial. N Engl J Med. patients has not been rigorously 1975;293:263-8. sive and fast-working for relief of [PMID: 237234] tested in clinical trials. Alcohol and individual heartburn episodes, 24. Lieberman DA. Med- tobacco use can also aggravate ical therapy for drawbacks of antacids are a rela- chronic reflux GERD and should be avoided to esophagitis. Long- tively brief duration of action and term follow-up. Arch reduce symptoms. Intern Med. 1987;147:1717-20. [PMID: 3116959] Which medications cause or 25. Simon TJ, Berlin RG, exacerbate GERD, and how should Drugs That May Cause or Gardner AH, et al. Exacerbate GERD Self-Directed Treat- clinicians counsel patients ment of Intermittent • Theophylline Heartburn: A Ran- regarding the use of these domized, Multicen- medications? • Nitrates ter, Double-Blind, • Anticholinergic agents Placebo-Controlled Certain medications may cause or Evaluation of • Calcium-channel blockers Antacid and Low exacerbate GERD by decreasing • α-Adrenergic antagonists Doses of an H(2)- Receptor Antagonist LES pressure or decreasing • Prostaglandins (Famotidine). Am J esophageal acid clearance (see Ther. 1995;2:304-313. • Sedatives [PMID: 11850668] Box) (22).

© 2008 American College of Physicians ITC2-6 In the Clinic Annals of Internal Medicine 5 August 2008 Table 2. Drug Treatment for GERD Agent Mechanism of Action Benefits Side Effects Notes Antacids Buffer gastric acid 20% efficacy rate Diarrhea, constipation Chewable forms increase saliva, which helps neutralize acid; faster onset of

action than an OTC H2-RA Alginic acids Create foamy raft 20% efficacy rate Diarrhea, constipation Often combined with antacid on surface of gastric pool

OTC H2-RAs Decrease gastric Less efficacy than Similar to prescription doses OTC doses are one half the standard Ranitidine acid secretion by prescription doses prescription dose 75 mg bid, binding to histamine cimetidine receptor on parietall cell 200 mg bid, famotidine 10 mg bid, nizatidine 75 mg bid, OTC PPIs Block gastric acid 80%–100% Similar to prescription doses Indicated for patients with symptoms Omeprazole secretion by binding efficacy rate at least 2 d/wk. May take 1–4 d before 20 mg bid to proton pump on achieving full effect parietal cell

Prescription H2-RA Decrease gastric acid 50%–60% Drug interactions with No difference in clinical efficacy among Ranitidine secretion by binding efficacy rate cimetidine, theophylline, agents when using standard doses; much 150–300 mg bid, to histamine receptor phenytoin, and warfarin less effective when erosive esophagitis is cimetidine on parietal cell present; indicated in mild-to-moderate 400 mg bid to tid, GERD; full doses needed to provide famotidine effective maintenance 20–40 mg bid, nizatidibe 150–300 mg bid Prescription Increase LES pressure Mild symptomatic Drowsiness, tremors, High incidence of side effects and prokinetic agents and improve gastric improvement without depression, irritability, questionable efficacy limit usefulness; Metoclopramide emptying improvement in extrapyramidal side may provide benefit in patients with 10–20 mg 30 min histologic, endoscopic, effects (20%– impaired gastric emptying qac and qhs or pH testing 50% incidence) Prescription PPIs Block gastric acid 80%–100% Long-term use associated Indicated in moderate-to-severe GERD; Omeprazole secretion by binding to efficacy rate with increase in serum should be given before meals for maximum 20–40 mg qd, the proton pump in gastrin, atrophic gastritis in pharmacologic effect. No substantial esomeprazole parietal cells Helicobacter pylori–infected complications from long-term therapy 40 mg qd, patients, decreased vitamin reported; no clear difference in clinical

lansoprazole B12 absorption efficacy among agents when standard 30–60 mg qd, doses are used. pantoprazole 40–80 mg qd, rabeprazole 20–40 mg qd

bid = twice daily; GERD = gastroesophageal reflux disease; H2-RA = histamine-2–receptor antagonist; LES = lower esophageal sphincter; OTC = over- the-counter; PPI = proton pump inhibitor; qd = once daily; qac = before every meal; qhs = every night; tid = three times daily.

