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Clinical Epidemiology and Natural History of Gastroesophageal Reflux Disease

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Clinical Epidemiology and Natural History of Gastroesophageal Reflux Disease CORE Metadata, citation and similar papers at core.ac.uk Provided by PubMed Central YALE JOURNAL OF BIOLOGY AND MEDICINE 72 (1999), pp. 81-92. Copyright © 2000. All rights reserved. Clinical Epidemiology and Natural History of Gastroesophageal Reflux Disease Amnon Sonnenberg and Hashem B. El-Serag Department of Veterans Affairs Medical Center and The University of New Mexico, Albuquerque, New Mexico In the MUSE classification ofgastroesophageal reflux disease (GERD), esophagitis is assessed by the presence ofmetaplasia, ulcer, stricture, or erosion, each being graded as absent, mild or severe. Daily reflux symptoms affect about 4 to 7 percent of the population; erosive esophagitis occurs in about 2 percent; the prevalence rate ofBarrett's metaplasia is 0.4 percent; and esophageal adeno- carcinoma leads to two deaths per million living population. In persons with GERD symptoms, about 20 percent arefound to have erosive esophagitis, while ulcers or strictures arefound in less than 5 percent of all patients with erosive esophagitis. No clear-cut temporal progression exists between successive grades ofdisease severity, as the most severe grade of GERD is reached at the onset ofthe disease. Mildforms ofGERD tend to be more common in women than men, while severe GERD characterized by erosive esophagitis, esophageal ulcer, stricture or Barrett's metaplasia are far more common in men than women. All forms of GERD affect Caucasians more often than African Americans or Native Americans. The prevalence of GERD is high among developed coun- tries in North America and Europe and relatively low in developing countries in Africa and Asia. During the past three decades, hospital discharges and mortality rates of gastric cancer, gastric ulcer and duodenal ulcer have declined, while those of esophageal adenocarcinoma and GERD have markedly risen. These opposing time trends suggest that corpus gastritis secondary to Helicobacter pylori infection protects against GERD. This hypothesis is consistent with the geo- graphic and ethnic distributions of GERD. Case-control studies also indicate that cases with ero- sive esophagitis are less likely to harbor active or chronic corpus gastritis than controls without esophagitis. INTRODUCTION history and focus attention on recent developments in these two areas. New data The general epidemiology of gastroe- are emerging to suggest that, besides pep- sophageal reflux disease (GERD)b was tic ulcer and gastric cancer, gastrointesti- presented in several previous articles [1- nal infection with Helicobacterpylori may 3]. Rather than provide another compre- also explain several characteristic features hensive review of GERD epidemiology, in of GERD epidemiology. We conclude by the present article we will discuss primar- listing the many remaining open questions ily its clinical epidemiology and natural of GERD. a To whom all correspondence should be addressed: Amnon Sonnenberg, M.D., M.Sc., Department of Veterans Affairs Medical Center 1 1 1-F, 1501 San Pedro Drive SE, Albuquerque, NM 87108. Tel.: 505-265-171 1; Fax: 505-256-5751; E-mail: [email protected]. b Abbreviations: GERD, gastroesophageal reflux disease; NSAIDs, non-steroidal anti- inflammatory drugs. 81 82 Sonnenberg and El-Serag: GERD epidemiology CLINICAL EPIDEMIOLOGY the submucosa. In a minority of patients, healing of erosions or ulcers results in Clinical presentation scarring and formation of a peptic stric- ture. The term gastroesophageal reflux dis- The Savary-Miller classification of ease (GERD) is used to describe the symp- GERD puts much emphasis on various toms and changes of the esophageal types of erosions, but lumps esophageal mucosa that result from reflux of stomach metaplasia, ulcers and strictures into one contents into the esophagus. GERD grade. Moreover, it does not account for patients present with symptoms of epigas- the frequent concurrence of Barrett's tric pain, heartburn, pharyngeal burning, epithelium with stricture or stricture with regurgitation of gastric contents, acidic erosions. The newer, more refined, MUSE taste and dysphagia. Such symptoms may classification grades esophagitis according be experienced daily, weekly or only few to presence of metaplasia, ulcer, stricture times per month. With respect to GERD, or erosion, each being assigned a value individual symptoms carry a sensitivity or ranging from 0 to 2, that is, absent, mild or specificity that, in general, do not exceed severe, respectively [5]. 