Handbook of Gastrointestinal Motility and Disorders of Gut-Brain Interactions

By Henry P. Parkman

Handbook of Gastrointestinal Motility and Disorders of Gut-Brain Interactions, Second Edition fills the void in GI literature for a short and concise go-to book for disorders of GI motility and gut and brain interactions. This exceptionally illustrated reference contains all the information needed for the latest knowledge on adults as well as adolescent and pediatric GI motility disorders, each systematically arranged by disorder and gut anatomy for easy reference. Each chapter includes extensive color pictures of each test as well as descriptions of how to perform and interpret the motility tests and how to incorporate them into patient care decisions.

Current advances in the field have led the way for new updates. A new section dedicated to systemic disorders and special topics, including gut autonomic disorders, cannabis and the gut, eating disorders, pediatric and adolescent disorders, nutritional therapies, and psychological management is included. This is the perfect book for those who encounter the common problems of dysphagia, heartburn, nausea, vomiting, gastroparesis, abdominal pain, gas and bloating, irritable bowel syndrome, constipation, and fecal incontinence and rare disorders in daily practice, including practicing physicians, gastroenterologists, motility laboratory personnel, surgeons and internists

• Provides a user-friendly style that reviews the latest and most up-to-date information on the evaluation of symptoms and diagnostic tests of GI motility and gut and brain interactions
• Presents a practical approach to the diagnosis of common and obscure disorders
• Discusses the latest options on management and therapy and explains how to integrate diagnostic information into decision-making and translate this into day-to-day patient care

• Language: English
• Publisher: Academic Press
• Release date: Jun 20, 2023
• ISBN: 9780443139109

Book preview

Section A

Esophageal disorders

Chapter 1: Understanding esophageal symptoms: Dysphagia, heartburn, and chest pain

Neil Nadparaa; Zubair Malikb; C. Prakash Gyawalic    a Department of Internal Medicine, Temple University, Philadelphia, PA, United States

b Section of Gastroenterology, Temple University, Philadelphia, PA, United States

c Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, United States

Abstract

Dysphagia, heartburn, and chest pain are among the most common esophageal symptoms encountered by gastroenterologists. As many as 45% of adults in the United States report one or more upper gastrointestinal (GI) symptoms annually, 1 of which heartburn accounts for 10%–20%, dysphagia/regurgitation for 8%–16%, and chest pain for 25%. 2–4 Esophageal symptoms significantly impact the quality of life, resulting in missed work days, as well as the impact on social and household activities, leading to an average of 3 days each of missed activity over the course of a year. Esophageal symptoms can provide clues to the etiology of esophageal disorders and can help triage diagnostic and therapeutic decisions. Understanding esophageal physiology and pathophysiology allows directed evaluation and precision management of disorders underlying these symptoms. Esophageal symptoms can be categorized into specific patterns: obstructive (dysphagia and regurgitation), perceptive (heartburn and chest pain), and atypical (belching and hiccups).

Keywords

Dysphagia, heartburn, and chest pain; Esophageal symptoms: dysphagia, heartburn, and chest pain; Obstructive (dysphagia and regurgitation); Perceptive (heartburn and chest pain); Atypical (belching and hiccups)

Key points

•Dysphagia, heartburn, and esophageal chest pain are among the most common esophageal symptoms encountered by physicians.

•An understanding of the esophageal physiology and pathophysiology directs the evaluation and management of disorders underlying symptoms of dysphagia, heartburn, and chest pain.

•Dysphagia can be stratified by anatomic location into oropharyngeal and esophageal and further differentiated into structural and neuromuscular etiologies.

•Neuromuscular etiologies dominate over structural obstructions in oropharyngeal dysphagia, while structural etiologies, often related to GERD, are more common than neuromuscular or motility disorders in esophageal dysphagia.

•Perceptive esophageal symptoms such as heartburn and chest pain may be caused by GERD, other mucosal processes like eosinophilic esophagitis, functional disorders, and motility disorders.

•Clinical evaluation includes history and physical examination, and when indicated, an empiric trial of a proton pump inhibitor if GERD is suspected and no alarm symptoms exist.

•Investigation of esophageal symptoms typically starts with an upper endoscopy but may include barium swallow, esophageal manometry, and ambulatory reflux monitoring.

•Functional esophageal disorders should be considered when organic etiologies have been ruled out, and treatment can include neuromodulators and psychological interventions.

Conflict of interest

No conflicts of interest exist. No writing assistance was obtained. No funding was obtained.

Disclosures

NN: None, ZM: None, CPG: Medtronic, Diversatek, Ironwood, IsoThrive, Quintiles, Takeda (consulting).

Introduction

Dysphagia, heartburn, and chest pain are among the most common esophageal symptoms encountered by gastroenterologists. As many as 45% of adults in the United States report one or more upper gastrointestinal (GI) symptoms annually,¹ of which heartburn accounts for 10%–20%, dysphagia/regurgitation for 8%–16%, and chest pain for 25%.²–⁴ Esophageal symptoms significantly impact the quality of life, resulting in missed work days, as well as an impact on social and household activities, leading to an average of 3 days each of missed activity over the course of a year.¹

Esophageal symptoms can provide clues to the etiology of esophageal disorders and can help triage diagnostic and therapeutic decisions. Understanding esophageal physiology and pathophysiology allows directed evaluation and precision management of disorders underlying these symptoms. Esophageal symptoms can be categorized into specific patterns: obstructive (dysphagia and regurgitation), perceptive (heartburn and chest pain), and atypical (belching and hiccups).

