Gastro-Oesophageal Reflux Disease

Acronym: GORD or GERD

See also - Childhood Gastro-Oesophageal Reflux Disease

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 2 to 3 times more common in men than women
• Barrett's oesophagus is 10 times as common in men. Prevalence increases over the age of 40.

Population based studies have shown that between 21 and 40% of people report suffering from "heartburn" in any 6 to 12 months period.¹

• There is a spectrum of disorders ranging from the commonest of endoscopy-negative 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.² 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. NSAIDs and doxycycline are especially notorious and must be taken with adequate water. Biphosphonates 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
• Pregnancy
• Obesity
• Tight clothes
• Big meals
• Surgery in achalasia of the cardia
• Hiatus hernia
• Drugs including tricyclics, anticholinergics, nitrates and calcium channel blockers, systemic sclerosis

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. 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, and is relieved by antacids.
Retrosternal discomfort, acid brash (regurgitation of acid or bile)
Water brash (excessive salivation)
Odynophagia that is pain on swallowing may be due to severe oesophagitis or stricture.

Atypical symptoms³

These include chest pain, epigastric pain, bloating, and pulmonary symptoms.

• 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 to 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)
• 24 hours pH monitoring to assess if symptoms coincide with acid in the oesophagus

• Oesophagitis from swallowed corrosives or drugs like NSAIDS
• Infection (especially in the immunocompromised); CMV, herpes, candida
• Peptic ulcer
• GI cancers
• Non-ulcer dyspepsia
• Oesophageal spasm

Oesophagitis/ulcer, anaemia, oesophageal stricture, Barrett's oesophagus (premalignant ectopic gastric mucosa).

The UK National Institute for Health and Clinical Excellence has published guidelines on the management of dyspepsia (including reflux symptoms) that impact on clinical practice.⁶

• Routine endoscopic investigation of dyspepsia is not necessary for patients without alarm symptoms (of any age) - see box below.
• However, referral for endoscopy is appropriate for patients aged 55 years and older with unexplained treatment resistant dyspepsia of more than four weeks' duration. Refer any patient with dysphagia or other alarm symptoms urgently - at any age!

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.⁷ 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.⁷

• Patients with reflux symptoms, but no alarm symptoms, should receive initial treatment with full dose proton pump inhibitors 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 proton pump inhibitor that provides effective relief of symptoms is more cost effective than the step-up approach.⁶ Start acid suppression at a healing dose for 1 to 2 months. Then either step up a level if still symptomatic, or step down once symptoms have improved to the lowest level that provides effect symptom control. All patients should have a treatment plan and should be told if they can stop if symptom free
• If endoscopy is carried out and oesophagitis is present, a healing dose of proton pump inhibitor should be prescribed for two months.
  In such patients symptoms usually relapse when treatment is withdrawn, and maintenance proton pump inhibitor therapy is usually required.

Systematic reviews for the Cochrane Collaboration⁸ have confirmed that proton pump inhibitors are more effective than H₂ receptor antagonists e.g. ranitidine, at healing oesophagitis and maintaining remission from mucosal injury and symptoms.
Long term management with proton pump inhibitors for over 10 years has been shown to be safe and effective, although the dose requirement may increase over time.⁹

Decision to Refer

Some patients with an inadequate response to therapy, or new emergent symptoms, it may become appropriate to refer 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 proton pump inhibitor (PPI) or an H₂ receptor (H₂RA) for a minimum of 2 weeks.
• Consider the possibility of cardiac or biliary disease as part of the differential diagnosis.

Lifestyle

Unfortunately, most patients do not respond to life-style advice and require further therapy.¹⁰ 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 within 3 hours of going to bed.
• Avoid drugs that affect oesophageal motility (nitrates, anti-cholinergics, tricyclic antidepressants) or damage the mucosa (NSAIDs, potassium salts, alendronate).

Drugs

The following treatments are available:¹¹

• Antacids with alginates can be used alone in mild cases or with other treatment when symptoms break through.
• H₂Antagonists
• Low dose (maintenance dose) proton pump inhibitors
• High dose (healing dose) proton pump inhibitors; usually a higher dose is required for about 1 or 2 months, to let the oesophageal mucosa heal and then a lower dose may be required long-term in chronic relapsing cases.

PPIs are usually produced in a lower and a higher dose tablet form, but sometimes it is necessary to give 2 higher dose tablets a day to suppress symptoms. About 70% of asthmatics with reflux can get improvement of peak flow by at least 20% with acid suppression but about 25% will require 2 higher dose tablets a day.¹²

• Patients over 80 should be treated the same as younger patients but with more attention to other morbidity and medication.
• GORD refers to endoscopically determined oesophagitis or endoscopy-negative reflux disease. Patients with uninvestigated 'reflux-like' symptoms should be managed as patients with uninvestigated dyspepsia. There is currently no evidence that H. pylori should be investigated in patients with GORD.
• Offer low-dose treatment, possibly on an as-required basis, with a limited number of repeat prescriptions.
• Review long-term patient care at least annually to discuss medication and symptoms.

