Esophagitis

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Practice Essentials

Common forms of esophagitis include reflux esophagitis, infectious esophagitis, pill esophagitis, eosinophilic esophagitis, and radiation and chemoradiation esophagitis. Candida esophagitis is the most common type of infectious esophagitis. The prognosis is good with rapid diagnosis and proper treatment; ultimately, it depends on the underlying disease. Esophagitis is commonly seen in adults and is uncommon in childhood.

Signs and symptoms

The history findings vary according to the type of esophagitis present. Symptoms of reflux esophagitis (the most common type) may include the following:

Patients with infectious esophagitis (eg, from Candida, cytomegalovirus [CMV], herpes simplex virus [HSV], or HIV) may be asymptomatic, but typical symptoms include the following:

Physical examination usually does not help confirm uncomplicated esophagitis but may reveal other potential sources of pain. The examination should include the following:

Complications of esophagitis may include the following:

See Clinical Presentation for more detail.

Diagnosis

Laboratory tests are usually unhelpful unless complications are present (eg, upper gastrointestinal [GI] hemorrhage). The following may be considered:

Routine radiography is not indicated unless complications are suspected. Considerations for the use of diagnostic procedures include the following:

Other studies that may be helpful include the following:

See Workup for more detail.

Management

Treatment includes the following components:

Treatment of reflux esophagitis may include the following:

Treatment of infectious esophagitis is directed at the underlying cause, as follows:

Treatment of nonreflux, noninfectious esophagitis depends on the underlying condition, as follows:

See Treatment and Medication for more detail.

Image library


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Peptic esophagitis. A rapid urease test (RUT) is performed on the esophageal biopsy sample. The result is positive for esophagitis.

Background

The most common cause of esophagitis is gastroesophageal reflux disease (GERD). (See Epidemiology.) Other important, but less common, types of esophagitis include infectious esophagitis (in patients who are immunocompromised), radiation esophagitis, and esophagitis from direct erosive effects of ingested medication or corrosive agents (see the image below). (See Pathophysiology.)

Go to Pediatric Esophagitis for complete information on this topic.


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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 dis....

Eosinophilic esophagitis has also emerged as an important cause of esophagitis in both children and adults. Other causes of esophagitis include systemic disease and trauma. (See Etiology.)

The prognosis is good with rapid diagnosis and proper treatment. Ultimately, prognosis depends on the underlying disease process. (See Prognosis.)

The history findings vary based on the type of esophagitis (eg, reflux or infectious). The physical examination usually is not helpful in confirming the diagnosis of uncomplicated esophagitis. However, the examination may reveal other potential sources of chest or abdominal pain. (See Clinical Presentation.)

Laboratory tests are usually unhelpful unless complications are present (eg, upper GI hemorrhage). Routine radiography is not indicated unless complications (eg, perforation, obstruction, bleeding) are suspected. Double-contrast esophageal barium studies and upper endoscopy are the recommended initial imaging studies; these tests should be viewed as complementary rather than competing in the evaluation of patients with dysphagia. (See Workup.)

Treatment begins with hemodynamic stabilization and pain management. Subsequent therapy depends on the cause of the esophagitis and on any complications present.[3] Surgery (fundoplication) is sometimes indicated in patients with severe pain who fail to respond to medical management. (See Treatment and Management and Medications.)

Pathophysiology

The pathophysiology of esophagitis depends on its etiology (see Etiology, below). Common forms of esophagitis include reflux esophagitis, infectious esophagitis, pill esophagitis, eosinophilic esophagitis, and radiation and chemoradiation esophagitis.

Reflux esophagitis

Reflux esophagitis develops when gastric contents are passively regurgitated into the esophagus. Reflux happens commonly; in most cases, it does not cause major harm, because natural peristalsis of the esophagus clears the refluxate back to the stomach. In other cases, where acid reflux from the stomach is persistent, the result is damage to the esophagus, causing symptoms and macroscopic changes. Gastric acid, pepsin, and bile irritate the squamous epithelium, leading to inflammation, erosion, and ulceration of the esophageal mucosa.

Infectious esophagitis

Infectious esophagitis is most commonly observed in immunosuppressed hosts but has also been reported in healthy adults and children. A wide range of abnormalities in host defense may predispose an individual to opportunistic infections, such as neutropenia, impaired chemotaxis and phagocytosis, alteration in humoral immunity, and impaired T-cell lymphocyte function.

Patients with systemic diseases (eg, diabetes mellitus, adrenal dysfunction, alcoholism) and those of advanced age can be predisposed to infectious esophagitis because of altered immune function. Steroids, cytotoxic agents, radiation, and immune modulators can also contribute to impaired host immune function. Disruption of mucosal protective barriers and antibiotics that suppress the normal bacterial flora may contribute to the invasive ability of commensal organisms.[4]

Common types of infectious esophagitis include the following:

Candida esophagitis results from fungal overgrowth in the esophagus, impaired cell-mediated immunity, or both.

Fungal overgrowth typically occurs in the setting of esophageal stasis resulting from abnormal esophageal motility (eg, achalasia or scleroderma) or mechanical causes (eg, strictures). Impaired cell-mediated immunity can result from immunosuppressive therapy (eg, with steroids or cytotoxic agents, which may suppress both lymphocyte function and granulocyte function), malignancy, or AIDS. Chronic mucocutaneous candidiasis is a congenital immunodeficiency state that is also associated with Candida esophagitis.

Illnesses that interfere with esophageal peristalsis, such as achalasia, progressive systemic sclerosis, and esophageal neoplasias, may contribute to fungal esophagitis.

Initially, herpes esophagitis is manifested by the development of small vesicles that subsequently rupture to form discrete superficial ulcers on the mucosa. In immunocompetent patients, the host response promotes healing of the ulcers, but in patients who are severely immunocompromised, the condition may progress from discrete areas of ulceration to a diffuse hemorrhagic esophagitis. Necrotic herpetic ulcers may become superinfected by candidiasis.