Obstructive symptoms

Dysphagia/regurgitation

Definition

Dysphagia refers to a subjective sensation of difficulty in swallowing, causing abnormality in food transit from the mouth to the stomach.⁵ Odynophagia is defined as pain with swallowing. The term dysphagia can be broken down into its Greek derivatives, dys meaning difficulty or disordered and phagia meaning to eat. Since both oropharyngeal and esophageal mechanisms participate in food transfer to the stomach, there are two types of dysphagia (Table 1). Oropharyngeal dysphagia compromises the transfer of food from the mouth to the proximal esophagus, while esophageal dysphagia impacts the transit of food in the tubular esophagus. Regurgitation consists of spontaneous retrograde movement of esophageal or gastric content back into the mouth; acidity and sour taste distinguish gastric regurgitation from esophageal regurgitation, which is bland and can taste similar to recently eaten food. Dysphagia is an alarm symptom that warrants prompt evaluation since it can result from both sinister and simple conditions and can impact adequate intake of nutrition, leading to weight loss.

Table 1

Dysphagia has a prevalence of 5%–8% in individuals over 50 years and is especially common in hospitalized patients and nursing home residents.⁴,⁶ Oropharyngeal dysphagia in particular increases in prevalence with age, with predominantly neurological etiologies including stroke, head injuries, Parkinson’s disease, and Alzheimer’s disease⁷ and potential complications of aspiration pneumonia, malnutrition, and potentially even death. In contrast, esophageal dysphagia has predominantly structural etiologies, mostly related to gastroesophageal reflux disease (GERD), other benign esophageal disorders, esophageal neoplasia, and less frequently, neuromuscular disorders like achalasia. Therefore, dysphagia can be associated with high morbidity, mortality, and healthcare cost burden.

Pathophysiology

Swallowing involves the integration and coordination of central and peripheral neural function as well as muscle function in three anatomic areas, the oral cavity, pharynx, and esophagus.⁸ In the oral preparatory phase, the food bolus is broken down by incisors to a finer consistency and size over a few seconds. Following this, during the pharyngeal phase, oropharyngeal musculature rapidly propels the food bolus from the pharynx into the esophagus through the upper esophageal sphincter (UES), which takes less than a second to complete. Finally, during the esophageal phase, the food bolus travels down the esophagus and through the lower esophageal sphincter (LES).⁸,⁹ Abnormalities of neurological control, muscular function, and obstructive processes can all lead to a breakdown of these intricate mechanisms for food transfer and lead to dysphagia.

Oropharyngeal dysphagia

Compromise in the propulsion of a food bolus from the oral cavity through the UES into the esophagus leads to symptoms of oropharyngeal dysphagia. The oropharyngeal phase of swallowing begins with contractions of the tongue and striated muscles of mastication, which are under the control of the motor nuclei of cranial nerves V, VII, and XII. The presence of the food bolus is recognized by sensory afferent nerve fibers that connect to the brain stem via the internal branch of the superior laryngeal nerve and the glossopharyngeal nerve to initiate oropharyngeal swallowing.¹⁰ Coordination of the pharyngeal phase involves several processes, including elevation of the soft palate for nasopharyngeal closure, UES opening, laryngeal closure, tongue loading and pulsion, and finally, pharyngeal clearance. Patients with oropharyngeal dysphagia can report delayed swallow initiation, chronic aspiration, nasopharyngeal regurgitation, drooling, and piecemeal swallowing. Symptoms typically arise within 1 second of initiating a swallow, and patients can often localize the site of dysfunction.¹¹ Neuromuscular causes of oropharyngeal dysphagia are more common than structural causes and commonly involve central and peripheral nervous system diseases, as well as myogenic mechanisms; structural abnormalities are much less common in oropharyngeal dysphagia.¹²

Esophageal dysphagia

Esophageal dysphagia consists of the sensation of obstruction of transit of food and/or liquids in the tubular esophagus. Consequently, the sensation may be localized to the retrosternal or suprasternal area, the base of the neck, or the epigastric area. Symptoms are typically localized at or above the level of the obstruction, and distal esophageal obstruction is sometimes localized to the sternal notch. Patients are able to accurately localize the level of obstruction within 2 cm about half of the time.¹³ Structural obstructive disorders are more common causes of esophageal dysphagia than neuromuscular disorders.

Evaluation and diagnostic testing

History and physical examination

A detailed clinical history and physical examination, taking symptom location, onset, duration, and progression into account, can be helpful in distinguishing between oropharyngeal and esophageal mechanisms of dysphagia (Fig. 1). Dysphagia localized to the pharynx or high neck occurring immediately upon initiation of swallowing, with associated aspiration, nasopharyngeal regurgitation, and postswallow residue can point toward oropharyngeal dysphagia, especially in individuals with coexisting neurological symptoms or disorders. A sensation of food stuck retrosternally a few seconds after initiating a swallow, with associated chest pain or odynophagia suggests an esophageal mechanism of dysphagia, especially in the context of GERD or atopic disorders. Important associated symptoms that need to be clarified include heartburn, weight loss, hematemesis, anemia, regurgitation, and respiratory symptoms.

Fig. 1

Fig. 1 Algorithm for the evaluation of dysphagia based on clinical history.

Additional key questions may differentiate structural from motor mechanisms of esophageal dysphagia. Structural mechanisms initially start with dysphagia only to solids, while motor disorders may manifest dysphagia to both solids and liquids at the outset. Associated heartburn may suggest a peptic stricture, while concurrent allergic rhinitis, asthma, and eczema might raise suspicion for eosinophilic esophagitis. Progressive worsening of dysphagia associated with weight loss may be concerning for neoplasm or achalasia. Longstanding uncontrolled GERD in a middle-aged, obese Caucasian male may suggest Barrett’s esophagus with possible neoplasia. Medications associated with pill-induced esophagitis include bisphosphonates, doxycycline, tetracycline, and quinidine. Intermittent, nonprogressive dysphagia limited to solids, particularly meat, might suggest an esophageal web or ring, such as a Schatzki ring at the esophagogastric junction (EGJ).

