AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Esophagitis (inflammation of the squamous esophageal epithelium) may result from various causes, including acid and nonacid gastroesophageal reflux (GER), food allergies, dysmotility due to various causes, infections, trauma, and iatrogenic causes. The clinical presentation, diagnostic evaluation, and management principles depend on the etiology; however, in the pediatric population, gastroesophageal reflux disease (GERD), infection, eosinophilic esophagitis, and corrosive ingestions account for most cases.

Pathophysiology

The pathophysiology of esophagitis can be categorized according to the etiology.

• Chemical esophagitis: Chemical esophagitis can result from GER or from the ingestion of corrosive substances such as certain medications or dishwasher cleaner.
• Reflux (peptic) esophagitis
• • Distal esophageal inflammation results when gastric and duodenal fluids, including gastric acid, pepsin, trypsin, and bile, are regurgitated into the esophagus. A decrease in the lower esophageal sphincter (LES) tone and altered motility increase esophageal clearance time and cause GER. Esophageal inflammation can further induce both mechanisms, creating a vicious cycle. Although decreased LES tone occurs in infantile GER and GERD and in dysmotility disorders, the single factor currently regarded as the most important in the pathogenesis of GERD is the repeated occurrence of inappropriate transient lower esophageal sphincter relaxations (TLESRs). Factors that increase esophageal clearance time include posture-gravity interactions, size and content of a meal, abnormal gastric emptying, and abnormal esophageal peristalsis.
  • Mild, early changes may include irritation of the esophageal mucosa with basal cell hyperplasia and thickening of the papillae. This progresses along a spectrum of severity that can lead to infiltration of inflammatory cells, ulcerations, scarring, and fibrosis with stenosis. Cellular metaplasia to columnar epithelium, known as Barrett esophagus, can also occur. Barrett esophagus is rare in the pediatric population; within the pediatric population, this condition is more frequent in adolescents than in younger children.
• Corrosive (caustic) esophagitis
• • Depending on the type, concentration, and volume of the ingested substance, varying degrees of chemical burns that involve different layers of the esophagus may occur. Superficial mucosal injury (first-degree), transmural mucosal injury with possible muscularis involvement (second-degree), or full-thickness injury (third-degree) can result. The condition can extend into periesophageal or perigastric tissues, resulting in perforation, peritonitis, or mediastinitis.
  • Household and garden materials are alkalis and cause a deep liquefaction necrosis with fat and protein digestion. Acids are less frequently encountered and typically lead to a more superficial coagulation necrosis with eschar formation.
  • Corrosive esophagitis induced by direct contact of the mucosa with a drug is mainly seen in cases that involve abnormal esophageal motility. Drugs implicated include doxycycline, clindamycin, tetracycline, ferrous sulphate, potassium chloride, quinidine, and anti-inflammatory agents. A pill trapped in the esophagus may cause ulceration and esophageal perforation 24-48 hours after ingestion.
• Eosinophilic esophagitis
• • Eosinophilic esophagitis can occur at any age.
  • In infants and young children, eosinophilic esophagitis presents with symptoms similar to those of GERD but fails to respond to conventional acid blockade therapy.
  • Dysphagia and food impaction can occur in older children and adolescents. Eosinophilic esophagitis is often seen in patients with atopy who have asthma, eczema, or chronic rhinitis or in those who have a family history of atopic disease.
  • Endoscopy may reveal a ringed appearance or linear furrows. Standard biopsy findings reveal severe eosinophilic infiltration; more than 15-20 eosinophils per high-magnification microscopic field are necessary for diagnosis.
  • In contrast to GERD, eosinophilic esophagitis involves the mucosa, submucosa, and, possibly, the muscularis. 
  • Multiple food antigens (eg, eggs, nuts, beef, wheat, fish, shellfish, corn, soy) can induce eosinophilic esophagitis; cow's milk protein is the most common precipitant.
  • Eosinophilic esophagitis is currently diagnosed based solely on endoscopy findings. Standardized skin-prick testing and radioallergosorbent testing (RAST) are helpful only in immunoglobulin E (IgE)–mediated disorders, including urticaria and anaphylaxis. These tests and IgE levels or serum eosinophil counts are not useful in the diagnosis of eosinophilic esophagitis, though about two thirds of children with EE have an increased peripheral eosinophilic count.
  • The exact pathophysiology of eosinophilic esophagitis is unknown, but contact of the allergen with the esophageal or intestinal mucosa is thought to be the initiating event. In recent years, animal models of oral and respiratory eosinophil-associated GI disorders have been developed. In these models, oral antigens induced the recruitment of eosinophils to the GI tract, including the esophagus and Peyer patches, and promoted GI inflammation and motility dysfunction. Interleukin-5 (IL-5), interleukin 13 (IL-13), and eotaxin-1, a chemokine specific to eosinophils, play a major role in eosinophil recruitment and T-cell proliferation and polarization in the tissues.
• Infectious esophagitis
• • This type of esophagitis develops most often in immunocompromised patients. Up to 10% of liver or kidney transplant recipients have herpes simplex virus (HSV) or cytomegalovirus (CMV) esophagitis.
  • HSV, CMV, and Candida species are the most frequent agents that cause esophagitis in immunocompromised patients. Occasionally, varicella-zoster virus causes esophagitis. In acute human immunodeficiency virus (HIV) infection, esophagitis can be seen as well.
• Radiation esophagitis
• • Radiation esophagitis is not a common occurrence because the esophagus is relatively resistant to radiation injury compared with the rest of the GI tract. However, radiation doses of greater than 30 Gy may result in retrosternal burning, dysphagia, and esophagitis. Doses of 50 Gy cause severe esophagitis, and doses of 60 Gy cause esophageal strictures, fistulas, or both.
  • Histologic changes start within 2 weeks of the radiation dose and consist of epithelial damage, sloughing, and necrosis, which can extend to the deeper layers. Resolution and healing occur within 3-4 weeks of the last radiation dose.

