Gastroesophageal reflux disease (GERD) is one of the most common diseases encountered by a primary care physician. It can significantly impact the quality of life of patients and, if untreated, may lead to serious complications such as esophageal adenocarcinoma. GERD is prevalent in 10-20% of Western populations and 5% in Asian populations.
The risk factors of GERD include obesity, poor dietary habits, mental stress, pregnancy, smoking, and alcohol consumption. Lower esophageal sphincter (LES) abnormalities and hiatus hernia are the two most common pathologies associated with GERD. This results in the backflow of acidic gastric content into the esophagus, which erodes the mucosal lining.
The most common symptoms include heartburn, regurgitation, and waterbrash. In most cases, GERD is diagnosed clinically. Endoscopy and esophageal pH monitoring are also helpful when an eight-week empiric therapy is not successful. Empirical proton pump inhibitor therapy has been revolutionary in the treatment of GERD.
Anti-reflux surgical procedures are rarely advised, only in cases of refractory GERD or when lifelong PPI use is not desirable. GERD can lead to the development of esophageal ulcers, Barrett’s esophagus, and even adenocarcinoma. Hence, early initiation of PPI therapy and keeping a high index of suspicion is crucial to prevent complication development.
Introduction Gastroesophageal Reflux Disease
Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal tract (GIT) related conditions encountered by a primary care physician. The Montreal Global evidence-based consensus defined GERD as a disease that develops when the reflux of gastroduodenal contents causes bothersome symptoms and/ or complications (1). GERD is a chronic condition, and in most cases, it does not develop any complications. It does, however, reduce the quality of life of the patient to a significant extent.
In a small number of patients, GERD can be a predisposing risk factor to a number of serious complications like esophageal adenocarcinoma. Proper diagnosis and treatment of GERD significantly improve the quality of life of the patient, in terms of physical and social vitality, and also wards off the risk of development of co-morbidities (2).
Epidemiology of GERD
Epidemiologic estimates of the prevalence of GERD report that 10-20% of the total population of the Western world experience typical symptoms of GERD at least weekly (3). Whereas in the Asian population, the prevalence of GERD is lower at almost 5%. The chronic nature of GERD depicts that it has lower incidence rates compared to prevalence rates. In the Western world, the incidence of GERD is 5 per 1000 person-years, whereas the average prevalence is 15 per 100 people. The higher prevalence of GERD among the Western population can be due to a greater percentage of its obese population (4). Obesity has a definitive association with reflux disease (5).
There is conflicting opinion regarding gender difference in the prevalence of GERD. An updated systematic review concludes that GERD is more common among females as compared to males (6). However, men are more likely to develop erosive esophagitis and Barret’s esophagus. Women usually do not develop esophageal mucosal erosion; hence they have the subtype of GERD called non-erosive reflux disease (NERD) (7). Similarly, esophageal adenocarcinoma is also eight times more common in males compared to females (8).
Etiologies and Risk Factors of Gastroesophageal Reflux Disease
Old age, obesity, pregnancy, poor dietary habits, mental stress, smoking, and alcohol consumption are some important risk factors for the development of GERD (9). There is a higher prevalence of GERD among the elderly population, and it is often complicated by bleeding from ulcers and esophageal stricture formation. Obesity and pregnancy are well-developed risk factors for GERD and are explained in detail in the next section. Poor dietary habits such as increased consumption of caffeine, tea, alcoholic beverages, fatty meals, and chocolate are predisposing factors to GERD. Similarly, taking large meals and lying down after heavy meals also increase the risk of reflux (10, 11).
Pathophysiology of Gastroesophageal Reflux Disease
The reflux of gastroduodenal contents into the esophagus and the gullet occurs occasionally in healthy individuals. But this reflux triggers peristaltic activity in the esophagus, which results in the clearing of the gullet and neutralization of the acidic gastric contents by the alkaline saliva. In some people with the aforementioned risk factors, reflux occurs more frequently, and the esophageal mucosa remains exposed to the acidic gastric juices for prolonged periods of time.
The esophagus is lined by stratified squamous non-keratinized epithelium, and it is not suited for an acidic environment. The low pH of the gastric acid can cause erosion of the esophageal lining leading to esophagitis and ulcer formation. In some cases, the epithelium of the lower thirds of the esophagus undergoes a metaplastic change from squamous to columnar epithelium. This is called Barrett’s esophagus (9, 11). The factors which can be attributed to the acidic reflux are explained as follows:
Lower Esophageal Sphincter Abnormalities
There are two types of lower esophageal sphincter (LES) abnormalities: reduced basal sphincter tone and inappropriate sphincter relaxation. Normally, the LES is tonically contracted to prevent the backflow of stomach acid. It relaxes only when there is a stimulus due to the food bolus. The food bolus causes distention of the esophagus, which triggers peristaltic activity in the longitudinal muscles of the esophagus and, at the same time, causes relaxation of the circular sphincteric muscles.