In tuberculous esophagitis, the esophagus is usually involved by erosion of the involved mediastinal lymph nodes abutting the esophagus.

Go to Cytomegalovirus Esophagitis for complete information on this topic.

Medication-induced esophagitis (pill esophagitis)

Medications associated with pill esophagitis cause injury by local or topical injury.[5] Antibiotics, potassium chloride, nonsteroidal anti-inflammatory drugs (NSAIDs), quinidine, emperonium bromide, and alendronate (Fosamax) account for 90% of the reported cases. The following are important pill and patient factors:

Eosinophilic esophagitis

The mechanism of eosinophilic esophagitis remains to be elucidated. However, a corrugated esophagus characterized by fine concentric mucosal rings is commonly observed in patients and is believed to be related to histamine released from sensitized mast cells in the esophageal wall. The release of histamine activates a cascade of reactions, culminating in acetylcholine release that contracts muscle fibers in the muscularis mucosae, resulting in the formation of concentric esophageal rings.[6, 7]

This hypothesis can be tested by performing endoscopic ultrasonography, which will reveal contraction of the muscle layers of the muscularis mucosae and may be related to immunoglobulin E (IgE) activation.

Radiation and chemoradiation esophagitis

Radiation therapy over 30 Gy to the mediastinum typically causes retrosternal burning and painful swallowing, which is usually mild and limited to the duration of therapy.[8]

Etiology

The various types of esophagitis are associated with differing causative conditions and risk factors.

Reflux esophagitis

Factors or conditions that may increase the risk of reflux esophagitis include the following:

Infectious esophagitis

Infectious agents known to cause esophagitis include the following:

Major predisposing factors for Candida esophagitis include antibiotic use, radiation therapy or chemotherapy, hematologic malignancies, and AIDS. Other conditions associated with an increased incidence of Candida esophagitis include esophageal stasis, alcoholism, malnutrition, and advanced age. Occasionally, Candida esophagitis can occur in otherwise healthy individuals with no underlying esophageal or systemic disease.[10, 11, 12, 13, 14, 15, 16]

Other infections of the esophagus are rare and most often develop in patients with neutropenia, AIDS, burns, trauma, or generalized sepsis. Actinomycosis may produce severe esophagitis with deep ulcers and fistulous tracts to the mediastinum, pleural space, tracheobronchial tree, and skin. The diagnosis can be confirmed by the presence of characteristic sulfur granules on endoscopic biopsy specimens.

In persons with HIV, the most significant risk factor for infectious esophagitis is a persistently low CD4 count, but reports exist of individuals who develop fungal esophagitis during the seroconversion phase.

Esophagitis associated with systemic illnesses

Systemic illnesses that can result in esophagitis include the following:

Esophagitis associated with pharmacologic or other therapy

Therapeutic interventions that can cause esophagitis include the following:

Epidemiology

Esophagitis is commonly seen in adults and is uncommon in childhood.[17, 18] The most common type of esophagitis is that associated with GERD (ie, reflux esophagitis). Candida esophagitis is the most common type of infectious esophagitis. Esophageal reflux symptoms occur monthly in 33-44% of the general population; up to 7-10% of people have daily symptoms.

International statistics

The incidence of symptoms of reflux is up to an order of magnitude higher than the prevalence of esophagitis. In the United Kingdom, patients presenting to a general practitioner with symptoms of reflux esophagitis show rates in the 40-65% range. However, a retrospective review of the results of more than 8000 diagnostic endoscopies in Hampshire showed that GERD accounted for 23% of all upper GI conditions.[19]

A review of the Swedish National Register estimated the prevalence of esophagitis (diagnosed by endoscopy) to be less than 5% in the 55-year-old group. Other reports have estimated the prevalence to be on the order of 2%.

Prevalence associated with other disorders

The prevalence of symptomatic infectious esophagitis is high in individuals with AIDS, leukemia, and lymphoma and is low (< 5%) in the general medical population.

Candida esophagitis is the most common type of infectious esophagitis. Herpes simplex virus type I is the second most common cause of infectious esophagitis . Although obtaining accurate figures regarding the prevalence of herpes esophagitis is difficult, this infection has been reported in approximately 1% of patients who are immunocompromised and in as many as 43% of patients at autopsy.[20, 21, 22, 23, 24, 25]

CMV is a recently recognized cause of esophagitis. Asymptomatic CMV infection is common worldwide, and a large percentage of the world’s population has been exposed to CMV. Before the AIDS epidemic, CMV infections of the esophagus were primarily found on postmortem examinations. The first clinical case of CMV esophagitis was not reported until 1985.

Unlike herpes esophagitis, CMV esophagitis almost never occurs in immunocompetent patients, and the vast majority of affected individuals are found to have AIDS. The incidence of CMV esophagitis—like that of other forms of infectious esophagitis—has declined among AIDS patients since the widespread use of highly active antiretroviral therapy.[26] However, CMV esophagitis has increased among patients with solid organ transplants,[27] in whom delayed-onset disease is typical because of increasing routine use of early CMV prophylaxis.[28]

Giant esophageal ulcers have been described in patients with AIDS in whom no other infectious etiology for the ulcers can be found. These ulcers have been termed idiopathic or HIV ulcers because they are believed to be caused by HIV. In fact, results of electron microscopy confirm the presence of HIV-like viral particles in these lesions.

Although some patients with HIV ulcers may have undergone recent seroconversion, most are found to have chronic AIDS with CD4 counts of less than 100 cells per cubic millimeter. HIV ulcers are more common than generally recognized, accounting for as many as 40% of all esophageal ulcers in patients with AIDS.[14, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38]

Prognosis

The prognosis is good with rapid diagnosis and proper treatment. Ultimately, prognosis depends on the underlying disease process.

