ESOPHAGEAL STRUCTURE AND FUNCTION
The esophagus is a hollow, muscular tube coursing through the posterior mediastinum joining the hypopharynx to the stomach with a sphincter at each end. It functions to transport food and fluid between these ends, otherwise remaining empty. The physiology of swallowing, esophageal motility, and oral and pharyngeal dysphagia are described in Chap. 53. Esophageal diseases can be manifested by impaired function or pain. Key functional impairments are swallowing disorders and excessive gastroesophageal reflux. Pain, sometimes indistinguishable from cardiac chest pain, can result from inflammation, infection, dysmotility, or neoplasm.
SYMPTOMS OF ESOPHAGEAL DISEASE
The clinical history remains central to the evaluation of esophageal symptoms. A thoughtfully obtained history will often expedite management. Important details include weight gain or loss, gastrointestinal bleeding, dietary habits including the timing of meals, smoking, and alcohol consumption. The major esophageal symptoms are heartburn, regurgitation, chest pain, dysphagia, odynophagia, and globus sensation.
Heartburn (pyrosis), the most common esophageal symptom, is characterized by a discomfort or burning sensation behind the sternum that arises from the epigastrium and may radiate toward the neck. Heartburn is an intermittent symptom, most commonly experienced after eating, during exercise, and while lying recumbent. The discomfort is relieved with drinking water or antacid but can occur frequently interfering with normal activities including sleep. The association between heartburn and gastroesophageal reflux disease (GERD) is so strong that empirical therapy for GERD has become accepted management. However, the term “heartburn” is often misused and/or referred to with other terms such as “indigestion” or “repeating,” making it important to clarify the intended meaning.
Regurgitation is the effortless return of food or fluid into the pharynx without nausea or retching. Patients report a sour or burning fluid in the throat or mouth that may also contain undigested food particles. Bending, belching, or maneuvers that increase intraabdominal pressure can provoke regurgitation. A clinician needs to discriminate among regurgitation, vomiting, and rumination. Vomiting is preceded by nausea and accompanied by retching. Rumination is a behavior in which recently swallowed food is regurgitated and then reswallowed repetitively for up to an hour. Although there is some linkage between rumination and mental deficiency, the behavior is also exhibited by unimpaired individuals who sometimes even find it pleasurable.
Chest pain is a common esophageal symptom with characteristics similar to cardiac pain, sometimes making this distinction difficult. Esophageal pain is usually experienced as a pressure type sensation in the mid chest, radiating to the mid back, arms, or jaws. The similarity to cardiac pain is likely because the two organs share a nerve plexus and the nerve endings in the esophageal wall have poor discriminative ability among stimuli. Esophageal distention or even chemostimulation (e.g., with acid) will often be perceived as chest pain. Gastroesophageal reflux is the most common cause of esophageal chest pain.
Esophageal dysphagia (Chap. 53) is often described as a feeling of food “sticking” or even lodging in the chest. Important distinctions are between uniquely solid food dysphagia as opposed to liquid and solid, episodic versus constant dysphagia, and progressive versus static dysphagia. If the dysphagia is for liquids as well as solid food, it suggests a motility disorder such as achalasia. Conversely, uniquely solid food dysphagia is suggestive of a stricture, ring, or tumor. Of note, a patient’s localization of food hang-up in the esophagus is notoriously imprecise. Approximately 30% of distal esophageal obstructions are perceived as cervical dysphagia. In such instances, the absence of concomitant symptoms generally associated with oropharyngeal dysphagia such as aspiration, nasopharyngeal regurgitation, cough, drooling, or obvious neuromuscular compromise should suggest an esophageal etiology.
Odynophagia is pain either caused by or exacerbated by swallowing. Although typically considered distinct from dysphagia, odynophagia may manifest concurrently with dysphagia. Odynophagia is more common with pill or infectious esophagitis than with reflux esophagitis and should prompt a search for these entities. When odynophagia does occur in GERD, it is likely related to an esophageal ulcer or deep erosion.
Globus sensation, alternatively labeled “globus hystericus,” is the perception of a lump or fullness in the throat that is felt irrespective of swallowing. Although such patients are frequently referred for an evaluation of dysphagia, globus sensation is often relieved by the act of swallowing. As implied by its alternative name (globus hystericus), globus sensation often occurs in the setting of anxiety or obsessive-compulsive disorders. Clinical experience teaches that it is often attributable to GERD.
Water brash is excessive salivation resulting from a vagal reflex triggered by acidification of the esophageal mucosa. This is not a common symptom. Afflicted individuals will describe the unpleasant sensation of the mouth rapidly filling with salty thin fluid, often in the setting of concomitant heartburn.
Endoscopy, also known as esophagogastroduodenoscopy (EGD), is the most useful test for the evaluation of the proximal gastrointestinal tract. Modern instruments produce high-quality, color images of the esophageal, gastric, and duodenal lumen. Endoscopes also have an instrumentation channel through which biopsy forceps, injection catheters for local delivery of therapeutic agents, balloon dilators, or hemostatic devices can be used. The key advantages of endoscopy over barium radiography are: (1) increased sensitivity for the detection of mucosal lesions, (2) vastly increased sensitivity for the detection of abnormalities mainly identifiable by color such as Barrett’s metaplasia or vascular lesions, (3) the ability to obtain biopsy specimens for histologic examination of suspected abnormalities, and (4) the ability to dilate strictures during the examination. The main disadvantages of endoscopy are cost and the utilization of sedatives or anesthetics.
Contrast radiography of the esophagus, stomach, and duodenum can demonstrate reflux of the contrast media, hiatal hernia, mucosal granularity, erosions, ulcerations, and strictures. The sensitivity of radiography compared with endoscopy for detecting reflux esophagitis reportedly ranges from 22–95%, with higher grades of esophagitis (i.e., ulceration or stricture) exhibiting greater detection rates. Conversely, the sensitivity of barium radiography for detecting esophageal strictures is greater than that of endoscopy, especially when the study is done in conjunction with barium-soaked bread or a 13-mm barium tablet. Barium studies also provide an assessment of esophageal function and morphology that may be undetected on endoscopy. Tracheoesophageal fistula, altered postsurgical anatomy, and extrinsic esophageal compression are conditions where radiographic imaging complements endoscopic assessment. Hypopharyngeal pathology and disorders of the cricopharyngeus muscle are better appreciated on radiographic examination than with endoscopy, particularly with rapid sequence or video fluoroscopic recording. The major shortcoming of barium radiography is that it rarely obviates the need for endoscopy. Either a positive or a negative study is usually followed by an endoscopic evaluation either to obtain biopsies, provide therapy, or clarify findings in the case of a positive examination or to add a level of certainty in the case of a negative one.
