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The prevalence of oesophagitis in “silent” gastro-oesophageal reflux disease: Higher than expected?
Digestive and Liver Disease 47 (2015) 12–13
Contents lists available at ScienceDirect
Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Commentary
The prevalence of oesophagitis in “silent” gastro-oesophageal reflux disease: Higher than expected? Frank Zerbib ∗ Gastroenterology and Hepatology Department, Saint André Hospital, Centre Hospitalier Universitaire de Bordeaux, Université de Bordeaux, Bordeaux, France
In clinical practice, especially in the primary care setting, the diagnosis of gastro-oesophageal reflux disease (GORD) relies on the presence of heartburn and/or regurgitation. These symptoms are part of the “typical reflux syndrome” as defined by the Montreal classification because they are considered to have high sensitivity and specificity for the diagnosis of GORD [1]. Another important component of the Montreal definition is the presence of patient reported symptoms considered to be troublesome, i.e. that adversely affect well-being [1]. In other settings such as specialized centres and clinical or epidemiological research programmes, GORD can also be diagnosed by endoscopy and ambulatory reflux monitoring (pH alone or pH-impedance recordings) [2]. The presence of erosive oesophagitis, observed in less than 50% of untreated patients with typical symptoms, can reliably document the presence of GORD [1]. Oesophagitis is considered to be an objective diagnostic criterion, provided mucosal breaks only are taken into account according to the Los Angeles classification [3]. In the current issue of Digestive and Liver Disease, Wei-Yi et al. report the prevalence of erosive oesophagitis in a large group of “asymptomatic” subjects from Taiwan [4]. Among 2568 subjects undergoing a medical check-up, erosive oesophagitis was found in 676 (26.3%) patients, the majority of them (59.2%) classified as “asymptomatic” (15.6% of the whole population). The multivariate analysis showed that asymptomatic oesophagitis was independently associated with female gender, lower educational level, low depression scores and low prevalence of metabolic syndrome. The prevalence of erosive oesophagitis in patients without typical reflux symptoms varies widely among countries, continents, and studies. A recent literature review reported a prevalence of 12.1% in Sweden, 8.6% in Italy, 6.1% in China, and from 1.6% to 22.8% in health-check programmes in 6 Asian countries [5]. In a recent study from Korea, the prevalence of “silent” erosive oesophagitis was reported to be as high as 44% [6]. A recent study in Northern Europe and Canada reported a prevalence of 22% in patients without heartburn and regurgitation [7]. Interestingly, in this study,
∗ Corresponding author at: Gastroenterology and Hepatology Department, Saint André Hospital, 1 rue Jean Burguet, F-33075 Bordeaux, France. Tel.: +33 5 56 79 58 06; fax: +33 5 56 79 47 81. E-mail address: [email protected]
the use of a validated and structured questionnaire, the Reflux Disease Questionnaire (RDQ), significantly increased (from 84.3% to 93.4%) the proportion of patients identified as having reflux symptoms compared to the standard physician interview. Indeed, among patients without reflux symptoms during the interview, 18/31 (58.1%) reported heartburn and regurgitation (frequency and severity) on the RDQ [7]. The results of the study from Wei-Ly et al., obtained with the use of the RDQ, are quite similar [4]. Overall, according to these studies, the prevalence of erosive oesophagitis is 15–20% in patients without heartburn and regurgitation, provided a structured questionnaire is used. The reasons for the discrepancies between physician interview and the use of a questionnaire are not clear. It is of note that, in the study by Vakil et al., the majority of patients not identified as having reflux symptoms on the RDQ had dyspeptic symptoms, and none of them were asymptomatic. We believe that the subjects of the Taiwanese study cannot be considered has having “silent” or “asymptomatic” GORD since only the “reflux domains” of the RDQ were taken into account and no data are provided regarding the number of completely asymptomatic subjects. Excluding patients with dyspeptic patients is probably a mistake. It is well known that many