Frequency

United States

GER is the most common esophageal disorder. Approximately 50% of infants aged 2-3 months and 67% of infants aged 4 months have daily regurgitations (thus, GER but not GERD). Approximately 8% of infants have an abnormal quantity of acid GER on pH probe findings that results in signs or symptoms (GERD). Histological esophagitis can be observed in 61-83% of infants with clinically significant esophagitis. Corrosive ingestions (ie, alkalis, acids, bleaches) account for 3-5% of reported accidental ingestions, or approximately 5,000-10,000 cases per year. The exact incidence of eosinophilic esophagitis is unknown, although the prevalence appears to be increasing in recent years in both the pediatric and adult population. Whether the increased diagnosis is due to recognition and surveillance bias is unknown.

Mortality/Morbidity

All types of esophagitis can be complicated by the development of strictures. GERD can be complicated by Barrett esophagus and, subsequently, by adenocarcinoma, although these 2 conditions are rare in the pediatric population. Enamel and dentine erosions can complicate GERD. Caustic esophagitis can result in perforation and life-threatening mediastinitis. Infectious esophagitis can result in ulcerations, fistula formation, and sepsis. After radiation therapy, strictures can occur within 1-10 years after the initial radiation treatment.

Race

No racial predilection is known.

Sex

A boy-to-girl ratio of 2:1 to 3:1 is observed in eosinophilic esophagitis.

