Gastro-oesophageal reflux disease

Contributed by Dr Neil Galletly, clinical research fellow, and Dr Andrew Thillainayagam, consultant physician, Hammersmith Hospital Trust and the London Clinic and senior lecturer at Imperial College.

The essentials

  • GORD has a significant impact on patients' quality of life.
  • Alarm symptoms require urgent referral for endoscopy.
  • Eradicating H pylori does not help healing or prevent relapse.
  • Most cases of GORD relapse after stopping treatment.
  • Annual incidence of cancer in Barrett's oesophagus is about 1 per cent.

1. WHAT IS GORD?

Gastro-oesophageal reflux disease (GORD) is a common disorder. It is one of the most frequently encountered gastrointestinal conditions in the primary care sector. This is where most cases of GORD are managed.

GORD can affect patients in all age groups. Up to 44 per cent of all adults complain of reflux symptoms at least once a month, and 7 per cent have daily symptoms. In the UK, a survey of 2,000 households revealed that 20 per cent of adults have significant GORD symptoms more than twice a week.

The mechanism
The term GORD refers to the backflow of gastric contents into the distal oesophagus, causing the oesophageal mucosa to be attacked by acid and pepsin.

One contributing factor is reduced pressure and inappropriate relaxation of the lower oesophageal sphincter.

The action of acid and pepsin may result in oesophagitis, with inflammation of the mucosa of the lower oesophagus, erosions and even ulcers. But fewer than half of patients will have reflux oesophagitis, and most patients have no detectable changes to the oesophageal mucosa at endoscopy. This is sometimes referred to as endoscopy-negative reflux disease (ENRD), or non-erosive reflux disease (which enjoys the unfortunate acronym NERD).

If oesophagitis is seen at endoscopy, severity is classified by the size and distribution of erosions or ulceration. There are two grading systems in use, the Los Angeles and Savary-Miller classifications. About 80-90 per cent of patients with oesophagitis have mild to moderate disease.

Heartburn is the predominant symptom of GORD. Other associated symptoms may include acid regurgitation (acid brash), belching and dysphagia. Symptoms are often nocturnal or associated with meals. The frequency and severity of heartburn does not correlate with the presence or the severity of oesophagitis, and patients with reflux oesophagitis and ENRD have a similar pattern of symptoms.

A significant minority of patients with GORD present with respiratory symptoms, such as a persistent cough, recurrent or refractory asthma, or dysphonia and may be seen initially by respiratory physicians and ENT surgeons. Other GORD patients present with non-cardiac chest pain owing to oesophageal spasm, and might be inappropriately referred to a cardiologist.

The burden of GORD
GORD seriously affects quality of life, proportional to the frequency and severity of the heartburn, and unrelated to the presence or absence of oesophagitis. Sleep is poor or interrupted in 75 per cent, and GORD patients report worse emotional well-being than patients with diabetes or hypertension. The good news is that quality of life improves rapidly after treatment.

KEY POINTS

  • GORD is one of the most frequently encountered gastrointestinal conditions in primary care.
  • Fewer than half of patients with GORD will have reflux oesophagitis.
  • Many patients with GORD present with respiratory symptoms or non-cardiac chest pain.
  • About 20 per cent of adults in the UK have GORD symptoms more than twice a week.

2. DIAGNOSIS OF GORD

A careful and accurate history is crucial to making the diagnosis of GORD. In most patients, heartburn is the key symptom.

It is best to tell the patient what you mean by heartburn (a burning feeling rising from the stomach or lower chest up towards the neck) because this identifies more patients with GORD than just using the word alone.

It is important to differentiate heartburn from dyspepsia (pain or discomfort centred in the upper abdomen). Dyspepsia may be a symptom of GORD, but does not predominate and is usually associated with conditions such as peptic ulcer disease and functional dyspepsia.

Alarm symptoms Alarm symptoms include dysphagia, weight loss, melaena or haematemesis.

If these are reported, urgent referral for endoscopy and investigation is essential. Most patients with a typical history for uncomplicated GORD should be managed empirically with a trial of acid-suppressing drugs.

If symptoms settle with treatment, this tends to confirm the diagnosis of GORD.

