Approach Considerations
Laboratory tests are usually unhelpful unless complications are present (eg, upper gastrointestinal [GI] hemorrhage). Routine radiography is not indicated unless complications (eg, perforation, obstruction, bleeding) are suspected. Electrocardiography (ECG) and troponin or other cardiac markers are needed when acute coronary syndrome is in the differential diagnosis.
A double-contrast esophageal barium study (esophagography) is recommended as the initial imaging study in patients presenting with dysphagia. However, a case can be made for initial upper endoscopy (esophagogastroduodenoscopy [EGD]) because this approach would reveal more diagnostic information (eg, inflammatory characteristics, ability to obtain samples for pathologic examination, cytologic examination, and viral and bacterial cultures).
The authors do not recommend barium studies for patients with absolute dysphagia or odynophagia. Upper endoscopy would be recommended under these circumstances. The authors view barium studies and upper endoscopy as complementary rather than competing tests in the evaluation of patients with dysphagia.
Diagnosis of metastatic cancer is best made by means of barium contrast radiography and computed tomography (CT) scanning.
See Pediatric Esophagitis for complete information on this topic.
Laboratory Studies
A complete blood (CBC) cell count is performed in patients with neutropenia or who are immunosuppressed.
A CD4 count and human immunodeficiency virus (HIV) test are performed in patients with risk factors for HIV.
A collagen disorder workup (eg, antinuclear antibody [ANA], anti-dsDNA) may be performed based on the underlying disease.
Esophageal Barium Studies (Esophagography)
A double-contrast esophageal barium study (esophagography) is recommended as the initial imaging study in patients presenting with dysphagia. A double-contrast esophageal barium study is also useful to investigate structural complications such as strictures and tumors. In other circumstances (eg, patients with absolute dysphagia or odynophagia), an initial upper endoscopy would be recommended; barium studies are less accurate for mucosal detail and can also reduce the capability of obtaining positive cultures.
Candida esophagitis
Because Candida esophagitis is primarily a mucosal disease, it often is difficult to recognize with single-contrast esophagography. By contrast, double-contrast esophagography has a sensitivity of 90% in detecting the condition.
On double-contrast studies, Candida esophagitis initially is manifested by discrete plaquelike lesions in the esophagus. Usually, the plaques are oriented longitudinally, appearing en face as linear or irregular filling defects with normal intervening mucosa (see the image below). The plaques may be localized or diffuse and usually are located in the upper or middle esophagus. Some patients may have multiple tiny plaques, which produce a finely granular or nodular appearance of the mucosa.
Infectious esophagitis. Candida esophagitis. Double-contrast esophagram shows linear plaquelike lesions in the esophagus, with normal intervening mucosa.
In advanced Candida esophagitis, the esophagus may have a grossly irregular or shaggy appearance as a result of innumerable plaques and pseudomembranes, with trapping of barium between the lesions (see the image below). This appearance is most commonly seen in patients with acquired immunodeficiency syndrome (AIDS); therefore, the presence of a shaggy esophagus should suggest the possibility of AIDS in patients who are not yet known to be positive for human immunodeficiency virus (HIV).
Infectious esophagitis. Two examples of advanced Candida esophagitis demonstrate a shaggy esophagus. In both images, the double-contrast esophagram shows a grossly irregular esophageal contour due to innumerable plaques and pseudomembranes, with the trapping of barium between lesions. Patients with this fulminant form of esophageal candidiasis are almost always found to have acquired immunodeficiency syndrome (AIDS).
Some of the plaques and pseudomembranes may eventually be sloughed off, producing one or more areas of ulceration on a background of diffuse plaque formation. Occasionally, the barium may also dissect beneath the pseudomembranes, resulting in an intramural dissection tract or double-barrel esophagus.
In patients with chronic stasis, such as those with advanced achalasia or scleroderma involving the esophagus, superimposed Candida esophagitis may manifest as tiny nodules, polypoid folds, or a lacy appearance in the esophagus. Other patients with scleroderma or achalasia may have a foamy esophagus with innumerable bubbles layering out in the barium column as a result of a yeast form of the infection (see the image below). Other rare complications of esophageal candidiasis include perforation, tracheobronchial fistulas, and aortoesophageal fistulas.
Infectious esophagitis. Candida esophagitis with a foamy esophagus. This patient has a dilated esophagus with beaklike narrowing (arrow) at the gastroesophageal junction as a result of long-standing achalasia. Innumerable tiny bubbles are layering out in the barium column due to infection by the yeast form of candidiasis.
