Clinical review

Oesophagus: Heartburn

John de Caestecker. 

Gastro-oesophageal reflux disease (GORD) is defined as symptoms or mucosal damage (oesophagitis) resulting from the exposure of the distal oesophagus to refluxed gastric contents. However, the symptoms of reflux oesophagitis do not equate with mucosal damage, and patients with endoscopic evidence of oesophagitis do not necessarily have the worst symptoms.

View larger version (71K): [in this window] [in a new window]   Presentation of gastro-oesophageal reflux disease

In primary care GORD is therefore best thought of in terms of symptoms: symptom control is the aim of most management strategies, and indeed typical symptoms can guide doctors to the correct diagnosis. Since frequency and intensity of symptoms are poorly predictive of the severity of mucosal damage, with the converse also applying, endoscopy may be less useful than commonly perceived. A variety of other tests are available to diagnose and assess the severity of disease if symptoms are atypical and results of endoscopy normal.

Nevertheless, oesophagitis resulting from GORD has become the commonest single diagnosis resulting from endoscopy carried out for dyspepsia, although whether this represents a true increase in prevalence or simply reflects a change in referral practice is unclear. There is little doubt that a spectrum of severity of disease exists, with most affected people never consulting a doctor and only a minority with unremitting symptoms or complications from the disease receiving attention from hospital specialists. Consequently, treatment of patients presenting in general practice may not be best guided by the outcome of most clinical trials, which have recruited patients from those referred to hospital.

	Terminology and aetiology

Top Terminology and aetiology Clinical features and... Natural course of GORD Investigation Treatment

Oesophagitis refers to endoscopic or histological evidence of an acute inflammatory process in the oesophagus. Only about 60% of patients in whom GORD is eventually diagnosed have endoscopic evidence of oesophagitis. Some evidence suggests that among patients in the community or those with atypical presenting symptoms the proportion with oesophagitis may be even lower.

View larger version (479K): [in this window] [in a new window]   Four grades of endoscopic oesophagitis. Top left: Grade 1 (single erosion with a sentinel fold of gastric mucosa). Top right: Grade 2. Bottom left: Grade 3. Bottom right: Grade 4 (stricture)

Hiatus hernia is present when gastric mucosal folds are observed more than 2-3 cm above the diaphragm by endoscopy or barium radiology and is found in about 30% of people aged over 50 years. However, most patients with an hiatus hernia do not have GORD, but about 90% of patients with marked oesophagitis have hiatus hernia. Thus, hiatus hernia may not result in GORD but can contribute to the disease. Hiatus hernia itself rarely gives rise to symptoms, although a large hernia may undergo torsion (volvulus) to cause acute epigastric or retrosternal pain with vomiting.

Both oesophageal and gastric factors affect the occurrence of reflux. The critical factor is lower oesophageal sphincter incompetence: most reflux occurs during transient relaxation of the lower oesophageal sphincter resulting from failed swallows (swallows not followed by a normal oesophageal peristaltic wave) and gastric distension (mostly after meals). Recent evidence has indicated that the diaphragmatic crural fibres surrounding the oesophageal hiatus act as an external sphincter in concert with the intrinsic lower oesophageal sphincter. Failure of this crural mechanism may allow a hiatus hernia to occur. The hernial sac may additionally provide a sump of gastric contents available for reflux once the lower oesophageal sphincter relaxes. Oesophageal acid clearance depends both on swallowed saliva and intact lower oesophageal peristalsis, which is impaired in about 30% of patients with GORD. Gastric acid production is usually normal in GORD, while delayed gastric emptying occurs in about 40%.

View larger version (45K): [in this window] [in a new window]   Main pathophysiological mechanisms in gastro-oesophageal reflux disease

Duodenogastro-oesophageal reflux of bile may play a subsidiary role to that of gastric acid and pepsin in patients with an intact stomach and has been implicated in the pathogenesis of Barrett's oesophagus and its sequelae.

Odynophagia, pain on swallowing, should be distinguished from dysphagia, difficulty in swallowing (see next article).

	Clinical features and presentation

Top Terminology and aetiology Clinical features and... Natural course of GORD Investigation Treatment

There is a spectrum of clinical presentation, ranging from symptoms alone to complications resulting from mucosal damage. Up to 40% of patients seen in hospital in whom reflux is eventually diagnosed have symptoms other than classic heartburn or pharyngeal acid regurgitation, including a variety of respiratory and pharyngeal symptoms.

	Natural course of GORD

Top Terminology and aetiology Clinical features and... Natural course of GORD Investigation Treatment

The condition is characteristically chronic and relapsing: in follow up studies at least two thirds of patients continue to take drugs continuously or intermittently for reflux symptoms for up to 10 years. Symptoms disappear in less than a fifth of those taking no drugs, and in the short term endoscopic evidence of oesophagitis may come and go independently of symptoms. There is no evidence that patients inevitably go on to develop severe erosive oesophagitis, Barrett's oesophagus, or stricture.

View larger version (51K): [in this window] [in a new window]   Overlap between symptoms, endoscopic evidence of damage, and physiological findings in reflux oesophagitis

Symptomatic relapse after discontinuing treatment is common and is chiefly dependent on initial severity of oesophagitis. In studies with large proportions of patients having initial severe oesophagitis, relapse rates of up to 80% at six months have been reported.

