Esophagitis

The most common cause of esophagitis is gastroesophageal reflux disease (GERD). 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 (eg, strong alkalis in liquid and granular forms[3] ) (see the image below). (See Pathophysiology.)

See Pediatric Esophagitis for complete information on this topic.

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.

Eosinophilic esophagitis has also emerged as an important cause of esophagitis in both children and adults.[4, 5] Other causes of esophagitis include systemic disease and trauma. (See Etiology.)

The prognosis is good with rapid diagnosis and proper treatment. Ultimately, the 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 Presentation.)

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. Double-contrast esophageal barium studies and upper endoscopy are the recommended initial diagnostic 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.[6] Surgery (fundoplication) is sometimes indicated in patients with severe pain who fail to respond to medical management. (See Treatment and Medication.)

The pathophysiology of esophagitis depends on its etiology (see Etiology). The 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 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 into 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[7, 8] but has also been reported in healthy adults and children. A wide range of abnormalities in the 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 an altered immune function. Steroids, cytotoxic agents, radiation, and immune modulators can also contribute to the impaired host immune function. Disruption of the mucosal protective barriers and antibiotics that suppress the normal bacterial flora may contribute to the invasive ability of commensal organisms.[9]

Common types of infectious esophagitis include the following:

• Fungal (eg, candidal) esophagitis
• Viral (eg, herpes) esophagitis
• Tuberculous esophagitis

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 acquired immunodeficiency syndrome (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.

See Cytomegalovirus Esophagitis for complete information on this topic.

Medication-induced esophagitis (pill esophagitis)

Medications associated with pill esophagitis cause damage by local or topical injury.[10, 11, 12] Antibiotics, potassium chloride, nonsteroidal anti-inflammatory drugs (NSAIDs), quinidine, emperonium bromide, and alendronate account for 90% of the reported cases. The following are important pill and patient factors:

• Chemical nature of drug
• Solubility
• Contact time with mucosa
• Size, shape, and pill coating
• Amount of water (ie, too little) taken to swallow pill (eg, alendronate)
• Preexisting esophageal pathology (eg, stricture, achalasia)

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.[13, 14]

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.[15]

More recent studies have suggested other potential etiopathophysiologic factors, such as an increased susceptibility to eosinophilic esophagitis when genetic predisposition is influenced by environmental factors,[4] or a co-occurrence of potential or probable celiac disease in adults with eosinophilic esophagitis.[16]

Radiation and chemoradiation esophagitis

Radiation dose over 30 Gy to the mediastinum typically causes retrosternal burning and painful swallowing, which is usually mild and limited to the duration of therapy.[17]

• A dose of 40 Gy causes mucosal redness and edema.
• A dose of 50 Gy causes a higher incidence and severity of esophageal damage.
• A dose of 60-70 Gy causes moderate-to-severe esophagitis with strictures, perforations, and fistulas.

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:

• Pregnancy
• Obesity
• Scleroderma
• Smoking
• Alcohol, coffee, chocolate, fatty or spicy foods
• Certain medications (eg, beta blockers, nonsteroidal anti-inflammatory drugs [NSAIDs], theophylline, nitrates, alendronate, calcium-channel blockers)
• Mental retardation requiring institutionalization
• Spinal cord injury
• Immunocompromised state
• Radiation therapy for chest tumors

Helicobacter pylori eradication therapy has been inversely related to reflux esophagitis; it is postulated that the ammonia (alkaline) produced by H pylori reduces the acidity of the stomach and, hence, protects the esophagus from acid spillage.

Infectious esophagitis

Infectious agents known to cause esophagitis include the following:

• Candida species: Candida albicans is the most common offending pathogen, ^[7] but other Candida species, such as C tropicalis, C glabrata, and C parapsilosis, have also been implicated as rare causes of esophagitis
• Noncandidal fungi (eg, Aspergillus, Histoplasma, Cryptococcus, Blastomyces)
• Herpes simplex virus (HSV)
• Cytomegalovirus (CMV)
• Varicella-zoster virus (VZV)
• Epstein-Barr virus (EBV)
• In hosts infected with human immunodeficiency virus (HIV), CMV, HSV, Mycobacterium avium-intracellulare, idiopathic
• Human papillomavirus (HPV) ^[18]
• Poliovirus
• Bacterial species (eg, normal flora, Mycobacterium tuberculosis, M avium-intracellulare, Staphylococcus, Streptococcus, Lactobacillus, Nocardia)
• Parasitic infections (eg, Chagas disease, Trypanosoma cruzi, Cryptosporidium, Pneumocystis, Leishmania donovani)

