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Gastro-oesophageal reflux disease

Nature Reviews Disease Primers volume 7, Article number: 55 (2021) Cite this article

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Abstract

Gastro-oesophageal reflux disease (GERD) is a common disorder in adults and children. The global prevalence of GERD is high and increasing. Non-erosive reflux disease is the most common phenotype of GERD. Heartburn and regurgitation are considered classic symptoms but GERD may present with various atypical and extra-oesophageal manifestations. The pathophysiology of GERD is multifactorial and different mechanisms may result in GERD symptoms, including gastric composition and motility, anti-reflux barrier, refluxate characteristics, clearance mechanisms, mucosal integrity and symptom perception. In clinical practice, the diagnosis of GERD is commonly established on the basis of response to anti-reflux treatment; however, a more accurate diagnosis requires testing that includes upper gastrointestinal tract endoscopy and reflux monitoring. New techniques and new reflux testing parameters help to better phenotype the condition. In children, the diagnosis of GERD is primarily based on history and physical examination and treatment vary with age. Treatment in adults includes a combination of lifestyle modifications with pharmacological, endoscopic or surgical intervention. In refractory GERD, optimization of proton-pump inhibitor treatment should be attempted before a series of diagnostic tests to assess the patient’s phenotype.

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Fig. 1: Global distribution of the burden of GERD.
Fig. 2: Epidemiological trends in GERD-related disorders.
Fig. 3: Mechanisms of symptom and mucosal injury generation in GERD.
Fig. 4: Possible integrated model of mucosal pathogenesis in GERD oesophageal injury and symptoms.
Fig. 5: Diagnostic strategies in GERD.
Fig. 6: Evaluation and management of GERD that is not responsive to PPI therapy.

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Authors and Affiliations

  1. The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical System, Case Western Reserve University, Cleveland, OH, USA

    Ronnie Fass

  2. Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium

    Guy E. Boeckxstaens

  3. Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Hashem El-Serag

  4. Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Rachel Rosen

  5. Wingate Institute of Neurogastroenterology, Royal London Hospital, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

    Daniel Sifrim

  6. Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA

    Michael F. Vaezi

Authors
  1. Ronnie Fass
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  2. Guy E. Boeckxstaens
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  3. Hashem El-Serag
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  4. Rachel Rosen
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  5. Daniel Sifrim
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  6. Michael F. Vaezi
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Contributions

Introduction (R.F.); Epidemiology (H.E.-S. and R.R.); Mechanisms/pathophysiology (D.S. and R.R.); Diagnosis, screening and prevention (M.F.V. and R.R.); Management (R.F. and R.R.); Quality of life (G.E.B.); Outlook (R.F., D.S., M.F.V. and R.R.); Overview of the Primer (R.F.).

Corresponding author

Correspondence to Ronnie Fass.

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Competing interests

R.F. receives adviser/speaker/consultant honoraria from Takeda, Daewoong, Medtronic, Phathom Pharmaceuticals, Neurogastrx, GERDCare, AstraZeneca, Eisai Pharmaceuticals and Johnson & Johnson. M.F.V. receives adviser/speaker/consultant honoraria from Ironwood, Phathom Pharmaceuticals and Diversatek; research funding for M.F.V. is provided by Diversatek. Research funding for D.S. is provided by Reckitt Benckiser, Jinshan Technology and Alfa Sigma. R.R., H.E.-S. and G.E.B. declare no competing interests.

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Nature Reviews Disease Primers thanks S. Bhatia, S. Bor, L. Lundell, E. Savarino and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Hiatal hernia

The sliding of the upper part of the stomach into the chest through the diaphragmatic hiatus.

Transient LES relaxations

(TLESRs). The sudden relaxation of the lower oesophageal sphincter (LES) that is not preceded by a swallow; a normal gastric venting mechanism that is the most common cause of gastro-oesophageal reflux.

Bilitec

A 24-hour intra-luminal catheter that records the frequency and duration of bile exposure in the oesophagus by using bilirubin as a surrogate marker for bile (currently not available for clinical use).

Pharyngeal pumping

A rhythmic contraction (pumping) of the pharynx in response to the presence of a food bolus.

Sjögren syndrome

An autoimmune inflammatory disorder characterized by xerophthalmia (dry eyes) and xerostomia (dry mouth).

Angle of His

The acute angle created between the cardia at the entrance to the stomach and the oesophagus.

Gastroparesis

A neuromuscular disorder of the stomach that is characterized by delayed solid food emptying in the absence of mechanical obstruction.

Eosinophilic oesophagitis

A chronic immune-antigen-mediated oesophageal disorder, characterized by symptoms related to oesophageal dysfunction and, histologically, by eosinophil-predominant inflammation.

Pill-induced injury

Oesophageal injury due to direct damage to the oesophageal mucosa by a pill.

pH–impedance monitoring

Detection of both acid and non-acid gastro-oesophageal reflux episodes with multichannel intra-oesophageal catheter by measuring intra-luminal changes in pH and impedance.

Rumination syndrome

An effortless regurgitation of undigested or partially digested food from the stomach into the mouth, followed by either re-chewing and re-swallowing or spitting of the regurgitate.

Breakthrough symptoms

Symptoms that occur while the patient is on medical therapy.

Tachyphylaxis

Diminishing biological response to a given drug when it is administered continually.

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Fass, R., Boeckxstaens, G.E., El-Serag, H. et al. Gastro-oesophageal reflux disease. Nat Rev Dis Primers 7, 55 (2021). https://doi.org/10.1038/s41572-021-00287-w

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