Endoscopic ultrasound (EUS) instruments combine an endoscope with an ultrasound transducer to create a transmural image of the tissue surrounding the endoscope tip. The key advantage of EUS over alternative radiologic imaging techniques is much greater resolution attributable to the proximity of the ultrasound transducer to the area being examined. Available devices can provide either radial imaging (360-degree, cross-sectional) or a curved linear image that can guide fine-needle aspiration of imaged structures such as lymph nodes or tumors. Major esophageal applications of EUS are to stage esophageal cancer, to evaluate dysplasia in Barrett’s esophagus, and to assess submucosal lesions.
Esophageal manometry, or motility testing, entails positioning a pressure-sensing catheter within the esophagus and then observing the contractility following test swallows. The upper and lower esophageal sphincters appear as zones of high pressure that relax on swallowing, while the intersphincteric esophagus exhibits peristaltic contractions. Manometry is used to diagnose motility disorders (achalasia, diffuse esophageal spasm) and to assess peristaltic integrity prior to the surgery for reflux disease. Technologic advances have enhanced esophageal manometry as high-resolution esophageal pressure topography (Fig. 347-1). Manometry can also be combined with intraluminal impedance monitoring. Impedance recordings use a catheter with a series of paired electrodes. Esophageal luminal contents in contact with the electrodes decrease (liquid) or increase (air) the impedance signal, allowing detection of anterograde or retrograde esophageal bolus transit.
High-resolution esophageal pressure topography (right) and conventional manometry (left) of a normal swallow. E, esophageal body; LES, lower esophageal sphincter; UES, upper esophageal sphincter.
GERD is often diagnosed in the absence of endoscopic esophagitis, which would otherwise define the disease. This occurs in the settings of partially treated disease, an abnormally sensitive esophageal mucosa, or without obvious explanation. In such instances, reflux testing can demonstrate excessive esophageal exposure to refluxed gastric juice, the physiologic abnormality of GERD. This can be done by ambulatory 24- to 48-h esophageal pH recording using either a wireless pH-sensitive transmitter that is anchored to the esophageal mucosa or a transnasally positioned wire electrode with the tip stationed in the distal esophagus. Either way, the outcome is expressed as the percentage of the day that the pH was less than 4 (indicative of recent acid reflux), with values exceeding 5% indicative of GERD. Reflux testing is useful with atypical symptoms or an inexplicably poor response to therapy. Intraluminal impedance monitoring can be added to pH monitoring to detect reflux events irrespective of whether or not they are acidic, potentially increasing the sensitivity of the study.
Hiatus hernia is a herniation of viscera, most commonly the stomach, into the mediastinum through the esophageal hiatus of the diaphragm. Four types of hiatus hernia are distinguished with type I, or sliding hiatal hernia, comprising at least 95% of the overall total. A sliding hiatal hernia is one in which the gastroesophageal junction and gastric cardia translocate cephalad as a result of weakening of the phrenoesophageal ligament attaching the gastroesophageal junction to the diaphragm at the hiatus and dilatation of the diaphragmatic hiatus. The incidence of sliding hernia increases with age. True to its name, sliding hernias enlarge with increased intraabdominal pressure, swallowing, and respiration. Conceptually, sliding hernias are the result of wear and tear: increased intraabdominal pressure from abdominal obesity, pregnancy, etc., along with hereditary factors predisposing to the condition. The main significance of sliding hernias is the propensity of affected individuals to have GERD.
Types II, III, and IV hiatal hernias are all subtypes of paraesophageal hernia in which the herniation into the mediastinum includes a visceral structure other than the gastric cardia. With type II and III paraesophageal hernias, the gastric fundus also herniates with the distinction being that in type II, the gastroesophageal junction remains fixed at the hiatus, whereas type III is a combined sliding and paraesophageal hernia. With type IV hiatal hernias, viscera other than the stomach herniate into the mediastinum, most commonly the colon. With type II and III paraesophageal hernias, the stomach inverts as it herniates and large paraesophageal hernias can lead to an upside down stomach, gastric volvulus, and even strangulation of the stomach. Because of this risk, surgical repair is often advocated for large paraesophageal hernias.
A lower esophageal mucosal ring, also called a B ring, is a thin membranous narrowing at the squamocolumnar mucosal junction (Fig. 347-2). Its origin is unknown, but B rings are demonstrable in about 10–15% of the general population and are usually asymptomatic. When the lumen diameter is less than 13 mm, distal rings are usually associated with episodic solid food dysphagia and are called Schatzki rings. Patients typically present older than 40 years, consistent with an acquired rather than congenital origin. Schatzki ring is one of the most common causes of intermittent food impaction, also known as “steakhouse syndrome” because meat is a typical instigator. Symptomatic rings are easily treated by dilation.
Radiographic anatomy of the gastroesophageal junction.
Web-like constrictions higher in the esophagus can be of congenital or inflammatory origin. Asymptomatic cervical esophageal webs are demonstrated in about 10% of people and typically originate along the anterior aspect of the esophagus. When circumferential, they can cause intermittent dysphagia to solids similar to Schatzki rings and are similarly treated with dilatation. The combination of symptomatic proximal esophageal webs and iron-deficiency anemia in middle-aged women constitutes Plummer-Vinson syndrome.
Esophageal diverticula are categorized by location with the most common being epiphrenic, hypopharyngeal (Zenker’s), and midesophageal. Epiphrenic and Zenker’s diverticula are false diverticula involving herniation of the mucosa and submucosa through the muscular layer of the esophagus. These lesions result from increased intraluminal pressure associated with distal obstruction. In the case of Zenker’s, the obstruction is a stenotic cricopharyngeus muscle (upper esophageal sphincter), and the hypopharyngeal herniation most commonly occurs in an area of natural weakness proximal to the cricopharyngeus known as Killian’s triangle (Fig. 347-3). Small Zenker’s diverticula are usually asymptomatic, but when they enlarge sufficiently to retain food and saliva they can be associated with dysphagia, halitosis, and aspiration. Treatment is by surgical diverticulectomy and cricopharyngeal myotomy or a marsupialization procedure in which an endoscopic stapling device is used to divide the cricopharyngeus.
Examples of small (A) and large (B, C) Zenker’s diverticula arising from Killian’s triangle in the distal hypopharynx. Smaller diverticula are evident only during the swallow, whereas larger ones retain food and fluid.
Epiphrenic diverticula are usually associated with achalasia or a distal esophageal stricture. Midesophageal diverticula may be caused by traction from adjacent inflammation (classically tuberculosis) in which case they are true diverticula involving all layers of the esophageal wall, or by pulsion associated with esophageal motor disorders. Midesophageal and epiphrenic diverticula are usually asymptomatic until they enlarge sufficiently to retain food and cause dysphagia and regurgitation. Symptoms attributable to the diverticula tend to correlate more with the underlying esophageal disorder than the size of the diverticula. Large diverticula can be removed surgically, usually in conjunction with a myotomy if the underlying cause is achalasia. Diffuse intramural esophageal diverticulosis is a rare entity that results from dilatation of the excretory ducts of submucosal esophageal glands (Fig. 347-4). Esophageal candidiasis and proximal esophageal strictures are commonly found in association with this disorder.