dyspeptic symptoms are GORD-related and respond to proton pump inhibitor therapy [8]; moreover, heartburn-negative functional dyspepsia is now recognized as possibly related to GORD in the Montreal classification [1]. GORD-related dyspeptic symptoms may therefore account for a high proportion of oesophagitis in patients without typical reflux symptoms. The concept of silent GORD, proposed nearly 10 years ago by Fass and Dickman, also includes Barrett’s oesophagus and its potential evolution towards oesophageal adenocarcinoma [9]. When considering these potential severe complications, the problem of unrecognized long-term reflux disease is threatening. However, it is of note that most studies in “asymptomatic” patients found only low grade oesophagitis, and, to date, longitudinal studies suggest that a small minority of them will progress to more severe forms and Barrett’s oesophagus [10] that is the only well identified risk factor for oesophageal carcinoma [1]. The determinants and risk factors for progression from Barrett’s oesophagus to adenocarcinoma are out of the scope of this article, but regarding this specific risk, the prevalence of Barrett’s oesophagus in asymptomatic patients (or in patients without typical reflux symptoms)
http://dx.doi.org/10.1016/j.dld.2014.10.006 1590-8658/© 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
F. Zerbib / Digestive and Liver Disease 47 (2015) 12–13
appears to be much more relevant than for low grade oesophagitis. As an example, in the literature review from Dent et al., the prevalence of endoscopy-suspected oesophageal metaplasia (no intestinal metaplasia confirmed on biopsies) in individuals without GORD symptoms, ranged from 1.8% to 9.4% [5]. Unfortunately, these data are not available in the study by Wei-Ly et al. In conclusion, the prevalence of erosive oesophagitis is relatively high in patients without typical GORD symptoms, which can be missed during the physician interview. These symptoms are best identified with structured questionnaires. Most of these patients have in fact GORD-related dyspeptic symptoms that also require a careful interview. Considering these results, and more importantly the prevalence of Barrett’s oesophagus in these patients, further research is needed to determine the best screening strategy and treatment options. Conflict of interest F. Zerbib is a consultant and speaker for Given Imaging. References [1] Vakil N, van Zanten SV, Kahrilas P, et al. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. American Journal of Gastroenterology 2006;101:1900–20 [quiz 43].
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[2] Sifrim D, Zerbib F. Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors. Gut 2012;61: 1340–54. [3] Armstrong D, Bennett JR, Blum AL, et al. The endoscopic assessment of esophagitis: a progress report on observer agreement. Gastroenterology 1996;111:85–92. [4] Wei-Li L, Hao-Chun Y, Shu-Hui W. Predictive factors of silent reflux in subjects with erosive oesophagitis. Digestive and Liver Disease 2015;47:24– 9. [5] Dent J, Becher A, Sung J, et al. Systematic review: patterns of reflux-induced symptoms and esophageal endoscopic findings in large-scale surveys. Clinical Gastroenterology and Hepatology 2012;10:863–73, e3. [6] Choi JY, Jung HK, Song EM, et al. Determinants of symptoms in gastroesophageal reflux disease: nonerosive reflux disease, symptomatic, and silent erosive reflux disease. European Journal of Gastroenterology and Hepatology 2013;25:764–71. [7] Vakil N, Wernersson B, Ohlsson L, et al. Prevalence of gastro-oesophageal reflux disease with upper gastrointestinal symptoms without heartburn and regurgitation. United European Gastroenterology Journal 2014;2: 173–8. [8] van Zanten SV, Flook N, Talley NJ, et al. One-week acid suppression trial in uninvestigated dyspepsia patients with epigastric pain or burning to predict response to 8 weeks’ treatment with esomeprazole: a randomized, placebocontrolled study. Alimentary Pharmacology and Therapeutics 2007;26: 665–72. [9] Fass R, Dickman R. Clinical consequences of silent gastroesophageal reflux disease. Current Gastroenterology Reports 2006;8:195–201. [10] Malfertheiner P, Nocon M, Vieth M, et al. Evolution of gastro-oesophageal reflux disease over 5 years under routine medical care – the ProGERD study. Alimentary Pharmacology and Therapeutics 2012;35:154–64.