Herpes esophagitis
On double-contrast esophagograms, herpes esophagitis usually manifests as multiple small, superficial ulcers in the upper or middle esophagus on an otherwise normal background mucosa (see the image below).
Infectious esophagitis. Herpes esophagitis. Double-contrast esophagram shows small, discrete ulcers (arrows) in the mid esophagus on a normal background mucosa. Note the radiolucent mounds of edema surrounding the ulcers. In the appropriate clinical setting, this appearance is highly suggestive of herpes esophagitis, since ulceration in candidiasis almost always occurs on a background of diffuse plaque formation.
The ulcers can have a punctate, linear, stellate, or volcanolike appearance, often with a thin halo of edema at the margins. The ulcers may be clustered together or widely separated with normal intervening mucosa. Severe herpes esophagitis may produce extensive ulceration and plaque formation, mimicking the appearance of Candida esophagitis.
Cytomegalovirus esophagitis
On double-contrast esophagrams, cytomegalovirus (CMV) esophagitis is typically manifested by one or more giant and relatively flat ulcers, sometimes associated with small satellite ulcers (see the image below).
Infectious esophagitis. Cytomegalovirus esophagitis in a patient with acquired immunodeficiency syndrome (AIDS). Double-contrast esophagram shows a large, flat ulcer in profile (large arrows) in the mid esophagus with a cluster of small satellite ulcers (small arrows). Because HIV esophagitis may produce identical radiographic findings, endoscopy is required to confirm the presence of cytomegalovirus before patients are treated.
These ulcers may be ovoid, elongated, or diamond shaped, and they are frequently surrounded by a radiolucent rim of edematous mucosa. Less commonly, CMV esophagitis appears as small superficial ulcers that are indistinguishable from the ulcers of herpes esophagitis on barium studies.
See Cytomegalovirus Esophagitis for complete information on this topic.
HIV esophagitis
The lesions usually appear on double-contrast esophagograms as one or more giant, flat ulcers (>1 cm in diameter) of the esophagus (see the image below). This finding is sometimes associated with a cluster of small satellite ulcers. The ulcers are often surrounded by a radiolucent rim of edema.
Infectious esophagitis. Two examples of giant human immunodeficiency virus (HIV) esophageal ulcers (arrows) in patients with acquired immunodeficiency syndrome (AIDS). In A, the ulcer is seen in profile, whereas in B, the ulcer is seen en face. Endoscopy is required to exclude cytomegalovirus as the cause of this finding before treating patients.
Tuberculous esophagitis
Barium studies or CT scanning may reveal extrinsic compression or displacement of the esophagus due to enlarged collections of nodes in the adjacent mediastinum. In some patients, traction diverticula may develop in the upper or middle esophagus.
Graft versus host disease
Barium contrast radiographs may reveal webs, rings, and tight strictures in the upper and middle esophagus.
Upper Endoscopy (Esophagogastroduodenoscopy)
Direct upper endoscopy (ie, esophagogastroduodenoscopy [EGD]) allows mucosal visualization and procurement of mucosal biopsies and brushings (see the image below). It is a useful procedure in evaluating the degree of mucosal damage and is indicated in patients with hematemesis, heme-positive stools, or suspected esophageal obstruction. [1] Definitive diagnosis of infectious esophagitis requires esophagoscopy with biopsy for histologic and microbiologic evaluation. [7]
Peptic esophagitis. A rapid urease test (RUT) was performed on the esophageal biopsy sample. The result was positive for Helicobacter pylori.
Upper endoscopy is indicated in patients older than 50 years with new onset of symptoms, in those with features suggesting more serious disease (eg, abdominal mass, anemia, vomiting, dysphagia), and in patients in whom repeated trials of medical therapy have failed. Endoscopy may be indicated on an emergency basis in cases of upper GI hemorrhage, obstruction, or perforation. Endoscopy with biopsy and cultures is required for the diagnosis of infectious esophagitis.
EGD is preferred in patients with odynophagia because this is a specific symptom of esophagitis. EGD is the main diagnostic tool used for esophagitis. As noted earlier, upper endoscopy should be thought of as complementary to, rather than competing with, barium studies in the evaluation of patients with dysphagia.
A wide variety of endoscopic findings are possible, depending on the underlying cause. For instance, in patients with tuberculous esophagitis, esophageal symptoms may result from direct extension from adjacent mediastinal structures. EGD reveals shallow ulcers, heaped-up lesions mimicking neoplasia, and extrinsic compression of the esophagus. Specimens should be sent for acid-fast stains and mycobacterial culture.