	Investigation

Top Terminology and aetiology Clinical features and... Natural course of GORD Investigation Treatment

GORD is a disease of different facets. No single investigation is capable of infallibly diagnosing the condition nor of assuring its relevance to symptoms in an individual case.

View larger version (51K): [in this window] [in a new window]   24 Hour recording of oesophageal pH in patient with gastro-oesophageal reflux disease but normal endoscopic appearance. Note close association between symptoms and reflux and large amount of daytime and night time reflux. (Reflux = intraoesophageal pH 4)

Choice of clinical investigation depends on presentation, the patient's age, presence or absence of "alarm" symptoms (such as dysphagia or weight loss), and the question to be answered. Thus, if the question is to decide if mucosal injury is present, endoscopy or barium radiology is most appropriate, whereas an acid perfusion test or 24 hour oesophageal pH monitoring with observation of symptom-reflux association is the most useful test in deciding if symptoms are due to oesophageal acid exposure.

Despite these considerations, in practice endoscopy is the most commonly performed initial investigation, combining inspection of the oesophagus with that of the stomach and duodenum to exclude other causes of dyspepsia. In up to two thirds of patients, however, the results of endoscopy are normal, particularly if patients are taking proton pump inhibitors or H₂ antagonists at the time of investigation.

Therefore, in young patients with longstanding typical symptoms (heartburn or pharyngeal acid regurgitation after meals and with postural changes) no investigation is necessary. Atypical symptoms, dysphagia, or presentation with short duration of symptoms in patients aged over 55 years usually require investigation. There are no a priori grounds for diagnosis or treatment of Helicobacter pylori infection in most patients, since there is no evidence at present of an association. Indeed, there is some evidence that eradication of infection, if present, may actually make acid suppression with proton pump inhibitors more difficult in GORD.

	Treatment

Top Terminology and aetiology Clinical features and... Natural course of GORD Investigation Treatment

Aims
For most patients, the aim is acceptable symptom control using the least treatment necessary to achieve this. Therefore, if symptom control is the aim, endoscopy to assess healing of oesophagitis is unnecessary. Indeed, it is now known that, at least for patients treated with proton pump inhibitors, absence of symptoms on treatment equates with healing of oesophagitis.

View larger version (47K): [in this window] [in a new window]   Endoscopic view of cancer in a Barrett's oesophagus

General measures
Patients should be advised to lose weight if overweight. There is no formal evidence to support this assertion, but success (though rarely achieved) may result in improved symptom control. Raising the head of the bed on 15 cm wooden blocks has been shown in a controlled trial to improve symptoms and healing of oesophagitis. There is little evidence that avoidance of specific foods has much effect on the course of the disease, but many patients have already identified and stopped eating foods that produce symptoms before consulting their doctor. Other potentially damaging drug treatment should also be reviewed.

Antacids and alginates
Antacids are effective for short term relief of symptoms. Although their efficacy is difficult to confirm in controlled trials, many sufferers, particularly those who do not consult a doctor, rely on self medication with antacids. Alginates work by forming a floating viscous raft on top of the gastric contents that provides a physical barrier to prevent reflux. To maximise this effect, they are therefore best taken after meals, otherwise they rapidly empty from the stomach and thus give only transient relief of symptoms by virtue of their antacid content.

Acid suppression therapy
The two major classes of agent available are the H₂ receptor antagonists and the proton pump inhibitors. There is little doubt that proton pump inhibitors are more rapidly and completely effective for both relieving symptoms and healing oesophagitis, regardless of disease severity. Because of this, a cost effectiveness argument has been made in favour of proton pump inhibitors as first choice treatments in all cases. However, the data on which these calculations have been made have generally come from hospital based clinical trials and may not be applicable to general practice.

Motility modifying drugs
These include metoclopramide and domperidone. Although both relieve symptoms of heartburn to a degree similar to H₂ receptor antagonists, they do not heal oesophagitis. In addition, metoclopramide has a relatively high incidence of side effects on the central nervous system. However, these drugs may be useful, particularly in patients with other dyspeptic symptoms such as nausea or early satiety.

Maintenance treatment
Only proton pump inhibitors, at standard or half standard doses, have been shown to be effective agents for maintenance of remission in those who require it. Indications for maintenance treatment include

• Severe oesophagitis, especially presenting with complications (such as stricture, bleeding, peptic ulcers)
• Barrett's oesophagus (although there is no evidence that continuous treatment prevents evolution to cancer)

Surgery
Laparoscopic anti-reflux surgery seems to be as successful as conventional surgery in controlling reflux in the short term without the disadvantages of a long hospital stay or convalescence. It has become an increasingly popular option for patients requiring long term medical treatment. The results from a randomised controlled trial comparing surgery with maintenance drug treatment are awaited.

	Footnotes

John de Caestecker is consultant gastroenterologist at Glenfield Hospital NHS Trust, Leicester.

The ABC of upper gastrointestinal tract is edited by Robert Logan, senior lecturer in the division of gastroenterology, University Hospital, Nottingham, Adam Harris, consultant physician and gastroenterologist, Kent and Sussex Hospital, Tunbridge Wells, J J Misiewicz, honorary consultant physician and honorary joint director of the department of gastroenterology and nutrition, Central Middlesex Hospital, London, and J H Baron, honorary professorial lecturer at Mount Sinai School of Medicine, New York, USA, and former consultant gastroenterologist, St Mary's Hospital, London. The series will be published as a book in Spring 2002.