Intramural esophageal pseudodiverticulosis associated with chronic obstruction. Invaginations of contrast into the esophageal wall outline deep esophageal glands.
Esophageal cancer occurs in about 4.5:100,000 people in the United States with the associated mortality being only slightly less at 4.4:100,000. It is about 10 times less common than colorectal cancer but kills about one-quarter as many patients. These statistics emphasize both the rarity and lethality of esophageal cancer. One notable trend is the shift of dominant esophageal cancer type from squamous cell to adenocarcinoma, strongly linked to reflux disease and Barrett’s metaplasia. Other distinctions between cell types are the predilection for adenocarcinoma to affect the distal esophagus in white males and squamous cell to affect the more proximal esophagus in black males with the added risk factors of smoking, alcohol consumption, caustic injury, and human papilloma virus infection (Chap. 109).
The typical presentation of esophageal cancer is of progressive solid food dysphagia and weight loss. Associated symptoms may include odynophagia, iron deficiency, and, with midesophageal tumors, hoarseness from left recurrent laryngeal nerve injury. Generally, these are indications of locally invasive or even metastatic disease manifest by tracheoesophageal fistulas and vocal cord paralysis. Even when detected as a small lesion, esophageal cancer has poor survival because of the abundant esophageal lymphatics leading to regional lymph node metastases.
Benign esophageal tumors are uncommon and usually discovered incidentally. In decreasing frequency of occurrence, cell types include leiomyoma, fibrovascular polyps, squamous papilloma, granular cell tumors, lipomas, neurofibromas, and inflammatory fibroid polyps. These generally become symptomatic only when they are associated with dysphagia and merit removal only under the same circumstances.
The most common congenital esophageal anomaly is esophageal atresia, occurring in about 1 in 5000 live births. Atresia can occur in several permutations, the common denominator being developmental failure of fusion between the proximal and distal esophagus associated with a tracheoesophageal fistula, most commonly with the distal segment excluded. Alternatively, there can be an H-type configuration in which esophageal fusion has occurred, but with a tracheoesophageal fistula. Esophageal atresia is usually recognized and corrected surgically within the first few days of life. Later life complications include dysphagia from anastomotic strictures or absent peristalsis and reflux, which can be severe. Less common developmental anomalies include congenital esophageal stenosis, webs, and duplications.
Dysphagia can also result from congenital abnormalities that cause extrinsic compression of the esophagus. In dysphagia lusoria, the esophagus is compressed by an aberrant right subclavian artery arising from the descending aorta and passing behind the esophagus. Alternatively vascular rings may surround and constrict the esophagus.
Heterotopic gastric mucosa, also known as an esophageal inlet patch, is a focus of gastric type epithelium in the proximal cervical esophagus; the estimated prevalence is 4.5%. The inlet patch is thought to result from incomplete replacement of embryonic columnar epithelium with squamous epithelium. The majority of inlet patches are asymptomatic, but acid production can occur as most contain fundic type gastric epithelium with parietal cells.
ESOPHAGEAL MOTILITY DISORDERS
Esophageal motility disorders are diseases attributable to esophageal neuromuscular dysfunction commonly associated with dysphagia, chest pain, or heartburn. The major entities are achalasia, diffuse esophageal spasm (DES), and GERD. Motility disorders can also be secondary to broader disease processes as is the case with pseudoachalasia, Chagas’ disease, and scleroderma. Not included in this discussion are diseases affecting the pharynx and proximal esophagus, the impairment of which is almost always part of a more global neuromuscular disease process.
Achalasia is a rare disease caused by loss of ganglion cells within the esophageal myenteric plexus with a population incidence of about 1:100,000 and usually presenting between age 25 and 60. With longstanding disease, aganglionosis is noted. The disease involves both excitatory (cholinergic) and inhibitory (nitric oxide) ganglionic neurons. Functionally, inhibitory neurons mediate deglutitive lower esophageal sphincter (LES) relaxation and the sequential propagation of peristalsis. Their absence leads to impaired deglutitive LES relaxation and absent peristalsis. Increasing evidence suggests that the ultimate cause of ganglion cell degeneration in achalasia is an autoimmune process attributable to a latent infection with human herpes simplex virus 1 combined with genetic susceptibility.
Long-standing achalasia is characterized by progressive dilatation and sigmoid deformity of the esophagus with hypertrophy of the LES. Clinical manifestations may include dysphagia, regurgitation, chest pain, and weight loss. Most patients report solid and liquid food dysphagia. Regurgitation occurs when food, fluid, and secretions are retained in the dilated esophagus. Patients with advanced achalasia are at risk for bronchitis, pneumonia, or lung abscess from chronic regurgitation and aspiration. Chest pain is frequent early in the course of achalasia, thought to result from esophageal spasm. Patients describe a squeezing, pressure-like retrosternal pain, sometimes radiating to the neck, arms, jaw, and back. Paradoxically, some patients complain of heartburn that may be a chest pain equivalent. Treatment of achalasia is less effective in relieving chest pain than it is in relieving dysphagia or regurgitation.
The differential diagnosis of achalasia includes DES, Chagas’ disease, and pseudoachalasia. Chagas’ disease is endemic in areas of central Brazil, Venezuela, and northern Argentina and spread by the bite of the reduviid (kissing) bug that transmits the protozoan, Trypanosoma cruzi. The chronic phase of the disease develops years after infection and results from destruction of autonomic ganglion cells throughout the body, including the heart, gut, urinary tract, and respiratory tract. Tumor infiltration, most commonly seen with carcinoma in the gastric fundus or distal esophagus, can mimic idiopathic achalasia. The resultant “pseudoachalasia” accounts for up to 5% of suspected cases and is more likely with advanced age, abrupt onset of symptoms (<1 year), and weight loss. Hence, endoscopy is a necessary part of the evaluation of achalasia. When the clinical suspicion for pseudoachalasia is high and endoscopy nondiagnostic, computed tomography (CT) scanning or EUS may be of value. Rarely, pseudoachalasia can result from a paraneoplastic syndrome with circulating antineuronal antibodies.
Achalasia is diagnosed by barium swallow x-ray and/or esophageal manometry; endoscopy has a relatively minor role other than to exclude pseudoachalasia. The barium swallow x-ray appearance is of a dilated esophagus with poor emptying, an air-fluid level, and tapering at the LES giving it a beak-like appearance (Fig. 347-5). Occasionally, an epiphrenic diverticulum is observed. In long-standing achalasia, the esophagus may assume a sigmoid configuration. The diagnostic criteria for achalasia with esophageal manometry are impaired LES relaxation and absent peristalsis. High-resolution manometry has somewhat advanced this diagnosis; three subtypes of achalasia are differentiated based on the pattern of pressurization in the nonperistaltic esophagus (Fig. 347-6). Because manometry identifies early disease before esophageal dilatation and food retention, it is the most sensitive diagnostic test.
