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COMMENTARY
Gastroesophageal reflux disease: clinical features* Michael Pettit
Pharm World Sci (2005) 27: 417–420
ª Springer 2005
M. Pettit (correspondence, e-mail:
[email protected]): Clinical Pharmacy Unit, Royal Sussex County Hospital, and University of Brighton, Eastern Road, Brighton, BN2 5BE, UK Key words GERD Heartburn Oesophagus Regurgitation Abstract Gastroesophageal reflux disease (GERD) is a chronic disease affecting up to 40% of people in the Western world. Risk factors associated with GERD include age and lifestyle habits, although the clinically relevant contribution of many of these factors is unclear. In GERD, refluxed gastric acid damages the oesophageal mucosa, generally when the pH falls below 4. GERD patients present a variety of symptoms, most commonly heartburn and regurgitation. Oesophageal complications associated with GERD include erosions, ulcers, peptic strictures, and Barrett’s oesophagus which is implicated in the development of oesophageal adenocarcinoma. Diagnosis of GERD is problematic due to the range of symptoms which may be presented to the physician and symptom severity is frequently unrelated to disease severity. While endoscopic monitoring may be used to assess the presence and severity of GERD, a lack of visible damage does not necessarily indicate an absence of GERD. Techniques used to diagnose GERD include addition of an acid solution into the oesophagus in order to replicate symptoms (Bernstein test) or 24-hour intra-oesophageal pH monitoring. Proton pump inhibitors are effective in the treatment of GERD, acting to reduce the acidity of the gastric juice and hence reduce oesophageal damage and symptoms associated with GERD. Symptoms most indicative of GERD are those associated with erosive oesophagitis, including heartburn and acid regurgitation. Less common GERD-associated symptoms include chest pain, a range of ear, nose and throat conditions, and asthma. In contrast to perceptions of the disease as ‘merely’ heartburn, the impact on patients’ quality of life can be profound. Increasing awareness of GERD by health care professionals has led to improved diagnosis and a greater appreciation of the need for maintenance therapy. Accepted April 2005 * This Commentary is accompanied by a Review article on pp. 432–435.
with defects in the lower oesophageal sphincter (LOS). Two main disorders are associated with GERD. Transient relaxations of the LOS (5–35 s) are associated with up to 80% of reflux episodes, while loss of LOS tone accounts for about 22% of episodes3. The main cause of damage to the oesophagus and of associated conditions is gastric acid, with damage generally occurring when the acidity in the oesophagus dips below pH 44. Increasing levels of acidity coupled with increased oesophageal exposure time can lead to more severe injury to the mucosa5. Approximately 5% of GERD patients have oesophageal ulcers2. Furthermore, peptic strictures are found in about 10% of patients with severe GERD and can lead to dysphagia. In some cases, the stricture can be so pronounced that complete closure of the oesophagus can result6. Another condition associated with GERD is Barrett’s oesophagus, a condition where the normal squamous epithelial lining of the mucosa is replaced by columnar epithelium, similar to that found in the lining of the stomach. This is more resistant to gastric acid and is more commonly detected in patients with long-term reflux problems (10–15% of GERD patients)2. Although this can lead to relief of GERD symptoms, Barrett’s oesophagus has been linked with the development of oesophageal adenocarcinoma, which is often initially diagnosed at advanced stages7. In 1991, it was reported that the diagnosis of this type of cancer was increasing more rapidly than any other type in the USA8. It has also been shown to be almost 16 times more prevalent in patients suffering from more frequent and severe heartburn9. Historically, GERD has not received the attention it deserves, with the majority of mild heartburn sufferers choosing to self-medicate, using a range of over-the-counter (OTC) treatments. The link between GERD and oesophageal adenocarcinoma, however, has increased perception of the seriousness of the disease.
Introduction Gastroesophageal reflux disease (GERD) has become the most common upper gastrointestinal disorder in the Western world and its incidence appears to be on the increase. The most common symptoms of this chronic disease, which results from abnormal reflux of acidic gastric contents, are heartburn, regurgitation and epigastric pain. Heartburn affects 20–40% of adults in the Western world, with more than 7% experiencing it daily1,2. Historically, the symptoms of GERD were not recognised as relating to one disease. Also most patients complaining of heartburn and regurgitation would have been diagnosed as having a hiatus hernia1. There is an increasing body of data, however, that points to GERD being responsible for a diverse group of conditions.