inadequacy as heartburn prophy- with famotidine 10 mg, famotidine 20 mg, laxis. Antacids may be combined antacid, or placebo demonstrated that as- with alginic acid, which acts as a needed antacids up to twice daily were barrier on top of stomach acids, superior to placebo for relief of sponta- 26. Robinson M, neous heartburn (25). Rodriguez-Stanley S, preventing contact between the Miner PB, et al. acids and the esophagus and help- Effects of antacid ing to prevent symptoms. Few A small study compared various antacid formulation on post- formulations in 20 patients with postpran- prandial well-designed clinical trials with oesophageal acidity dial heartburn and found that chewable in patients with a antacids exist. history of episodic tablets and effervescent bicarbonate had heartburn. Aliment longer durations of action than swallowed Pharmacol Ther. A study that randomly assigned 565 patients 2002;16:435-43. with heartburn to as-needed treatment tablets (26). [PMID: 11876696]

H2-receptor antagonists, which prescription medications, and

bind to H2 receptors on gastric which medications are available?

parietal cells to reduce gastric acid Various PPIs and H2-receptor secretion, are a first-line therapy for antagonists are available by pre- uncomplicated GERD with mild scription, and some are available or intermittent symptoms. They over the counter (Table 2). There is start reducing gastric acid within 1 debate about whether initial treat- to 2 hours of dosing, and effects ment should use a step-down or last up to 9 hours. Drawbacks of a step-up approach (Figure 1). The

H2-receptor antagonists are the step-down approach involves start- delay in effect and the fact that ing with once- or twice-daily PPI 27. Euler AR, Murdock tolerance may develop. Given in a therapy and decreasing to the least RH Jr, Wilson TH, et al. Ranitidine is effec- standard dose, H2-receptor antago- potent acid-suppression therapy tive therapy for ero- nists provide adequate symptom that controls symptoms. The step- sive esophagitis. Am J Gastroenterol. relief in 50% to 60% of patients up approach involves initiating 1993;88:520-4. [PMID: 8470632] with mild-to-moderate GERD therapy with standard or even non- 28. Kahrilas PJ, Fennerty and heal endoscopic esophagitis in prescription doses of an H -receptor MB, Joelsson B. 2 High- versus stan- 48% (1). antagonist and titrating up to the dard-dose ranitidine most potent acid-suppression ther- for control of heart- One study randomly assigned 328 patients burn in poorly apy that controls symptoms. Effi- responsive acid with erosive esophagitis to either ranitidine reflux disease: a cacy studies and cost-effectiveness prospective, con- 300 mg 4 times daily, ranitidine 150 mg 4 trolled trial. Am J times daily, or placebo for up to 12 weeks. models have not shown superiority Gastroenterol. of either approach. 1999;94:92-7. Symptom relief and healing of esophagitis [PMID: 9934737] was better in both ranitidine groups than One study involving patients on long-term 29. Inadomi JM, Jamal R, with placebo (27). Murata GH, et al. PPI therapy found that more than one half Step-down management of gastroe- Another trial in 481 patients found no dif- were able to step down from PPI therapy sophageal reflux without increasing symptoms or limiting disease. Gastro- ference in efficacy between ranitidine 150 enterology. mg and 300 mg twice daily in relief of quality of life. Forty-one of 71 (58%) were 2001;121:1095-100. asymptomatic 1 year after going off PPI [PMID: 11677201] heartburn symptom. This study also found 30. Dean BB, Gano AD that 59% of patients still had some symp- therapy. Twenty-four of 71 (34%) required Jr, Knight K, et al. H -receptor antagonists, 5 of 71 (7%) Effectiveness of pro- toms after 6 weeks of ranitidine therapy 2 ton pump inhibitors required prokinetic agents, 1 of 71 (1%) in nonerosive reflux (28). disease. Clin Gas- required both, and 11 of 71 (15%) remained troenterol Hepatol. asymptomatic without medication (29). 2004;2:656-64. Proton pump inhibitors [PMID: 15290657] PPIs, which block gastric acid 31. Lind T, Havelund T, Symptomatic medical treatment of Carlsson R, et al. secretion by binding to the proton reflux esophagitis has improved Heartburn without pump in parietal cells, are advised oesophagitis: effi- dramatically since PPIs became cacy of omeprazole for patients with GERD symptoms therapy and features available in 1989. PPIs provide determining thera- at least twice a week. Typical first- rapid symptomatic relief and heal- peutic response. line therapy is a 14-day course of Scand J Gastroen- ing of esophagitis in the highest terol. 1997;32:974-9. over-the-counter omeprazole, the [PMID: 9361168] percentage of patients. 32. Richter JE, Peura D, only PPI with U.S. Food and Drug Benjamin SB, et al. Efficacy of omepra- Administration (FDA) approval for A systematic review of 7 trials that evalu- zole for the treat- over-the-counter use. PPIs are ated PPIs in patients with nonerosive reflux ment of sympto- disease found that the therapeutic gain of matic acid reflux more effective than H2-receptor disease without PPIs over placebo for sufficient heartburn esophagitis. Arch antagonists for acute treatment of Intern Med. severe or erosive esophagitis. H - control was 30% to 35% (30). 2000;160:1810-6. 2 [PMID: 10871975] receptor antagonists are ineffective 33. Gardner JD, Ciociola A trial in 509 patients with no esophagitis AA, Robinson M, et for long-term maintenance of these on endoscopy compared omeprazole 20 al. Determination of conditions. PPIs may take up to 4 the time of onset of mg daily, omeprazole 10 mg daily, and action of ranitidine days to relieve symptoms, but placebo. At 4 weeks, the proportion of and famotidine on intra-gastric acidity. patients do not seem to develop patients with complete resolution of heart- Aliment Pharmacol tolerance to PPIs as they can with burn in each group was 46%, 31%, and Ther. 2002;16:1317- 26. [PMID: 12144582] 13%, respectively (31). H2-receptor antagonists.