Achalasia with esophageal dilatation, tapering at the gastroesophageal junction, and an air-fluid level within the esophagus. The example on the left shows sigmoid deformity with very advanced disease.
Three subtypes of achalasia: classic (A), with esophageal compression (B), and spastic achalasia (C) imaged with pressure topography. All are characterized by impaired lower esophageal sphincter (LES) relaxation and absent peristalsis. However, classic achalasia has minimal pressurization of the esophageal body, whereas substantial fluid pressurization is observed in achalasia with esophageal compression, and spastic esophageal contractions are observed with spastic achalasia.
There is no known way of preventing or reversing achalasia. Therapy is directed at reducing LES pressure so that gravity and esophageal pressurization promote esophageal emptying. Peristalsis rarely, if ever, recovers. However, in many instances, remnants of peristalsis masked by esophageal pressurization and dilatation prior to therapy are demonstrable following effective treatment. LES pressure can be reduced by pharmacologic therapy, pneumatic balloon dilatation, or surgical myotomy. No large, controlled trials of the therapeutic alternatives exist, and the optimal approach is debated. Pharmacologic therapies are relatively ineffective but are often used as temporizing therapies. Nitrates or calcium channel blockers are administered before eating, advising caution because of their effects on blood pressure. Botulinum toxin, injected into the LES under endoscopic guidance, inhibits acetylcholine release from nerve endings and improves dysphagia in about 66% of cases for at least 6 months. Sildenafil and alternative phosphodiesterase inhibitors effectively decrease LES pressure, but practicalities limit their clinical use in achalasia.
The only durable therapies for achalasia are pneumatic dilatation and Heller myotomy. Pneumatic dilatation, with a reported efficacy ranging from 32–98%, is an endoscopic technique using a noncompliant, cylindrical balloon dilator positioned across the LES and inflated to a diameter of 3–4 cm. The major complication is perforation with a reported incidence of 0.5–5%. The most common surgical procedure for achalasia is laparoscopic Heller myotomy, usually performed in conjunction with an antireflux procedure (partial fundoplication); good to excellent results are reported in 62–100% of cases. A European randomized controlled trial demonstrated an equivalent response rate of approximately 90% for both pneumatic dilation and laparoscopic Heller myotomy at 2-year follow-up. Occasionally, patients with advanced disease fail to respond to pneumatic dilatation or Heller myotomy. In such refractory cases, esophageal resection with gastric pull-up or interposition of a segment of transverse colon may be the only option other than gastrostomy feeding.
An endoscopic approach to LES myotomy has been introduced, referred to as per oral esophageal myotomy. This technique involves the creation of a tunnel within the esophageal wall through which the circular muscle of the LES and distal esophagus are transected with electrocautery. Short-term studies of efficacy have been favorable. Potential advantages over the conventional laparoscopic approach include avoidance of surgical disruption of the diaphragmatic hiatus and more rapid recovery.
In untreated or inadequately treated achalasia, esophageal dilatation predisposes to stasis esophagitis. Prolonged stasis esophagitis is the likely explanation for the association between achalasia and esophageal squamous cell cancer. Tumors develop after years of achalasia, usually in the setting of a greatly dilated esophagus with the overall squamous cell cancer risk increased 17-fold compared to controls.
DIFFUSE ESOPHAGEAL SPASM (DES)
DES is manifested by episodes of dysphagia and chest pain attributable to abnormal esophageal contractions with normal deglutitive LES relaxation. Beyond that, there is little consensus. The pathophysiology and natural history of DES are ill defined. Radiographically, DES has been characterized by tertiary contractions or a “corkscrew esophagus” (Fig. 347-7), but in many instances, these abnormalities are actually indicative of achalasia. Manometrically, a variety of defining features have been proposed including uncoordinated (“spastic”) activity in the distal esophagus, spontaneous and repetitive contractions, or high-amplitude and prolonged contractions. The current consensus, derived from high-resolution manometry studies, is to define spasm by the occurrence of contractions in the distal esophagus with short latency relative to the time of the pharyngeal contraction, a dysfunction indicative of impairment of inhibitory myenteric plexus neurons. When defined in this restrictive fashion (Fig. 347-8), DES is actually much less common than achalasia.
Diffuse esophageal spasm. The characteristic “corkscrew” esophagus results from spastic contraction of the circular muscle in the esophageal wall; more precisely, this is actually a helical array of muscle. These findings are also seen with spastic achalasia.
Esophageal pressure topography of the two major variants of esophageal spasm: jackhammer esophagus (left) and diffuse esophageal spasm (right). Jackhammer esophagus is defined by the extraordinarily vigorous and repetitive contractions with normal peristaltic onset and normal latency of the contraction. Diffuse esophageal spasm is similar but primarily defined by a short latency (premature) contraction.
Esophageal chest pain closely mimics angina pectoris. Features suggesting esophageal pain include pain that is nonexertional, prolonged, interrupts sleep, meal-related, relieved with antacids, and accompanied by heartburn, dysphagia, or regurgitation. However, all of these features exhibit overlap with cardiac pain, which still must be the primary consideration. Furthermore, even within the spectrum of esophageal diseases, both chest pain and dysphagia are also characteristic of peptic or infectious esophagitis. Only after these more common entities have been excluded by evaluation and/or treatment should a diagnosis of DES be pursued.
Although the defining criteria are in flux, DES is diagnosed by manometry. Endoscopy is useful to identify alternative structural and inflammatory lesions that may cause chest pain. Radiographically, a “corkscrew esophagus,” “rosary bead esophagus,” pseudodiverticula, or curling can be indicative of DES, but these are also found with spastic achalasia. Given these vagaries of defining DES, and the resultant heterogeneity of patients identified for inclusion in therapeutic trials, it is not surprising that trial results have been disappointing. Only small, uncontrolled trials exist, reporting response to nitrates, calcium channel blockers, hydralazine, botulinum toxin, and anxiolytics. The only controlled trial showing efficacy was with an anxiolytic. Surgical therapy (long myotomy or even esophagectomy) should be considered only with severe weight loss or unbearable pain. These indications are extremely rare.