The physical examination should include an ear nose and throat (ENT) examination, a neurological examination, and a skin examination. An ENT examination may identify structural etiologies in the oropharynx and larynx and may need to be performed by an ENT specialist, potentially using a transnasal fiberoptic scope. A full neurological exam may identify neuromuscular abnormalities that predispose to oropharyngeal dysphagia. A skin exam is also important to identify atopic disorders, as well as connective tissue diseases including scleroderma and CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia).

Validated questionnaires

Several validated questionnaires can be used to objectively quantify dysphagia symptoms (Table 2). There are separate questionnaires available for oropharyngeal and esophageal dysphagia. These questionnaires are useful in following dysphagia symptoms over time and after therapy, as well as for research purposes.

Table 2

The Sydney Swallow Questionnaire (SSQ) is a 17-item instrument that uses a visual-analogue scale to measure symptom severity in oropharyngeal dysphagia.¹⁴ The tool is specifically designed to evaluate oral and pharyngeal phase impairments in swallowing. The questions assess anatomic region, type of dysfunction, and consistency of swallowed bolus. A higher score indicates more severe swallowing impairment.

The Swallowing Quality of Life (SWAL-QOL) questionnaire is considered the gold standard for the evaluation of the quality of life in patients with oropharyngeal dysphagia.¹⁵ The questionnaire is a 44-item instrument divided into various domains: general burden, eating desire, eating duration, food selection, communication, fear, mental health, social functioning, fatigue, and sleep. Domain scores range from 0 (impaired quality of life) to 100 (no impairment). The SWAL-QOL has the drawback of being too long for routine practical use, so the SWAL-CARE instrument was developed which is an abridged 15-item tool that assesses the quality of care and patient satisfaction.¹⁵

The Brief Esophageal Dysphagia Questionnaire (BEDQ) score is a 10-item questionnaire that measures esophageal dysphagia frequency, severity, as well as food impaction. Symptom frequency and severity are measured on a 6-point Likert scale from never to daily or severe, and food impactions are measured on a 6-point Likert scale from never to more than 4 times in 12 months. The questionnaire demonstrated good internal consistency, reliability, and construct validity and is helpful in differentiating dysphagia due to mechanical obstruction from motor dysfunction.¹⁶

The Eckardt symptom score (ESS) is a 4-item self-report used to quantify achalasia symptom severity using dysphagia, regurgitation, retrosternal pain, and weight loss in clinical and research settings.¹⁷ Dysphagia, regurgitation, retrosternal pain, and weight loss each receive points between 0 and 3. The overall ESS is the sum of the individual scores, ranging from 0 to 12. Scores greater than 3 indicate clinically significant symptoms, of which dysphagia accounts for most of the variance. The ESS demonstrates fair internal consistency and split-half reliability and validity.¹⁸ ESS could be strengthened by the inclusion of a cognitive component to understand patients’ interpretation and responses to each item in the questionnaire.

Diagnostic testing

After a thorough clinical history and physical examination, the clinician should be able to distinguish oropharyngeal dysphagia from esophageal dysphagia and initiate specific diagnostic testing targeting each type of dysphagia (Table 3). Dysphagia also needs to be distinguished from globus sensation, which is a constant perception of a lump in the throat rather than difficulty with food transit; globus sensation is unrelated to swallowing.

Table 3

Oropharyngeal dysphagia

Videofluoroscopic modified barium swallow is the test of choice for evaluation of oropharyngeal dysphagia, which has particular value in not just identification of the mechanism of dysphagia but also provides a therapeutic role in the prescription of the optimal head and neck position and food consistency conducive to optimal oropharyngeal food transfer. The modified barium swallow identifies oropharyngeal neuromuscular dysfunction, structural abnormalities such as a Zenker’s diverticulum, the level of bolus flow and clearance, and differences in clearance among different bolus consistencies (solids, pureed liquids, and thin liquids). Speech pathologists can recommend specific swallow recommendations and strengthening exercises when neuromuscular dysfunction is encountered to improve tolerance of oral nutrition.

Transnasal fiberoptic laryngoscopy or fiberoptic endoscopic examination of swallowing (FEES) enables inspection of the oropharynx and larynx for structural lesions. A transnasal fiberoptic laryngoscopy evaluates for structural lesions in the oropharynx and larynx and can help triage management decisions. FEES provides real-time visualization of swallow function while food or liquid is ingested., including response to different food consistencies.

High-resolution esophageal manometry, combined with stationary impedance, can complement videofluoroscopy by evaluating pharyngeal as well as UES function during swallowing.¹⁹ Dysfunction at the level of the UES can arise from abnormalities in relaxation or resting tone, as well as from structural lesions like webs.

Esophageal

Upper endoscopy is the initial test of choice in evaluating esophageal dysphagia, as it provides both diagnostic and therapeutic value. Endoscopy allows for visual inspection of the esophageal mucosa or for structural lesions, biopsies for inflammatory, infectious, or rheumatologic causes, and therapeutic interventions such as dilation. Since biopsies are indicated for the diagnosis or exclusion of eosinophilic esophagitis, and endoscopic dilation is therapeutic for esophageal strictures and rings, endoscopy is cost-effective when these disorders are suspected since barium radiography only provides a mechanism for dysphagia without specific diagnosis or therapy.²⁰

A barium esophagram assesses swallowing and bolus transit by having the patient swallow liquid barium and sometimes a 13 mm barium pill, following which a series of x-rays are obtained in various positions. A barium study identifies structural abnormalities such as rings, strictures, diverticula, motor disorders, and neoplastic processes. A timed upright barium swallow with ingestion of 8 oz barium and upright x-ray films at 1 min, 2 min, and 5 min allows assessment of esophageal emptying in achalasia before and particularly after achalasia management.²¹ A preendoscopy barium swallow is helpful when a proximal esophageal lesion or complex stricture is suspected to provide a road map for the endoscopist and to reduce the risk of perforation during endoscopy.