Initiate therapy with over-the-counter

H2-receptor antagonist or standard-dose

H2-receptor antagonist

Persistent symptoms

Increase therapy to higher degree of efficacy Symptom relief

Persistent symptoms

Symptom relief Maintain therapy at lowest Increase therapy to higher degree of level that completely controls efficacy symptoms

Persistent symptoms

Increase therapy to higher degree of Symptom relief efficacy

Step-down Therapy

Initiate treatment with daily or twice-daily proton pump inhibitor

Symptom relief

Decrease therapy to lower degree of efficacy Symptoms persist

Symptom relief

Symptoms persist Increase therapy to level that Decrease therapy to lower degree of achieves complete symptom efficacy relief and maintain

Symptom relief

Decrease therapy to lower degree of Symptoms persist efficacy

Figure 1. Step-up vs. step-down drug therapy for gastroesophageal relux disease.

A randomized trial in 355 patients with few comparative studies of nonpre- GERD symptoms found that omeprazole scription H2-receptor antagonists 20 mg daily provided superior relief com- have indicated that famotidine and pared with omeprazole 10 mg daily and ranitidine may have higher potency with placebo (32). than cimetidine, and cimetidine and ranitidine may have faster How should clinicians select from onset of effect on gastric pH than among available antireflux famotidine (33). Research generally medications? also indicates that the various PPIs

In general, the various H2-receptor are equally efficacious in equipotent antagonists are equally efficacious in doses and carry similar adverse equipotent doses and carry similar effect profiles. For patients with the adverse effect profiles. However, a uncommon form of GERD with

5 August 2008 Annals of Internal Medicine In the Clinic ITC2-9 © 2008 American College of Physicians severe esophagitis, however, follow-up studies, there is ongoing esomeprazole may be somewhat worry that long-term use might more effective than other PPIs (34). cause other adverse effects.

