Synonyms: gastro-esophageal reflux disease (GERD); reflux oesophagitis
A certain amount of gastro-oesophageal reflux of acid is normal and there is a natural protective mechanism of the lower oesophagus. If reflux is prolonged or excessive it may cause breakdown of this protection with inflammation of the oesophagus (oesophagitis).
Reflux is two to three times more common in men than in women. Symptoms of gastro-oesophageal reflux are common; about 25% of adults experience heartburn and 5% have symptoms daily.
- There is a spectrum of disorders ranging from the most common endoscopy-negative gastro-oesophageal reflux disease (GORD) to oesophageal mucosal damage, which can progress to ulceration and stricture formation, although only about 8% will have moderate or severe oesophagitis.
- Abnormalities of the lower oesophageal sphincter may facilitate excessive reflux of gastric contents including acid and sometimes bile from the stomach into the oesophagus.
- Bile is particularly caustic and reflux of duodenal contents is more troublesome than reflux of gastric contents alone. There is little correlation between severity of symptoms and findings on endoscopy.
- Sometimes drugs that have not been taken with an adequate amount of water stick in the oesophagus and are slowly released causing oesophagitis. Non-steroidal anti-inflammatory drugs (NSAIDs) and doxycycline are especially notorious and must be taken with adequate water. Bisphosphonates can be extremely troublesome. Oesophageal reflux is recognised as a risk factor for oesophageal cancer.
Factors that predispose to reflux include:
- Increased intra-abdominal pressure.
- Inadequate cardiac sphincter for anatomical reasons or factors that reduce tone, and also poor oesophageal peristalsis.
- Smoking, alcohol, fat, coffee.
- Tight clothes.
- Big meals.
- Surgery in achalasia of the cardia.
- Systemic sclerosis.
- Hiatus hernia.
- Drugs including tricyclic antidepressants, anticholinergics, nitrates and calcium-channel blockers.
Most of these predisposing factors increase intra-abdominal pressure and a fatty meal delays gastric emptying but the listed drugs and smoking relax the tone of the cardiac sphincter. NB: there is no relationship between Helicobacter pylori infection and GORD.
- Heartburn is a burning feeling, rising from the stomach or lower chest up towards the neck, that is related to meals, lying down, stooping and straining. It is relieved by antacids.
- Retrosternal discomfort, acid brash - regurgitation of acid or bile.
- Water brash - this is excessive salivation.
- Odynophagia (pain on swallowing) may be due to severe oesophagitis or stricture.
These include chest pain, epigastric pain and bloating.
- Non-cardiac chest pain caused by GORD has been found in up to 50% of patients with chest pain and normal coronary angiography. Usually there is no relationship to exercise and this helps to differentiate most cases of reflux-induced chest pain from true angina.
- Respiratory symptoms include chronic hoarseness (the Cherry-Donner syndrome), chronic cough, and asthmatic symptoms like wheezing and shortness of breath. Episodic or chronic aspiration can cause pneumonia, lung abscess and interstitial pulmonary fibrosis. In 6-10% of patients with chronic cough, GORD is the underlying cause.
- Endoscopy is the investigation of choice.
- Perform FBC to exclude significant anaemia.
- Barium swallow may show hiatus hernia (fluid level on CXR does not prove oesophagitis).
- Oesophageal pH monitoring to assess if symptoms coincide with acid in the oesophagus. This can be done with:
- Naso-oesophageal pH catheter (24-hour study).
- Wireless pH capsule (Bravo®).
- Oesophageal impedance and pH via nasal catheter (can give quantitative information about the amount of fluid refluxed).
Endoscopic grading of oesophagitis
- Grade 1: single or multiple erosions on a single fold. Erosions may be exudative or erythematous.
- Grade 2: multiple erosions affecting multiple folds. Erosions may be confluent.
- Grade 3: multiple circumferential erosions.
- Grade 4: ulcer, stenosis or oesophageal shortening.
- Grade 5: Barrett's epithelium. Columnar metaplasia in the form of circular or non-circular (islands or tongues) extensions.
- Grade A: one or more mucosal breaks no longer than 5 mm, none of which extends between the tops of the mucosal folds.
- Grade B: one or more mucosal breaks more than 5 mm long, none of which extends between the tops of two mucosal folds.
- Grade C: mucosal breaks that extend between the tops of two or more mucosal folds but which involve <75% of the mucosal circumference
- Grade D: mucosal breaks which involve ≥75% of the mucosal circumference
- Oesophagitis from swallowed corrosives or drugs like NSAIDs.
- Infection (especially in the immunocompromised): cytomegalovirus, herpes, candidiasis.
- Peptic ulcer.
- Gastrointestinal (GI) cancers.
- Non-ulcer dyspepsia.
- Oesophageal spasm.
The National Institute for Health and Care Excellence (NICE) in the UK has published guidelines on the management of dyspepsia (including reflux symptoms) which impact on clinical practice.