65 percent or 80 percent, respectively [4]. Barrett's epithelium is considered a The frequency and severity of symptoms premalignant lesion, as the incidence rate from gastroesophageal reflux do not corre- of esophageal adenocarcinoma developing late with the amount of morphologic from Barrett's mucosa is 1 percent per changes of the mucosa seen on endoscop- year [6]. In the International Classification ic examination of the esophagus. of Diseases, esophageal adenocarcinoma Most commonly used grading sys- is listed as "cardiac cancer." The demo- tems of GERD are based on the Savary- graphic characteristics and time trends of Miller classification [5]. Subjects with esophageal adenocarcinoma (or cancer of reflux symptoms but no macroscopically the gastric cardia) are very similar to those visible lesions are said to have reflux dis- of GERD. They are strikingly different ease without esophagitis, sometimes from those of adenocarcinoma in the gas- referred to as "grade 0." Peptic esophagitis tric body and antrum or squamous carci- is graded according to the extent and noma of the esophagus. Despite these severity of macroscopically visible ero- obvious similarities and its origin from sions: single patchy, large confluent or cir- Barrett's metaplasia, however, esophageal cumferential erosions representing grade I, adenocarcinoma is not included in the II, or III, respectively. The terms "compli- classification of esophagitis. cated esophagitis" or "grade IV" relate to esophagitis accompanied by Barrett's Prevalence rates mucosa, ulcers or strictures. The syn- onyms "Barrett's esophagus," "epitheli- Daily reflux symptoms affect about 4 um" or "metaplasia" refer to the replace- to 7 percent of the population, while ment of esophageal squamous epithelium esophageal adenocarcinoma leads to 2.5 by a gastric type of columnar epithelium deaths per million living population [2-3]. with (or without) intestinal metaplasia that The prevalence rates of the other presenta- reaches 2 to 3 cm above the lower tions of reflux disease in the middle range esophageal sphincter. Barrett's epithelium between these two extremes are far less is more susceptible than the regular squa- well characterized. A recent study from mous epithelium of the esophagus to the China estimated a 5 percent prevalence development of deep ulcers that reach into rate of erosive esophagitis [7]. Of those Sonnenberg and El-Serag: GERD epidemiology 83 presenting with symptoms suggestive of salivary secretion interferes with normal GERD, 18.5 percent were found to have esophageal clearance and also results in an erosive esophagitis. A Swedish study increased risk for erosive esophagitis [15]. reported an incidence rate of 120 new Presently, there are no risk factors cases of erosive esophagitis per 100,000 known to disrupt tissue resistance, except per year [8]. Assuming a case history of 20 for non-steroidal anti-inflammatory drugs years yields a crude estimate 2.4 percent (NSAIDs). Several authors have suggested for the prevalence rate. Ulcers or strictures that more severe forms of peptic esophagi- were found in less than 5 percent of all tis, associated with large confluent ero- patients with erosive esophagitis. Lastly, a sions, strictures and Barrett's esophagus, post-mortem study from Olmsted County are more common in patients on chronic in Minnesota found a prevalence rate of consumption of NSAIDs [16-18]. In the 0.4 percent for Barrett's esophagus [9]. population of veterans, many of the dis- Since symptoms are a poor indicators eases commonly treated with NSAIDs, for disease severity, a study trying to such as osteoarthritis, back pain or tension assess the true prevalence of erosive headache, were associated with a small but esophagitis and its complications would nevertheless significant odds ratio of about need to subject a large group of persons to 1.4 for reflux esophagitis [16]. upper gastrointestinal endoscopy. For Frequent occurrence of nighttime obvious reasons, such a study is difficult reflux can irritate the pharyngeal and and expensive to conduct. Because symp- laryngeal structures and result in laryngitis tomatic patients are more likely to under- or even hoarseness and aphonia. go endoscopy, incidence and prevalence Aspiration of gastric contents has been rates based largely on routine endoscopy associated with asthma, pneumonia, and reports may overestimate the prevalence bronchiectasies [19-21]. In our epidemio- rate of erosive esophagitis in the general logical study of GERD among U.S. mili- population. The prevalence of GERD tary veterans, we found both erosive varies markedly between different popula- esophagitis and esophageal stricture to be tions [1, 10]. During the past three decades significantly associated with sinusitis, the prevalence of GERD has increased aphonia, pharyngitis, laryngeal stenosis, more than two-fold, and previously report- laryngitis, chronic bronchitis, asthma, ed data may no longer apply to present day chronic obstructive pulmonary disease, populations [3]. With all these caveats in pulmonary fibrosis,
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