Risk factors A variety of risk factors including lifestyle habits and use of certain types of medication may affect the prevalence of GERD, as shown in Table 1. Since the incidence of GERD can be markedly different in different populations, it is likely that a number of other factors yet to be elucidated, including environmental factors, are also involved2.
Diagnosis
The diagnosis of GERD can be problematic for two main reasons. First, patients may be present with any or none of a diverse range of symptoms. Second, the severity of symptoms is often unrelated to the severity of the disease. Accordingly, a number of protocols have been recommended for the diagnosis of GERD10,11. MeaPathophysiology sures recommended include empirical medical therAlthough the pathophysiology of GERD is complex apy, use of the Bernstein test, the use of upper and still not fully understood, it is primarily associated oesophageal endoscopy, or 24-hour pH monitoring.
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Table 1 Risk factors associated with gastroesophageal reflux disease (GERD) Risk factor
Details
Mechanism
Lifestyle habits
Eating spicy or acidic food
Acts as an irritant and increases gastric acid production Reduction of oesophageal peristalsis or LOS pressure Increased intra-abdominal pressure Increased gastric distension which can increase transient LOS relaxations Eating meals before bedtime can increase the chance of reflux episodes as, if the patient is in an upright position, the reflux material can be cleared by gravity Increased acid production. It is unclear whether stress leads to GERD or vice versa Oestrogen and progesterone reduce LOS tone during pregnancy. Increased abdominal pressure Unknown Unknown Unknown Increased intra-abdominal pressure Need not be coupled with aberrant LOS function. Increases the volume of gastric acid Weakens oesophageogastric junction, and hinders oesophageal clearance Can result in reduction of peristalsis or LOS pressure
Alcohol intake, smoking, eating fatty foods or chocolate Posture, tight belts etc. Meal size Meal time
Stress High risk groups
Related disorders
Pregnant women Elderly Caucasians Men Obesity Gastric acid hypersecretion Hiatus hernia
Medications
Nitrates, calcium channel blockers, b-blockers, anti-cholinergics, theophylline Non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin
NSAIDs interfere with mucosal healing and may be involved in destruction of oesophagus
LOS – Lower oesophageal sphincter.
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Endoscopy can detect damage to the oesophageal mucosal surface, but this may only develop in 40–60% of patients with GERD symptoms12,13. A lack of mucosal damage, therefore, does not rule out the possibility of GERD. The Bernstein test involves instilling 0.1 N hydrochloric acid into the oesophagus through a nasogastric tube, and is considered positive if the patient perceives pain or burning during the acid instillation14. The drawback of the test is the variable sensitivity, and this has prompted many modifications to the original technique15. Twenty-four hour intraoesophageal pH monitoring has a higher sensitivity in GERD diagnosis. However, it is costly and should be used only when there is symptomatic evidence of GERD, but no evidence of mucosal damage, or due to a lack of response to medical therapy10. Determination of the severity of GERD is clinically useful, as it indicates the risk for local complications and helps to determine the best treatment, especially with regard to long-term therapy. The most recently developed well-validated system is the Los Angeles (LA) classification16. This classification has four grades increasing in severity from A to D. The A endoscopic classification system is dependent on the presence, length and circumferential extent of clearly visible breakages in the surface of the mucosa. Grades A and B can be considered mild and moderate, respectively; grades C and D are severe and associated with a much higher risk of developing major complications such as
peptic stricture, deep ulceration and Barrett’s oesophagus. Another diagnostic approach is to establish whether treatment with high-dose proton pump inhibitors (PPIs) causes a reduction in symptoms17–19. PPIs reduce the amount of acid produced in the stomach, and have been shown to control symptoms more effectively than other therapeutic agents in the treatment of GERD, including H2-antagonists, which reduce gastric acidity by a different mechanism20. This empirical approach to the diagnosis of GERD has obvious advantages over 24-hour intra-oesophageal pH monitoring in terms of cost and availability to physicians. It is also less invasive and unpleasant for patients. Since GERD is a chronic condition, maintenance therapy may also be necessary, usually at a lower dose than for initial treatment 21. In one study, after initial treatment with PPIs, oesophagitis recurred in up to 80% of patients in the absence of maintenance treatment22.