Minimal morbidity and mortality result from mild symptoms of esophagitis. Pain from moderate-to-severe symptoms may produce anxiety and lost work and may lead to medical evaluations for more serious causes of pain.

Complicated esophagitis may lead to esophageal strictures (typically long, smooth, tapered areas of narrowing), malnutrition, and, rarely, perforation or bleeding. In addition to strictures, serious GI complications of esophagitis include Barrett esophagus and adenocarcinoma. Aspiration of gastric contents is a potentially serious respiratory complication that occurs more often in children. It may be associated with bronchospasm, pneumonitis, and apnea.

Severe esophagitis may lead to dysphagia, pain, odynophagia, and malnutrition. Rarely, life-threatening bleeding occurs and may lead to death. Outcomes and survival in these patients are related to the severity of their underlying systemic illness.

Recurrence is a frequent problem in patients with reflux. Many patients require maintenance therapy for relapse of symptoms.

Infectious esophagitis

Candida esophagitis is usually self-limiting, and most patients have a marked response to treatment with antifungal agents. However, necrotic mucosal debris and fungal mycelia in the esophagus occasionally form a mycetoma (ie, fungus ball) that causes obstruction. In other patients, severe Candida esophagitis may lead to development of strictures. Other complications include ulceration and hemorrhage and, rarely, fistula formation into the bronchial tree.[39]

In immunocompetent patients, herpes esophagitis often resolves spontaneously within 1-2 weeks with conservative treatment involving analgesia and sedation. Rare complications of herpes esophagitis include perforation, tracheoesophageal fistulas, and dissemination to other organs.

Patient Education

Lifestyle changes recommended to reduce the frequency and amount of gastric contents that may reflux back into the esophagus include the following:

Educate patients on the disease process and the importance of early medical evaluation at the onset of symptoms.

To prevent pill esophagitis, instruct patients to take medications with plenty of water while sitting upright. Avoid certain medications (eg, alendronate) in patients with known esophageal varices. Alendronate in patients who are cirrhotic could precipitate GI bleeding from erosions over an esophageal varix.

For patient education information, see the Heartburn/GERD/Reflux Center and Esophagus, Stomach, and Intestine Center, as well as Reflux Disease (GERD), Heartburn, and Understanding Heartburn/GERD Medications.

History

The history findings vary based on the type of esophagitis.

Symptoms of reflux esophagitis

The most common complaint in patients with esophagitis is heartburn (dyspepsia), a burning sensation in the midchest caused by contact of stomach acid with inflamed esophageal mucosa. Symptoms often are maximal while the person is supine, bending over, or wearing tight clothing or after the person has eaten a large meal. The patient may complain of water brash, a bitter taste of refluxed gastric contents often associated with heartburn.[1]

The American College of Gastroenterology (ACG) published updated guidelines for the diagnosis and treatment of GERD in 2005. According to the ACG guidelines, regurgitation, heartburn, or both are the symptoms most specific for GERD. The guidelines state that for patients with symptoms of uncomplicated GERD, the diagnosis of GERD may be assumed and empirical therapy begun. Patients who show signs of GERD complications or other illness or who do not respond to therapy should be considered for further diagnostic testing.[40]

Other common symptoms of esophagitis include upper abdominal discomfort, nausea, bloating, and fullness. Less common symptoms of esophagitis include dysphagia, odynophagia, cough, hoarseness, wheezing, and hematemesis.

The patient may experience chest pain indistinguishable from that of coronary artery disease. Pain is often midsternal, with radiation to the neck or arm, and may be associated with shortness of breath and diaphoresis. Chest pain may be relieved with nitrates if esophageal spasm is involved, further confounding diagnostic evaluation.

Infants with gastroesophageal reflux are at greater risk of aspiration. Symptoms include weight loss, regurgitation, excessive crying, backache, respiratory distress, and apnea.

Symptoms of infectious esophagitis

Infectious esophagitis is primarily seen in patients who are immunocompromised. The most common causes of infectious esophagitis are fungal (Candida species), herpetic (herpes simplex virus), and viral (cytomegalovirus [CMV]). A history of immunosuppression, steroid therapy, recent antibiotic use, or systemic illness supports the diagnosis. Although patients may be asymptomatic, typical symptoms include the following:

Candida esophagitis is usually manifested clinically by dysphagia and/or odynophagia in a patient with 1 or more predisposing factors for the condition. Symptoms are variable in severity, ranging from mild difficulty in swallowing to such intense odynophagia that the patient is unable to eat or swallow saliva. Other patients may present with chest pain or GI tract bleeding; occasionally, patients are asymptomatic.

Herpes esophagitis is most commonly seen in immunocompromised patients with AIDS, an underlying malignancy, or a debilitating illness or in patients who have been treated with radiation, steroids, or chemotherapy.[41] However, it occasionally occurs as an acute self-limiting disease in otherwise healthy patients who have no underlying immunologic problems. Patients with herpes esophagitis typically present with an acute onset of severe odynophagia. Other presenting findings include dysphagia, chest pain, and upper GI tract bleeding.

CMV esophagitis is usually manifested by the development of severe odynophagia, dysphagia, or both, in patients with AIDS. In affected individuals, evidence of CMV infection may be present in other organs or tissues, such as the retina, liver, and colon. Occasionally, odynophagia may be so severe that the patients develop sitophobia (fear of eating), and parenteral alimentation is required.

Patients with HIV ulcers typically present with acute onset of severe odynophagia, dysphagia, or both. If the ulcers develop at the time of seroconversion, a characteristic maculopapular rash may be seen on the upper half of the body.