NONSPECIFIC MANOMETRIC FINDINGS
Manometric studies done to evaluate chest pain and/or dysphagia often report minor abnormalities (e.g., hypertensive or hypotensive peristalsis, hypertensive LES) that are insufficient to diagnose either achalasia or DES. These findings are of unclear significance. Reflux and psychiatric diagnoses, particularly anxiety and depression, are common among such individuals. A lower visceral pain threshold and symptoms of irritable bowel syndrome are noted in more than half of such patients. Consequently, therapy for these individuals should either target the most common esophageal disorder, GERD, or more global conditions such as depression or somatization neurosis that are found to be coexistent.
GASTROESOPHAGEAL REFLUX DISEASE (GERD)
The current conception of GERD is to encompass a family of conditions with the commonality that they are caused by gastroesophageal reflux resulting in either troublesome symptoms or an array of potential esophageal and extraesophageal manifestations. It is estimated that 15% of adults in the United States are affected by GERD, although such estimates are based only on population studies of self-reported chronic heartburn. With respect to the esophagus, the spectrum of injury includes esophagitis, stricture, Barrett’s esophagus, and adenocarcinoma (Fig. 347-9). Of particular concern is the rising incidence of esophageal adenocarcinoma, an epidemiologic trend that parallels the increasing incidence of GERD. There were about 8000 incident cases of esophageal adenocarcinoma in the United States in 2013 (half of all esophageal cancers); it is estimated that this disease burden has increased two- to sixfold in the last 20 years.
Endoscopic appearance of (A) peptic esophagitis, (B) a peptic stricture, (C) Barrett’s metaplasia, and (D) adenocarcinoma developing within an area of Barrett’s esophagus.
The best-defined subset of GERD patients, albeit a minority overall, have esophagitis. Esophagitis occurs when refluxed gastric acid and pepsin cause necrosis of the esophageal mucosa causing erosions and ulcers. Note that some degree of gastroesophageal reflux is normal, physiologically intertwined with the mechanism of belching (transient LES relaxation), but esophagitis results from excessive reflux, often accompanied by impaired clearance of the refluxed gastric juice. Restricting reflux to that which is physiologically intended depends on the anatomic and physiologic integrity of the esophagogastric junction, a complex sphincter comprised of both the LES and the surrounding crural diaphragm. Three dominant mechanisms of esophagogastric junction incompetence are recognized: (1) transient LES relaxations (a vagovagal reflex in which LES relaxation is elicited by gastric distention), (2) LES hypotension, or (3) anatomic distortion of the esophagogastric junction inclusive of hiatus hernia. Of note, the third factor, esophagogastric junction anatomic disruption, is both significant unto itself and also because it interacts with the first two mechanisms. Transient LES relaxations account for about 90% of reflux in normal subjects or GERD patients without hiatus hernia, but patients with hiatus hernia have a more heterogeneous mechanistic profile. Factors tending to exacerbate reflux regardless of mechanism are abdominal obesity, pregnancy, gastric hypersecretory states, delayed gastric emptying, disruption of esophageal peristalsis, and gluttony.
After acid reflux, peristalsis returns the refluxed fluid to the stomach and acid clearance is completed by titration of the residual acid by bicarbonate contained in swallowed saliva. Consequently, two causes of prolonged acid clearance are impaired peristalsis and reduced salivation. Impaired peristaltic emptying can be attributable to disrupted peristalsis or superimposed reflux associated with a hiatal hernia. With superimposed reflux, fluid retained within a sliding hiatal hernia refluxes back into the esophagus during swallow-related LES relaxation, a phenomenon that does not normally occur.
Inherent in the pathophysiologic model of GERD is that gastric juice is harmful to the esophageal epithelium. However, gastric acid hypersecretion is usually not a dominant factor in the development of esophagitis. An obvious exception is with Zollinger-Ellison syndrome, which is associated with severe esophagitis in about 50% of patients. Another caveat is with chronic Helicobacter pylori gastritis, which may have a protective effect by inducing atrophic gastritis with concomitant hypoacidity. Pepsin, bile, and pancreatic enzymes within gastric secretions can also injure the esophageal epithelium, but their noxious properties are either lessened without an acidic environment or dependent on acidity for activation. Bile warrants attention because it persists in refluxate despite acid-suppressing medications. Bile can transverse the cell membrane, imparting severe cellular injury in a weakly acidic environment, and has also been invoked as a cofactor in the pathogenesis of Barrett’s metaplasia and adenocarcinoma. Hence, the causticity of gastric refluxate extends beyond hydrochloric acid.
Heartburn and regurgitation are the typical symptoms of GERD. Somewhat less common are dysphagia and chest pain. In each case, multiple potential mechanisms for symptom genesis operate that extend beyond the basic concepts of mucosal erosion and activation of afferent sensory nerves. Specifically, hypersensitivity and functional pain are increasingly recognized as cofactors. Nonetheless, the dominant clinical strategy is empirical treatment with acid inhibitors, reserving further evaluation for those who fail to respond. Important exceptions to this are patients with chest pain or persistent dysphagia, each of which may be indicative of more morbid conditions. With chest pain, cardiac disease must be carefully considered. In the case of persistent dysphagia, chronic reflux can lead to the development of a peptic stricture or adenocarcinoma, each of which benefits from early detection and/or specific therapy.
Extraesophageal syndromes with an established association to GERD include chronic cough, laryngitis, asthma, and dental erosions. A multitude of other conditions including pharyngitis, chronic bronchitis, pulmonary fibrosis, chronic sinusitis, cardiac arrhythmias, sleep apnea, and recurrent aspiration pneumonia have proposed associations with GERD. However, in both cases, it is important to emphasize the word association as opposed to causation. In many instances, the disorders likely coexist because of shared pathogenetic mechanisms rather than strict causality. Potential mechanisms for extraesophageal GERD manifestations are either regurgitation with direct contact between the refluxate and supraesophageal structures or via a vagovagal reflex wherein reflux activation of esophageal afferent nerves triggers efferent vagal reflexes such as bronchospasm, cough, or arrhythmias.
Although generally quite characteristic, symptoms from GERD need to be distinguished from symptoms related to infectious, pill, or eosinophilic esophagitis, peptic ulcer disease, dyspepsia, biliary colic, coronary artery disease, and esophageal motility disorders. It is especially important that coronary artery disease be given early consideration because of its potentially lethal implications. The remaining elements of the differential diagnosis can be addressed by endoscopy, upper gastrointestinal series, or biliary tract ultrasonography as appropriate. The distinction among etiologies of esophagitis is usually easily made by endoscopy with mucosal biopsies, which are necessary to evaluate for infection or eosinophilic inflammation. In terms of endoscopic appearance, infectious esophagitis is diffuse and tends to involve the proximal esophagus far more frequently than does reflux esophagitis. The ulcerations seen in peptic esophagitis are usually solitary and distal, whereas infectious ulcerations are punctate and diffuse. Eosinophilic esophagitis characteristically exhibits multiple esophageal rings, linear furrows, or white punctate exudate. Esophageal ulcerations from pill esophagitis are usually singular and deep at points of luminal narrowing, especially near the carina, with sparing of the distal esophagus.