High-resolution manometry (HRM) is indicated when a motility disorder is suspected on initial testing, or when endoscopy and/or barium studies are inconclusive in the context of esophageal dysphagia.²² Manometry assesses the coordination of peristalsis particularly the esophageal body and LES, using solid-state circumferential sensors on an esophageal catheter that records intraluminal pressure in the esophagus. The pressure data is displayed using an image-based HRM paradigm that provides a three-dimensional rendering of esophageal peristalsis, consisting of time on the x axis, length along the esophagus on the y axis, and vigor of contraction represented by color contours on the z axis (Fig. 2).²³ High-resolution manometry is considered the gold standard for the assessment of esophageal motor function, with higher sensitivity and specificity compared to conventional manometry.²⁴,²⁵ The Chicago classification is a hierarchical diagnostic algorithm useful in the interpretation of HRM findings and is currently in its fourth iteration.²⁶

Fig. 2

Fig. 2 Clouse plots of supine swallows on esophageal high-resolution manometry. (A) Normal esophageal motility, with normal esophageal body peristalsis and normal relaxation of the lower esophageal sphincter. (B) Type II achalasia, with absent esophageal body peristalsis, nonrelaxing lower esophageal sphincter, and panesophageal compartmentalization of pressure. (C) Hypercontractile esophagus, with very high esophageal body contraction vigor, but with the relaxation of the lower esophageal sphincter. (D) Ineffective esophageal motility, where esophageal body contraction vigor is weak, and the lower esophageal sphincter relaxes. There is also a separation between the lower esophageal sphincter and the crural diaphragmatic impression, indicative of a hiatal hernia.

The functional lumen imaging probe (FLIP) is an impedance-based procedure that can complement diagnostic testing of dysphagia, especially when the mechanism of dysphagia remains unclear following alternate testing.¹⁹ The procedure involves the placement of a catheter with impedance electrodes and a pressure sensor encased in a compliant balloon following sedated upper endoscopy. The balloon is filled with fluid of known conductance; since the voltage of electrical current, the volume of fluid within the balloon, and impedance (resistance) to flow of current are known, the cross-sectional area of fluid distribution, and hence, the diameter of the esophageal lumen within which the balloon is distended can be calculated.²⁷ As volumetric distension of the balloon proceeds, the relationship between cross-sectional area and intra-balloon pressure provides a measurement of distensibility, measured as the distensibility index. The distensibility index is low when the EGJ or the tubular esophagus is poorly compliant, as seen in structural or motor disorders. FLIP can complement the assessment of LES function and diagnosis of obstructive processes such as achalasia, as well as the measurement of luminal diameter in eosinophilic esophagitis or strictures.²⁸

Management

In addition to the management of the specific underlying etiologic disorder, a multidisciplinary approach is utilized in oropharyngeal dysphagia, involving speech pathologists, nutritionists, and gastroenterologists. Minimizing pulmonary aspiration and optimizing nutrition are important goals of treatment and sometimes require temporary or permanent enteral feeding through a gastrostomy or jejunostomy tube. Speech pathologists can provide specific recommendations regarding food consistencies and optimal swallow positions in the management of oropharyngeal dysphagia. Cricopharyngeal myotomy is sometimes done for cricopharyngeal dysfunction, especially when Zenker’s diverticulum is encountered.

The management of esophageal dysphagia is tailored to the underlying cause, which is often structural and related to GERD. Esophageal strictures or rings are treated with balloon dilation during endoscopy, sometimes accompanied by forceps disruption of the stricture.²⁹ Acid suppression with proton pump inhibitors (PPI) can help manage concurrent GERD, and prolong the duration of the benefit of dilation. Eosinophilic esophagitis is managed with PPI, topical swallowed steroids, and/or food elimination diets, complemented with endoscopic stricture dilation when necessary.³⁰ Motility disorders such as achalasia can be managed with pneumatic dilation or per oral endoscopic myotomy during endoscopy, or Heller myotomy during laparoscopic surgery; botulinum toxin injection can be used to temporize symptoms and in individuals who are considered a high surgical risk for definitive management.¹⁹ Unresectable tumors can be managed with the placement of an intraluminal stent that can be placed during endoscopy. A gastrostomy or enterostomy tube may be necessary for patients with severe obstruction not amenable to endoscopic or surgical intervention. Functional dysphagia is treated with neuromodulators or cognitive behavioral therapy.³¹

Perceptive symptoms

Heartburn

Definition

Heartburn (pyrosis) is typically described as a burning sensation in the retrosternal area, often occurring in the postprandial period or while supine. Heartburn is experienced by roughly 1 in 5 adults in the United States, and as many as 10%–20% of the Western world may have GERD.² Acid regurgitation consists of retrograde movement of gastric content into the mouth or hypopharynx, typically sour or acidic in taste. Heartburn and acid regurgitation are typical GERD symptoms (Table 4). In the setting of heartburn, GERD can be erosive or nonerosive. Erosive GERD is identified by the presence of visible breaks in the distal esophageal mucosa, seen in approximately a third of GERD patients who are treatment naïve, and less than 10% of those on PPI therapy.³² Nonerosive reflux disease (NERD) manifests with normal esophageal mucosa but with evidence of abnormal esophageal acid exposure on reflux monitoring.³³ Heartburn is not specific to GERD and can also be seen with other esophageal processes such as motor disorders including achalasia (opposite of reflux), eosinophilic esophagitis, and functional disorders, as well as nonesophageal processes such as angina (Table 4).