When ordering GERD medica- There has been concern about the tions for a patient, clinicians should potential for PPIs to increase the choose the least-expensive product risk for colorectal cancer because 34. Castell DO, Kahrilas PJ, Richter JE, et al. that is effective for managing the drugs elevate serum gastrin Esomeprazole (40 levels, and in vitro studies show mg) compared with symptoms and preventing compli- lansoprazole (30 mg) cations and should prescribe the that high gastrin levels are associ- in the treatment of erosive esophagitis. lowest effective dose for the mini- ated with increased growth and Am J Gastroenterol. mum duration needed. proliferation of colon cancer cells. 2002;97:575-83. [PMID: 11922549] However, two reports that exam- 35. Schindlbeck NE, How long should patients continue ined the potential link between Klauser AG, Berghammer G, et al. pharmacologic therapy for GERD? PPIs and increased colorectal Three year follow up of patients with Reflux symptoms disappear in only cancer risk found no statistically gastrooesophageal a minority of patients (35), but significant overall association reflux disease. Gut. 1992;33:1016-9. about 20% of patients with GERD between long-term PPI use and [PMID: 1356887] 36. Hetzel DJ, Dent J, have adequate symptom control colorectal cancer (39, 40). Reed WD, et al. with intermittent, nonprescription Healing and relapse Research has found possible associ- of severe peptic therapy and lifestyle modification. esophagitis after ations between long-term use of treatment with Although many patients need to omeprazole. remain on long-term GERD ther- PPIs and bone health, risk for Gastroenterology. gastroenteritis and other infection, 1988;95:903-12. apy to control symptoms, others [PMID: 3044912] and vitamin B12 deficiency. 37. Carlsson R, Dent J, may be able to reduce dosage or Watts R, et al. Gastro- cease treatment once symptoms are In an observational study, more than 1 oesophageal reflux disease in primary controlled and the esophagus has year of PPI therapy was associated with a care: an interna- healed. Clinicians may periodically 44% increased risk for hip fracture among tional study of different treatment consider trying step-down therapy people older than 50 years. The strength strategies with of the association with hip fractures omeprazole. Interna- to a lower-dose PPI or switching tional GORD Study from a PPI to an H -receptor increased with both the dosage and the Group. Eur J Gas- 2 duration of PPI therapy (41). troenterol Hepatol. antagonist. 1998;10:119-24. [PMID: 9581986] A nested case–control study performed in 38. Vigneri S, Termini R, About 50% to 80% of patients with Leandro G, et al. A 364683 patients on acid-suppressive drugs comparison of five esophagitis have recurrence after 6 found higher rates of community-acquired maintenance thera- to 12 months of follow-up, regard- pies for reflux pneumonia among these patients than esophagitis. N Engl J less of the agent used to achieve among those who did not use this type of Med. 1995;333:1106- 10. [PMID: 7565948] healing or symptom control (36, therapy (2.45 compared with 0.6 per 100 39. Yang YX, Hennessy 37). Patients with severe GERD person-years) (42). S, Propert K, et al. Chronic proton need long-term PPI maintenance pump inhibitor ther- An observational study found that current apy and the risk of therapy to control symptoms and use of PPIs, but not use of H2-receptor colorectal cancer. prevent complications. Standard or antagonists, was associated with an Gastroenterology. even high doses of H -receptor 2007;133:748-54. 2 increased risk for bacterial gastroenteritis [PMID: 17678926] antagonists are not generally appro- 40. Robertson DJ, Lars- (RR, 2.9 [CI, 2.5 to 3.5]) (43). son H, Friis S, et al. priate maintenance therapy for Proton pump Another observational study found that inhibitor use and risk severe GERD (38). of colorectal cancer: the adjusted rate ratio of Clostridium diffi- a population-based, cile–associated disease with current use of case-control study. What are the adverse effects of Gastroenterology. long-term acid-suppression PPIs was 2.9 (CI, 2.4 to 3.4) and with use of 2007;133:755-60. H -receptor antagonists was 2.0 (CI, 1.6 to [PMID: 17678921] therapy? 2 41. Yang YX, Lewis JD, 2.7) (44). Epstein S, Metz DC. Short-term adverse effects with Long-term proton PPIs are uncommon and typically pump inhibitor ther- A study that investigated whether long- apy and risk of hip limited to headaches, nausea, con- term treatment with omeprazole or H2- fracture. JAMA. stipation, diarrhea, and pruritus. Yet 2006;296:2947-53. receptor antagonists alters vitamin B12 lev- [PMID: 17190895] despite evidence from careful els in patients with the Zollinger–Ellison