Tuberculous esophagitis occurs primarily in patients with advanced pulmonary or mediastinal tuberculosis or in immunocompromised patients who have disseminated tuberculosis or other mycobacterial diseases.

Physical Examination

The physical examination usually is not helpful in confirming the diagnosis of uncomplicated esophagitis. However, the examination may reveal other potential sources of chest or abdominal pain.

Perform a rectal examination (eg, stool guaiac) to identify the presence of occult bleeding.

Examine the oral cavity (for thrush or ulcers). Oropharyngeal candidiasis is commonly associated with esophageal candidiasis; therefore, the presence of oral thrush may be helpful in suggesting the diagnosis of Candida esophagitis in the appropriate clinical setting. Nevertheless, only 50-75% of patients with Candida esophagitis have oropharyngeal disease, and some patients with oropharyngeal candidiasis and dysphagia are found to have other types of esophagitis; therefore, the correct diagnosis cannot always be suggested on the basis of clinical presentation.

Look for signs of immunosuppression and skin signs of systemic disease (eg, telangiectasias and sclerodactyly in scleroderma).

Although the presence of herpes labialis (cold sores) or herpetic lesions of the oropharynx should suggest the presence of herpetic esophagitis in the appropriate clinical setting, most patients have no concurrent oropharyngeal herpetic lesions. Moreover, some patients with odynophagia and oral herpes eventually are found to have Candida esophagitis. Therefore, the presence of other herpetic lesions is not accurately predictive of herpes esophagitis in patients with odynophagia. There are rare reports of concomitant herpetic and candidal esophagitis.[20]

Complications of Esophagitis

Various complications of esophagitis may be noted, including the following:

Approach Considerations

Laboratory tests are usually unhelpful unless complications are present (eg, upper GI hemorrhage). Routine radiography is not indicated unless complications (eg, perforation, obstruction, bleeding) are suspected.

Double-contrast esophageal barium studies are 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 pathological examination, cytological examination, 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).

Go to Pediatric Esophagitis for complete information on this topic.

Lab Studies

A complete blood count (CBC) is performed in patients with neutropenia or who are immunosuppressed.

A CD4 count and HIV test are performed in patients with risk factors for HIV.

A collagen workup (eg, antinuclear antibody [ANA], anti-dsDNA) may be performed based on the underlying disease.

Barium Studies

Double-contrast esophageal barium studies are 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), 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. In 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 mid esophagus. Some patients may have multiple tiny plaques, which produce a finely granular or nodular appearance of the mucosa.


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Infectious esophagitis. Candida esophagitis. Double-contrast esophagram shows linear plaquelike lesions in the esophagus, with normal intervening muco....

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 AIDS; therefore, the presence of a shaggy esophagus should suggest the possibility of AIDS in patients who are not yet known to be HIV positive.


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Infectious esophagitis. Two examples of advanced Candida esophagitis demonstrate a shaggy esophagus. In both images, the double-contrast esophagram sh....

Some of the plaques and pseudomembranes may eventually be sloughed off, producing 1 or more areas of ulceration on a background of diffuse plaque formation. Occasionally, 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.


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Infectious esophagitis. Candida esophagitis with a foamy esophagus. This patient has a dilated esophagus with beaklike narrowing (arrow) at the gastro....

Herpes esophagitis

On double-contrast esophagrams, herpes esophagitis usually manifests as multiple, small, superficial ulcers in the upper or mid esophagus on an otherwise normal background mucosa (see the image below).


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Infectious esophagitis. Herpes esophagitis. Double-contrast esophagram shows small, discrete ulcers (arrows) in the mid esophagus on a normal backgrou....

The ulcers can have a punctate, linear, stellate, or volcano-like 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 1 or more giant and relatively flat ulcers, sometimes associated with small satellite ulcers (see the image below).


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Infectious esophagitis. Cytomegalovirus esophagitis in a patient with AIDS. Double-contrast esophagram shows a large, flat ulcer in profile (large arr....

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.

Go to Cytomegalovirus Esophagitis for complete information on this topic.

HIV esophagitis

The lesions usually appear on double-contrast esophagrams as 1 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.


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Infectious esophagitis. Two examples of giant HIV esophageal ulcers (arrows) in patients with AIDS. In A, the ulcer is seen in profile, whereas in B, ....

Tuberculous esophagitis

Barium studies or computed tomography (CT) 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 mid esophagus.

Graft versus host disease

Barium contrast radiographs may reveal webs, rings, and tight strictures in the upper and mid esophagus.

Upper Endoscopy

Direct upper endoscopy (ie, 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]


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Peptic esophagitis. A rapid urease test (RUT) is performed on the esophageal biopsy sample. The result is positive for esophagitis.

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 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 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 (GVHD), 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 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.

Electrocardiography

Electrocardiography (ECG) and troponin or other cardiac markers are needed when acute coronary syndrome is in the differential diagnosis.

Histologic Findings

Histologic findings vary according to the etiology. For example, fungal and viral infections occur at differing locations in esophagitis-associated ulcers (see the image below).[1]


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Esophagitis. Location of fungal and viral infections in ulcers.

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:

Candida plaques are typically creamy white or pale yellow, with 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. 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 on 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:

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

CMV infects submucosal fibroblasts and endothelial cells, not the squamous epithelium. Diagnosis depends on biopsies from the 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; 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 2-4 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 endothelial cells or fibroblasts near the base of the ulcers. A lymphomonocytic inflammatory response is also seen at the site of infection.

Go to 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 HIV infection. 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, which rarely occur, affect the esophagus with a blistering process and desquamation of large areas of 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 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.

Approach Considerations

Treatment begins with hemodynamic stabilization and pain management. Subsequent therapy depends on the cause of the esophagitis and on any complications present. Surgery (fundoplication) is sometimes indicated in patients with severe pain who fail to respond to medical management.