In some cases, the tone of the LES decreases, and it does not remain tonically contracted in the absence of a stimulus. Due to this, a rise in the intra-abdominal pressure or lying flat can cause regurgitation of the stomach acid. In other cases, the basal tone of LES is normal, but there is more frequent and inappropriate relaxation of the sphincter, which causes regurgitation (12).
Hiatal hernia is a condition characterized by upward protrusion of the stomach into the thoracic cavity through an opening in the diaphragm. In the sliding type of hiatus hernia, there is an increased risk of acid reflux due to the loss of the oblique angle between the esophagus and cardia (13). Additionally, the pressure gradient between the abdominal and thoracic cavities, which is normally maintained by the pinching effect of the diaphragm, is no longer present. Studies report that almost 15% of patients who are diagnosed with erosive esophageal ulcers or Barrett’s esophagus also have a coexisting hiatus hernia (14).
In the developed world, the most common, preventable risk factor of GERD is obesity (9, 11). Obesity results in elevated intraabdominal pressure due to increased fat deposition around the abdominal viscera. The increased intrabdominal pressure causes reflux of gastric contents. Moreover, obesity is associated with a decrease in the tone of the lower esophageal sphincter. The mechanism for reduced LES tone in obese patients is not well-understood. A plausible explanation could be that the persistently increased gastric distention in obese patients due to poor eating habits leads to LES relaxation (9-12).
Gestational reflux is very common, affecting up to 80% of pregnant women (15). The markedly raised intraabdominal pressure in pregnancy due to the gravid uterus is the main reason for regurgitation. Additionally, hormonal changes during pregnancy can also cause the LES to relax, leading to backflow of acid. Gestational GERD resolves after delivery in almost all cases, however, it can be very troublesome during pregnancy.
Impaired Esophageal Clearance
Impaired saliva production and defective peristaltic activity of the esophagus lead to impaired clearance of food contents admixed with gastric acid from the esophagus. Decreased saliva production seen in patients with xerostomia renders them unable to clear the esophagus, which leads to esophagitis and peptic strictures (12).
Clinical Presentation and Symptoms of Gastroesophageal Reflux Disease
The most common presenting complaints in patients with GERD include heartburn, regurgitation, dyspepsia, waterbrash, and retrosternal chest pain. A telephone survey of over 21,000 adults reported that 28% of them experienced GERD-like symptoms, and 6% of them experienced heartburn severe enough to interfere with their quality of life (16). Regurgitation was reported by 43% of the population (16). Waterbrash is excessive salivation that occurs when the salivary glands are stimulated by the refluxed acid, which almost always co-exists with regurgitation.
Regurgitation can also cause choking in some patients, especially when lying flat. In such cases, the patient complains of being woken up at night due to an uncomfortable sensation of choking. Retrosternal chest pain can also be a presenting symptom, and sometimes it may be severe enough to mimic angina. This type of pain is caused by reflux-induced esophageal spasms. It is crucial to rule out cardiac pain through detailed history and investigations before labeling it atypical chest pain due to GERD (1, 17).
Other symptoms like odynophagia and dysphagia are less common. They may be associated with uncomplicated erosive esophagitis, but a high index of suspicion must be kept in patients resenting with progressive dysphagia. This can be due to a developing stricture or malignancy (17, 18). Some extra-esophageal symptoms like asthma, chronic cough, and laryngitis are also particularly common, especially in the elderly population (19). Obesity, GERD, and asthma: the triad of inflammation have a strong association with a relatively less understood mechanism (20, 21).
Diagnosis of Gastroesophageal Reflux Disease
In most cases, the diagnosis of GERD is clinical, based on characteristic symptoms like heartburn and regurgitation. American College of Gastroenterology (ACG) guidelines recommend starting an eight-week course of proton pump inhibitors (PPIs) empirically when a patient presents with classical GERD symptoms (17). It is important to rule out any red flag signs before going for an empirical PPI course. The red flag signs include any history of dysphagia, unintentional weight loss, recurrent vomiting, change in the color of stool (melena), any signs of anemia, and age over 55 years (22).
The investigation of choice in the case of patients who fail to respond to an eight-week empiric course of PPIs is diagnostic endoscopy. Endoscopy is also recommended if any alarm symptoms are present or there is a recurrence of symptoms after PPIs are discontinued (17). On endoscopy, erosive esophagitis of Los Angeles Grade 2, 3, or 4, long segment Barrett’s mucosa (more than 3cm), or peptic strictures are diagnostic of GERD (17, 23). The LA scoring system is most widely used to grade erosive esophagitis. LA grade 1 is not considered to be diagnostic of GERD whereas LA grade 2 is diagnostic of GERD if coexisting with the typical symptoms and response to PPI (17).