Table 4

Pathophysiology

The most important pathophysiological mechanism triggering reflux is transient lower esophageal sphincter relaxation (TLESR), which is the basis for the venting of air ingested with food. Thus, TLESR is a physiologic phenomenon that may occur more often in patients with GERD, with a compliant EGJ that allows reflux of gastric contents. In some individuals, disruption of the EGJ barrier from the presence of a hiatus hernia, and/or a hypotensive LES can contribute.³⁴ Certain food items such as chocolate, coffee, and alcohol can further reduce LES tone, and increase the potential for reflux. Increased intraabdominal pressure in obese individuals can increase the potential for reflux.

Not all reflux episodes result in symptoms, and only 20% of reflux episodes correlate with symptomatic heartburn on esophageal reflux monitoring.³⁵ The sensation of heartburn may arise from the stimulation of mucosal chemoreceptors, which can be sensitized by repetitive acid exposure. The exact mechanism that triggers sensation from chemoreceptor stimulation with some reflux episodes and not others remains unclear. In healthy individuals, physiologic reflux is rapidly cleared by secondary peristalsis which clears the volume of the refluxate, and primary peristalsis which brings saliva to the distal esophagus for neutralization of mucosal acidification. Esophageal acid clearance may be impaired in esophageal hypomotility, and in settings with diminished salivary function, where the likelihood of esophageal mucosal damage and symptoms may be higher. Esophageal hypersensitivity may also impact the perception of heartburn.³⁶

Evaluation and diagnostic testing

A detailed clinical history and examination are important in the initial evaluation of heartburn, but the symptom of heartburn is not specific to GERD. Associated symptoms may affect the diagnostic approach. Dysphagia or odynophagia are alarm symptoms that may prompt early endoscopy to evaluate for complications of reflux such as erosive esophagitis, stricture, or neoplasia, and to rule out an alternate mechanism for symptoms such as eosinophilic esophagitis, other mucosal disorders, and achalasia. Extraesophageal symptoms such as chronic cough, hoarseness, throat clearing, globus, or wheezing may co-occur with heartburn, but the likelihood of a reflux mechanism is low when extraesophageal symptoms are encountered in isolation without heartburn.

Validated questionnaires

There are several validated questionnaires that are useful in quantifying symptoms, but these have modest sensitivity and specificity for GERD and are more useful in clinical research than in day-to-day GERD evaluation (Table 5).

Table 5

GERDQ is a 6-item self-reported measure of reflux symptom severity. The survey evaluates four positive predictors of GERD (heartburn, regurgitation, sleep disruption due to symptoms, and increases in usage of GERD medications) and two negative predictors (epigastric pain and nausea).¹⁸ Points are awarded based on the frequency of symptoms per week and the total score correlates modestly with the likelihood of GERD. Validation studies showed that GERDQ had sensitivity, specificity, and positive predictive values of 72%, 72%, and 87%, respectively.³⁷

GERD-HRQL is used to address changes in typical GERD symptoms of heartburn and regurgitation with medical or surgical treatment.³⁸ This consists of 15 questions related to heartburn and regurgitation that are rated from 1 through 5 points for a total score of 75, with higher scores indicating worse symptoms. The score can be broken down into a total score, a heartburn score, and a regurgitation score.

The reflux disease questionnaire (RDQ) comprises 12 questions assessing the frequency and severity of heartburn, regurgitation, and dyspepsia, scored on a 5-point Likert scale.³⁹ The three-component scores for heartburn, regurgitation, and dyspepsia are averaged to provide scores between 1 and 5, and a higher score indicates worse reflux disease.

Diagnostic testing

A pragmatic initial diagnostic and therapeutic intervention for uncomplicated heartburn without alarm symptoms consists of a PPI trial (Table 5). Improvement of heartburn following PPI use has modest sensitivity but suboptimal specificity for GERD-related heartburn.⁴⁰ In the absence of alarm symptoms, symptomatic management can continue without the immediate need for invasive diagnostic testing, although confirmation of abnormal acid exposure can be considered on a case-by-case basis prior to long-term PPI therapy.

An upper endoscopy is indicated in the presence of alarm or red flag features, and risk factors for Barrett’s esophagus. Alarm features include new onset dyspepsia or dysphagia, gastrointestinal bleeding, iron deficiency anemia, unexplained weight loss, dysphagia, odynophagia, or persistent nausea and vomiting. Guidelines also recommend screening for Barrett’s esophagus in the presence of longstanding GERD, tobacco use, obesity, hiatal hernia, and a first-degree relative with Barrett’s esophagus and/or adenocarcinoma. Endoscopy can evaluate for other causes of heartburn including pill esophagitis, infectious esophagitis, eosinophilic esophagitis, Barrett’s esophagus, and esophageal neoplasia, among others.