Go to Pediatric Esophagitis for complete information on this topic.

Hemodynamic Stabilization

Initial care is directed toward complications (eg, bleeding, perforation) that require hemodynamic stabilization. Admit the patient when significant bleeding, perforation, obstruction, or volume depletion occurs.

Pain Management

Chest pain of esophageal origin cannot be differentiated accurately from chest pain associated with coronary artery disease. Therefore, prehospital protocols should be followed for management of chest pain potentially caused by coronary artery disease. When the cause of the pain is uncertain, oxygen is generally indicated.

Treatment of Reflux Esophagitis

Previously, histamine-2 receptor antagonist (H2RA) therapy was recommended as the initial treatment for esophagitis associated with gastroesophageal reflux disease (GERD); however, newer evidence in cost-effectiveness analysis and symptomatic relief suggests proton pump inhibitors (PPIs) (omeprazole 20 mg daily, pantoprazole 40 mg daily, or lansoprazole 30 mg daily for 4-8 wk) to be superior to ranitidine, cimetidine, and placebo.

The 2005 ACG GERD guidelines recommend PPIs as more effective than H2RAs for GERD based on highest-level evidence. The guidelines state that greater percentage of patients with reflux esophagitis healed when treated with PPIs than with H2RA.[40]

Cisapride, a gastroprokinetic agent, and sucralfate, a coating agent, are less effective but may be useful in selected patients or as second-line agents. Cisapride is only available through an investigational limited-access program because of its potential for risk of serious cardiac arrhythmias and death.

Some authorities suggest PPIs and histamine-2 receptor antagonists for patients with ulcerlike-dominant symptoms (eg, nocturnal symptoms, relief with food) and gastroprokinetic agents for patients with dysmotility dominant symptoms (eg, nausea, bloating).

Although no consensus on treatment choice exists, prescribing for 2-4 weeks with reassessment is reasonable. Some patients with relapse may require long-term maintenance therapy.

According to the 2005 ACG guidelines, patients whose GERD symptoms could not be controlled with antacids and lifestyle modifications, but were relieved by PPIs, are likely to require long-term, even life-long, maintenance therapy.[40]

Treatment of Infectious Esophagitis

Treatment is directed at the underlying cause. The goal of medical care is to treat the underlying cause and minimize morbidity.

Fungal esophagitis

Medical therapy for fungal conditions falls into 3 categories, as follows:

The choice of agent depends on the severity of infection and degree of host defense impairment. Most patients with fungal esophagitis who are immunocompetent can be treated with a topical antifungal agent. They are virtually devoid of adverse effects and have few, if any, drug-drug interactions because they are not absorbed.

In a study at the digestive endoscopy unit of a Brazilian hospital, Wilheim et al found the incidence of esophageal candidiasis to be low, determining that 40 out of 2,672 patients (1.5%) who underwent esophagogastroduodenoscopy had endoscopic findings compatible with the disorder.[44] Just over half of these 40 patients were male, and 65% of them were inpatients. Of the 90% of patients in whom associated diseases were identified, 21 (52.5%) were infected with HIV. Among the 21 patients under age 50 years, 82.6% were HIV positive.

Endoscopy revealed severe forms of esophagitis in 50% of patients in the Wilheim study with a CD4 count below 200 cells/µL. Candida species other than Candida albicans were isolated in 22.7% and 45% of HIV-positive and HIV-negative patients, respectively. Six patient Candida samples were found to be fluconazole-resistant, while 2 samples had dose-dependent susceptibility to this agent.

Herpes esophagitis

Herpes simplex virus (HSV) esophagitis diagnosed at endoscopy is typically treated with acyclovir, foscarnet (for acyclovir-resistant cases), or famciclovir (an acyclovir analog).

Cytomegalovirus esophagitis

Cytomegalovirus (CMV) esophagitis is treated differently from HIV esophagitis. However, these 2 entities cannot be reliably differentiated on the basis of the clinical and radiographic findings; thus, endoscopy is required for a definitive diagnosis before patients are treated. When multiple esophageal biopsy specimens, brushings, and/or viral cultures are obtained, endoscopy has a sensitivity of greater than 95% in the diagnosis of CMV esophagitis.

CMV esophagitis is usually treated with ganciclovir and foscarnet, which are potent antiviral agents that have significant bone marrow and renal toxicities, respectively.

Go to Cytomegalovirus Esophagitis for complete information on this topic.

HIV esophagitis

In contrast to CMV esophagitis, HIV esophagitis is treated with oral corticosteroid therapy, usually for longer than 1 month, in conjunction with antiretroviral therapy for HIV.

Varicella-zoster virus esophagitis

Varicella-zoster virus (VZV) esophagitis is typically with acyclovir, famciclovir, or foscarnet (for acyclovir-resistant cases).

Epstein-Barr virus esophagitis

Epstein-Barr virus (EBV) esophagitis is treated with acyclovir. Long-term maintenance therapy may be required to suppress oral hairy leukoplakia.

Human papillomavirus esophagitis

Human papillomavirus (HPV) esophagitis is often asymptomatic; thus, no treatment is usually needed. Systemic interferon alfa, bleomycin, and etoposide have been used, with variable results.

Mycobacterium tuberculosis esophagitis

Standard antituberculous therapy is used for immunocompetent hosts.

Bacterial esophagitis

Infection by normal flora, usually observed in immunocompromised patients, is extremely rare in healthy hosts. Infections are often polymicrobial and include Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus viridans, and Bacillus species.

Bacterial esophagitis is treated with broad-spectrum beta-lactam antibiotics, usually in combination with an aminoglycoside. Adjustments are based on response and culture results.

Esophagitis Associated with Systemic Illnesses

Treatment of nonreflux, noninfectious esophagitis depends on the underlying condition.