Major predisposing factors for Candida esophagitis include antibiotic use, radiation therapy or chemotherapy, hematologic malignancies, and acquired immunodeficiency syndrome (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.[19, 20, 21, 22, 23, 24, 25]

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:

• Skin disorders, including epidermolysis bullosa, pemphigus vulgaris, bullous pemphigoid, cicatricial pemphigoid, drug-induced skin disorders (eg, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), and others (eg, lichen planus, psoriasis, acanthosis nigricans, leukoplakia)
• Eosinophilic esophagitis
• Behçet disease
• Graft versus host disease (GVHD)
• Inflammatory bowel disease ( Crohn disease)
• Sarcoidosis
• Chronic granulomatous disease
• Metastatic cancer
• Collagen vascular disease
• Motility disorders of the esophagus lead to poor acid clearing, with resulting epithelial damage (ie, gastroesophageal reflux disease in scleroderma)

Esophagitis associated with pharmacologic or other therapy

Therapeutic interventions that can cause esophagitis include the following:

• Medications (eg, pill esophagitis), including alendronate, antibiotics (eg, tetracycline), potassium, NSAIDs, quinidine, and chemotherapeutic agents (eg, dactinomycin, bleomycin, cytarabine, daunorubicin, 5-fluorouracil, methotrexate, vincristine)
• Radiation esophagitis may occur with radiation treatment of cancers located in the chest (ie, lung, esophagus, mediastinum)
• Sclerosant and band ligation therapy for varices can cause necrosis of the esophageal tissues and mucosal ulcers; incidence and severity are higher with sclerosant therapy; later, strictures can develop

Pill esophagitis is thought to be secondary to chemical irritation of the esophageal mucosa by certain medications (eg, iron, potassium, quinidine, aspirin, steroids, tetracyclines, NSAIDs), especially when these medications are swallowed with too little fluid.

Esophagitis is commonly seen in adults and is uncommon in childhood.[26, 27] The most common type of esophagitis is that associated with gastroesophageal reflux disease (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; as many as 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 of esophagitis in the range of 40%-65%. However, a retrospective review of the results of more than 8000 diagnostic endoscopies in Hampshire showed that GERD accounted for 23% of all upper gastrointestinal conditions.[28]

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 in association with other disorders

The prevalence of symptomatic infectious esophagitis is high in individuals with acquired immunodeficiency syndrome (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 (HSV) 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.[29, 30, 31, 32, 33, 34]

Cytomegalovirus (CMV) is a 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.[35] However, CMV esophagitis has increased among patients with solid organ transplants,[36] in whom delayed-onset disease is typical because of the increasing routine use of early CMV prophylaxis.[37]

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 (human immunodeficiency virus) 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 lower than 100 cells/μL. HIV ulcers are more common than is generally recognized, accounting for as many as 40% of all esophageal ulcers in patients with AIDS.[23, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47]

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 gastrointestinal 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 to prevent relapse of symptoms.

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 the development of strictures. Other complications include ulceration and hemorrhage and, rarely, fistula formation into the bronchial tree.[48]

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.

Complications

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

• Bleeding and stricture formation
• Barrett esophagus occurs when the normal squamous epithelium of the esophagus is replaced with columnar epithelium, and it is linked to the development of esophageal cancer; a systematic review of patients with Barrett esophagus also indicated a link between Barrett esophagus and colonic cancer (7.6% of patients with Barrett esophagus had colonic cancer vs 1.6% in controls) ^[2]
• Perforation with mediastinitis, though rare, is a serious complication
• Volume depletion and weight loss may occur secondary to the inability to swallow
• Laryngitis, aspiration pneumonitis, and bronchospasm may occur if the gastric contents are refluxed up to the level of the larynx.
• In infants, apnea and failure to thrive

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

• Elevate the head of the bed with 6-inch blocks (sleeping on extra pillows is discouraged because this actually may increase reflux by increasing intra-abdominal pressure caused by the patient bending at the waist)
• Avoid lying down for several hours after meals.
• Reduce meal size
• Lose weight
• Quit smoking
• Avoid alcohol and caffeine
• Avoid citrus, spicy or fatty foods, and chocolate
• Avoid aggravating medications such as aspirin and other over-the-counter nonsteroidal anti-inflammatory drugs

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 gastrointestinal bleeding from erosions over an esophageal varix.

