Drs Rami Sweis and Natascha Cieplik (pictured) explain how gastro-oesophageal reflux disease presents, how and why to treat it, and when to refer
Read this article to learn more about:
- typical and atypical reflux symptoms
- the pathophysiology of GORD
- lifestyle modification and pharmacological therapy.
1 Know what GORD is and the reasons to treat
Gastro-oesophageal reflux disease (GORD) is found in 10–20% of people in the Western world.1 It is associated with decreased work productivity and absenteeism,2 low sleep scores, and a decrease in physical functioning.3
Although GORD is unrelated to age and sex, there is an association with lower income and obesity.4,5 The 2006 Montreal classification defines GORD as '...a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications'.6
Typical reflux symptoms
Typical reflux symptoms are heartburn (more than two episodes per week) and regurgitation. Heartburn is defined as a retrosternal burning sensation while regurgitation is perceived as the retrospective flow of gastric contents that can reach the hypopharynx or mouth. Other symptoms might include chest pain, epigastric pain, belching, and dysphagia (swallowing problems).1
Atypical reflux symptoms
Atypical or extra-oesophageal symptoms that can be associated with gastro-oesophageal reflux include cough, laryngitis, asthma, and dental erosions; however, these are typically multifactorial and, where linked to reflux, do not commonly occur in the absence of other more typical symptoms.6
Reasons to treat
Left untreated, acid reflux can lead to mucosal damage with further complications such as reflux oesophagitis, peptic stricture, or Barrett’s oesophagus, sometimes with progression towards dysplasia and malignancy. On the other hand, reflux can also present as endoscopy negative disease, which may or may not respond to acid-reducing therapy.
2 Know how GORD presents
Gastro-oesophageal reflux disease is classified according to findings at endoscopy and/or ambulatory pH testing.7 Barium swallow should not be used to define reflux disease.8
Thirty to forty percent of people with GORD have endoscopic evidence of oesophagitis.9 The severity of inflammation is defined by the Los Angeles classification and can range from a few mucosal breaks that are no longer than 5 mm (Grade A) to mucosal breaks that can involve more than three-quarters of the oesophageal mucosa circumference (Grade D);10 however patients often progress or regress between grades of oesophagitis.11 Barrett's oesophagus, a change of mucosa in the distal oesophagus from squamous to columnar lined epithelium, might be a consequence of untreated oesophagitis.
Non-erosive reflux disease
With the advent of acid-reducing medication, up to 70% of patients with reflux symptoms do not have oesophagitis and are classified as having non-erosive reflux disease (NERD). Typically, these patients have pathological oesophageal acid exposure and/or positive reflux-symptom association on ambulatory pH monitoring.12
Some patients present with typical reflux symptoms but are found to have normal endoscopy and pH study results. According to Rome III, functional heartburn is an episodic burning in the absence of objective evidence of gastro-oesophageal reflux based on pH testing, dysmotility, or any structural, mucosal, or anatomical pathology.7
3 Understand the pathophysiology
The anti-reflux barrier (the oesophago-gastric junction [OGJ]) lies between the oesophagus and stomach and comprises the intrinsic lower oesophageal sphincter (LOS) and the diaphragmatic crura. A disruption of this barrier or a wide separation of the LOS from the diaphragm (sliding hiatus hernia) can contribute towards reflux disease.13 In health, the resting tonic state of the OGJ helps reduce the incidence of reflux. The OGJ normally relaxes to allow for the passage of gastric contents (swallow or vomit).
There are also spontaneous relaxations (transient lower oesophageal relaxations [TLOSRs]) through which we often belch; TLOSRs are the most frequent mechanism of reflux.14 Patients with GORD, however, do not necessarily have increased TLOSRs, rather the frequency of reflux during TLOSRs seems to be higher compared with healthy controls.15
Factors thought to stimulate relaxation of the LOS include fat, caffeine, smoking, and certain drugs (e.g. calcium channel antagonists, nitrates).16 Physiological mechanisms that help counteract the magnitude or consequence of acid reflux include swallowing and neutralisation (e.g. by saliva).
4 Other conditions may mimic GORD
Swallowing problems might be the cause or consequence of GORD or may not be related to GORD at all, although symptoms can be similar.
An important differential diagnosis is achalasia, the most common primary motility disorder whereby the LOS does not relax and oesophageal peristalsis is lost. Although normally presenting with dysphagia, up to two-thirds of patients with the condition also describe heartburn, primarily because of fermentation of retained food products at the bottom of the oesophagus.17 Endoscopy, barium swallow, and manometry are required for an appropriate diagnosis.