A minority of patients have persistent symptoms despite PPI therapy and this group remain 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.¹⁰Therapeutic options include:

• Doubling the dose of PPI therapy
• Adding an H₂RA at bedtime
• Extending the length of treatment

Prokinetic drugs, such as metoclopramide 10mg 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 documented NSAID-induced ulcer who must unavoidably continue with NSAID's (eg severe Rheumatoid Arthritis) should remain on maintenance doses of PPIs.
• Patients with severe reflux oesophagitis should remain on maintenance dose 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.
NB:
Sudden or progressive worsening of symptoms if over 55 years old, or the development of dysphagia, anaemia, persistent vomiting or weight loss at any age, merits urgent referral for endoscopy (2 week rule - as per local guidelines).

Proximal stomach herniates through the diaphragmatic hiatus into the thorax.

• 80% are sliding hernias, where the gastro-oesphageal junction slides up into the chest.
• The rest are paraoesophageal or rolling hernias where the gastro-oesophageal junction remains in the abdomen, but a bulge of stomach herniates up into the chest alongside the oesophagus.

Epidemiology

Hiatus hernia is common (30% if >50 years) and 50% have symptomatic gastro-oesophageal reflux. Obesity is a risk factor.

Investigations

A barium swallow is the best diagnostic test.

Management

Advise weight loss and treat reflux symptoms as above.
Surgery (Nissen's fundoplication) may be indicated if symptoms are intractable or there is recurrent stricturing.

This is performed to re-establish lower oesophageal sphincter tone.

• The procedure involves wrapping the gastric fundus around the lower oesophagus, closing the hiatus, and securing the wrap in the abdomen. There are various types of procedure: Nissen, Toupet, Hill.
• Access via a large laparotomy incision, or use of laparoscopy. The latter, in the most skilled hands, achieves similar results to open surgery, with less morbidity, pain, hospital dependency and expense.¹⁴
• Patients treated surgically have significantly less symptoms when drug therapy was discontinued, but not when patients were permitted to take anti-reflux medications in their usual fashion. Studies have shown that 62% patients still use anti-reflux medication after surgery, compared with 92% of the non surgical group. Patients must not expect that surgery will remove all need for antisecretory medications.¹⁵

Acid reflux (and probably reflux of duodenal contents including bile) are risk factors for development of a Barrett's oesophagus. This is when the normal stratified squamous epithelium of the oesophagus is replaced by columnar epithelium of the gastric type.
It is well recognised as being potentially pre-malignant, but the risk of adenocarcinoma developing may be as low as 0.5% per year.
Acid suppression and surgical treatment of reflux do not seem to affect prognosis,^16,17 but regular endoscopy should be performed to detect change early and to permit early treatment in all those who are fit enough to survive such surgery. This is said to be a cost-effective form of cancer surveillance.¹⁸

Reflux of gastric contents is very common in infants. Possibly poor tone in the cardiac sphincter is involved but the liquid diet of babies is more important.
Babies do not complain of heartburn, but they may cry and have disturbed sleep. There may be significant vomiting with poor weight gain and risk of inhalation.

Epidemiology

Approximately 85% of infants vomit during the first week of life and another 10% have symptoms by 6 weeks of age.
Symptoms abate without treatment in 60% of infants by 2 years of age, as these infants begin to assume an upright position and eat solid foods.
Reflux is commonest between 1 and 4 months old, but sometimes it persists in teenagers. Reflux may cause wheeze and cough. In premature babies it can cause apnoea and bradycardia.

Management

This involves conservative measures like upright positioning after feeding, elevating the head of the bed, prone positioning and providing small, frequent feeds thickened with cereal. The prone position increases the risk of Sudden infant death syndrome (SIDS) and it has been argued that there may be an association between reflux and SIDS.¹⁹Keeping the baby seated is not recommended.

• Thickening the feed of bottle-fed babies can make a considerable difference, especially if there is poor weight gain. Sometimes Infant Gaviscon is mixed with food.
• Acid suppression with a H₂ antagonist or even a PPI may be required in severe cases, especially if there are resultant pulmonary problems.
• It has been argued that the mechanism of reflux in infants is such that prokinetic agents are a more logical form of treatment than acid suppression.²⁰ However, the problem is what to use. The BNF do not recommend metoclopramide in children and young adults because of extrapyramidal effects. Domperidone is less troublesome but is not recommended in those weighing less than 15kg. Due to reports of fatal cardiac arrhythmias or sudden death, from July 2000, cisapride was restricted to a limited access programme supervised by a paediatric gastrologist in the USA and in Europe, to patients treated within a clinical trial or safety study or registry programme. A Cochrane review concluded that there was little evidence of benefit from cisapride and that selective reporting of positive results had been misleading.²¹

Prognosis

Most cases are benign with 55% resolved by 10 months and 80% resolved by 18 months. Not all infants require medications to control the symptoms. Surgery is required in a minority of patients.

• In patients whose reflux persists into later childhood, chronic cough, wheeze, clubbing, and recurrent pneumonias are a continuing theme.
• Growth and weight gain are adversely affected in two thirds of patients. Cerebral palsy, Down syndrome, developmental delay, and Sandifer syndrome are all associated with reflux. Two thirds of patients have delayed gastric emptying, and one third have aspiration pneumonia.