Narrative ReviewPhenotypes of Gastroesophageal Reflux Disease: Where Rome, Lyon, and Montreal Meet
Section snippets
Syndromes Defined by Heartburn and/or Reflux Esophagitis
Recognizing the complexity of the GERD universe, the Montreal Definition of GERD introduced an umbrella definition stipulating that GERD could be consequent from gastric reflux causing either troublesome symptoms or complications.1 Under that umbrella definition were esophageal syndromes including reflux esophagitis and the typical reflux syndrome. Focus first on reflux esophagitis characterized in the Los Angeles (LA) classification as A, B, C, or D by the severity of endoscopically defined
Barrett’s Esophagus
A considerable body of data supports the conclusion that BE results from chronic excessive exposure to gastroesophageal refluxate: (1) markedly increased esophageal acid exposure as on pH-metry; (2) high-grade erosive esophagitis often precedes the development of BE; and (3) shared associations of BE and high-grade esophagitis with LES hypotension, hiatus hernia, ineffective esophageal motility, and central obesity.22,23 The association with central obesity potentially implicates the systemic
Regurgitation-Dominant Reflux Disease
Regurgitation-dominant disease is a distinct GERD phenotype because of its reduced response to therapy compared with heartburn-dominant disease.38,39 This makes intuitive sense because the mechanisms by which regurgitation occurs are somewhat distinct. Specifically, gross failure of the EGJ with or without a hiatal hernia facilitates flow of gastric content into the esophagus of sufficient volume such that either fluid movement is perceived within the esophagus or the refluxate gains entry to
Extraesophageal Manifestations of Gastroesophageal Reflux Disease
Management of putative extraesophageal manifestations of GERD is challenging given the protean manifestations often proposed. Critical questions that need to be addressed with these patients are as follows: (1) Does the patient have abnormal reflux and how can that be detected? (2) Is reflux causing the extraesophageal symptom? (3) By what mechanism is this occurring? Unfortunately, it is much easier to formulate these questions than it is to answer them.
Conventional physiological testing for
Chest Pain
GERD-related chest pain represents another phenotype in which establishing causality is often tenuous and by association. This has several explanations. Not least among them is the differential diagnosis of chest pain, which is broad, with reflux being the ultimate cause in only a minority.64 When present, the clinical characteristics of esophageal chest pain can be indistinguishable from those in coronary artery disease. The best and often difficult means of establishing causation is by
Conclusions
Many terms in medicine that are singularly meant to reflect a specific process, in fact, comprise multiple facets of variable proportions with interactions among themselves and with other distinct pathophysiologies. We have proposed that GERD is one of these terms. Figure 3 attempts to conceptualize this for some of the GERD syndromes that we have discussed. Evidently GERD is a family of syndromes with a complex matrix of contributing pathophysiology. Consequently, the concept of one size fits
References (67)
- et al.
Risk factors for the detection of Barrett's esophagus in patients with erosive esophagitis
Gastrointest Endosc
(2009) - et al.
Esophageal disorders
Gastroenterology
(2016) - et al.
Superficial esophageal mucosal afferent nerves may contribute to reflux hypersensitivity in nonerosive reflux disease
Gastroenterology
(2017) - et al.
Perception of gastro-oesophageal reflux
Best Pract Res Clin Gastroenterol
(2010) - et al.
The effect of auditory stress on perception of intraesophageal acid in patients with gastroesophageal reflux disease
Gastroenterology
(2008) - et al.
Role of obesity in the pathogenesis and progression of Barrett's esophagus
Gastroenterol Clin North Am
(2015) - et al.
Effect of diagnosis, surveillance, and treatment of Barrett's oesophagus on health-related quality of life
Lancet Gastroenterol Hepatol
(2018) - et al.
Prevalence of metaplasia at the gastro-oesophageal junction
Lancet
(1994) - et al.
Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial
Lancet
(2018) - et al.
New screening techniques in Barrett's esophagus: great ideas or great practice?
Gastroenterology
(2018)
Regurgitation is less responsive to acid suppression than heartburn in patients with gastroesophageal reflux disease
Clin Gastroenterol Hepatol
Transient lower esophageal sphincter relaxations and reflux: mechanistic analysis using concurrent fluoroscopy and high-resolution manometry
Gastroenterology
Effective treatment of rumination with Nissen fundoplication
J Gastrointest Surg
Normal values of pharyngeal and esophageal 24-hour pH impedance in individuals on and off therapy and interobserver reproducibility
Clin Gastroenterol Hepatol
Measurement of salivary pepsin to detect gastroesophageal reflux disease is not ready for clinical application
Clin Gastroenterol Hepatol
Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis
Gastroenterology
Management of gastroesophageal reflux disease
Gastroenterology
Response of chronic cough to acid-suppressive therapy in patients with gastroesophageal reflux disease
Chest
Both pre-transplant and early post-transplant antireflux surgery prevent development of early allograft injury after lung transplantation
J Gastrointest Surg
Esophageal intraluminal baseline impedance differentiates gastroesophageal reflux disease from functional heartburn
Clin Gastroenterol Hepatol
The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus
Am J Gastroenterol
Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification
Gut
Obesity is an independent risk factor for GERD symptoms and erosive esophagitis
Am J Gastroenterol
Characteristics of reflux episodes and symptom association in patients with erosive esophagitis and nonerosive reflux disease: study using combined impedance-pH off therapy
Am J Gastroenterol
Clinical spectrum and risk factors associated with asymptomatic erosive esophagitis as determined by Los Angeles classification: a cross-sectional study
PLoS One
Erosive esophagitis is a risk factor for Barrett's esophagus: a community-based endoscopic follow-up study
Am J Gastroenterol
Eight weeks of esomeprazole therapy reduces symptom relapse, compared with 4 weeks, in patients with Los Angeles grade A or B erosive esophagitis
Clin Gastroenterol Hepatol
Endoscopic reflux esophagitis and Helicobacter pylori infection in young healthy Japanese volunteers
Digestion
Modern diagnosis of GERD: the Lyon Consensus
Gut
Development and validation of a mucosal impedance contour analysis system to distinguish esophageal disorders
Gastroenterology
Microalterations of esophagus in patients with non-erosive reflux disease: in-vivo diagnosis by confocal laser endomicroscopy and its relationship with gastroesophageal reflux
Am J Gastroenterol
Neuronal plasticity: increasing the gain in pain
Science
Exploring the neurophysiological basis of chest wall allodynia induced by experimental oesophageal acidification - evidence of central sensitization
Neurogastroenterol Motil
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Conflicts of interest These authors disclose the following: John E. Pandolfino has consulted for Medtronic, Sandhill Scientific, and Ethicon, has received grants from Medtronic, has served as a speaker for Medtronic, Sandhill Scientific, Takeda, and Ethicon, and has received stock options from Crospon; and Peter J. Kahrilas has consulted for Ironwood Pharmaceuticals and Bayer. The remaining author discloses no conflicts.
Funding Supported by R01 DK092217 from the US Public Health Service (P.J.K. and J.E.P.).