Behçet disease esophagitis

Treatment consists of corticosteroids for serious inflammation and chlorambucil or azathioprine for long-term therapy.

Graft versus host disease esophagitis

This condition is treated with dilation and antireflux measures and the use of prednisone, cyclosporine, azathioprine, and thalidomide.

Inflammatory bowel disease esophagitis

Esophagitis associated with inflammatory bowel disease is treated by means of corticosteroid therapy for inflammatory lesions and dilation for strictures. Surgery may be needed to treat fistulas and strictures.

Eosinophilic esophagitis

The treatment of eosinophilic esophagitis continues to evolve. Various interventions, such as complete avoidance of precipitating food allergens, esophageal dilatation, corticosteroids, cromolyn sodium, and leukotriene inhibitors, have been performed. Until the natural history of this disease is understood more fully and appropriate trials are performed, the treatment of this condition will continue to be empirical.

One study suggests that a 15-day course of treatment with budesonide is well tolerated with no serious side effects and is highly effective for remission in adolescent and adult patients with eosinophilic esophagitis.[45]

In 2013, the American College of Gastroenterology issued a new guideline for the diagnosis and management of eosinophilic esophagitis.[43] Recommendations for treatment include the following:

Dietary therapy

A diet eliminating 6 food groups that are likely to trigger allergies may help to ease the symptoms of eosinophilic esophagitis in adults, according to a study of 67 patients with active disease.[46, 47] The 6 food groups (cereals, milk, eggs, fish/seafood, legumes/peanuts, and soy) were eliminated and then reintroduced sequentially, 1 at a time.[3, 4]

Of the 67 patients, 49 (73.1%) exhibited significant drops in peak eosinophil counts before foods were reintroduced. In all, 35.71% of the patients had 1 food trigger, 30.95% had 2, and 33.3% had 3 or more. The most common food triggers, in descending order of frequency, were cow’s milk, wheat, eggs, and legumes. Patients who continued to avoid the allergy-triggering foods maintained a histopathologic and clinical remission for as long as 3 years.

Metastatic cancer esophagitis

This condition is treated by means of radiation therapy and palliation with stents.

Esophagitis Associated with Pharmacologic or Other Therapy

Treatment of esophagitis linked to medications or radiation therapy depends on the underlying cause.

Medication-related esophagitis (pill esophagitis)

The offending medication should be stopped. Control of acid reflux may accelerate healing. Patients should take medication with plenty of water while sitting in the upright position.

Radiation and chemoradiation esophagitis

Healing may not occur for several months after cessation of radiation therapy. Treatment is with viscous lidocaine and sucralfate. Stricture formation is a common complication and may require endoscopy for dilation.

Diet and Activity

No particular diet restrictions are necessary; however, if the patient has odynophagia or is unable to consume calories orally, then gastric feeding or parenteral feeding may be needed. No limitations on patient physical activity are necessary.

Consultations

Consult a gastroenterologist to facilitate diagnosis and treatment. A gastroenterologist should also be consulted for cases involving moderate-to-severe bleeding, perforation, or suspected obstruction. Consulting an infectious disease specialist may be necessary in difficult cases. A surgical consultation may be necessary for perforation and fistulas. Other consultations may be sought as indicated.

Long-Term Monitoring

The patient should receive follow-up care from his or her primary care provider. Refer the patient for endoscopy in the presence of suspected complications such as strictures, minor bleeding not requiring admission, and failure of medical therapy.

Medical, surgical, and endoscopic treatments are available for patients with erosive esophagitis caused by chronic GERD. The Agency for Healthcare Research and Quality has produced a comparative review of the efficacy and safety of these treatments.[48]

Medication Summary

Medications used to treat esophagitis vary depending on the etiology. Treatment goals for reflux esophagitis include pain relief, decreased acid production, decreased acid reflux, and protection of the esophageal mucosa. Multiple pharmacologic agents are available, including histamine-2 receptor antagonists, proton pump inhibitors (PPIs), gastroprokinetic agents, and protective agents.[49]

Therapy for infectious esophagitis is directed at the underlying condition, with the goal of minimizing symptoms and preventing complications. The choice of the therapeutic agent depends on the severity of infection and the degree of host defense impairment.

Ranitidine hydrochloride (Zantac, Zantac 75, Zantac 150)

Clinical Context:  Ranitidine hydrochloride competitively inhibits histamine at the H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Cimetidine (Tagamet HB 200)

Clinical Context:  Cimetidine inhibits histamine at H2 receptors of gastric parietal cells, decreasing gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Famotidine (Pepcid, Pepcid AC)

Clinical Context:  Famotidine competitively inhibits histamine at H2 receptors of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.

Class Summary

These agents decrease gastric acid production by blocking histamine-2 (H2) receptors in gastric cells. Some authorities recommend using larger doses than those used for peptic ulcer disease.

Sucralfate (Carafate)

Clinical Context:  Sucralfate binds to positively charged proteins in exudates and forms a viscous, adhesive substance that protects the gastrointestinal lining against pepsin, peptic acid, and bile salts. It is used for short-term duodenal ulcer management.

Class Summary

These medications coat the ulcerated surfaces and are used mainly for peptic ulcer disease. They may be used as a second agent with an H2 antagonist and in radiation esophagitis.

Omeprazole (Prilosec)

Clinical Context:  Omeprazole decreases gastric acid secretion by inhibiting the parietal cell H+/K+-ATP pump. It is used for up to 4 weeks to treat and relieve symptoms of active duodenal ulcers. It may be used up to 8 weeks to treat all grades of erosive esophagitis.

Lansoprazole (Prevacid, Prevacid SoluTab)

Clinical Context:  Lansoprazole decreases gastric acid secretion by inhibiting the parietal cell H+/K+-ATP pump. It is used for up to 4 weeks to treat and relieve symptoms of active duodenal ulcers. It may be used up to 8 weeks to treat all grades of erosive esophagitis.