Esophageal pH monitoring/ Ambulatory pH impedance monitoring
If endoscopy shows no evidence of GERD and symptoms persist, then off therapy, esophageal pH monitoring is recommended (17). In this test, a slim catheter is tethered to the gastroesophageal junction. The catheter is attached to a pH-sensitive radio probe that detects any changes in pH while the person carries out routine tasks. Any pH in the esophagus below 4 for more than 6% of the study time is diagnostic of GERD (23, 24).
Treatment and Management of Gastroesophageal Reflux Disease
Most of the risk factors for GERD are preventable, and in mild to moderate cases, the symptoms can be resolved by lifestyle changes. Obese patients should be advised to lose weight (17). Avoidance of dietary triggers like caffeine, tea, chocolate, and alcoholic beverages is helpful in relieving symptoms. Patients who experience nocturnal symptoms should be advised to raise the bedhead and avoid consuming large meals before bedtime (11, 25)
Proton pump inhibitors
PPIs remain the treatment of choice for GERD. The ACG guidelines recommend the administration of the lowest effective dose of PPI 30 to 60 minutes before meals. Initially, an 8-week trial should be given, followed by an attempt to discontinue the use of PPIs. If the symptoms return on discontinuation, patients may require life-long therapy with PPIs. In patients with non-erosive reflux disease (NERD), on-demand or intermittent PPI therapy is recommended. But in patients with LA grade 3 or 4 erosive esophagitis, lifelong PPI therapy along with follow-up monitoring is recommended (17).
The long-term use of indefinite PPIs does not come without risk. PPIs can cause parietal cell hyperplasia and hypertrophy, which leads to acid rebound on discontinuation. They also hinder the absorption of certain nutrients like iron, magnesium, and vitamin B12 (26). There is conflicting evidence regarding the monitoring of magnesium levels for PPI-induced hypomagnesemia. The AGA Best Practice Recommendation concluded that there is no benefit of magnesium level monitoring in long-term PPI users (27).
A large-scale randomized controlled trial of over 16,000 compared adverse effects due to the use of a PPI (Pantoprazole) for three years with a placebo. The study concluded that PPI users had a modestly increased risk of infections like salmonella, campylobacter, and Clostridium difficile infection compared to the placebo group (28). Indefinite use of PPIs has also been shown to increase the risk of fractures (26). H2 receptor blockers and antacids like sucralfate are not recommended for GERD. Sucrulafate is recommended by the ACG in gestational GERD (17).
Anti-reflux surgical procedures
Surgical management for GERD has two indications: refractory GERD that is unresponsive to PPI therapy and the personal preference of the patient for surgical management due to the inconvenience of lifelong PPI use (17).
Laparoscopic Nissen Fundoplication is considered the gold standard anti-reflux surgical procedure. It involves creating a new valve mechanism at the lower end of the esophagus through a laparoscopic approach (29, 30). Many studies have reported the superior efficacy of this procedure in improving GERD symptoms and patient satisfaction (17, 30)
Magnetic sphincter augmentation is a comparatively new procedure, less invasive, and more readily reversible than laparoscopic fundoplication. In this procedure, a network of titanium beads with magnetic cores is placed around the lower esophageal sphincter to increase LES pressure and prevent reflux (17). There are not many randomized controlled trials that compare the risk versus benefit ratio of MSA and fundoplication.
Prognosis and Complications of Gastroesophageal Reflux Disease
GERD generally carries a good prognosis in 90% of the patients. The symptoms resolve completely with PPI therapy in most patients. In the remaining patients with refractory GERD, surgical procedures are effective. However, if GERD is not properly treated, it carries a serious risk of complication development, such as esophageal ulcer formation, Barrett’s esophagus, esophageal strictures, and even adenocarcinoma of the lower esophagus.
Erosive Esophagitis: Prolonged exposure to acid can cause erosion of the esophageal mucosa and subsequent development of ulceration. Based on the endoscopic findings, the degree of erosion is graded by the Los Angeles Classification of Reflux Esophagitis. No treatment is required for LA Grade 1 esophagitis. While the other grades are treated with PPIs.
Barrett’s Esophagus: This is a premalignant condition in which the squamous lining of the lower esophagus is replaced by columnar mucosa. It is found in 10% of the patients undergoing gastroscopy for GERD-related symptoms. PPI therapy or anti-reflux surgery has failed to report regression of the metaplastic changes.
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