Ambulatory esophageal pH and pH-impedance monitoring is helpful in patients with persistent symptoms despite empiric PPI trials, primarily to define the presence of pathologic GERD. Ambulatory reflux monitoring can quantify esophageal acid exposure and determine correlation symptoms with reflux events. Esophageal pH monitoring can be performed either with a transnasal catheter (24-h study) or with a wireless probe that attaches to the distal esophageal mucosa and communicates with a recorder worn on the belt (48–96 h study) (Fig. 3).⁴¹ pH-impedance monitoring also uses a transnasal catheter, which has both pH sensors and pairs of electrodes to assess impedance. The advantage of impedance monitoring is that all reflux episodes are detected irrespective of pH, which increases sensitivity for detection of reflux episodes, allows the test to be performed on PPI therapy, and increases the likelihood of reflux-symptom association (Fig. 4). Additionally, pH-impedance monitoring can be performed on patients without prior documentation of GERD, testing is performed off antisecretory agents, and any form of ambulatory reflux monitoring can be utilized.⁴²,⁴³ In the patient with evidence of GERD on prior testing and persistent symptoms, ambulatory pH-impedance monitoring is performed on maximal PPI therapy to determine if reflux parameters persist despite therapy, which defines refractory GERD and prompts escalation to invasive reflux management.⁴²,⁴⁴

Fig. 3

Fig. 3 Images of reflux episodes on ambulatory pH monitoring, which should always be performed off antisecretory therapy, as only acidic reflux episodes are detected. (A) Acid reflux episodes on single-channel wireless pH monitoring. (B) Acid reflux episodes on dual channel catheter-based pH monitoring. Note that one of the episodes is followed by a patient report of heartburn.

Fig. 4

Fig. 4 Images of reflux episodes on ambulatory pH-impedance monitoring. This can be performed either off antisecretory therapy (in unproven GERD), or on maximal antisecretory therapy when symptoms persist despite management of known (proven) GERD. (A) Acid reflux episode, demonstrating pH drop on the pH channel, and retrograde propagation of a drop in impedance indicating proximal migration of refluxate. (B) Nonacid reflux episode, where retrograde propagation of a drop in impedance is noted without a concurrent drop in pH.

Esophageal manometry: In patients with heartburn and dysphagia with normal upper endoscopy, manometry is helpful in evaluating for conditions that can mimic reflux disease. These include rumination syndrome and motility disorders such as achalasia. Manometry is also helpful in evaluating peristaltic function before antireflux surgery.

Management

The mainstay of management of reflux-related heartburn is the reduction of gastric acid production, which decreases the noxious characteristics of the refluxate, thereby reducing the sensation of heartburn.⁴⁵ Common antisecretory medications include PPIs (pantoprazole, omeprazole, esomeprazole, lansoprazole, dexlansoprazole) and histamine-2 receptor antagonists (H2RAs) (famotidine, ranitidine, and cimetidine). PPIs are typically taken once or twice a day, 30–45 min prior to a meal for maximal effect; H2RAs do not need to be taken prior to meals. Treatment typically starts with once-daily PPI and can be stepped up to twice a day or stepped down to a H2RA if symptoms improve. Patients with erosive esophagitis, Barrett’s esophagus, or eosinophilic esophagitis should remain on a PPI despite symptom resolution. Lifestyle changes of value include avoiding large meals, avoiding lying down within 2–3 h of a meal, sleeping with the head end of the bed raised, weight loss, and avoiding alcohol and tobacco use. Some individuals may benefit from avoiding food triggers, typically citrus, tomatoes, acidic food items, coffee, and chocolate.

In well-characterized GERD refractory to medical management, invasive antireflux measures can be considered. These consist of a complete (Nissen) or partial (toupet or dor) fundoplication, magnetic sphincter augmentation, or transoral incisionless fundoplication with or without hiatus hernia repair.⁴⁶ Radiofrequency application has been studied but does not uniformly reduce esophageal acid exposure, and controlled trials suggest inconsistent symptom resolution.

Specific management of nonreflux etiologies of heartburn, including EoE, infectious or pill esophagitis, and motor disorders can be considered when these conditions are identified.

Chest pain of esophageal origin

Among patients with substernal chest pain, 33%–50% are due to musculoskeletal pain, 10%–20% have a GI etiology, and another 10%–15% have a cardiac cause.⁴⁷,⁴⁸ Chest pain accounts for nearly 8 million annual visits to the emergency department in the United States and noncardiac chest pain has estimated costs of roughly 315 million USD annually.³ Recurring substernal chest pain is alarming and significantly affects the quality of life, with a substantial economic burden because of the utilization of emergency facilities. Establishing a diagnosis for an esophageal cause for chest pain can help reduce unnecessary healthcare utilization and improve patient quality of life.

Definition

Chest pain of esophageal origin is suspected when a cardiopulmonary cause of retrosternal pain has been ruled out, such as acute coronary syndrome, aortic dissection, pulmonary thromboembolism, and pericardial tamponade, and local etiologies such as musculoskeletal pain and costochondritis are excluded on physical examination. Noncardiac chest pain has a prevalence of 13% in the general population, and the most common mechanism is GERD.⁴⁷ Other causes include esophageal motility disorders such as achalasia, spastic esophageal disorders, eosinophilic esophagitis, esophageal visceral hypersensitivity, and functional chest pain. Esophageal chest pain can be identical to cardiac pain, characterized by a burning or squeezing sensation in the substernal region radiating to the jaw, back, or neck. The pain can last minute to hours and often resolves spontaneously, with antacids, or with nitroglycerin, although relief with antacids alone is insufficient to rule out cardiac pain. Heartburn is often used interchangeably with chest pain by patients.

Pathophysiology

The sensation of esophageal chest pain is thought to be due to the stimulation of chemoreceptors by acid or hyperosmolar substances, mechanoreceptors by distension or spasm, and thermoreceptors by hot or cold food items. Acid reflux can produce pain through stimulation of esophageal chemoreceptors: the vanilloid receptor 1 (TRPV1) and the acid-sensing ion channels (ASIC). Upregulation of TRPV1 has been proposed to lead to acid hypersensitivity in patients with esophageal chest pain.⁴⁹ In addition to peripheral sensitization with noxious triggers such as acid, central sensitization can affect the processing of peripheral stimuli.