The complications of GERD are related to chronic esophagitis (bleeding and stricture) and the relationship between GERD and esophageal adenocarcinoma. However, both esophagitis and peptic strictures have become increasingly rare in the era of potent antisecretory medications. Conversely, the most severe histologic consequence of GERD is Barrett’s metaplasia with the associated risk of esophageal adenocarcinoma, and the incidence of these lesions has increased, not decreased, in the era of potent acid suppression. Barrett’s metaplasia, endoscopically recognized by tongues of reddish mucosa extending proximally from the gastroesophageal junction (Fig. 347-9) or histopathologically by the finding of specialized columnar metaplasia, is associated with a substantially increased risk for development of esophageal adenocarcinoma.
Barrett’s metaplasia can progress to adenocarcinoma through the intermediate stages of low- and high-grade dysplasia (Fig. 347-10). Owing to this risk, areas of Barrett’s and especially any included areas of mucosal irregularity should be extensively biopsied. The rate of cancer development is estimated at 0.1–0.3% per year, but vagaries in definitional criteria and of the extent of Barrett’s metaplasia requisite to establish the diagnosis have contributed to variability and inconsistency in this risk assessment. The group at greatest risk is obese white males in their sixth decade of life. However, despite common practice, the utility of endoscopic screening and surveillance programs intended to control the adenocarcinoma risk has not been established. Also of note, no high-level evidence confirms that aggressive antisecretory therapy or antireflux surgery causes regression of Barrett’s esophagus or prevents adenocarcinoma.
Histopathology of Barrett’s metaplasia and Barrett’s with high-grade dysplasia. H&E, hematoxylin and eosin.
Although the management of Barrett’s esophagus remains controversial, the finding of dysplasia in Barrett’s, particularly high-grade dysplasia, mandates further intervention. In addition to the high rate of progression to adenocarcinoma, there is also a high prevalence of unrecognized coexisting cancer with high-grade dysplasia. Nonetheless, treatment remains controversial. Esophagectomy, intensive endoscopic surveillance, and mucosal ablation have all been advocated. Currently, esophagectomy is the gold standard treatment for high-grade dysplasia in an otherwise healthy patient with minimal surgical risk. However, esophagectomy has a mortality ranging from 3–10%, along with substantial morbidity. That, along with increasing evidence of the effectiveness of endoscopic therapy with purpose-built radiofrequency ablation devices, has led many to favor this therapy as a preferable management strategy.
TREATMENT Gastroesophageal Reflux Disease (GERD)
Lifestyle modifications are routinely advocated as GERD therapy. Broadly speaking, these fall into three categories: (1) avoidance of foods that reduce LES pressure, making them “refluxogenic” (these commonly include fatty foods, alcohol, spearmint, peppermint, tomato-based foods, and possibly coffee and tea); (2) avoidance of acidic foods that are inherently irritating; and (3) adoption of behaviors to minimize reflux and/or heartburn. In general, minimal evidence supports the efficacy of these measures. However, clinical experience dictates that subsets of patients are benefitted by specific recommendations, based on their unique history and symptom profile. A patient with sleep disturbance from nighttime heartburn is likely to benefit from elevation of the head of the bed and avoidance of eating before retiring, but those recommendations are superfluous for a patient without nighttime symptoms. The most broadly applicable recommendation is for weight reduction. Even though the benefit with respect to reflux cannot be assured, the strong epidemiologic relationship between body mass index and GERD and the secondary health gains of weight reduction are beyond dispute.
The dominant pharmacologic approach to GERD management is with inhibitors of gastric acid secretion, and abundant data support the effectiveness of this approach. Pharmacologically reducing the acidity of gastric juice does not prevent reflux, but it ameliorates reflux symptoms and allows esophagitis to heal. The hierarchy of effectiveness among pharmaceuticals parallels their antisecretory potency. Proton pump inhibitors (PPIs) are more efficacious than histamine2 receptor antagonists (H2RAs), and both are superior to placebo. No major differences exist among PPIs, and only modest gain is achieved by increased dosage.
Paradoxically, the perceived frequency and severity of heartburn correlate poorly with the presence or severity of esophagitis. When GERD treatments are assessed in terms of resolving heartburn, both efficacy and differences among pharmaceuticals are less clear-cut than with the objective of healing esophagitis. Although the same overall hierarchy of effectiveness exists, observed efficacy rates are lower and vary widely, likely reflecting patient heterogeneity.
Reflux symptoms tend to be chronic, irrespective of esophagitis. Thus, a common management strategy is indefinite treatment with PPIs or H2RAs as necessary for symptom control. The side effects of PPI therapy are generally minimal. Vitamin B12 and iron absorption may be compromised and susceptibility to enteric infections, particularly Clostridium difficile colitis, increased with treatment. Population studies have also suggested a slight increased risk of bone fracture with chronic PPI use suggesting an impairment of calcium absorption, but prospective studies have failed to corroborate this. Nonetheless, as with any medication, PPI dosage should be minimized to that necessary for the clinical indication.
Laparoscopic Nissen fundoplication, wherein the proximal stomach is wrapped around the distal esophagus to create an antireflux barrier, is a surgical alternative to the management of chronic GERD. Just as with PPI therapy, evidence on the utility of fundoplication is strongest for treating esophagitis, and controlled trials suggest similar efficacy to PPI therapy. However, the benefits of fundoplication must be weighed against potential deleterious effects, including surgical morbidity and mortality, postoperative dysphagia, failure or breakdown requiring reoperation, an inability to belch, and increased bloating, flatulence, and bowel symptoms after surgery.
Eosinophilic esophagitis (EoE) is increasingly recognized in adults and children around the world. Current prevalence estimates identified 4–6 cases per 10,000 with a predilection for white males. The increasing prevalence of EoE is attributable to a combination of an increasing incidence and a growing recognition of the condition. There is also an incompletely understood, but important, overlap between EoE and GERD that confuses diagnosis of the disease.
EoE is diagnosed based on the combination of typical esophageal symptoms and esophageal mucosal biopsies demonstrating squamous epithelial eosinophil-predominant inflammation. Alternative etiologies of esophageal eosinophilia include GERD, drug hypersensitivity, connective tissue disorders, hypereosinophilic syndrome, and infection. Current evidence indicates that EoE is an immunologic disorder induced by antigen sensitization in susceptible individuals. Dietary factors play an important role in both the pathogenesis and treatment of EoE. Aeroallergens may also contribute, but the evidence is weaker. The natural history of EoE is unclear, but an increased risk of esophageal stricture development paralleling the duration of untreated disease has been noted.