Endoscopy has a limited role in diagnosis, particularly in the resource-limited NHS. There is no consensus as to its timing or overall usefulness in patients with this disease. More than half of patients with GORD will have ENRD and therefore endoscopy will appear normal. A clear indication for endoscopy is the presence of alarm symptoms. Other possible uses include the investigation of symptoms that are atypical or slow to respond to treatment, and to provide reassurance where patients remain anxious about their symptoms.

Evidence shows that 'on demand' or intermittent therapy with the proton pump inhibitor (PPI) esomeprazole is cost-effective in patients with ENRD.

There is a strong case for establishing the diagnosis early. The rationale would be the potential for reducing overall PPI expenditure, which takes up a large proportion of the national drug budget. A barium swallow is not much help in diagnosing GORD. It may show reflux of contrast from the stomach into the oesophagus, but the presence of reflux does not establish the diagnosis, and the absence of reflux does not rule out GORD. Oesophageal strictures or deep ulceration may be seen, but erosions are not shown in a barium swallow.

Ambulatory 24-hour monitoring of oesophageal pH can show that the symptoms are related to an oesophageal pH of less than 4.0. This diagnostic process should be reserved for patients where the diagnosis of GORD is in doubt after a trial of treatment and an endoscopy, or to confirm the diagnosis before referral for anti-reflux surgery.

KEY POINTS

  • Tell the patient what you mean by 'heartburn'; this identifies more patients with GORD.
  • Alarm symptoms include dysphagia, weight loss, melaena or haematemesis.
  • Endoscopy is normal in half of GORD patients.
  • A barium swallow is not helpful.
  • Ambulatory 24-hour monitoring of oesophageal pH can confirm the diagnosis of GORD if this is considered essential.

3. INITIAL MANAGEMENT OF GORD

The goals for the initial management of patients with GORD are to relieve symptoms and to heal any oesophagitis.

Although lifestyle modification, antacids and H2-receptor antagonists (H2RAs) have a limited role in the treatment of mild GORD, PPIs are the current mainstay of therapy for the condition.

Lifestyle modifications, such as smoking cessation and losing weight, are often advised. These measures benefit the patient's general health, so doctors should continue to advocate them, but in reality they have been shown to have little or no effect on symptoms.

Avoidance of foods and drinks that exacerbate symptoms might reduce postprandial symptoms, but does not affect nocturnal symptoms or healing of oesophagitis.

Antacids and H2RAs
Antacids and H2RAs provide better symptom relief in GORD than placebo, although the absolute benefit is small. Their role in healing oesophagitis is less clear. Antacids offer more rapid symptom relief than H2RAs, but H2RAs have a longer duration of action. They are appropriate for infrequent episodic or postprandial heartburn, either alone or in combination. However, antacids should probably not be used for persistent or frequent heartburn, particularly because ranitidine exhibits tachyphylaxis in long-term use.

PPIs are effective for resolving GORD symptoms and healing reflux oesophagitis, so patients with oesophagitis or more than infrequent mild symptoms should be treated initially with a standard (healing) dose of a PPI. Symptomatic relief following empirical therapy with PPIs helps to confirm the diagnosis.

NICE guidelines on dyspepsia advise that PPIs are offered at the lowest dose possible to control symptoms with a limited number of repeat prescriptions.

Consider stopping treatment after four to eight weeks, although most patients will relapse symptomatically and endoscopically. For long-term use, a maintenance dose of half the normal dose is appropriate.

Patients with severe oesophagitis or complications, such as oesophageal stricture or Barrett's oesophagus, should not stop PPI therapy.

A failure of response might be due to poor compliance, severe acid reflux, acid hypersensitivity of the oesophagus, or an incorrect diagnosis of the condition.

Eradicating H pylori and GORD
There is no evidence to suggest that the eradication of Helicobacter pylori helps in the healing of oesophagitis, reduces heartburn or prevents relapse.

In fact, eradication of H pylori can actually increase gastric acid production, potentially exacerbating GORD and making PPI therapy less effective.

KEY POINTS

  • Lifestyle modifications have little or no effect on GORD symptoms.
  • Antacids and H2RAs provide only a small absolute benefit and should probably not be used for persistent or frequent heartburn.
  • PPIs are effective for resolving GORD symptoms and healing reflux oesophagitis.
  • Stop treatment after four to eight weeks; use half-strength doses for maintenance.