Contents lists available at ScienceDirect
Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Commentary
The prevalence of oesophagitis in “silent” gastro-oesophageal reflux disease: Higher than expected? Frank Zerbib ∗ Gastroenterology and Hepatology Department, Saint André Hospital, Centre Hospitalier Universitaire de Bordeaux, Université de Bordeaux, Bordeaux, France
In clinical practice, especially in the primary care setting, the diagnosis of gastro-oesophageal reflux disease (GORD) relies on the presence of heartburn and/or regurgitation. These symptoms are part of the “typical reflux syndrome” as defined by the Montreal classification because they are considered to have high sensitivity and specificity for the diagnosis of GORD [1]. Another important component of the Montreal definition is the presence of patient reported symptoms considered to be troublesome, i.e. that adversely affect well-being [1]. In other settings such as specialized centres and clinical or epidemiological research programmes, GORD can also be diagnosed by endoscopy and ambulatory reflux monitoring (pH alone or pH-impedance recordings) [2]. The presence of erosive oesophagitis, observed in less than 50% of untreated patients with typical symptoms, can reliably document the presence of GORD [1]. Oesophagitis is considered to be an objective diagnostic criterion, provided mucosal breaks only are taken into account according to the Los Angeles classification [3]. In the current issue of Digestive and Liver Disease, Wei-Yi et al. report the prevalence of erosive oesophagitis in a large group of “asymptomatic” subjects from Taiwan [4]. Among 2568 subjects undergoing a medical check-up, erosive oesophagitis was found in 676 (26.3%) patients, the majority of them (59.2%) classified as “asymptomatic” (15.6% of the whole population). The multivariate analysis showed that asymptomatic oesophagitis was independently associated with female gender, lower educational level, low depression scores and low prevalence of metabolic syndrome. The prevalence of erosive oesophagitis in patients without typical reflux symptoms varies widely among countries, continents, and studies. A recent literature review reported a prevalence of 12.1% in Sweden, 8.6% in Italy, 6.1% in China, and from 1.6% to 22.8% in health-check programmes in 6 Asian countries [5]. In a recent study from Korea, the prevalence of “silent” erosive oesophagitis was reported to be as high as 44% [6]. A recent study in Northern Europe and Canada reported a prevalence of 22% in patients without heartburn and regurgitation [7]. Interestingly, in this study,
∗ Corresponding author at: Gastroenterology and Hepatology Department, Saint André Hospital, 1 rue Jean Burguet, F-33075 Bordeaux, France. Tel.: +33 5 56 79 58 06; fax: +33 5 56 79 47 81. E-mail address: [email protected]
the use of a validated and structured questionnaire, the Reflux Disease Questionnaire (RDQ), significantly increased (from 84.3% to 93.4%) the proportion of patients identified as having reflux symptoms compared to the standard physician interview. Indeed, among patients without reflux symptoms during the interview, 18/31 (58.1%) reported heartburn and regurgitation (frequency and severity) on the RDQ [7]. The results of the study from Wei-Ly et al., obtained with the use of the RDQ, are quite similar [4]. Overall, according to these studies, the prevalence of erosive oesophagitis is 15–20% in patients without heartburn and regurgitation, provided a structured questionnaire is used. The reasons for the discrepancies between physician interview and the use of a questionnaire are not clear. It is of note that, in the study by Vakil et al., the majority of patients not identified as having reflux symptoms on the RDQ had dyspeptic symptoms, and none of them were asymptomatic. We believe that the subjects of the Taiwanese study cannot be considered has having “silent” or “asymptomatic” GORD since only the “reflux domains” of the RDQ were taken into account and no data are provided regarding the number of completely asymptomatic subjects. Excluding patients with dyspeptic patients is probably a mistake. It is well known that many dyspeptic symptoms are GORD-related and respond to proton pump inhibitor therapy [8]; moreover, heartburn-negative