© 2008 American College of Physicians ITC2-10 In the Clinic Annals of Internal Medicine 5 August 2008 syndrome found that B12 levels, but not serum Postsurgical side effects, such as bloat- folate levels, were substantially lower in ing, flatulence, diarrhea, and dyspha- patients treated with omeprazole, suggesting gia, may be long-lasting. More serious that serum vitamin B levels should be moni- 12 complications, including esophageal tored in patients with the Zollinger–Ellison syn- perforation and death, have been drome treated with PPIs (45). reported. Laparoscopic antireflux sur- When should clinicians consider gery seems to be equal in effectiveness to open surgery, with greatly decreased surgical therapy for GERD? 42. Laheij RJ, Sturken- morbidity. boom MC, Hassing Nissen fundoplication is the most RJ, et al. Risk of common surgical intervention for community- Is it necessary to evaluate for acquired pneumonia GERD. This procedure aims to restore Barrett’s esophagus periodically? and use of gastric acid-suppressive the physiology and anatomy of the Barrett’s esophagus is premalignant drugs. JAMA. gastroesophageal junction by wrapping 2004;292: 1955-60. intestinal metaplasia of the mucosa of [PMID: 15507580] the gastric fundus around the distal the lower esophagus that occurs in 43. García Rodríguez LA, Ruigómez A, Panés J. esophagus. The FDA has also response to chronic exposure to acidic Use of acid-sup- pressing drugs and approved several endoscopic proce- stomach contents. Barrett’s esophagus the risk of bacterial dures for treatment of GERD, includ- significantly increases the risk for gastroenteritis. Clin Gastroenterol Hepa- ing endoscopic suturing and radio- esophageal adenocarcinoma. The risk tol. 2007;5:1418-23. [PMID: 18054750] frequency ablation of the lower for adenocarcinoma from Barrett’s 44. Dial S, Delaney JA, esophageal sphincter. esophagus is 30 to 40 times that of the Barkun AN, Suissa S. Use of gastric acid- general population, or approximately suppressive agents Antireflux surgery is an option for and the risk of 0.5% to 1.0% per year (49). community- patients who have responded well to acquired Clostridium difficile-associated PPI therapy but who are concerned Barrett’s esophagus is detected in 8% disease. JAMA. about the costs and other conse- to 20% of patients with chronic 2005;294: 2989-95. [PMID: 16414946] quences of taking daily medication on GERD. White race, male gender, 45. Termanini B, Gibril F, Sutliff VE, et al. Effect a long-term basis. Preoperative evalua- chronic duration of reflux symptoms, of long-term gastric tion before surgery should include and positive family history are risk acid suppressive therapy on serum documentation of GERD with pH factors for Barrett’s esophagus. Older vitamin B12 levels in patients with monitoring and esophageal manome- age; white race; male gender; obesity; Zollinger-Ellison syn- try. Patients who have not responded smoking; use of LES-relaxing drugs; drome. Am J Med. 1998;104:422-30. to medical therapy may have increased frequency, greater severity, [PMID: 9626024] and longer duration of reflux symp- 46. Spechler SJ. Medical symptoms not caused by GERD. or invasive therapy toms; hiatal hernia; and duration of for GERD: an acidu- lous analysis. Clin Although surgical therapy is effica- Barrett’s esophagus are risk factors for Gastroenterol Hepa- cious, a review comparing the efficacy, esophageal adenocarcinoma in a tol. 2003;1:81-8. [PMID: 15017499] prevention of complications, safety patient with known Barrett’s esopha- 47. Dire CA, Jones MP, Rulyak SJ, Kahrilas PJ. profile, convenience, and costs of med- gus. Clinical severity of symptoms The economics of ical or surgical fundoplication therapy laparoscopic Nissen fundoplication. Clin for GERD suggested that antireflux Gastroenterol Hepa- Consider surgery as an option for tol. 2003;1:328-32. surgery had no clear advantage com- [PMID: 15017676] pared with medical therapy, and that patients with well-documented GERD 48. Spechler SJ, Lee E, who require long-term PPI maintenance Ahnen D, et al. medical therapy may be safer and Long-term outcome therapy but show satisfactory relief of of medical and sur- more cost-effective (46). Fundoplica- symptoms and who: gical therapies for gastroesophageal tion reduces costs associated with PPI • Are older than 50 years reflux disease: follow- use in the short term, but it does not up of a randomized • Consider long-term medication a financial controlled trial. reduce total costs because many burden JAMA. 2001;285: • Are noncompliant with drug therapy 2331-8. [PMID: patients subsequently return to long- 11343480] term use of PPIs (47). In a follow-up • Prefer a single surgical intervention to 49. Hogan WJ. long-term drug treatment Spectrum of supra- study conducted 11 to 13 years after esophageal compli- • Experience prominent symptoms of cations of gastro- antireflux surgery, approximately 60% regurgitation, even with medical control esophageal reflux of the patients were again receiving of heartburn symptoms disease. Am J Med. 1997;103:77S-83S. medical therapy (48). [PMID: 9422629]

5 August 2008 Annals of Internal Medicine In the Clinic ITC2-11 © 2008 American College of Physicians 50. Lieberman DA, alone is unreliable in distinguish- guidelines notes the lack of clear Oehlke M, Helfand M. Risk factors for ing patients with Barrett’s esopha- evidence that screening reduces Barrett’s esophagus in community-based gus from those with GERD alone. esophageal adenocarcinoma mortal- practice. GORGE ity and states that screening in consortium. Gas- One study of 2641 patients undergoing troenterology Out- high-risk patients should be indi- comes Research endoscopy found that the risk for Barrett‘s Group in Endoscopy. esophagus in patients with symptoms vidualized (53). The guidelines note Am J Gastroenterol. that the yield of screening is highest 1997;92:1293-7. lasting more than 5 years was 5 times that [PMID: 9260792] of patients with symptoms of less than 1 in white men older than 50 years 51. Streitz JM Jr, Andrews CW Jr, Ellis year (50). with longstanding heartburn but do FH Jr. Endoscopic not define the specific duration of surveillance of Bar- rett’s esophagus. Although strong evidence is not symptoms after which screening is Does it help? J Tho- rac Cardiovasc Surg. available to support a screening indicated. Most experts suggest 1993;105:383-7; dis- recommendation or to define the that patients with chronic GERD cussion 387-8. [PMID: 8445916] appropriate timing and interval of have endoscopy at least once during 52. Peters JH, Clark GW, Ireland AP, et al. screening, consensus is that upper their lifetime to screen for Barrett’s Outcome of adeno- endoscopy should be done in esophagus, regardless of whether carcinoma arising in Barrett’s esophagus patients with chronic GERD to symptoms are controlled. A case- in endoscopically surveyed and non- screen for Barrett’s esophagus, control study found that GERD surveyed patients. J dysplastic changes, and early symptoms lasting longer than 13 Thorac Cardiovasc Surg. 1994;108:813- esophageal cancer. At least two years were associated with Barrett’s 21; discussion 821-2. [PMID: 7967662] studies suggest that endoscopic esophagus (54). surveillance of patients with Bar- rett’s esophagus detects carcinoma How should clinicians manage at an early stage and can improve patients once Barrett’s esophagus long-term survival rates (51, 52). is present? Once Barrett’s esophagus has been However, the American College detected, surveillance endoscopy of Gastroenterology practice with biopsy should be performed at