In patients with graft versus host disease, generalized desquamation is visible on EGD.
In patients with metastatic cancer, EGD is used to exclude primary esophageal cancer.
In patients with pill esophagitis, EGD findings range from reddened edematous mucosa to small superficial ulcers to large ulcers with heaped up inflamed margins, often with exudate.
Blind Brush Cytology
Blind brush cytology has been used in the past; however, with the availability of esophagogastroduodenoscopy (EGD), its use has diminished. It is performed by passing a cytology brush in a sheath similar to a nasogastric or orogastric tube. Once the end of the catheter is in the mid esophagus, the brush is extended and brushings are taken. Finally, the brush is withdrawn back into the sheath. This is performed without any direct visualization, as occurs when brushings are performed during an EGD.
Histologic Findings
Histologic findings of esophagitis vary according to the etiology. For example, fungal and viral infections occur at differing locations in esophagitis-associated ulcers (see the image below). [1]
Candida esophagitis
Oral thrush is a frequent finding and is often an indicator of esophageal involvement. Oral thrush can be absent in 25% of cases of Candida esophagitis. Candida infection is frequently asymptomatic.
The grading scale for candidal esophagitis is as follows:
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Grade 1 - A few raised white plaques up to 2 mm in size, no ulceration
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Grade 2 - Multiple raised white plaques more than 2 mm in size, no ulceration
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Grade 3 - Confluent, linear, nodular, elevated plaques with ulceration
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Grade 4 - Grade 3 with narrowed lumen
Candida plaques are typically creamy white or pale yellow, with an underlying raw mucosa. Brushings should be obtained with a sheathed cytology brush, spread onto slides, and stained with periodic acid-Schiff, silver, or Gram stains. The presence of mycelial forms and masses of budding yeast is consistent with candidal infection. Cultures are seldom indicated because Candida species are commensal organisms, and differentiating normal flora from infection is difficult. Cultures are useful for resistant Candida or Aspergillus.
Herpes esophagitis
The diagnosis of herpes simplex virus (HSV) esophagitis is made at endoscopy. The earliest esophageal lesions are rounded 1- to 3-mm vesicles in the middle to distal esophagus. The centers slough to form discrete circumscribed ulcers with raised edges.
Advanced HSV esophagitis may be indistinguishable from candidal esophagitis. Plaques, cobblestoning, or a shaggy ulcerative appearance is observed.
HSV preferentially infects epithelial cells. Biopsy should be performed from ulcer margins of islands of squamous mucosa for histology and culture. The ulcer base is devoid of epithelial cells and is inadequate to diagnose HSV esophagitis.
The epithelial cells at the edge of the ulcers are characterized by the following:
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Multinucleated giant cells
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Ballooning degeneration
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Ground glass intranuclear Cowdry type A inclusion bodies
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Margination of chromatin
Immunologic staining of centrifugation cultures is more sensitive than routine histology. Immunohistologic stains using monoclonal antibodies to HSV antigens or in situ hybridization techniques may improve the yield in difficult cases.
Cytomegalovirus esophagitis
Cytomegalovirus (CMV) infects submucosal fibroblasts and endothelial cells, not the squamous epithelium. Diagnosis depends on biopsies obtained by esophagogastroduodenoscopy (EGD). Superficial erosions with serpiginous nonraised borders in the middle to distal esophagus are observed. With infection progression, shallow ulcerations may deepen and expand for 5-10 cm. Tissue is needed for confirmation of the diagnosis; obtain multiple biopsies from the ulcer base.
The most constant feature of CMV esophagitis is mucosal ulceration; the ulcers may be single or multiple. These lesions can be shallow or deep, and not infrequently, they are several centimeters or more in diameter. Infected epithelial cells in the esophagus become enlarged by a factor of two to four times (hence the term cytomegalic cells), and they contain eccentrically placed intranuclear inclusion bodies with surrounding halos.
In contrast to herpes esophagitis, small granular cytoplasmic inclusions are seen in the endothelial cells or fibroblasts near the base of the ulcers. A lymphomonocytic inflammatory response is also seen at the site of infection.
See Cytomegalovirus Esophagitis for complete information on this topic.
Varicella-zoster virus esophagitis
Varicella-zoster virus (VZV) can cause severe esophagitis. The key to diagnosis is finding concurrent dermatologic VZV lesions. The appearance on EGD ranges from occasional vesicles to discrete ulcerative lesions to a confluence of ulcerations with necrosis.