NICE guidelines for urgent referral for suspected upper GI cancer
- Dysphagia - food sticking on swallowing, at any age.
- Dyspepsia at any age combined with one or more of the following 'alarm' symptoms:
- Weight loss
- Proven anaemia
- Dyspepsia in a patient aged 55 years or more with at least one of the following 'high-risk' features:
- Onset of dyspepsia <1 year previously.
- Continuous symptoms since onset.
- Dyspepsia combined with at least one of the following known 'risk factors':
- Family history of upper GI cancer in more than two first-degree relatives.
- Barrett's oesophagitis.
- Pernicious anaemia.
- Peptic ulcer surgery over 20 years previously.
- Known dysplasia, atrophic gastritis, intestinal metaplasia.
- Upper abdominal mass.
In a prospective observational study the prevalence of gastric cancer was 4% (and serious benign disease 13%) in a cohort of patients referred urgently for alarm symptoms.
Referral for dysphagia or major weight loss at any age, together with those older than 55 years with alarm symptoms, would have detected 92% of the cancers found in the cohort. In contrast, the presence of typical reflux symptoms was less likely to indicate the presence of malignancy.
Routine endoscopic investigation of dyspepsia is not necessary for patients (of any age) without alarm symptoms.
Unfortunately most patients do not respond to lifestyle advice and require further therapy. However, the following are recommended:
- Reduce weight.
- Stop smoking.
- Reduce alcohol intake.
- Raise the head of the bed at night.
- Take small, regular meals.
- Avoid hot drinks, alcohol and eating during the three hours before going to bed.
- Avoid drugs which affect oesophageal motility (nitrates, anticholinergics, tricyclic antidepressants) or damage the mucosa (NSAIDs, potassium salts, alendronate).
Patients with reflux symptoms but no alarm symptoms, should receive initial treatment with full-dose proton pump inhibitors (PPIs) for one month.
- In cases of uninvestigated dyspepsia, eradication therapy for H. pylori can also be provided if infection is evident on serology or urea breath test. Where there is known GORD (ie post-gastroscopy), H. pylori eradication is not recommended.
- If symptoms return after treatment, and long-term acid suppression is required, a step-down strategy to the lowest dose of PPI that provides effective relief of symptoms is more cost-effective than the step-up approach.Start acid suppression at a healing dose for one to two months. Then either step up a level if still symptomatic, or step down, once symptoms have improved, to the lowest level that provides effective symptom control. All patients should have a treatment plan and should be told if they can stop if symptom-free.
Referral for endoscopy
It may become appropriate to refer some patients with an inadequate response to therapy, or new emergent symptoms, to a specialist for a second opinion.
- Review medications for possible causes of dyspepsia; for example, calcium antagonists, nitrates, theophyllines, bisphosphonates, steroids and NSAIDs. Patients undergoing endoscopy should be free from medication with either a PPI or an H2-receptor antagonist (H2RA) for a minimum of two weeks.
- Consider the possibility of cardiac or biliary disease as part of the differential diagnosis.
- If endoscopy is carried out and oesophagitis is present, a healing dose of PPI should be prescribed for two months.
- In such patients, symptoms usually relapse when treatment is withdrawn, and maintenance PPI therapy is usually required.
PPIs are more effective than H2RAs in relieving heartburn in patients with GORD who are treated empirically and in those with endoscopy-negative reflux disease, although the degree of benefit is greater for those treated empirically.PPIs are a safe class of medication to use long-term in persons in whom there is a clear need for the maintenance of extensive acid inhibition.
Clinical Editor's note
November 2017 - Dr Hayley Willacy draws your attention to the recently reported study concerning long-term use of PPI medicines and an increased risk of gastric cancer. Researchers from Hong Kong studied 63,397 people who'd been treated for stomach infection with H. pylori bacteria. Taking PPIs was associated with a more than doubling (2.44) in the risk of developing stomach cancer, while taking H2 blockers was not associated with any such heightened risk. 153 (0.24%) people developed stomach cancer after triple therapy. The average time between triple therapy and the development of stomach cancer was just under 5 years. More frequent use was associated with greater risk, with daily use linked to a more than quadrupling in risk (4.55) compared with weekly use. And the longer PPIs were used, the greater was the risk of developing stomach cancer, rising to 5-fold after more than a year, to more than 6-fold after two or more years, and to more than 8-fold after three or more years. This is an observational study and there are significant confounding factors; all the participants were Chinese, who are known to have a higher risk of developing gastric cancer than Western populations. Alcohol and tobacco use were also not routinely recorded during the study and cannot be eliminated as causative factors.
Most patients with reflux symptoms are treated with lifestyle interventions and medication. However, there is evidence that laparoscopic fundoplication surgery is more effective than medical management for the treatment of GORD, at least in the short to medium term.