EoE should be strongly considered in children and adults with dysphagia and esophageal food impactions. In preadolescent children, symptom presentations of EoE include chest or abdominal pain, nausea, vomiting, and food aversion. Other symptoms in adults may include atypical chest pain and heartburn, particularly heartburn that is refractory to PPI therapy. An atopic history of food allergy, asthma, eczema, or allergic rhinitis is present in the majority of patients. Peripheral blood eosinophilia is demonstrable in up to 50% of patients, but the specificity of this finding is problematic in the setting of concomitant atopy. The characteristic endoscopic esophageal findings are loss of vascular markings (edema), multiple esophageal rings, longitudinally oriented furrows, and punctate exudate (Fig. 347-11). Histologic confirmation is made with the demonstration of esophageal mucosal eosinophilia (greatest density ±15 eosinophils per high-power field) (Fig. 347-12). Complications of EoE include esophageal stricture, narrow-caliber esophagus, food impaction, and esophageal perforation.
Endoscopic features of (A) eosinophilic esophagitis (EoE), (B) Candida esophagitis, (C) giant ulcer associated with HIV, (D) and a Schatzki ring.
Histopathology of eosinophilic esophagitis (EoE) showing infiltration of the esophageal squamous epithelium with eosinophils. Additional features of basal cell hyperplasia and lamina propria fibrosis are present. Eosinophilic inflammation can also be seen with gastroesophageal reflux disease.
The goals of EoE management are symptom control and the prevention of complications. Once esophageal eosinophilia is demonstrated, patients typically undergo a trial of PPI therapy as a practical means of excluding a contribution of GERD to the esophageal mucosal inflammation. PPI-responsive esophageal eosinophilia, characterized by elimination of mucosal eosinophilia, occurs in 30–50% of cases of suspected EoE. Patients with persistent symptoms and eosinophilic inflammation following PPI therapy are subsequently considered for EoE treatments such as elimination diets or swallowed topical glucocorticoids. Elemental formula diets are a highly effective therapy that have primarily been studied in children but are limited by palatability. Notably, allergy testing by means of either serum IgE or skin prick testing has demonstrated poor sensitivity and specificity in the identification of foods that incite the esophageal inflammatory response. Allergy testing combining skin prick and atopy patch testing has been effective in children with EoE, but additional validation is needed. Empiric elimination of common food allergies (milk, wheat, egg, soy, nuts, and seafood) followed by systematic reintroduction has been an effective diet therapy in both children and adults with EoE. The intent of the elimination diet approach is the identification of a single food trigger or a small number of food triggers. Swallowed, topical glucocorticoids (fluticasone propionate or budesonide) are highly effective, but recurrence of disease is common following the cessation of therapy. Systemic glucocorticoids are reserved for severely afflicted patients refractory to less morbid treatments. Esophageal dilation is very effective at relieving dysphagia in patients with fibrostenosis. Dilation should be approached conservatively because of the risk of deep, esophageal mural laceration or perforation in the stiff-walled esophagus that is characteristic of the disease.
With the increased use of immunosuppression for organ transplantation as well as chronic inflammatory diseases and chemotherapy along with the AIDS epidemic, infections with Candida species, herpesvirus, and cytomegalovirus (CMV) have become relatively common. Although rare, infectious esophagitis also occurs among the nonimmunocompromised, with herpes simplex and Candida albicans being the most common pathogens. Among AIDS patients, infectious esophagitis becomes more common as the CD4 count declines; cases are rare with a CD4 count >200 and common when <100. HIV itself may also be associated with a self-limited syndrome of acute esophageal ulceration with oral ulcers and a maculopapular skin rash at the time of seroconversion. Additionally, some patients with advanced disease have deep, persistent esophageal ulcers treated with oral glucocorticoids or thalidomide. However, with the widespread use of protease inhibitors, a reduction in these HIV complications has been noted.
Regardless of the infectious agent, odynophagia is a characteristic symptom of infectious esophagitis; dysphagia, chest pain, and hemorrhage are also common. Odynophagia is uncommon with reflux esophagitis, so its presence should always raise suspicion of an alternative etiology.
Candida is normally found in the throat, but can become pathogenic and produce esophagitis in a compromised host; C. albicans is most common. Candida esophagitis also occurs with esophageal stasis secondary to esophageal motor disorders and diverticula. Patients complain of odynophagia and dysphagia. If oral thrush is present, empirical therapy is appropriate, but co-infection is common, and persistent symptoms should lead to prompt endoscopy with biopsy, which is the most useful diagnostic evaluation. Candida esophagitis has a characteristic appearance of white plaques with friability. Rarely, Candida esophagitis is complicated by bleeding, perforation, stricture, or systemic invasion. Oral fluconazole (200–400 mg on the first day, followed by 100–200 mg daily) for 14–21 days is the preferred treatment. Patients refractory to fluconazole may respond to itraconazole, voriconazole, or posaconazole. Alternatively, poorly responsive patients or those who cannot swallow medications can be treated with an intravenous echinocandin (caspofungin 50 mg daily for 7–21 days).
Herpes simplex virus type 1 or 2 may cause esophagitis. Vesicles on the nose and lips may coexist and are suggestive of a herpetic etiology. Varicella-zoster virus can also cause esophagitis in children with chickenpox or adults with zoster. The characteristic endoscopic findings are vesicles and small, punched-out ulcerations. Because herpes simplex infections are limited to squamous epithelium, biopsies from the ulcer margins are most likely to reveal the characteristic ground-glass nuclei, eosinophilic Cowdry’s type A inclusion bodies, and giant cells. Culture or polymerase chain reaction (PCR) assays are helpful to identify acyclovir-resistant strains. Acyclovir (200 mg orally five times a day for 7–10 days) can be used for immunocompetent hosts, although the disease is typically self-limited after a 1- to 2-week period in such patients. Immunocompromised patients are treated with acyclovir (400 mg orally five times a day for 14–21 days), famciclovir (500 mg orally three times a day), or valacyclovir (1 g orally three times a day). In patients with severe odynophagia, intravenous acyclovir, 5 mg/kg every 8 h for 7–14 days, reduces this morbidity.
CMV esophagitis occurs primarily in immunocompromised patients, particularly organ transplant recipients. CMV is usually activated from a latent stage. Endoscopically, CMV lesions appear as serpiginous ulcers in an otherwise normal mucosa, particularly in the distal esophagus. Biopsies from the ulcer bases have the greatest diagnostic yield for finding the pathognomonic large nuclear or cytoplasmic inclusion bodies. Immunohistology with monoclonal antibodies to CMV and in situ hybridization tests are useful for early diagnosis. Data on therapy for CMV esophagitis are limited. Treatment studies of CMV gastrointestinal disease have demonstrated effectiveness of both ganciclovir (5 mg/kg every 12 h intravenously) and foscarnet (90 mg/kg every 12 h intravenously). Valganciclovir (900 mg two times a day), an oral formulation of ganciclovir, can also be used. Therapy is continued until healing, which may take 3–6 weeks. Maintenance therapy may be needed for patients with relapsing disease.