Another disorder that can mimic GORD is eosinophilic oesophagitis (EoE), which is diagnosed with biopsies from the oesophagus. This is an allergic hypersensitivity-response to an unknown food antigen leading to eosinophil activation and a fibro-inflammatory reaction of the oesophageal wall.
Eosinophilic oesophagitis can lead to food bolus obstruction, dysphagia, chest pain, and/or reflux-like symptoms.18,19 Interestingly, EoE can also overlap with GORD so treatment (commonly with topical steroids) is likely also to include proton-pump inhibitor (PPI) therapy.19
Other disorders that need to be excluded are oesophageal tumours, proximal or distal diverticula, and large hiatus hernias.
5 Know about available treatments
The aim of GORD therapy is to reduce symptoms and prevent complications. Common strategies include:20
- lifestyle modification, for example:
- avoiding greasy, spicy, or acidic foods, alcohol, and nicotine
- avoiding late meals
- losing weight
- With acid-reducing therapy, a step-up approach is usually recommended. For patients with mild symptoms, over-the-counter medications (antacids and alginates) may be sufficient
- For patients with endoscopy-proven oesophageal inflammation or where symptoms cannot be controlled with lifestyle changes or antacids, histamine2 receptor antagonists (H2 RA; ranitidine) and PPIs (e.g. omeprazole) should be considered
- Proton pump inhibitors seem to be more effective for mucosal healing and nonerosive reflux disease than H2 RA.21,22 Proton pump inhibitor efficacy is dose-dependent so doubling PPI dose or frequency can improve outcome, particularly in severe oesophagitis.22 The addition of H2 RA before bed can help improve nocturnal symptoms23
- In patients who have dysphagia with hypotensive contractions alongside proven reflux, a prokinetic agent is sometimes considered (e.g. domperidone,24 erythromycin,25,26 bethanechol27).
[NB At time of publication, not all treatments detailed above are licensed for the aforementioned indications; the prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council's Good practice in prescribing and managing medicines and devices for further information.28]
6 Know when to refer
In the absence of alarm symptoms (e.g. dysphagia, gastrointestinal bleeding, anaemia, unintentional weight loss, and persisting vomiting) for most patients presenting with typical reflux symptoms, a PPI will commonly resolve or reduce symptoms sufficiently so that further testing is not required. The sensitivity of high-dose PPIs as a diagnostic tool for GORD (the PPI test) can be as high as 80%.29,30 Despite this, symptoms persist in up to one third of people on acid-reducing therapy.31
Where symptoms are refractory, or if there is dysphagia or any concern regarding mucosal or anatomical pathology, an endoscopy should be considered.32 Endoscopy can identify mucosal changes such as oesophagitis, ulcers, peptic strictures, tumours, and Barrett's oesophagus. Additionally, biopsies can be taken to exclude dysplasia, as well as EoE.
Oesophageal physiology studies
If endoscopy is normal and symptoms persist, the guidelines from the British Society of Gastroenterology recommend oesophageal physiology studies; manometry and ambulatory pH monitoring.33
Manometry (whereby a catheter with pressure sensors is passed through the nares) is required to exlude oesophageal motility disorders which might occur alongside or as a consequence of reflux. Crucially, primary motor disorders (achalasia or spasm) should be excluded before invasive treatment for GORD (e.g. surgery) is considered.33
Ambulatory pH monitoring
Most patients with reflux symptoms do not require a pH study. Often a typical history, a good response to acid-suppressive medication, or finding erosive oesophagitis or Barrett's oesophagus is sufficient to secure a diagnosis. Testing is recommended for patients who do not respond adequately to acid-reducing therapy with a non-diagnostic endoscopy, those with atypical symptoms, and (crucially) for those who are considering anti-reflux surgery.33
Ambulatory pH monitoring can be catheter-based (whereby a sensor is passed through the nares and taped so that it lies 5 cm proximal to the LOS) or wireless (whereby the sensor is 'sutured' in the same position proximal to the LOS). The test is commonly undertaken while patients are off acid-reducing therapy to diagnose GORD.
Studies can also be performed while the patient is on medication with impedance-pH monitoring (another catheter-based test with the addition of impedance sensors that determine the direction of bolus movement and proximal extent of reflux regardless of acidity). Impedance-pH monitoring can identify breakthrough acid reflux if the PPI regimen is not helping, or can look for the reflux of contents from the gastro-duodenum that are not acidic.34–36
7 Surgery may be appropriate for some people
Patients who have only partial response to acid-reducing therapy or who do not wish to persist with the medication might consider anti-reflux surgery. Symptom relief of more than 80% has been reported with surgery in carefully selected individuals,37 but patients should be informed of the 0.26–0.8% postoperative mortality rate as well as the not insignificant risk of post-operative side-effects, including dysphagia and gas-bloat syndrome.38,39
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- Becher A, El-Serag H. Systematic review: the association between symptomatic response to proton pump inhibitors and health-related quality of life in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2011; 34 (6): 618–627.