For patient education information, see the Heartburn & GERD Center and Digestive Disorders Center, as well as Acid Reflux (GERD), Heartburn FAQs, and GERD and Heartburn Medications.

The history findings vary based on the type of esophagitis. Esophageal food impaction can be the initial presentation of proton pump inhibitor (PPI)-responsive eosinophilic esophagitis.[49]

Symptoms of reflux esophagitis

The most common complaint in patients with esophagitis is heartburn (dyspepsia), a burning sensation in the midchest caused by the contact of stomach acid with the 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 gastroesophageal reflux disease (GERD) in 2013.[50] According to the ACG guidelines, regurgitation and heartburn, separately or in conjunction, are the symptoms most specific for GERD. For patients with symptoms of uncomplicated GERD, the diagnosis of GERD may be assumed and empiric PPI therapy begun. For patients who show signs of GERD complications or other illness or who do not respond to therapy, further diagnostic testing should be considered.

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 the diagnostic evaluation.

Infants with gastroesophageal reflux are at a 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) and viral (herpes simplex virus and 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:

• Onset of difficult or painful swallowing (ie, dysphagia, odynophagia)
• Heartburn
• Retrosternal discomfort or pain
• Nausea, vomiting
• Fever, sepsis
• Abdominal pain
• Epigastric pain
• Hematemesis (occasionally)
• Anorexia, weight loss (depends on chronicity and severity of underlying illness)
• Cough

Candida esophagitis is usually manifested clinically by dysphagia and/or odynophagia in a patient with one 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 gastrointestinal (GI) tract bleeding; occasionally, patients are asymptomatic.

Herpes esophagitis is most commonly seen in immunocompromised patients with acquired immunodeficiency syndrome (AIDS), an underlying malignancy, or a debilitating illness or in patients who have been treated with radiation, steroids, or chemotherapy.[51] 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 human immunodeficiency virus 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.

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.[29]

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.

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.

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.

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 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 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]

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:

• Grade 1 - A few raised white plaques up to 2 mm in size, no ulceration
• Grade 2 - Multiple raised white plaques more than 2 mm in size, no ulceration
• Grade 3 - Confluent, linear, nodular, elevated plaques with ulceration
• 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:

• Multinucleated giant cells
• Ballooning degeneration
• Ground glass intranuclear Cowdry type A inclusion bodies
• 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.

Treatment begins with hemodynamic stabilization and pain management. 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.

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

Therapy after initial management depends on the cause of the esophagitis and on any complications present. Surgery (fundoplication) is sometimes indicated in patients with severe symptoms who fail to respond to medical management (eg, some patients with esophagitis and chronic gastroesophageal reflux disease [GERD]).[54]

In general, no particular dietary 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. (See also Diet.) No limitations on patient physical activity are necessary.

See Pediatric Esophagitis for complete information on this topic.

Previously, histamine-2 receptor antagonist (H2RA) therapy was recommended as the initial treatment for esophagitis associated with gastroesophageal reflux disease (GERD); however, subsequent studies of cost-effectiveness and symptomatic relief suggested that proton pump inhibitors (PPIs) (eg, omeprazole 20 mg/day, pantoprazole 40 mg/day, or lansoprazole 30 mg/day for 4-8 weeks) are superior to ranitidine, cimetidine, and placebo.

The 2013 GERD guidelines from the American College of Gastroenterology (ACG) emphasize that PPIs are more effective than H2RAs for GERD on the basis of the highest-level evidence.[50] No significant differences among the various PPIs currently available were noted.