Low-grade High-grade No dysplasia dyspasia dysplasia

Surveillance Surveillance every 6 Surgical Nonsurgical every 3 to 5 months for 12 months, candidate candidate years then at 12 months

No further Persistent Esophagectomy Ablation therapy dysplasia low-grade or intensive or continued dysplasia surveillance every surveillance at 3 months if focal 3- to 6-month high-grade intervals dysplasia

Surveillance Surveillance every 2 to 3 every 12 years months

Figure 2. Proposed surveillance and management algorithm for patients with Barrett’s esophagus based on grade of dysplasia detected by endoscopic biopsy.

© 2008 American College of Physicians ITC2-12 In the Clinic Annals of Internal Medicine 5 August 2008 53. Wang KK, Sampliner least every 3 years (depending on prevent complications. Clinicians RE. Updated guide- the grade of dysplasia) to detect should monitor for symptoms lines 2008 for the diagnosis, surveil- neoplastic transformation (53). that suggest complications of can- lance, and therapy of Barrett’s esopha- Because active inflammation can be cer, stricture, or ulceration; screen gus. Am J Gastroen- misinterpreted as dysplasia, mucosal for Barrett’s esophagus when terol. 2002; 103: 788- 797. [PMID: healing should be achieved before appropriate; and ensure that med- 12190150] biopsies are obtained. Diagnosis of 54. Conio M, Filiberti R, ical therapy controls symptoms in Blanchi S, et al. Risk high-grade dysplasia requires factors for Barrett’s the most cost-effective manner. esophagus: a case- repeated endoscopy to exclude control study. Int J concomitant cancer (Figure 2). When should clinicians consider Cancer 2002; 97: 225-229. gastroenterology referral for the 55. El-Serag HB, Aguirre Among patients with Barrett’s T, Kuebeler M, Sam- treatment of a patient with pliner RE. The length esophagus, acid suppression is GERD? of newly diagnosed especially important because it may Barrett’s oesophagus Consider consultation with a spe- and prior use of acid play a role in retarding progression suppressive therapy. cialist if patients are refractory to Aliment Pharmacol of dysplasia (55). Barrett’s esopha- Ther. 2004;19:1255- therapy or if atypical symptoms or gus alone is not an indication for 60. [PMID: 15191506] complications develop. Because 56. Csendes A, surgical therapy for GERD (56). Braghetto I, Korn O, most patients’ symptoms are con- Cortés C. Late sub- jective and objective How frequently should clinicians trolled with PPI therapy, symptoms evaluations of antireflux surgery in see patients with GERD and what that do not respond to PPI therapy patients with reflux are the components of good may not be caused by GERD. esophagitis: analysis of 215 patients. follow-up? Referral is also advised when evalu- Surgery. 1989;105: 374-82. [PMID: GERD is a chronic condition that ating for Barrett’s esophagus or for 2784232] usually requires ongoing follow-up possible surgical intervention for and maintenance therapy to GERD.

Treatment... Dietary and behavioral modifications may be effective in treatment of GERD. Many patients with mild GERD have adequate relief of symptoms with

antacids and over-the-counter H2-receptor antagonists and PPIs. Prescription medications, particularly PPIs, are indicated for moderate-to-severe GERD. There is ongoing debate about whether initial treatment should use a step-down or a step-up approach. Many patients with moderate-to-severe GERD require indefinite maintenance therapy to control symptoms and prevent complications. There is no clear evidence of serious adverse effects from long-term PPI use. Consider antireflux surgery in patients who have responded well to PPI therapy and who are not interested in long-term medical therapy. Clinicians should provide follow-up to monitor for complications and to ensure that medical maintenance therapy controls symptoms in the most cost-effective manner. Patients with chronic GERD should have endoscopy at least once to screen for Barrett’s esophagus.