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- Vakil N, van Zanten S, Kahrilas P et al. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol 2006; 101 (8): 1900–1920; quiz 43.
- Galmiche J, Clouse R, Balint A et al. Functional esophageal disorders. Gastroenterology 2006; 130 (5): 1459–1465.
- Saleh C, Smout A, Bredenord A. The diagnosis of gastro-esophageal reflux disease cannot be made with barium esophagograms. Neurogastroenterol Motil 2015 ; 27 (2): 195–200.
- Fass R, Sifrim D. Management of heartburn not responding to proton pump inhibitors. Gut 2009; 58 (2): 295–309.
- Lundell L, Dent J, Bennett J et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut 1999; 45 (2): 172–180. >
- Labenz J, Nocon M, Lind T et al. Prospective follow-up data from the ProGERD study suggest that GERD is not a categorial disease. Am J Gastroenterol 2006; 101 (11): 2457–2462.
- Hershcovici T, Fass R. Nonerosive reflux disease (NERD)—an update. J Neurogastroenterology Motil 2010; 16 (1): 8–21. >
- Bredenoord A, Weusten B, Timmer R, Smout A. Intermittent spatial separation of diaphragm and lower esophageal sphincter favors acidic and weakly acidic reflux. Gastroenterology 2006; 130: 334–340. >
- Pandolfino J, Zhang Q, Ghosh S et al. Transient lower esophageal sphincter relaxations and reflux: mechanistic analysis using concurrent fluoroscopy and high-resolution manometry. Gastroenterology 2006; 131 (6): 1725–1733. >
- Sifrim D, Holloway R. Transient lower esophageal sphincter relaxations: how many or how harmful? Am J Gastroenterol 2001; 96 (9): 2529–2532. >
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- Prasad G, Talley N, Romero Y et al. Prevalence and predictive factors of eosinophilic esophagitis in patients presenting with dysphagia: a prospective study. Am J Gastroenterol 2007; 102 (12): 2627–2632. >
- Kumar M, Sweis R, Wong T. Eosinophilic oesophagitis: investigations and management. Postgrad Med J 2014; 90 (1063): 273–281. >
- Fox M, Forgacs I. Gastro-oesophageal reflux disease. BMJ 2006; 332 (7533): 88–93. >
- Armbrecht U, Abucar A, Hameeteman W et al. Treatment of reflux oesophagitis of moderate and severe grade with ranitidine or pantoprazole—comparison of 24-hour intragastric and oesophageal pH. Aliment Pharmacol Ther 1997; 11 (5): 959–965. >
- Richter J, Campbell D, Kahrilas P et al. Lansoprazole compared with ranitidine for the treatment of nonerosive gastroesophageal reflux disease. Arch Intern Med 2000; 160 (12): 1803–1809. >
- Peghini P, Katz P, Bracy N, Castell D. Nocturnal recovery of gastric acid secretion with twice-daily dosing of proton pump inhibitors. Am J Gastroenterol 1998; 93 (5): 763–767. >
- Maddern G, Horowitz M, Jamieson G. The effect of domperidone on oesophageal emptying in diabetic autonomic neuropathy. Br J Clin Pharmac 1985; 19: 441–444. >
- Chang C, Shiau Y, Lin C et al. Improvement of esophageal and gastric motility after 2-week treatment of oral erythromycin in patients with non-insulin-dependent diabetes mellitus. J Diabetes Complications 2003; 17 (3): 141–144.
- Chrysos E, Tzovaras G, Epanomeritakis E et al. Erythromycin enhances oesophageal motility in patients with gastro-oesophageal reflux. ANZ J Surg 2001; 71 (2): 98–102.
- Agrawal A, Hila A, Tutuian R et al. Bethanechol improves smooth muscle function in patients with severe ineffective esophageal motility. J Clin Gastroenterol 2007; 41 (4); 366–370.
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- Johnsson F, Hatlebakk J, Klintenberg A et al. One-week esomeprazole treatment: an effective confirmatory test in patients with suspected gastroesophageal reflux disease. Scand J Gastroenterol 2003; 38 (4): 354–359.
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- NICE. Dyspepsia and reflux disease: Investigation and management of dyspepsia, symptoms suggestive of gastro-oesophageal reflux disease, or both. Clinical Guideline 184. NICE, September 2014. Available at: www.nice.org.uk/guidance/cg184
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