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

Some authorities recommend PPIs and H2RAs 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 2013 ACG guidelines, GERD patients whose symptoms continue after discontinuance of PPI therapy and those with complications such as erosive esophagitis and Barrett esophagus are likely to require long-term, even life-long, maintenance therapy.[50] For patients who require long-term PPI therapy, it should be administered at the lowest effective dose, including on-demand or intermittent therapy.

Treatment of infectious esophagitis is based on the patient's immune status, disease severity, and risk of complications.[7] The goal of medical care is to treat the underlying cause and minimize morbidity.

Fungal esophagitis

Medical therapy for fungal conditions falls into the following three categories:

• Topically active agents include nystatin, clotrimazole, and oral amphotericin B
• Orally administered absorbable agents include fluconazole and itraconazole ^[55]
• Parenterally administered agents include amphotericin B, fluconazole, and flucytosine

The choice of agent depends on the severity of infection and the 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 these agents 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 of 2,672 patients (1.5%) who underwent esophagogastroduodenoscopy (EGD) had endoscopic findings compatible with the disorder.[55] 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 human immunodeficiency virus (HIV). Among the 21 patients younger than 50 years, 82.6% were HIV-positive.

In this study, endoscopy revealed severe forms of esophagitis in 50% of patients 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. In six patients, the Candida samples were found to be fluconazole-resistant, whereas two 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 two 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.

See 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 treated 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 in 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.

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

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 (Crohn 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 (see Diet), esophageal dilatation, corticosteroids, cromolyn sodium, and leukotriene inhibitors, have been employed. Until the natural history of this disease is understood more fully and appropriate trials are performed, treatment of this condition will continue to be empiric.

In a 2014 review of the clinical, endoscopic, and histologic features of eosinophilic esophagitis in adults and children, Dellon and Liacouras noted that this condition can be treated with topical corticosteroids or dietary strategies.[56] Endoscopic dilation is an important tool for the treatment of fibrostenotic complications. Unresolved issues include phenotypes, optimal treatment end points, the role of maintenance therapy, and treatment of refractory disease. Ideally, eosinophilic esophagitis is managed by a multidisciplinary team comprised of gastroenterologists, allergists, pathologists, and dietitians.

A study by Straumann et al suggested 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.[57]

Rokkas et al conducted a network meta-anaylsis that included 1011 patients and 15 therapeutic interventions. They concluded that budesonide 1 mg orodispersible tablet twice daily was the most effective treatment for eosinophilic esophagitis.[58]

In a study by Rothenberg et al, QAX576, a monoclonal antibody to interleukin (IL)-13, was found to be efficacious in the treatment of patients with eosinophilic esophagitis refractory to proton-pump inhibitors (PPIs).[59] Intravenous QAX576 or placebo was given at weeks 0, 4, and 8, and patients were followed for 6 months. Efficacy was to be declared if the lower 90% confidence limit for the proportion of responders (those with a greater than 75% decrease in peak eosinophil counts at week 12) on QAX576 was 35% or greater.

Twenty-three patients completed this study up to week 12; 18 continued to the end of the study.[59] For the proximal and distal esophageal biopsies combined, the responder rate was 40.0% for QAX576, compared with 12.5% for placebo. QAX576 was well tolerated. Although the primary end point was not met, the mean esophageal eosinophil count decreased by 60% with QAX576 versus a 23% increase with placebo. The decrease was sustained for up to 6 months.

Metastatic cancer esophagitis

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

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.

A diet eliminating six food groups (six-food elimination diet [SFED]) 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.[60, 61] The six food groups (cereals, milk, eggs, fish/seafood, legumes/peanuts, and soy) were eliminated and then reintroduced sequentially, one at a time.[6, 9]

Of the 67 patients in this study, 49 (73.1%) exhibited significant drops in peak eosinophil counts before foods were reintroduced.[60, 61] In all, 35.71% of the patients had one food trigger, 30.95% had two, and 33.3% had three or more. The most common food triggers, in descending order of frequency, were cow 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.