On histologic examination, epithelial cells with VZV show edema, ballooning degeneration, and multinucleated giant cells with intranuclear eosinophilic inclusion bodies. Immunohistochemical staining using monoclonal antibodies is helpful to differentiate VZV from HSV.
Epstein-Barr virus esophagitis
Histologic features of esophageal lesions associated with Epstein-Barr virus are similar to those of oral hairy leukoplakia.
HIV esophagitis
Multiple, small, aphthoid lesions are observed during the period of transient fever, chills, malaise, and rash of early infection with human immunodefiency virus (HIV). Later, giant deep ulcers extending up several centimeters are observed. Fistula formation, perforation, hemorrhage, or superinfection may complicate large ulcers.
Human papillomavirus esophagitis
Human papillomavirus (HPV) esophagitis is asymptomatic. Lesions are typically found in the middle to distal esophagus. They may appear as erythematous macules, white plaques, nodules, or exuberant frondlike lesions. The diagnosis of HPV esophagitis is made based on histology. Koilocytosis, giant cells, and cytologic atypia are visible on immunohistochemical stains.
Esophagitis from drug-induced skin disease
Drug-induced skin diseases can affect the esophagus with a blistering process and desquamation of large areas of the epithelium. Both focal and long strictures and webs may form.
Behçet disease esophagitis
Esophageal involvement is rare. Esophageal lesions include ulcerations that can tunnel the mucosa, strictures, fistulous tracts, and perforations.
Graft versus host disease esophagitis
Histologic changes in acute graft versus host disease (GVHD) are observed in the squamous epithelium, including the esophagus. Chronic GVHD damages the esophagus more extensively.
Inflammatory bowel disease esophagitis
The esophagus can be involved in Crohn disease. Aphthous ulcers are observed in the esophagus. Inflammatory strictures, sinus tracts, filiform polyps, and fistulas to adjacent structures may be observed. Histology shows diffuse and nodular lymphoid aggregates; 50% of EGD biopsy specimens show noncaseating granulomas.
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Esophagitis. Location of fungal and viral infections in ulcers.
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Peptic esophagitis. A rapid urease test (RUT) was performed on the esophageal biopsy sample. The result was positive for Helicobacter pylori.
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Corrosive esophagitis. This is a vinegar-induced esophageal burn. The patient had a fish bone in her throat. She ingested vinegar in an attempt to dissolve the fish bone but to no avail; this led to corrosive esophagitis.
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Infectious esophagitis. Candida esophagitis. Double-contrast esophagram shows linear plaquelike lesions in the esophagus, with normal intervening mucosa.
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Infectious esophagitis. Two examples of advanced Candida esophagitis demonstrate a shaggy esophagus. In both images, the double-contrast esophagram shows a grossly irregular esophageal contour due to innumerable plaques and pseudomembranes, with the trapping of barium between lesions. Patients with this fulminant form of esophageal candidiasis are almost always found to have acquired immunodeficiency syndrome (AIDS).
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Infectious esophagitis. Candida esophagitis with a foamy esophagus. This patient has a dilated esophagus with beaklike narrowing (arrow) at the gastroesophageal junction as a result of long-standing achalasia. Innumerable tiny bubbles are layering out in the barium column due to infection by the yeast form of candidiasis.
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Infectious esophagitis. Herpes esophagitis. Double-contrast esophagram shows small, discrete ulcers (arrows) in the mid esophagus on a normal background mucosa. Note the radiolucent mounds of edema surrounding the ulcers. In the appropriate clinical setting, this appearance is highly suggestive of herpes esophagitis, since ulceration in candidiasis almost always occurs on a background of diffuse plaque formation.
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Infectious esophagitis. Cytomegalovirus esophagitis in a patient with acquired immunodeficiency syndrome (AIDS). Double-contrast esophagram shows a large, flat ulcer in profile (large arrows) in the mid esophagus with a cluster of small satellite ulcers (small arrows). Because HIV esophagitis may produce identical radiographic findings, endoscopy is required to confirm the presence of cytomegalovirus before patients are treated.
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Infectious esophagitis. Two examples of giant human immunodeficiency virus (HIV) esophageal ulcers (arrows) in patients with acquired immunodeficiency syndrome (AIDS). In A, the ulcer is seen in profile, whereas in B, the ulcer is seen en face. Endoscopy is required to exclude cytomegalovirus as the cause of this finding before treating patients.