CLINICAL BOTTOM LINE

Practice Improvement How do U.S. stakeholders evaluate 119 measures of quality of care to the quality of care for patients use in the 2008 Physician Quality with GERD? Reporting Initiative (PQRI), an The Center for Medicare & Medic- initiative that will financially aid Services (CMS) has developed reward participating physicians

5 August 2008 Annals of Internal Medicine In the Clinic ITC2-13 © 2008 American College of Physicians who meet defined quality stan- use of endoscopic therapy for dards. Of these measures, one GERD (58); 2007 American Col- involves GERD (see Box). The lege of Gastroenterology practice rationale for this measure is that guidelines on esophageal reflux test- many patients with GERD remain 57. Canadian Associa- ing (59); 2001 Society of American tion of Gastroen- on medication for years, and Gastrointestinal and Endoscopic terology GERD Con- sensus Group. experts suspect that not all patients Surgeons consensus guidelines on Canadian Consensus have regular reassessment to deter- Conference on the the surgical treatment of GERD management of gas- mine whether medication is still (60); and 2008 American College of troesophageal reflux disease in adults - needed. Research indicates that Gastroenterology guidelines on the update 2004. Can J patients on long-term GERD Gastroenterol. diagnosis, surveillance, and manage- 2005;19:15-35. therapy may be able to have their [PMID: 15685294] ment of Barrett’s esophagus (53). 58. Falk GW, Fennerty medications modified on the basis MB, Rothstein RI. of the presence or absence of AGA Institute medical position state- symptoms. ment on the use of Centers for Medicare & Medicaid endoscopic therapy What do professional Services: 2008 Physician Quality for gastro- Reporting Initiative esophageal reflux organizations recommend disease. Gastro- Measure #77: Assessment of GERD enterology. regarding the management of 2006;131: 1313-4. Symptoms in Patients Receiving [PMID: 17030198] patients with GERD? Chronic Medication for GERD 59. Practice Parameters Committee of the In 2005, the American College of Description: Percentage of patients American College of Gastroenterology published >18 years with the diagnosis of Gastroenterology. updated guidelines on diagnosis GERD who have been prescribed ACG practice guide- continuous PPI or H -receptor antag- lines: esophageal 2 reflux testing. Am J and treatment of GERD (1). The onist therapy who received an annual Gastroenterol. guidance in this article generally assessment of their GERD symptoms 2007;102:668-85. after 12 months of therapy. [PMID: 17335450] reflects the recommendations in 60. Society of American those guidelines. Other GERD Numerator: Patients who had an Gastrointestinal and annual assessment of their GERD Endoscopic Sur- treatment guidelines include a 2005 symptoms after 12 months of geons. Guidelines for Surgical Treat- Canadian Association of Gastro- therapy. ment of Gastroe- enterology consensus conference on Denominator: All patients >18 years sophageal Reflux with a diagnosis of GERD who have Disease (GERD). the management of GERD in 2001. Accessed at been prescribed >12 months of www.sages.org/ adults (57); a 2006 American Gas- continuous PPI or H2-receptor publications/ antagonist therapy. publication.php?id= trointestinal Association Institute 22 on 10 June 2008. Medical Position Statement on the

PIER Modules pier.acponline.org c Access the following PIER modules: GERD, Barrett’s Esophagus, and Upper Gastro- intestinal Endoscopy. PIER modules provide evidence-based, updated information on current diagnosis, treatment, and management, in an electronic format designed for rapid in the clinic access at the point of care. Patient Education Resources lini www.annals.org/intheclinic/ Tool Kit Access the Patient Information material that appears on the following page for duplication and distribution to patients. Gastroesophageal www.acponline.org/patients_families/pdfs/health/heartburn_report.pdf Access American College of Physicians: ACP Special Report: Understanding and Treating Reflux Disease Heartburn ec Quality Improvement Tools pier.acponline.org/qualitym/t004.html Access the CMS PQRI quality measure for GERD with administrative criteria and background material. Practice Guidelines http://www.acg.gi.org/physicians/clinicalupdates.asp#guidelines Access American College of Gastroenterology practice guidelines in th

© 2008 American College of Physicians ITC2-14 In the Clinic Annals of Internal Medicine 5 August 2008 WHAT YOU SHOULD KNOW In the Clinic Annals of Internal Medicine ABOUT GASTROESOPAHAGEAL annals.org REFLUX DISEASE (GERD)