Clinical manifestations Not all GERD symptoms are recognised as indicative of GERD, particularly if heartburn is absent. Only as a result of recent increases in awareness and knowledge of the disease is GERD diagnosis improving. Figure 1 indicates the range of symptoms associated with GERD.
Figure 1 The ‘‘pyramid’’ of symptoms associated with gastroesophageal reflux disease (GERD). The incidence of these diseases being indicative of GERD decreases towards the apex of the pyramid. Adapted from Richter23. Erosive oesophagitis and endoscopy-negative reflux disease Symptoms resulting from erosive oesophagitis (EO) are most commonly recognised as being associated with GERD. These include heartburn, which occurs in 68% of GERD patients and is considered a good marker for the disease – despite the fact that 48% of patients without GERD also reported heartburn in the same study 24. Additional EO-related symptoms which may also be observed in patients with endoscopynegative reflux disease (in which there is no endoscopic evidence of oesophageal erosions) are regurgitation, epigastric pain, and retrosternal pain and burning24. Of the range of symptoms known to be associated with GERD, only heartburn and regurgitation are significantly more prevalent in patients suffering from GERD than in the general population24. Thus an individual without these two symptoms, presenting with other atypical symptoms that may be related to GERD, is more likely to have a non-GERD-related disorder. Only when occurring together are symptoms associated with GERD likely to result from reflux disease. It is important, therefore, that physicians are aware of the full range of GERD symptoms to facilitate an accurate diagnosis when patients present with atypical symptoms, as described below.
Quality of life
The perception that GERD was identical with heartburn previously led to the widespread belief that its effect on patients’ quality of life (QoL) was negligible. However, several studies have presented data which dispel that notion. For example, GERD has been shown to impair QoL to a greater extent than duodenal ulcers, untreated hypertension, mild congestive heart failure, angina, or the menopause30. Quality of life data are generally gathered by means of patient questionnaires using a variety of validated instruments. Different dimensions of QoL in GERD are measured and compared with reference populations, including healthy individuals or other disease populations. In one study in GERD patients, for all dimensions tested (physical functioning, role-physical, bodily pain, general health, vitality, social function, role-emotional, and mental health), mean health-related QoL scores were significantly lower for GERD sufferers compared with the general population31. One instrument which is gaining increasing recognition for measuring the effect of GERD on QoL is the Quality of Life in Reflux and Dyspepsia (QOLRAD) system. This calculates scores for patients with GERD based on five domains encompassing emotional distress, sleep disturbance, food and drink problems, physical/social functioning, and vitality. QOLRAD has advantages over more generic QoL instruments, in Extra-oesophageal symptoms that it takes account of sleep disturbance, an indicaIn some patients, chest pain may result from GERD, tion of the nocturnal effects of GERD32. and can mimic angina pectoris25. A variety of ear, nose and throat complications are associated with GERD, which primarily result directly or indirectly Conclusion from refluxed gastric acid. Symptoms can also include GERD is a chronic, potentially debilitating disease, hoarseness, chronic cough, globus, pharyngitis, with symptoms which affect the majority of adults to a sinusitis, vocal chord granuloma, subglottic stenosis, varying degree. The correct early diagnosis and and even laryngeal cancer26. Less commonly associ- treatment of GERD is problematic due to the varying ated conditions include asthma27, dental erosion due severity of a wide range of presenting symptoms. to acid in the mouth28, and acid aspiration, which can Public perception of the disease as trivial has led to cause pulmonary damage6. This is more common in many patients self-medicating with ineffective OTC recumbent patients and those with imperfect auto- treatments. Such treatments may provide inadequate nomic control, such as young children and patients suppression of gastric acid and therefore sufficient with depressed consciousness29. symptom control may not be achieved. 419
The link between GERD and oesophageal adenocarcinoma, however, has increased the profile of the disease. The majority of treatments rely on protection from gastric acid often through the blockade of H2-receptors or inhibition of the proton pump in the gastric mucosa. PPIs have been found to be more effective than H2-antagonists in the treatment of GERD and for maintenance therapy. The challenge now facing health care professionals is first, to recognise the various symptoms of GERD and to aim for more rapid diagnosis and second, to commence effective treatment for patients suffering from GERD.
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