Age

Reflux esophagitis occurs in all age groups. In infancy, the typical onset is during the second month of life, with a peak in the fourth month. However, some studies report the occurrence of GERD and peptic esophagitis throughout childhood. With corrosive esophagitis, unintentional ingestions usually occur in children younger than 5 years, whereas nonaccidental ingestions in adolescents may suggest a suicide attempt.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Reflux esophagitis
• • Emesis is typically effortless and is accompanied by frequent regurgitation in infants. However, less commonly, emesis may be forceful and projectile. Hematemesis may also be observed. Hiccoughs that last a long time and hard swallows are subtle signs of gastroesophageal reflux disease (GERD) in infants and young children.
  • Nonspecific signs such as crying, irritability, sleep or feeding problems, arching of the back, and colic may suggest esophageal pain in infants.
  • Infants may also demonstrate head tilting that can mimic torticollis, neck cocking, and opisthotonic posturing with arching of the back (Sandifer syndrome) or other neurobehavioral manifestations.
  • Apnea, chronic respiratory illnesses (pneumonia, wheezing, stridor), and asthma exacerbation may be associated with chronic GERD. Food aversion and failure to thrive or weight loss are frequent manifestations. Anemia due to iron deficiency may result from occult blood loss.
  • Abdominal pain, dysphagia, heartburn, and chest or epigastric pain may occur in older children and adolescents.
• Corrosive esophagitis
• • Coughing, crying, and vomiting following ingestion may be initial symptoms.
  • Dysphagia, refusal to drink, and mouth or chest pain with drooling and salivation may follow. Respiratory distress and stridor can result from airway obstruction and glottic edema.
  • To help determine the potential for morbidity, always try to obtain the original container or exact product name of the caustic substance ingested.
  • Dysphagia and chest pain may occur after ingestion of pill forms of antibiotics or any of the medications mentioned above.
• Eosinophilic esophagitis
• • Consider eosinophilic esophagitis when GERD symptoms, including regurgitation, irritability, food refusal, and failure to thrive in infants, do not respond to aggressive anti-reflux therapy.
  • Dysphagia, food impaction, and chest pain may occur in older children and adolescents.
• Radiation esophagitis
• • Retrosternal chest pain and dysphagia occur.
  • Strictures that present with dysphagia can occur up to 10 years after the treatment.
• Infectious esophagitis
• • Mouth ulcers, thrush, fever blisters, or skin lesions (viral) may be the presenting concerns.
  • Odynodysphagia, refusal to drink, and dysphagia may occur, especially with viral and fungal esophagitis.
  • Fever, dyspnea, or atypical chest pain may also occur.
  • In immunocompetent patients, HSV infection can present with fever, odynodysphagia, and acute-onset retrosternal pain. Oropharyngeal lesions are usually absent. Rarely, HSV, CMV, and HIV can cause an asymptomatic esophagitis.

Physical

• Assess vital signs because a patient may exhibit tachypnea, increased work of breathing, tachycardia, fever, or hypoxia, especially following caustic ingestions.
• Carefully examine the oropharynx for thrush (suggestive of candidal esophagitis), dental enamel and dentine erosions (suggestive of acid gastroesophageal reflux [GER]), burns, erythema, plaques, and ulcerations; however, oral findings may not be present, even with more severe esophageal or gastric burns.
• Examination of the skin may reveal eczema. The respiratory examination may reveal signs of asthma or reactive airway disease.
• In newborns who have esophagitis as a complication of congenital infections, intrauterine growth retardation, lymphadenopathy, hepatitis, organomegaly, and CNS abnormalities can be observed.
• Check stools for heme positivity in any child with possible esophagitis.