In gastroesophageal reflux disease (GERD), • Sometimes you may need a test to stomach acid washes up into the esopha- measure acid or pressure or to look at gus. The esophagus is the tube that carries the esophagus lining. food from the mouth to the stomach. GERD can harm the lining of the esophagus and Is there a treatment? cause what many people call “heartburn” • GERD can be treated by stopping the or “acid indigestion.” Some people with things that make it worse. GERD may also have a cough, a sore throat, • Taking medicines that block stomach breathing problems, trouble swallowing, acid can also help. or bad breath. Is GERD dangerous? Things that can cause GERD or make it worse: • If GERD is not treated, it can cause • Pregnancy bleeding or scars that block the • Smoking esophagus. • Alcohol • GERD may make changes in the lining • Being overweight of the esophagus called “Barrett’s esophagus.” Barrett’s esophagus can • Some foods (fatty or fried foods, turn into cancer. chocolate, mint, garlic, onions, citrus fruits or juices, carbonated beverages) • People who have GERD for many years • Lying down after eating should get checked for Barrett’s esophagus. How will the doctor know if problems are • Tell your doctor if you have trouble caused by GERD? swallowing, weight loss, vomiting, • Your doctor may give you medicine to make you have less stomach acid. If bleeding, loss of appetite, or chest the medicine helps, your problems pain. were probably from GERD and you • In a few cases, an operation may be probably won’t need any tests. needed.

For More Information Web Sites with Good Information on GERD American College of Physicians: ACP Special Report: Understanding and Treating Heartburn http://www.acponline.org/patients_families/pdfs/health/ heartburn_report.pdf National Digestive Diseases Information Clearinghouse: Heartburn, Hiatal Hernia, and GERD http://digestive.niddk.nih.gov/ddiseases/pubs/gerd/index.htm Patient Information Patient CME Questions

1. A 56-year-old woman is evaluated Evaluation by an otolaryngologist dis- She has a remote history of gastroe- because of continuing symptoms due to closed laryngeal inflammation suggestive sophageal reflux disease. Physical exami- refractory gastroesophageal reflux that of gastroesophageal reflux disease, and nation is normal. have not improved despite lifestyle modi- the patient is referred to you. She is oth- Which of the following is the most fications and treatment with a twice- erwise asymptomatic and does not report appropriate management at this time? daily proton pump inhibitor (omeprazole heartburn, regurgitation, dysphagia, or 40 mg). The patient continues to have weight loss. The patient maintains an A. Schedule upper endoscopy occasional substernal chest pain associ- active lifestyle and currently takes no B. Schedule a barium swallow ated with some epigastric burning. She medications. Physical examination and C. Discontinue alendronate has not had dysphagia, regurgitation, routine laboratory studies are normal. D. Begin a proton pump inhibitor E. Begin metoclopramide weight loss, or a change in bowel habits. Which of the following should be done She has no cardiac risk factors. next? Physical examination is normal except for A. Upper endoscopy slight overweight. Upper endoscopy is B. Esophageal manometry also normal. C. Ambulatory 24-hour esophageal pH Which of the following is the most monitoring appropriate treatment at this time? D. Barium swallow A. Schedule consultation for E. Trial of acid-suppression therapy evaluation for antireflux surgery 4. An obese 62-year-old man is evaluated B. Increase the proton pump inhibitor because of heartburn and frequent throat to 3 times daily clearing. Gastroesophageal reflux disease C. Change to a different proton pump (GERD) is diagnosed and therapy with a inhibitor proton pump inhibitor (omeprazole 40 D. Add trazodone to the current mg), twice daily, is initiated. He is advised regimen of lifestyle modifications that help prevent E. Add ranitidine at bedtime to the GERD. current regimen After 6 weeks, he is reevaluated because 2. An otherwise-healthy 28-year-old man the cough, although somewhat better, has a 4-month history of epigastric dis- persists. He has no postnasal drip. His comfort and heartburn. Symptoms are heartburn has resolved. usually exacerbated postprandially, espe- Which of the following is the best next cially after eating spicy foods. The patient step in this patient’s management? does not report dysphagia, weight loss, or decreased appetite. He has an active A. Change his medication to lifestyle and takes no medications. Physi- intranasal corticosteroids and cal examination is normal except for mild antihistamines epigastric tenderness. Routine laboratory B. Order 24-hour esophageal pH studies are normal. monitoring C. Refer him for fundoplication Which of the following is most appropri- D. Continue the proton pump inhibitor ate at this time? therapy and reevaluate him in 6 A. Upper endoscopy weeks B. Esophageal manometry C. Ambulatory 24-hour esophageal pH 5. An 84-year-old woman has a 2-day his- monitoring tory of severe substernal chest pain when D. Barium swallow swallowing. She does not have dysphagia. E. Trial of acid-suppression therapy Two days ago, the patient began taking alendronate for osteoporosis. Other med- 3. A 32-year-old woman has a 4-month ications are a daily aspirin and an history of hoarseness and throat clearing. angiotensin-converting enzyme inhibitor.

Questions are largely from the ACP’s Medical Knowledge Self-Assessment Program (MKSAP). Go to www.annals.org/intheclinic/ to obtain up to 1.5 CME credits, to view explanations for correct answers, or to purchase the complete MKSAP program.