Esophageal dysmotility, particularly spastic disorders, may be epiphenomena for esophageal visceral hypersensitivity since pain may persist despite inhibition of esophageal contraction. Studies have shown that sustained longitudinal esophageal smooth muscle contraction and discoordination between circular and longitudinal smooth muscle may correlate with chest pain.⁵⁰

Evaluation and diagnostic testing

GERD-related chest pain can mimic cardiac causes of chest pain, and therefore, a thorough cardiac workup is essential prior to esophageal evaluation. Testing could include serum biomarkers, electrocardiogram, stress test, cardiac ultrasound, and coronary angiography. The Rosa Angina Questionnaire (RAQ) and Seattle Angina Questionnaire (SAQ) can be used to evaluate patients with chest pain concerning coronary artery disease. The HEART score is also utilized for early risk stratification of patients presenting to the emergency room with chest pain.

The diagnostic and therapeutic approach to esophageal chest pain from GERD is similar to the approach for heartburn described above. Upper endoscopy is indicated when alarm features are present. Ambulatory reflux monitoring off PPI is particularly useful, as abnormal reflux metrics on reflux monitoring predict response to acid suppression. High-resolution manometry can evaluate for underlying motility disorders.⁵¹

Management

Management is dictated by the specific mechanism of esophageal chest pain. GERD is treated as described above for heartburn, with acid suppression; invasive antireflux therapy may be considered for well-characterized GERD. Specific management can be offered for motor disorders, including smooth muscle relaxants, botulinum toxin injection, and rarely, disruption or myotomy of the LES when obstructive motor findings are encountered. Esophageal hypersensitivity and functional chest pain can be treated with neuromodulators including tricyclic antidepressants, selective serotonin reuptake inhibitors, other antidepressants, atypical analgesics, and dronabinol.³¹,⁵² Nonpharmacological therapies including cognitive and behavioral therapy, biofeedback, hypnotherapy, and acupuncture may also be helpful.

Functional esophageal disorders

Dysphagia, heartburn, and chest pain can all have functional etiologies, especially when organic etiologies described above have been excluded and symptoms continue. Functional disorders must meet ROME IV criteria of at least 3 months of symptoms with an onset at least 6 months before diagnosis. For diagnosis of conventional functional esophageal disorders, mechanical obstruction, major motor disorders, and GERD must be ruled out; however, functional disorders can overlap with disorders like GERD.³¹

The underlying pathophysiology of functional esophageal disorders is thought to be esophageal hypersensitivity and hypervigilance. Esophageal hypersensitivity can cause nonpainful esophageal stimuli to be perceived as painful and exaggerated. Studies show that intraesophageal balloon distension causes pain at lower distension volumes in patients with esophageal hypersensitivity.⁵³ Possible mediators of functional symptoms include serotonin, bradykinin, tachykinin, and neurotrophins.³¹,⁵⁴ There is a higher likelihood of affective disorders like anxiety and depression, other functional gastrointestinal disorders like irritable bowel syndrome and functional dysphagia, extraintestinal functional disorders like fibromyalgia and chronic fatigue syndrome, and other disorders like migraine. Functional heartburn and functional chest pain are diagnosed when symptoms persist despite the absence of reflux disease, other mucosal esophageal disorders, or esophageal motor disorders as a mechanism for symptoms. Functional dysphagia requires the exclusion of mucosal, structural, or motor mechanisms of esophageal obstructive processes.⁵⁴

Questionnaires can be helpful in identifying factors that potentiate functional symptoms and thus in guiding treatment. The esophageal hypervigilance and symptom-specific anxiety (EHAS) questionnaire is a 15-item scale that is useful in evaluating the role of hypervigilance and anxiety in esophageal symptoms such as dysphagia and heartburn.⁵⁵ Scores from the EHAS may be helpful in guiding clinical interventions to reduce anxiety such as CBT and pharmacological interventions.

Treatment of functional esophageal disorders consists of both pharmacological and nonpharmacological interventions. Neuromodulators such as tricyclic antidepressants (imipramine, amitriptyline), SSRIs (sertraline, paroxetine, citalopram), SNRIs (venlafaxine), trazodone, mirtazapine, theophylline, and gabapentin are used. Psychological interventions with cognitive behavioral therapy, biofeedback, hypnotherapy, and acupuncture may also be helpful.³¹,⁵⁴

Conclusion

Dysphagia, heartburn, and chest pain are frequently encountered in both primary care and esophageal clinical practice. An understanding of the pathophysiology and etiologies of each of these symptoms is of value in initiating evaluation and planning management. Systematic evaluation using clinical history, physical examination, and targeted diagnostic testing leads to an effective management approach for these common esophageal symptoms.

Board-style questions

1.A 68-year-old male is referred to the GI clinic for evaluation of dysphagia for 5 months. He reports experiencing prompt regurgitation immediately upon attempting to swallow solid foods. He also complains of a sense of aspiration (choking) upon attempting to swallow, occasional coughing, and chronic halitosis. Once food passes the region of the throat, he has no retrosternal sensation of food sticking. He denies heartburn, chest pain, weight loss, nausea, and vomiting. On physician exam, his vitals are normal and his BMI is 23. The abdominal exam is unremarkable.

Which of the following is the most appropriate diagnostic test to perform next?