Causes

• Reflux or peptic esophagitis
• • GER is the most common cause of esophagitis among infants and children. Although a significant proportion of infants have symptoms of GER, only a minority develop GERD and esophagitis. Conversely, infants can have peptic esophagitis without GER (silent GERD). Mild GER is common, with symptoms peaking in infants younger than 6 months. Spontaneous resolution occurs by age 1 year in 70-80% of patients and by age 2 years in 80-90% of patients. A small minority of patients continues to experience reflux symptoms, with a variable time to resolution. The resolution in infants correlates with solid food intake, slowing caloric intake, growth, upright positioning, and increased truncal tone.
  • Systemic disorders that cause delayed gastric emptying and poor esophageal motility can induce GER and esophagitis. These disorders include cystic fibrosis, severe combined immunodeficiency, cerebral palsy, increased intracranial pressure, and celiac disease. Esophagitis can be a manifestation of Crohn disease, scleroderma, glycogen-storage disease type 1b, and chronic granulomatous disease. Neurologic impairment, medications, and certain diseases, including those that cause musculoskeletal abnormalities, may exacerbate GER.
  • Factors that decrease the tone of the lower esophageal sphincter include a diet rich in fat, caffeine, chocolate, and alcohol. Increased intra-abdominal pressure in obesity and pregnancy, hormonal changes during pregnancy, and smoking also promote acid GER.
• Infectious esophagitis: Infectious esophagitis occurs most often in those who are immunocompromised (eg, malignancies, acquired immunodeficiency syndrome [AIDS], long-term steroid or immunosuppressive use, diabetes, congenital immunodeficiencies). It can also occur in immunocompetent patients and is often associated with a preexistent esophageal damage due to chemical or physical causes. Overall, Candida organisms and HSV are the most commonly encountered agents. HSV and CMV are the most common viral pathogens, while varicella-zoster virus and enterovirus are rarely encountered.
• • Viral
  • • HSV is the only viral pathogen also commonly found in the immunocompetent host. Usually, no oropharyngeal lesions are present, and the diagnosis can be delayed because of an atypical presentation. In the immunosuppressed patient, vesicular lesions are observed, but, more commonly, ulcers with a characteristic raised yellow border are observed via endoscopy. The mucosa may also appear normal.
    • CMV is observed more commonly in patients with AIDS and in recipients of bone marrow or solid organ transplants. Esophagitis and enterocolitis are the most common CMV GI infections. Consider CMV in the newborn with physical findings consistent with congenital infection and symptoms of esophagitis (a rare complication).
    • Papillomavirus infection can develop in neonates born to mothers with the infection.
  • Fungal, protozoal
  • • Candida albicans is the most common infective agent in immunocompromised or immunocompetent patients; it can be associated with inhaled steroid therapy. Oral candidiasis is not predictive of esophageal involvement, except in the immunocompromised child. The lesions can be localized or can involve the entire esophagus. In immunocompromised patients, extensive esophagitis may be present without oral candidiasis. The typical finding on endoscopy is a raised, white, adherent lesion with erythematous borders that cannot be washed out or brushed off.
    • Rare pathogens may include Aspergillus species, Torulopsis glabrata, and Cryptosporidium species in patients with AIDS. Megaesophagus may be a late complication of Chagas disease caused by Trypanosoma cruzi.
  • Bacterial
  • • Various gram-negative bacilli and gram-positive cocci may be pathogens. This is usually secondary to an extension from a retroesophageal, retropharyngeal, or paravertebral abscess; spinal osteomyelitis; pleuritis; mediastinal lymphadenitis; pericarditis; or diphtheria. Iatrogenic trauma and perforation from procedures may contribute. Pill adherence to the esophagus may result in an ulcer and secondary bacterial infection.
    • Helicobacter pylori, usually found in gastric mucosa, has been observed in the metaplastic changes with Barrett epithelium of the esophagus.
• Corrosive esophagitis: This condition may follow the ingestion of various household cleaning products. Of such ingestions, 95% occur inside in the home, usually in the kitchen or bathroom. Nearly 73% occur while a product is in use, and 24% occur while a product is in storage. Almost 50% of ingested products were transferred out of their original containers. The volume of the product ingested does not necessarily correlate with the degree of tissue injury. Although alkalis and acids are encountered most commonly, detergents; disc batteries; and overheated food, milk, or formula can also cause corrosive esophagitis.
• • Alkalis
  • • Alkalis account for approximately 70% of corrosive ingestions; lye (sodium hydroxide) ingestions are the most common. Potassium hydroxide and ammonium hydroxide are also observed. Drain pipe cleaners, oven cleaners, powdered laundry detergents, and dishwasher detergents all include an alkali. Alkalis have no taste; thus, a child may ingest a larger amount.
    • The concentrations of base vary from liquid agents (10-25%) to industrial strength (30-35%) to granular agents (50-95%). Crystalline forms may cause linear burns, whereas liquid may lead to circular burns. Lesions vary from mild oral lesions to severe deep liquefaction necrosis that affects all layers of the esophagus.
  • Acids
  • • Acid ingestions account for approximately 20% of corrosive ingestions and include hydrochloric, sulfuric, oxalic, and nitric acids. Acids tend to taste bitter, which usually limits the amount ingested.
    • Toilet bowl cleaners, drain cleaners, and rust and stain removers are some of the products that contain acids, ranging in concentration from 8-65%. Liquid chlorine bleaches contain a less concentrated hydrochloric acid.
    • Coagulation necrosis and thick eschar formation are usually limited to the mucosa and superficial muscle layers; perforation is less likely to occur.
• Miscellaneous causes
• • Traumatic esophagitis can occur after nasogastric tube placement or after esophageal or gastric suctioning. This was found to be the first cause of esophagitis in newborns who had undergone vigorous nasopharyngeal aspiration.
  • Ingestion of foreign bodies such as zinc-containing coins, toys, sharp objects, and disc batteries can cause pressure sores or chemical lesions.
  • Radiation- and chemotherapy-induced (doxorubicin) esophagitis and esophagitis secondary to epidermolysis bullosa are very rarely encountered in the pediatric population.
  • Food allergies and eosinophilic esophagitis can cause esophagitis.
  • Systemic diseases such as Crohn disease, chronic granulomatous disease, scleroderma, polyarteritis nodosa, graft-versus-host disease, Behcet and glycogen-storage disease type 1 can cause esophagitis.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Eosinophilic gastroenteropathy
GI bleeding
Radiation therapy complications