MECHANICAL TRAUMA AND IATROGENIC INJURY
Most cases of esophageal perforation are from instrumentation of the esophagus or trauma. Alternatively, forceful vomiting or retching can lead to spontaneous rupture at the gastroesophageal junction (Boerhaave’s syndrome). More rarely, corrosive esophagitis or neoplasms lead to perforation. Instrument perforation from endoscopy or nasogastric tube placement typically occurs in the hypopharynx or at the gastroesophageal junction. Perforation may also occur at the site of a stricture in the setting of endoscopic food disimpaction or esophageal dilation. Esophageal perforation causes pleuritic retrosternal pain that can be associated with pneumomediastinum and subcutaneous emphysema. Mediastinitis is a major complication of esophageal perforation, and prompt recognition is key to optimizing outcome. CT of the chest is most sensitive in detecting mediastinal air. Esophageal perforation is confirmed by a contrast swallow, usually Gastrografin followed by thin barium. Treatment includes nasogastric suction and parenteral broad-spectrum antibiotics with prompt surgical drainage and repair in noncontained leaks. Conservative therapy with NPO status and antibiotics without surgery may be appropriate in cases of contained perforation that are detected early. Endoscopic clipping or stent placement may be indicated in nonoperated iatrogenic perforations or nonoperable cases such as perforated tumors.
Vomiting, retching, or vigorous coughing can cause a nontransmural tear at the gastroesophageal junction that is a common cause of upper gastrointestinal bleeding. Most patients present with hematemesis. Antecedent vomiting is anticipated but not always evident. Bleeding usually abates spontaneously, but protracted bleeding may respond to local epinephrine or cauterization therapy, endoscopic clipping, or angiographic embolization. Surgery is rarely needed.
Radiation esophagitis can complicate treatment for thoracic cancers, especially breast and lung, with the risk proportional to radiation dosage. Radiosensitizing drugs such as doxorubicin, bleomycin, cyclophosphamide, and cisplatin also increase the risk. Dysphagia and odynophagia may last weeks to months after therapy. The esophageal mucosa becomes erythematous, edematous, and friable. Submucosal fibrosis and degenerative tissue changes and stricturing may occur years after the radiation exposure. Radiation exposure in excess of 5000 cGy has been associated with increased risk of esophageal stricture. Treatment for acute radiation esophagitis is supportive. Chronic strictures are managed with esophageal dilation.
Caustic esophageal injury from ingestion of alkali or, less commonly, acid can be accidental or from attempted suicide. Absence of oral injury does not exclude possible esophageal involvement. Thus, early endoscopic evaluation is recommended to assess and grade the injury to the esophageal mucosa. Severe corrosive injury may lead to esophageal perforation, bleeding, stricture, and death. Glucocorticoids have not been shown to improve the clinical outcome of acute corrosive esophagitis and are not recommended. Healing of more severe grades of caustic injury is commonly associated with severe stricture formation and often requires repeated dilatation.
Pill-induced esophagitis occurs when a swallowed pill fails to traverses the entire esophagus and lodges within the lumen. Generally, this is attributed to poor “pill taking habits”: inadequate liquid with the pill or lying down immediately after taking a pill. The most common location for the pill to lodge is in the mid-esophagus near the crossing of the aorta or carina. Extrinsic compression from these structures halts the movement of the pill or capsule. Since initially reported in 1970, more than 1000 cases of pill esophagitis have been reported, suggesting that this is not an unusual occurrence. A wide variety of medications are implicated with the most common being doxycycline, tetracycline, quinidine, phenytoin, potassium chloride, ferrous sulfate, nonsteroidal anti-inflammatory drugs (NSAIDs), and bisphosphonates. However, virtually any pill can result in pill esophagitis if taken carelessly.
Typical symptoms of pill esophagitis are the sudden onset of chest pain and odynophagia. Characteristically, the pain will develop over a period of hours or will awaken the individual from sleep. A classic history in the setting of ingestion of recognized pill offenders obviates the need for diagnostic testing in most patients. When endoscopy is performed, localized ulceration or inflammation is evident. Histologically, acute inflammation is typical. Chest CT imaging will sometimes reveal esophageal thickening consistent with transmural inflammation. Although the condition usually resolves within days to weeks, symptoms may persist for months and stricture can develop in severe cases. No specific therapy is known to hasten the healing process, but antisecretory medications are frequently prescribed to remove concomitant reflux as an aggravating factor. When healing results in stricture formation, dilation is indicated.
FOREIGN BODIES AND FOOD IMPACTION
Food or foreign bodies may lodge in the esophagus causing complete obstruction, which in turn can cause an inability to handle secretions (foaming at the mouth) and severe chest pain. Food impaction may occur due to stricture, carcinoma, Schatzki ring, eosinophilic esophagitis, or simply inattentive eating. If it does not spontaneously resolve, impacted food can be dislodged endoscopically. Use of meat tenderizer enzymes to facilitate passage of a meat bolus is discouraged because of potential esophageal injury. Glucagon (1 mg IV) is sometimes tried before endoscopic dislodgement. After emergent treatment, patients should be evaluated for potential causes of the impaction with treatment rendered as indicated.
ESOPHAGEAL MANIFESTATIONS OF SYSTEMIC DISEASE
SCLERODERMA AND COLLAGEN VASCULAR DISEASES
Scleroderma esophagus (hypotensive LES and absent esophageal peristalsis) was initially described as a manifestation of scleroderma or other collagen vascular diseases and thought to be specific for these disorders. However, this nomenclature subsequently proved unfortunate and has been discarded because an estimated half of qualifying patients do not have an identifiable systemic disease, and reflux disease is often the only identifiable association. When scleroderma esophagus occurs as a manifestation of a collagen vascular disease, the histopathologic findings are of infiltration and destruction of the esophageal muscularis propria with collagen deposition and fibrosis. The pathogenesis of absent peristalsis and LES hypotension in the absence of a collagen vascular disease is unknown. Regardless of the underlying cause, the manometric abnormalities predispose patients to severe GERD due to inadequate LES barrier function combined with poor esophageal clearance of refluxed acid. Dysphagia may also be manifest but is generally mild and alleviated by eating in an upright position and using liquids to facilitate solid emptying.
A host of dermatologic disorders (pemphigus vulgaris, bullous pemphigoid, cicatricial pemphigoid, Behçet’s syndrome, and epidermolysis bullosa) can affect the oropharynx and esophagus, particularly the proximal esophagus with blisters, bullae, webs, and strictures. Glucocorticoid treatment is usually effective. Erosive lichen planus, Stevens-Johnson syndrome, and graft-versus-host disease can also involve the esophagus. Esophageal dilatation may be necessary to treat strictures.