In a cost utility analysis that compared the SFED with topical corticosteroids for first-line therapy of eosinophilic esophagitis, Cotton et al noted that although both therapies had similar efficacy, the six-food elimination diet was less expensive and more cost effective overall.[62]

In a study that evaluated patient-related costs for the SFED, Asher Wolf et al found that compared to an unrestricted diet, the cost of the SFED was higher ($92.54 vs $79.84, respectively; P = 0.0001) at a standard grocery store, and the SFED required the purchase of a higher proportion of items at another store (32% vs 3%, respectively; P = 0.0001).[63] The costs and number of items requiring a trip to a second store for both diets were similar when shopping at specialty grocery stores.

Consult a gastroenterologist to facilitate the 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.

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 gastroesophageal reflux disease. The Agency for Healthcare Research and Quality has produced a comparative review of the efficacy and safety of these treatments.[64]

In May 2020, the American Gastroenterological Association (AGA) Institute and the Joint Task Force on Practice Parameters (JTF) from the American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma & Immunology issued clinical practice recommendations on the management of eosinophilic esophagitis.[65]

In patients with symptomatic esophageal eosinophilia, the use of proton pump inhibition is suggested over no treatment.

In patients with eosinophilic esophagitis (EoE), topical glucocorticosteroid use is recommended over no treatment.

In patients with EoE, topical glucocorticosteroid use is suggested over employment of oral glucocorticosteroids.

In patients with EoE, use of an elemental diet is suggested over no treatment.

In patients with EoE, use of an empiric, six-food elimination diet is suggested over no treatment.

In patients with EoE, an allergy testing–based elimination diet is suggested over no treatment. However, because the accuracy of currently available allergy-based testing for the identification of specific EoE food triggers is potentially limited, patients may desire alternative medical or dietary treatments over an exclusively testing-based elimination diet.

In patients with EoE in remission after short-term use of topical glucocorticosteroids, continuation of these topical agents is suggested over discontinuation of therapy. However, patients who strongly wish to avoid long-term topical steroid use and its possible adverse effects and/or who give lower importance to the prevention of potential long-term, undesirable outcomes of EoE (ie, recurrent dysphagia, food impaction, esophageal stricture) could reasonably prefer treatment cessation following initial remission, provided that clinical follow-up is maintained.

In adult patients in whom dysphagia has resulted from a stricture associated with EoE, endoscopic dilation is suggested over no dilation.

The use of anti–immunoglobulin E (anti-IgE) treatment for EoE is suggested against.

For more information, please go to Eosinophilic Esophagitis.

For more Clinical Practice Guidelines, please go to Guidelines.

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 (H2RAs), proton pump inhibitors (PPIs), gastroprokinetic agents, and protective agents.

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.

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.

Ranitidine hydrochloride (Zantac, Zantac 75, Zantac 150)

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. As of April 1, 2020, ranitidine was withdrawn from the market due to an increasing number of products containing the contaminant known as N-Nitrosodimethylamine (NDMA), a probable carcinogen in humans. Moreover, nizatidine (Axid), another H2 receptor blocker, has also been withdrawn because of contamination with NDMA.. 

Cimetidine (Tagamet HB 200)

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

Famotidine (Pepcid, Pepcid AC)

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 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. These drugs are also useful in radiation esophagitis.

Sucralfate (Carafate)

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 agents inhibit gastric acid secretion by inhibiting the H+/K+ -ATPase enzyme system in the 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.

Omeprazole (Prilosec)

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)

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.)

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)

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)

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

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

Clotrimazole

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

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)

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

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

Anidulafungin (Eraxis)

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)

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)

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 the 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

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.

Acyclovir (Zovirax)

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

Foscarnet (Foscavir)

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

Ganciclovir (Cytovene)

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

Famciclovir (Famvir)

Famciclovir undergoes 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

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.

Prednisone

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)

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

Class Summary

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

Montelukast (Singulair)

Montelukast blocks the action of leukotriene D4 on the leukotriene receptors in the lungs and bronchial tree, which has been associated with asthma, including airway edema, smooth muscle contraction, and cellular activity associated with the symptoms.

Zafirlukast (Accolate)

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

Class Summary

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

Cromolyn sodium

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

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

Cyclosporine (Neoral, Sandimmune)

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)

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 causes variable alterations in antibody production.

Class Summary

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

Chlorambucil (Leukeran)

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 the 2 strands of helical DNA and subsequent interference with replication.