functional dyspepsia is now recognized as possibly related to GORD in the Montreal classification [1]. GORD-related dyspeptic symptoms may therefore account for a high proportion of oesophagitis in patients without typical reflux symptoms. The concept of silent GORD, proposed nearly 10 years ago by Fass and Dickman, also includes Barrett’s oesophagus and its potential evolution towards oesophageal adenocarcinoma [9]. When considering these potential severe complications, the problem of unrecognized long-term reflux disease is threatening. However, it is of note that most studies in “asymptomatic” patients found only low grade oesophagitis, and, to date, longitudinal studies suggest that a small minority of them will progress to more severe forms and Barrett’s oesophagus [10] that is the only well identified risk factor for oesophageal carcinoma [1]. The determinants and risk factors for progression from Barrett’s oesophagus to adenocarcinoma are out of the scope of this article, but regarding this specific risk, the prevalence of Barrett’s oesophagus in asymptomatic patients (or in patients without typical reflux symptoms)
http://dx.doi.org/10.1016/j.dld.2014.10.006 1590-8658/© 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
F. Zerbib / Digestive and Liver Disease 47 (2015) 12–13
appears to be much more relevant than for low grade oesophagitis. As an example, in the literature review from Dent et al., the prevalence of endoscopy-suspected oesophageal metaplasia (no intestinal metaplasia confirmed on biopsies) in individuals without GORD symptoms, ranged from 1.8% to 9.4% [5]. Unfortunately, these data are not available in the study by Wei-Ly et al. In conclusion, the prevalence of erosive oesophagitis is relatively high in patients without typical GORD symptoms, which can be missed during the physician interview. These symptoms are best identified with structured questionnaires. Most of these patients have in fact GORD-related dyspeptic symptoms that also require a careful interview. Considering these results, and more importantly the prevalence of Barrett’s oesophagus in these patients, further research is needed to determine the best screening strategy and treatment options. Conflict of interest F. Zerbib is a consultant and speaker for Given Imaging. References [1] Vakil N, van Zanten SV, Kahrilas P, et al. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. American Journal of Gastroenterology 2006;101:1900–20 [quiz 43].
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[2] Sifrim D, Zerbib F. Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors. Gut 2012;61: 1340–54. [3] Armstrong D, Bennett JR, Blum AL, et al. The endoscopic assessment of esophagitis: a progress report on observer agreement. Gastroenterology 1996;111:85–92. [4] Wei-Li L, Hao-Chun Y, Shu-Hui W. Predictive factors of silent reflux in subjects with erosive oesophagitis. Digestive and Liver Disease 2015;47:24– 9. [5] Dent J, Becher A, Sung J, et al. Systematic review: patterns of reflux-induced symptoms and esophageal endoscopic findings in large-scale surveys. Clinical Gastroenterology and Hepatology 2012;10:863–73, e3. [6] Choi JY, Jung HK, Song EM, et al. Determinants of symptoms in gastroesophageal reflux disease: nonerosive reflux disease, symptomatic, and silent erosive reflux disease. European Journal of Gastroenterology and Hepatology 2013;25:764–71. [7] Vakil N, Wernersson B, Ohlsson L, et al. Prevalence of gastro-oesophageal reflux disease with upper gastrointestinal symptoms without heartburn and regurgitation. United European Gastroenterology Journal 2014;2: 173–8. [8] van Zanten SV, Flook N, Talley NJ, et al. One-week acid suppression trial in uninvestigated dyspepsia patients with epigastric pain or burning to predict response to 8 weeks’ treatment with esomeprazole: a randomized, placebocontrolled study. Alimentary Pharmacology and Therapeutics 2007;26: 665–72. [9] Fass R, Dickman R. Clinical consequences of silent gastroesophageal reflux disease. Current Gastroenterology Reports 2006;8:195–201. [10] Malfertheiner P, Nocon M, Vieth M, et al. Evolution of gastro-oesophageal reflux disease over 5 years under routine medical care – the ProGERD study. Alimentary Pharmacology and Therapeutics 2012;35:154–64.