Esomeprazole (Nexium, Nexium I.V.)

Clinical Context:  Esomeprazole decreases gastric acid secretion by inhibiting the parietal cell H+/K+-ATP pump. It is used for up to 4 weeks to treat and relieve symptoms of active duodenal ulcers. It may be used up to 8 weeks to treat all grades of erosive esophagitis.

Rabeprazole (Aciphex)

Clinical Context:  Rabeprazole decreases gastric acid secretion by inhibiting the parietal cell H+/K+-ATP pump. It is used for up to 4 weeks to treat and relieve symptoms of active duodenal ulcers. It may be used up to 8 weeks to treat all grades of erosive esophagitis.

Pantoprazole (Protonix)

Clinical Context:  Pantoprazole decreases gastric acid secretion by inhibiting the parietal cell H+/K+-ATP pump. It is used for up to 4 weeks to treat and relieve symptoms of active duodenal ulcers. It may be used up to 8 weeks to treat all grades of erosive esophagitis.

Class Summary

These agents inhibit gastric acid secretion by inhibiting the H+/K+ -ATPase enzyme system in gastric parietal cells. Products such as pantoprazole, lansoprazole, esomeprazole, and rabeprazole have been approved by the FDA and are at least as effective as the time-honored omeprazole.

Clotrimazole

Clinical Context:  Clotrimazole is a nonabsorbable imidazole. It is a broad-spectrum synthetic antifungal agent that inhibits the growth of yeasts by altering cell membrane permeability.

Nystatin

Clinical Context:  Nystatin is a nonabsorbable polyene antifungal agent obtained from Streptomyces noursei. It binds to sterols in the cell membrane of susceptible fungi, with a resulting change in membrane permeability, allowing leakage of intracellular components. It is indicated for the treatment of oral candidiasis.

Fluconazole (Diflucan)

Clinical Context:  Fluconazole is a synthetic triazole fungistatic agent. It is a highly selective inhibitor of fungal cytochrome P-450 sterol C-14 alpha demethylation.

Amphotericin B deoxycholate

Clinical Context:  Conventional amphotericin B binds to sterols in the cell membrane and alters permeability. It is used in patients with granulocytopenia. The oral route is infrequently used and has no advantage over oral clotrimazole or nystatin.

Anidulafungin (Eraxis)

Clinical Context:  Anidulafungin is an antifungal agent of the echinocandin class. It inhibits synthesis of 1,3-beta-D-glucan, an essential component of fungal cell walls. It is indicated to treat esophageal candidiasis, candidemia, and other forms of candidal infections (eg, intra-abdominal abscesses, peritonitis).

Itraconazole (Sporanox, Sporanox PulsePak)

Clinical Context:  Itraconazole is a synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

Flucytosine (Ancobon)

Clinical Context:  Although the exact mode of action is unknown, it is proposed that flucytosine acts directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and indirectly by intracellular metabolism, where it is converted to 5-fluorouracil after penetrating fungal cells. It inhibits RNA and protein synthesis. It is active against Candida and Cryptococcus species and generally is used in combination with amphotericin B.

Class Summary

Antifungal agents are topical or systemic agents used to treat fungal infections.

Acyclovir (Zovirax)

Clinical Context:  Acyclovir is a synthetic purine nucleoside analog that stops replication of viral DNA. It is used to treat HSV esophagitis.

Foscarnet (Foscavir)

Clinical Context:  Foscarnet is an organic analog of inorganic pyrophosphate that inhibits replication of HSV and CMV. It is used to treat acyclovir-resistant cases.

Ganciclovir (Cytovene)

Clinical Context:  Ganciclovir is an acyclic nucleoside analog that inhibits replication of herpes viruses. It is active against CMV and HSV.

Famciclovir (Famvir)

Clinical Context:  Famciclovir is goes through biotransformation to active penciclovir. Penciclovir has inhibitory activity against varicella-zoster virus (VZV) and herpes simplex virus types 1 and 2. It may be used for herpes and VZV esophagitis.

Class Summary

Antiviral agents are used to treat herpes simplex virus (HSV) or cytomegalovirus (CMV) infections. In addition to the drugs listed below, famciclovir (Famvir), a prodrug of the antiviral agent penciclovir, which is not currently recommended for treatment, may replace acyclovir in prophylaxis and treatment.

Prednisone

Clinical Context:  Prednisone is administered in immunosuppressive doses, which may vary based on the underlying disease process. The dose is usually slowly tapered over weeks to months. An equivalent dose of methylprednisolone (Solu-Medrol) may be used instead of prednisone.

Methylprednisolone (Medrol, Solu-Medrol)

Clinical Context:  Methylprednisolone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body’s immune response to diverse stimuli. Corticosteroids may be used in various conditions such as eosinophilic esophagitis, Behçet disease esophagitis, inflammatory disease esophagitis, or HIV esophagitis.

Montelukast (Singulair)

Clinical Context:  Montelukast inhibits effects by the leukotriene receptor, which has been associated with asthma, including airway edema, smooth muscle contraction, and cellular activity associated with the symptoms.

Zafirlukast (Accolate)

Clinical Context:  Zafirlukast selectively prevents the action of leukotrienes released by mast cells and eosinophils.

Class Summary

Leukotriene inhibitors can be used to treat eosinophilic esophagitis. Examples of leukotriene inhibitors include montelukast and zafirlukast.

Cromolyn sodium

Clinical Context:  Cromolyn inhibits the release of histamine, leukotrienes, and other mediators from sensitized mast cells exposed to specific antigens. It has no intrinsic anti-inflammatory, antihistamine, or vasoconstrictive effects.