(a)Barium videofluoroscopy

(b)Upper endoscopy with biopsy

(c)Esophageal manometry

(d)Ambulatory pH testing

(a)Barium videofluoroscopy (correct answer): The patient’s primary symptoms of dysphagia associated with regurgitation of undigested foods with chronic halitosis suggests oropharyngeal dysphagia and can be a classic presentation for Zenker’s diverticulum, an outpouching of the upper portion of the esophagus. Other symptoms include aspiration (which can lead to pneumonia), coughing, and the sensation of food getting stuck. It is located in the cervical esophagus, and the best initial test is barium videofluoroscopy to identify the diverticulum.

(b)Upper endoscopy: Endoscopy is used to visualize the mucosal surface of the upper GI tract, including the esophagus, stomach, and duodenum. Endoscopy is often the gold standard and initial diagnostic test in a patient with esophageal-type dysphagia with alarm symptoms. Biopsies can be taken to evaluate for eosinophilic esophagitis. However, in a patient with symptoms concerning Zenker’s diverticulum, barium esophagram is a more appropriate, safe, and cost-effective initial choice. The endoscope can enter the diverticulum and there is a risk of perforation.

(c)Esophageal manometry: This test is used when the clinical history is consistent with an esophageal motility disorder, or when esophageal-type dysphagia remains unexplained following endoscopy and/or barium esophagography. Patients with motility disorders often report dysphagia to solid and liquid foods. This patient has dysphagia to solid foods only, which is less likely a motility disorder.

(d)Ambulatory pH testing: This test is often used to evaluate a patient with symptoms of gastroesophageal reflux disease (GERD) with persisting symptoms despite empiric PPI therapy. This patient denies symptoms of heartburn, chest pain, nausea, or vomiting so GERD is less likely.

2.A 54-year-old male presents to the clinic with 5 months of a burning sensation in his chest, occurring 3-4 times a week. His symptoms are worse at night and with coffee and carbonated beverages. He often eats fast food and eats dinner very late. He denies dysphagia, odynophagia, unintentional weight loss, nausea, vomiting, chest pain with exertion, or shortness of breath. He has no other medical problems and is not on any medications. On exam, his vitals are normal, and his BMI is 37. The abdominal exam is unremarkable, and he has no tenderness on palpation. EKG is unremarkable.

What is the most appropriate next step in management?

(a)Empiric trial of PPI

(b)Upper endoscopy

(c)Ambulatory pH testing

(d)Esophageal manometry

(a)Empiric trial of a PPI (correct answer): In patients with a clinical diagnosis of GERD, a trial of PPI as well as lifestyle and dietary changes should be initiated prior to any further testing. This patient’s symptom of heartburn that is worse at night and with particular foods/drinks is consistent with GERD. A trial of once-daily PPI for 8 weeks can be initiated for this patient. At the follow-up appointment, the dose of the medication can be titrated depending on the patient’s response to therapy. Patients need clear counseling on how to correctly take a PPI for maximal efficacy.

(b)Upper endoscopy: This patient has no red flag or alarm symptoms, such as dysphagia or weight loss, that warrant an EGD. In patients with typical GERD symptoms, a PPI trial and lifestyle changes should first be initiated. In patients whose symptoms do not respond to PPI or have alarm features, an EGD can be helpful to evaluate for other causes such as Barrett’s esophagus, esophageal stricture, and EoE. An endoscopy may be considered to screen for Barrett’s esophagus in patients with longstanding reflux, especially in Caucasian males who are obese, and who smoke and drink alcohol.

(c)Ambulatory pH testing: This test is able to quantify the level and frequency of acid exposure in the esophagus. It is typically done in patients considering antireflux surgery or in patients who have refractory symptoms despite maximal PPI therapy.

(d)Esophageal manometry: This test is used to evaluate patients with suspected motility disorders such as achalasia. He has no symptoms of dysphagia to solids or liquids.

3.A 28-year-old male presents with a 6-month history of dysphagia. He states his symptoms have worsened over the last 6 weeks and he now has trouble swallowing solids and liquids. He often describes a feeling of chest fullness after he eats. He denies any weight loss, abdominal pain, nausea, or vomiting. He has no other medical problems and does not take any other medications. He traveled to South America 2 years ago and had flu-like symptoms for about a week during the time he was traveling.

What is the best test to make the diagnosis?

(a)Barium esophagram

(b)Upper endoscopy

(c)Esophageal manometry

(d)FEES testing

(a)Barium esophagram: This test is the most common initial test done in patients coming in with complaints concerning achalasia, but the question is asking for the best or gold standard test. The bird’s beak sign is often seen radiologically, which refers to a persistently dilated lower esophagus due to failed LES relaxation.

(b)Upper endoscopy: EGD can be done to visualize the esophagus when there is a concern for a structural cause. Dysphagia to solids only is more commonly seen in mechanical obstruction. However, a rapidly progressing mass can also lead to dysphagia in liquids but it is less common. This patient is young and does not have comorbidities that would be risk factors concerning malignancy. This patient's EGD would be normal in achalasia. The best test to evaluate a motility disorder is manometry.

(c)Esophageal manometry (correct answer): This patient’s symptoms of progressive dysphagia to solids and liquids are concerning for a motility disorder like achalasia. He may have secondary achalasia due to Chagas disease given his recent travel to South America. Achalasia is a motor disorder of the distal esophagus which causes failure of the lower esophageal sphincter to relax during swallowing. Manometry testing with the use of the Chicago classification is the best test to make the diagnosis because it’s able to measure esophageal lumen pressures that are surrogate markers for esophageal peristalsis and sphincter function.

(d)FEES testing: This patient’s symptoms do not correlate with oropharyngeal dysphagia which would have symptoms of difficulty initiating a swallow, drooling, aspiration, and regurgitation. He also does not have risk factors that would predispose him to oropharyngeal dysphagia. FEES testing and MBS are helpful in evaluating oropharyngeal dysphagia.

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