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Few helpful diagnostic laboratory studies for esophagitis are available.
• A CBC count may reveal anemia (usually iron deficiency with blood loss) or a nonspecific leukocytosis. A peripheral eosinophilia may be observed in patients with eosinophilic esophagitis.
• Erythrocyte sedimentation rate, C-reactive protein level, albumin level, platelet count. Enzyme-linked immunosorbent assays (ELISAs), acute/convalescent titers, and polymerase chain reaction (PCR) for viral etiologies may be of benefit, although often not in the acute management.
• Serum albumin levels may be decreased in patients with corrosive esophagitis or CMV infection.
• Stool sample findings may be heme positive.

Imaging Studies

• Plain radiography: An increased retrotracheal space may appear on lateral chest radiography with paraesophageal infections or abscesses. Chest radiography may reveal evidence of aspiration pneumonia following a corrosive ingestion.
• Barium studies
• • An upper GI study is helpful in defining any anatomic abnormalities such as esophageal strictures, gastric outlet obstruction, pyloric stenosis, or intestinal malrotation. Esophageal motility abnormalities can be revealed with this examination. An upper GI study should be considered in all patients with persistent emesis and in whom esophagitis is suspected. Additionally, a barium swallow test can be performed to demonstrate swallowing abnormalities. These studies are not helpful in diagnosing gastroesophageal reflux (GER).
  • Performing a double-contrast upper GI study in older compliant children may be more sensitive. Mucosal irregularities, ulcers, nodules, plaques, and cobblestoning may be observed. Following a caustic ingestion, mucosal edema, dilatation, atony, or strictures are visualized.
  • An upper GI study may produce normal results even with underlying pathology or if lack of patient cooperation leads to the performance of a suboptimal study.
• Gastroesophageal scintigraphy: Gastroesophageal scintigraphy (milk scan) can be useful in revealing the gastric-emptying rate and GER that leads to pulmonary aspiration but is not specific for esophagitis.
• Esophageal pH probe monitoring: This can be used to document the severity of acid GER on the day of the study but does not necessarily indicate that esophagitis is present.
• Intraluminal impedance: Findings from this study document nonacid GER that would otherwise be missed with esophageal pH probe.
• CT scanning: This may be useful for visualizing paraesophageal abscesses that may extend into the esophagus and is also useful in evaluating perforations.
• Esophageal manometry: This study can help clarify a differential diagnosis, although it is not usually performed in the evaluation of esophagitis.

