Gastroesophageal reflux disease (GERD) is defined as a “condition which develops when the reflux of gastric contents causes troublesome symptoms or complications.” The estimated prevalence of GERD in North America is 20% (specifically defined as heartburn and/or regurgitation occurring at least once a week), and it has been increasing due to the obesity epidemic. The true prevalence is likely higher as many patients take over the counter acid reducing medications without seeking formal medical care.
The economic impact of GERD is very high, totaling $15–$20 billion a year in direct and indirect costs. The direct costs of GERD are an estimated $9–$10 billion per year. These costs include inpatient and outpatient visits, diagnostic procedures, and medications (with proton pump inhibitors accounting for the highest share of the cost). Indirect costs are a result of decreased quality of life, workplace absenteeism, and decrease in productivity.
A subset of patients with GERD present with noncardiac chest pain (NCCP). NCCP is a recurring angina-like retrosternal chest pain that is not due to cardiac causes and is a chronic disorder that reduces the quality of life of the patient but has no impact on mortality. NCCP contributes significantly to poor quality of life and increased economic burden, as patients often continue to have symptoms for years and frequently undergo multiple and repeated workups to rule out cardiac origins of chest pain. The estimated prevalence of NCCP is 25%. It affects both males and females equally. Prevalence generally decreases with increasing age. Patients with NCCP are younger, consume more alcohol, smoke, and are more likely to suffer from anxiety compared to patients with ischemic heart disease.
Etiology and Pathogenesis
The etiology and pathogenesis of GERD are multifactorial. In approximately 60% of patients, the lower esophageal sphincter (LES) is mechanically incompetent. In the remaining 40%, reflux occurs secondary to transient relaxations in the LES that are not triggered by swallowing, but rather likely secondary to gastric distention. About 30% of patients with GERD have a defect in esophageal peristalsis resulting in ineffective esophageal motility and delayed gastric emptying. Hiatal hernias can contribute to the development of GERD as well, as there can be loss of external compression around the LES paired with external compression of a distended stomach. Conditions that produce increased intraabdominal pressure (e.g., obesity), as well as a decrease in intrathoracic pressure (e.g., obstructive sleep apnea, which frequently coexists with obesity), can create an unfavorable pressure gradient that the LES may not be able to counterbalance, thus resulting in reflux. In addition to these mechanical factors, the acidity of gastric reflux can contribute to the severity of symptoms, as well as the volume and frequency of reflux episodes. GERD also commonly occurs in pregnancy, likely secondary to a combination of mechanical factors (weight gain, increase in intraabdominal pressure) and physiologic factors (increased progesterone).
GERD is the most common esophageal cause of NCCP in patients with and without coronary artery disease. The mechanism by which GERD causes NCCP, however, is poorly understood. One proposed mechanism involves peripheral sensitization of esophageal afferents leading to increased sensation of physiologic and pathologic stimuli. In one study, healthy subjects exposed to acid in the distal esophagus experienced a decrease in the pain threshold in the proximal esophagus. In response to the same stimulus, subjects with NCCP experienced a more profound sensitization of the upper esophagus that lasted longer than in healthy subjects, and additionally had a decrease in the pain threshold in the anterior chest wall, or development of secondary somatic allodynia, suggesting central sensitization as a likely mechanism. ,
Patients with GERD frequently present with heartburn and regurgitation, and less commonly dysphagia, which is usually secondary to ineffective peristalsis. Patients may also present with atypical symptoms of GERD such as NCCP, chronic cough, aspiration pneumonia, pulmonary fibrosis, hoarseness, globus, and dental erosions. , NCCP is characterized by recurrent angina-like retrosternal chest pain in the absence of cardiac causes of chest pain.
The diagnosis of GERD in patients who present with typical symptoms such as heartburn or regurgitation is often done clinically. In these patients, a trial of empiric proton-pump inhibitor (PPI) therapy is recommended. A good response to a PPI trial confirms the presumptive diagnosis in this setting. However, this strategy is not without limitations, as a PPI trial has a sensitivity of 78% and specificity of 54%. Additional diagnostic testing, including esophagogastroduodenoscopy, esophageal manometry, and esophageal pH monitoring may be required in patients who do not respond to a trial of PPI therapy or who present with atypical or worrisome symptoms. Upper GI endoscopy is performed to assess for evidence of mucosal damage and is indicated in patients presenting with GERD with alarm symptoms, as only 50%–60% of patients with GERD have evidence of mucosal damage (positive predictive value 53%). Upper GI endoscopy can be useful to exclude other pathologies such as eosinophilic esophagitis, gastritis, peptic ulcer disease, Barrett’s esophagus, esophageal strictures, and malignancy.
Esophageal manometry is of limited use in the diagnosis of GERD, but can be used to confirm proper placement of a pH probe, to rule out primary motility disorders such as achalasia, and for surgical planning.
Esophageal pH monitoring is considered the gold standard for the diagnosis of GERD. An esophageal pH probe is placed while the patient is not taking acid reducing medications. Measurements are taken 5 cm above the LES, and the patient keeps a symptom diary that is correlated to pH measurements. The test is less useful in correlating episodes of reflux to NCCP because of the low likelihood of patients having an episode of chest pain during the test. The test may be more useful for those patients that are being considered for antireflux surgery. A barium swallow has very little use in the diagnosis of GERD. It has a low sensitivity (20%), and the presence of barium reflux is of questionable significance as a proportion of subjects with normal pH esophageal pH will have spontaneous barium reflux.
In patients who present with NCCP secondary to GERD, it is prudent to rule out cardiac causes of chest pain such as coronary artery disease and pericarditis. Patients should be referred to a cardiologist for testing that may include electrocardiography, echocardiography, stress testing, and other diagnostic modalities to rule out a cardiac etiology.
The differential diagnosis of GERD includes esophageal motility disorders such as achalasia, esophageal strictures, malignancy, gastritis, peptic ulcer disease, esophagitis (eosinophilic, viral, or fungal), coronary artery disease (i.e., angina pectoris), and pericarditis. Table 23.1 illustrates the multiple causes of noncardiac chest pain.
|Esophageal motility disorders (e.g., diffuse esophageal spasms, achalasia)|
|Pill (drug-induced) esophagitis|
|Mallory–Weiss syndrome, Boerhaave syndrome|
|Pancreatitis, biliary colic, cholangitis|
|Zoster neuralgia, postherpetic neuralgia|
|Orthopedic/Rheumatologic||Degenerative disc disease, spinal stenosis, nerve root compression|
|Chronic pain disorders|