Laparoscopic insertion of a magnetic bead band:
- With the patient under general anaesthesia, an implant is placed so that it encircles the distal oesophagus at the gastro-oesophageal junction.
- The implant is then secured in place. The implant consists of a ring of interlinked titanium beads, each with a weak magnetic force which holds the beads together to keep the distal oesophagus closed.
- When the patient swallows, the magnetic force is overcome, allowing the ring to open. After swallowing, magnetic attraction brings the beads together and the distal oesophagus is again closed.
- MRI is contra-indicated after this procedure.
- NICE currently recommends that the evidence on the safety and efficacy of laparoscopic insertion of a magnetic bead band for GORD is limited in quantity. Therefore, this procedure should only be used with special arrangements for clinical governance, consent and audit, or for research.
Symptoms persist in a minority of patients despite PPI therapy and this group remains a challenge to treat.
Some evidence suggests that once patients develop the disease, severity is determined early and patients seem to continue with that phenotype long-term.Therapeutic options include:
- Doubling the dose of PPI therapy.
- Adding an H2RA at bedtime.
- Extending the length of treatment.
- Surgery (see section above).
Prokinetic drugs, such as metoclopramide 10 mg tds, may occasionally help symptoms by promoting gastric emptying and increasing the tone in the cardiac sphincter. Specific groups should be given continuous, rather than intermittent, therapy:
- Patients with a documented NSAID-induced ulcer, who must unavoidably continue with NSAIDs (eg, severe rheumatoid arthritis), should remain on maintenance doses of PPIs.
- Patients with severe reflux oesophagitis should remain on maintenance doses of PPI to prevent its recurrence.
- Patients with complicated reflux disease (stricture, ulcer, haemorrhage) should be left on 'full-dose' PPI.
The cheapest effective PPI should be used.
- Oesophageal stricture.
- Barrett's oesophagus:
- This is premalignant ectopic gastric mucosa.
- Patients with chronic GORD are at increased risk of developing the changes of Barrett's oesophagus.
- The risk increases with longer duration and increased frequency of gastro-oesophageal symptoms.
Further reading and references
Endoluminal gastroplication for gastro-oesophageal reflux disease; NICE Interventional Procedure Guidance, July 2011
Endoscopic radiofrequency ablation for gastro-oesophageal reflux disease; NICE Interventional Procedure Guidance, August 2013
Ford AC, Moayyedi P; Treatment of chronic gastro-oesophageal reflux disease. BMJ. 2009 Jul 14339:b2481. doi: 10.1136/bmj.b2481.
Gillies RS, Stratford JM, Booth MI, et al; Oesophageal pH monitoring using the Bravo catheter-free radio capsule. Eur J Gastroenterol Hepatol. 2007 Jan19(1):57-63.
Genta RM, Spechler SJ, Kielhorn AF; The Los Angeles and Savary-Miller systems for grading esophagitis: utilization and correlation with histology. Dis Esophagus. 2011 Jan24(1):10-7. doi: 10.1111/j.1442-2050.2010.01092.x.
Hatlebakk JG; Endoscopy in gastro-oesophageal reflux disease. Best Pract Res Clin Gastroenterol. 2010 Dec24(6):775-86. doi: 10.1016/j.bpg.2010.09.005.
Fox M, Forgacs I; Gastro-oesophageal reflux disease, BMJ, January 2006.
Suspected cancer: recognition and referral; NICE Clinical Guideline (2015) (Last updated July 2017)
Kapoor N, Bassi A, Sturgess R, et al; Predictive value of alarm features in a rapid access upper gastrointestinal cancer service. Gut. 2005 Jan54(1):40.
Moayyedi P, Talley NJ; Gastro-oesophageal reflux disease. Lancet. 2006 Jun 24367(9528):2086.
van Pinxteren B, Sigterman KE, Bonis P, et al; Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev. 2010 Nov 10(11):CD002095. doi: 10.1002/14651858.CD002095.pub4.
Thomson AB, Sauve MD, Kassam N, et al; Safety of the long-term use of proton pump inhibitors. World J Gastroenterol. 2010 May 2116(19):2323-30.
Cheung KS, Chan EW, Wong AYS, et al; Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study. Gut. 2017 Oct 31. pii: gutjnl-2017-314605. doi: 10.1136/gutjnl-2017-314605.
Wileman SM, McCann S, Grant AM, et al; Medical versus surgical management for gastro-oesophageal reflux disease (GORD) in adults. Cochrane Database Syst Rev. 2010 Mar 17(3):CD003243. doi: 10.1002/14651858.CD003243.pub2.
Nencioni M, Asti E, Saino G, et al; Magnetic oesophageal sphincter for the treatment of gastro-oesophageal reflux disease: results of a prospective clinical trial. Chir Ital. 2009 Mar-Apr61(2):187-92.
Laparoscopic insertion of a magnetic bead band for gastro-oesophageal reflux disease; NICE Interventional Procedure Guidance, September 2012
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