Procedures

Esophagogastroduodenoscopy (EGD) allows more definitive visualization of the esophageal mucosa. Biopsy samples are always obtained to look for histologic confirmation; in fact, the lower esophageal tract is well known as an area in which discrepancies between endoscopic and histologic findings are often found. If needed, brushings and cultures can be obtained. Therapeutic procedures such as dilatation of esophageal strictures can also be performed.

• In eosinophilic esophagitis, various patterns of morphological alterations are described upon endoscopy, including furrowing of the mucosa and mucosal rings. Typically, neither the gastric nor the duodenal mucosa is concomitantly involved.
• With infectious esophagitis in immunocompromised patients, such as children with cancer, EGD with biopsy may be a valuable tool in helping to treat esophagitis in children with fever. Biopsy is the most sensitive and accurate method in diagnosing fungal esophagitis.
• Following a corrosive ingestion, endoscopy should usually be performed within 24-48 hours in all patients. This helps to determine the degree of mucosal burns and ulcerations and the risk of complications of the esophagus, stomach, and duodenum. Late-forming ulcers and fibrin deposits may not be observed if endoscopy is performed in the first 12 hours. A string can be placed through the endoscope into the esophagus and can be left in place to help with subsequent dilatations by the surgeons.
• An earlier procedure allows assessment of the extent of injury and burns and possible perforations. Circumferential ulcers and mucosal sloughing indicate greater severity.