Class Summary

Mast cell stabilizers such as cromolyn may be used for eosinophilic esophagitis.

Cyclosporine (Neoral, Sandimmune)

Clinical Context:  Cyclosporine is an 11-amino acid cyclic peptide and natural product of fungi. It acts on T-cell replication and activity. It is a specific modulator of T-cell function and an agent that depresses cell-mediated immune responses by inhibiting helper T-cell function. Preferential and reversible inhibition of T lymphocytes in the G0 or G1 phase of cell cycle is suggested. It binds to cyclophilin, an intracellular protein, which, in turn, prevents the formation of interleukin 2 and the subsequent recruitment of activated T cells.

Azathioprine (Imuran)

Clinical Context:  Azathioprine is an imidazolyl derivative of 6-mercaptopurine. Many of the biological effects are similar to those of the parent compound. Both compounds are eliminated rapidly from the blood and are oxidized or methylated in erythrocytes and the liver. No azathioprine or mercaptopurine is detectable in urine 8 hours after the drug is taken. It antagonizes purine metabolism and inhibits the synthesis of DNA, RNA, and proteins. It works primarily on T cells and suppresses hypersensitivities of the cell-mediated type; it also and causes variable alterations in antibody production.

Class Summary

Immunosuppressive agents such as cyclosporine and azathioprine may be used for graft versus host disease esophagitis.

Chlorambucil (Leukeran)

Clinical Context:  Chlorambucil is a bifunctional, slow-acting aromatic nitrogen mustard derivative that interferes with DNA replication, transcription, and nucleic acid function by alkylation. It alkylates and cross-links strands of DNA. Alkylation takes place through the formation of the highly reactive ethylenimonium radical. The probable mode of action involves cross-linkage of the ethylenimonium derivative between 2 strands of helical DNA and subsequent interference with replication.

Class Summary

Alkylating agents include nitrogen mustards such as chlorambucil. These agents can be used in the treatment of Behçet disease esophagitis.

Author

Deepika Devuni, MBBS, Resident Physician, Department of Internal Medicine, University Of Connecticut School of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

John W Birk, MD, FACG, Associate Professor of Medicine, Director, Gastroenterology and Hepatology Fellowship Program, University of Connecticut School of Medicine; Chief, Division of Gastroenterology, University of Connecticut Health Center

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Sajid Ansari, MD Consulting Staff, Department of Gastroenterology, St Anthony's Medical Center

Sajid Ansari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, and Missouri State Medical Association

Disclosure: Nothing to disclose.

Simmy Bank, MD Chair, Professor, Department of Internal Medicine, Division of Gastroenterology, Long Island Jewish Hospital, Albert Einstein College of Medicine

Disclosure: Nothing to disclose.

Maurice A Cerulli, MD, FACP, FACG, FASGE, AGAF Associate Professor of Clinical Medicine, Albert Einstein College of Medicine of Yeshiva University; Associate Professor of Clinical Medicine, Hofstra Medical School

Maurice A Cerulli, MD, FACP, FACG, FASGE, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, and New York Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Chin Hung Chung, MBBS, FRCS(Glasg), FHKAM(Surgery) Chief of Service, Department of Accident and Emergency, North District Hospital, Hong Kong

Chin Hung Chung, MBBS, FRCS(Glasg), FHKAM(Surgery) is a member of the following medical societies: American College of Surgeons and Royal College of Surgeons of Edinburgh

Disclosure: Nothing to disclose.

Steven C Dronen, MD, FAAEM Chair, Department of Emergency Medicine, LeConte Medical Center

Steven C Dronen, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Eugene Hardin, MD, FAAEM, FACEP Former Chair and Associate Professor, Department of Emergency Medicine, Charles Drew University of Medicine and Science; Former Chair, Department of Emergency Medicine, Martin Luther King Jr/Drew Medical Center

Disclosure: Nothing to disclose.

James Li, MD Former Assistant Professor, Division of Emergency Medicine, Harvard Medical School; Board of Directors, Remote Medicine

Disclosure: Nothing to disclose.

Sandeep Mukherjee, MB, BCh, MPH, FRCPC Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Chun-hing Ludwig Tsoi MB, ChB, MPH, MRCP, FRCS(Edin), Senior Medical Officer, Accident and Emergency Department, Tseng Kwan O Hospital, Hong Kong; Chairman, Committee on Training, Hong Kong St John Ambulance

Chun-hing Ludwig Tsoi is a member of the following medical societies: Royal College of Physicians of the United Kingdom and Royal College of Surgeons of Edinburgh

Disclosure: Nothing to disclose.

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Peptic esophagitis. A rapid urease test (RUT) is performed on the esophageal biopsy sample. The result is positive for esophagitis.

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.

Infectious esophagitis. Candida esophagitis. Double-contrast esophagram shows linear plaquelike lesions in the esophagus, with normal intervening mucosa.

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 AIDS.

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.

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.

Infectious esophagitis. Cytomegalovirus esophagitis in a patient with 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.

Infectious esophagitis. Two examples of giant HIV esophageal ulcers (arrows) in patients with 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.

Peptic esophagitis. A rapid urease test (RUT) is performed on the esophageal biopsy sample. The result is positive for esophagitis.

Esophagitis. Location of fungal and viral infections in ulcers.

Esophagitis. Location of fungal and viral infections in ulcers.

Peptic esophagitis. A rapid urease test (RUT) is performed on the esophageal biopsy sample. The result is positive for esophagitis.

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.

Infectious esophagitis. Candida esophagitis. Double-contrast esophagram shows linear plaquelike lesions in the esophagus, with normal intervening mucosa.

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 AIDS.

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.

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.

Infectious esophagitis. Cytomegalovirus esophagitis in a patient with 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.

Infectious esophagitis. Two examples of giant HIV esophageal ulcers (arrows) in patients with 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.