4. LONG-TERM MANAGEMENT OF GORD
Most cases of GORD relapse after stopping treatment, but this can take several months to occur. Long-term management should aim to maintain remission and prevent complications, although no intervention has yet been shown to reduce the incidence of adenocarcinoma.

Medical therapy
Patients who relapse after stopping their treatment should be restarted on the successful medication and then have their treatment stepped down.

The object is to maintain these patients on the cheapest drug that effectively controls their symptoms, usually half-dose PPIs, but a few might manage on H2RAs.

Patients who relapse after several months can be maintained on intermittent short courses of drugs, rather than continuous therapy. ENRD can be maintained with 'on-demand' therapy, using medication only on the days when patients feel their symptoms returning. Patients with severe oesophagitis or complications such as oesophageal stricture should be maintained on PPIs. Maintenance dose esomeprazole might be more effective in severe oesophagitis. PPIs and H2RAs appear safe for long-term use.

Anti-reflux surgery
The aim of anti-reflux surgery is to restore the competence of the lower oesophageal sphincter, so reducing reflux. This is achieved by fundoplication - wrapping the gastric fundus around the lower oesophagus. Open fundoplication and long-term PPI therapy are equally effective over five years. Surgery might appear an attractive alternative to long-term drug therapy, but most patients having open fundoplication end up on anti-reflux medication again after 10 years.

Laparoscopic surgery has replaced open surgery in most centres, but so far, data from clinical trials is limited. Surgery should not be reserved for failures of medical therapy. These patients often do less well with surgery, sometimes due to incorrect diagnosis.

Novel procedures
Several novel endoscopic anti-reflux procedures have recently been developed.

These include radiofrequency energy to the lower oesophagus to produce a stenosis, endoscopic suturing to produce a plication at the lower oesophagus, and the injection of bulking agents to the lower oesophageal sphincter.

It is possible that one or two of these procedures might become cost-effective substitutes for long-term PPI treatment.

KEY POINTS

  • Long-term management should maintain remission and prevent complications.
  • Some cases of ENRD can be maintained with 'on-demand' therapy.
  • Most patients who have open fundoplication are taking medication again at 10 years.

5. COMPLICATIONS OF GORD

Most cases of GORD are mild and uncomplicated. The potential complications include oesophageal ulceration, oesophageal (peptic) stricture, Barrett's oesophagus and oesophageal adenocarcinoma. Chronic cough and asthma also seem to be associated with GORD.

These complications are more likely to occur in patients with reflux oesophagitis than in those who have ENRD.

Oesophageal ulcer
Ulceration is found in the most severe grades of oesophagitis, and there is a small risk of bleeding and of perforation. Treatment is with high-dose PPIs. A repeat endoscopy after six to eight weeks of treatment will check for ulcer healing and exclude carcinoma.

A stricture can cause dysphagia to solid foods and result in food bolus impaction. Patients require urgent endoscopy or barium swallow. Treatment is with high dose PPIs and endoscopic dilatation with balloons or dilators as required. Repeat dilatations might be necessary. Chronic GORD and acid damage to the lower oesophagus can result in the replacement of native squamous epithelium by a length of metaplastic columnar epithelium, known as Barrett's oesophagus. If the segment is less than 3cm in length, the patient is said to have short segment Barrett's oesophagus.

The metaplastic epithelium of Barrett's oesophagus can develop areas of dysplasia that eventually progress to adenocarcinoma. The risk relates to the length of columnar-lined oesophagus. The annual incidence is low at about 1 per cent, maybe even less. The role of endoscopic surveillance is controversial.

Most centres offer patients endoscopy every one to three years with multiple biopsies of the Barrett's segment. If dysplasia is present, more frequent endoscopic surveillance is offered.

Neither medical nor surgical therapy has been shown to prevent the development of cancer in Barrett's oesophagus, but as normalisation of oesophageal pH decreases cell proliferation in Barrett's mucosa, most authorities recommend long-term high-dose PPI therapy for all patients with Barrett's oesophagus.

KEY POINTS

  • Complications of GORD include ulceration, stricture and Barrett's oesophagus.
  • Oesophageal ulceration has a small risk of bleeding and of perforation.
  • Long-term high-dose PPI therapy is usually given to all patients who have Barrett's oesophagus.

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