Histologic Findings

• Reflux esophagitis
• • The following 3 types of histologic changes occur in reflux esophagitis:
  • • Intraepithelial infiltration of inflammatory cells (small number of eosinophils, lymphocytes and neutrophils, and squiggle cells)
    • Epithelial alterations (basal cell hyperplasia, basal cell spongiosis, abnormal nuclei and increased mitosis, balloon cells)
    • Changes in the lamina propria (elongation and increased number of papillae and vascular dilatation of papillae)
  • Metaplasia of squamous epithelium to columnar epithelium or Barrett esophagus can occur. This pathology is rare in the pediatric population compared with adult populations.
• Allergic esophagitis or eosinophilic esophagitis: Histologic changes in allergic or eosinophilic esophagitis are similar to those seen in reflux esophagitis, but the eosinophilia is more severe, with 20 or more eosinophils per high-magnification microscopic field. In some cases, small microabscesses of eosinophils are present, and the inflammatory lesions can extend into the muscular layer of the esophagus.
• Candidal esophagitis: Erythema, friability, and adherent white plaques that cover the mucosa are seen macroscopically in candidal esophagitis. The plaques are composed of acute inflammatory exudate mixed with necrotic debris, pseudohyphae, and budding yeast. Because Candida species can often be found in the esophagus without clinical significance, diagnosis of candidal esophagitis depends on the presence of squamous epithelium with invading hyphal forms. Invasive candidiasis can produce transmural inflammation, necrosis, and possible perforation.
• HSV esophagitis: Shallow ulcers are the typical lesions of HSV esophagitis. An acute, nonspecific inflammatory exudate covers the ulcer. Biopsy samples collected from around the ulcer may reveal a viral cytopathic effect in the squamous epithelium (nuclei with clear appearance and condensed chromatin at the periphery) or aggregates of macrophages around herpetic ulcers.
• CMV esophagitis: The viral cytopathic effect of CMV esophagitis is seen in the stromal elements, endothelium, and submucosal glandular epithelium rather than in the squamous epithelium. Therefore, biopsy samples taken from the base of the ulcer can be more informative than those taken from around the ulcer.
• Corrosive esophagitis: This type of esophagitis may reveal polymorphonuclear cell infiltration, vessel thrombosis, bacterial invasion, and granulation tissue following second- and third-degree burns. Fibrous tissue, collagen deposition, and stricture formation may occur after 2 weeks.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Symptomatic treatment may include antacids for mild reflux esophagitis or viral esophagitis in the immunocompetent host. Prone and elevated head positioning, feeding recommendations (eg, thickening formula, providing smaller and more frequent feedings, fasting for at least 2 h before sleeping in older children), and other conservative reflux measures may be used for mild gastroesophageal reflux (GER).
• Although gastroesophageal reflux disease (GERD) may be initially treated with histamine 2 (H2)–receptor antagonists, tachyphylaxis quickly develops. Proton pump inhibitors (PPIs) should be used when peptic esophagitis is diagnosed because the effect of PPI is more sustained and powerful.¹ A recent study of healthy children reports that erosive esophagitis treated with adequate doses of PPIs has a low relapse rate and does not require maintenance with PPIs or H2-blocker therapy.²
• Infectious esophagitis requires the appropriate antiviral, antifungal, or antibiotic therapy based on the causative organism.
• For corrosive esophagitis with alkalis or acids, any continued exposure to the eye, mouth, and skin should be ceased and the area flushed with water. Airway, breathing, circulation, and the overall cardiorespiratory status should be addressed following any possible ingestion.
• • Although large quantities of fluid (eg, water, milk) have often been given to dilute the corrosive agent, be aware that, if perforation has occurred, these fluids may extravasate, leading to mediastinitis. Large volumes of fluid may also induce vomiting, but a small amount of water or milk may wash away any residual agent from the mucosal surface.
  • If alkaline or acidic fluids are given, an exothermic reaction can occur.
  • Induced emesis or gastric lavage for GI decontamination is contraindicated and may exacerbate esophageal injury or lead to aspiration.
  • Charcoal is not recommended.
  • Endotracheal intubation or tracheostomy may be required if severe upper airway edema is present.
  • Hospitalization for the administration of intravenous fluids and, possibly, tube feedings should probably occur for most children who have ingested a caustic agent.
  • Broad-spectrum antibiotics may be used in severe cases to prevent secondary infection, and steroids may be used in an attempt to decrease stricture formation.
• The treatment of eosinophilic esophagitis is still widely debated.
• • Evidence shows that food allergy is the most common cause of EE, and different approaches to removing the causative food antigens are available.
  • • Patch testing can help determine the allergen (most commonly milk, eggs, nuts, beef, wheat, fish, shellfish, corn, and soy).
    • Selective elimination of implicated foods based on allergy testing, or, in certain cases, initiation of elemental diet is required. 
    • For 1-3 months, patients are placed on an exclusion diet or an elemental diet, and repeat endoscopies with biopsies are often necessary to determine both improvement and the time to start progressive reintroduction of foods.
    • Elemental diet has higher success rate than testing-based elimination diet.³
  • Other treatments, such as anti-inflammatory medications, mast cell stabilizers, and leukotriene receptor antagonists, have also been used.
  • Oral corticosteroids were demonstrated to be effective in treating symptoms and normalizing the histology, but the disease recurs when these agents are discontinued.
  • • Since 1998, multiple studies demonstrated effectiveness of swallowed topical corticosteroids delivered from a metered dose inhaler in treating clinical symptoms and abnormal histology associated with eosinophilic esophagitis.⁴
    • In this form of administration, patients should be instructed to administer the metered dose inhaler without using a spacer. The inhaler should be inserted into the mouth and sprayed with the lips sealed around the device; the powder should then be swallowed and not rinsed. The patient should not eat or drink for at least 30 minutes. The treatment course is usually between 6-8 weeks. However, similar to the effect seen with oral steroid treatment, the disease generally recurs upon discontinuation of treatment.
    • The use of topical steroid for maintenance treatment has not been studied. The adverse effects in this form of treatment are thought to be significantly less compared with oral steroid because of the much smaller dose and the rapid metabolism by the liver with first-pass effect. 
  • • Oral cromolyn sodium and other mast cell stabilizers have not been shown to be effective. Recent studies have demonstrated benefits from leukotriene-receptor antagonists in adults, and studies of monoclonal antibodies directed against IL-5 are ongoing.⁵

Surgical Care

• For reflux esophagitis, consider Nissen fundoplication in severe cases unresponsive to aggressive medical management. With the availability of PPIs, the surgical indication is now restricted to less than 1% of all cases. Patients with associated delay in gastric emptying may require a pyloroplasty. A gastrostomy or jejunostomy tube may be placed to assist with feeding.
• For bacterial esophagitis, drainage of a paraesophageal abscess may be required.
• For corrosive esophagitis, surgical management of perforations and revisions may be required.

Consultations

• Consult a gastroenterologist, especially if endoscopy or biopsy is required for definitive diagnosis.
• For corrosive ingestions, always notify a local Poison Control Center. Their staff can help to identify problematic active ingredients and provide immediate management and monitoring guidelines. A gastroenterologist and, possibly, a surgeon need to be consulted. A significant number of patients have esophageal burns without oral burns.

Diet

• No dietary changes are required once proper medical treatment is successfully initiated. However, foods that exacerbate reflux or delay gastric emptying (eg, fats, fried foods, tomatoes, caffeine) should be restricted.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Depending on the etiology of the esophagitis, medications directed at treating gastroesophageal reflux (GER), treating or preventing infection, and decreasing inflammation may be required.

Drug Category: Histamine (H2)-receptor antagonists

These agents decrease the secretion and volume of gastric acid by competitively blocking H2 receptors in gastric cells.

Drug Name	Famotidine (Pepcid)
Description	Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentrations.
Adult Dose	20-40 mg PO bid for up to 12 wk; alternatively, 20 mg IV q12h
Pediatric Dose	Neonates: 0.5 mg/kg PO qd Infants and children <16 years: 0.5 mg/kg PO bid; not to exceed 40 mg bid; doses up to 2 mg/kg/d have been used in clinical studies
Contraindications	Documented hypersensitivity
Interactions	May decrease effects of ketoconazole and itraconazole (decreases bioavailability)
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Adjust dose or discontinue with renal dysfunction

Drug Category: Prokinetic agents

These agents augment cholinergic activity and improve motility in the GI tract. However, no evidence-based efficacy in GERD is available.

Drug Category: Proton pump inhibitors

These drugs inhibit the H⁺/K⁺/-ATPase pump in gastric parietal cells, thus inhibiting gastric acid secretion.

Drug Name	Lansoprazole (Prevacid)
Description	Inhibits gastric acid secretion by specifically inhibiting H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells. Give with or before the first meal of the day.
Adult Dose	Treatment: 30-60 mg PO qd for up to 8 wk; an additional 8 wk may be tried in those patients who failed to respond or for a recurrence of esophagitis Maintenance: 15 mg PO qd
Pediatric Dose	<10 kg: 7.5 mg PO qd for up to 12 wk 10-30 kg: 15 mg PO qd or bid for up to 12 wk ≥30 kg: 30 mg PO qd or bid for up to 12 wk
Contraindications	Documented hypersensitivity
Interactions	Cytochrome P450 isoenzyme CYP2C19 and CYP3A3/4 substrate; increases theophylline clearance mildly (10%); may increase warfarin effects; may interfere with the absorption of ketoconazole, ampicillin, iron salts, and digoxin; sucralfate delays and decreases lansoprazole absorption by 30%; cranberry juice significantly reduces gastric pH and may reduce effectiveness of PPIs
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Symptomatic response to therapy does not preclude the presence of gastric malignancy; use with caution in patients with liver disease, reduce dosage with severe impairment; Prevacid SoluTabs contain aspartame, which is metabolized to phenylalanine and must be used with caution in patients with phenylketonuria

Drug Category: Antifungal agents

Appropriate use of these agents depends on the severity of the candidal esophagitis and the host's age and immune status. One of several antifungal agents may be required for treatment. Nystatin or clotrimazole troches may be adequate for immunocompetent hosts.

Drug Name	Ketoconazole (Nizoral)
Description	Potential for development of resistance with ketoconazole. Fungistatic activity. Imidazole broad-spectrum antifungal agent; inhibits synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.
Adult Dose	200 mg PO bid for 4 doses, then 200 mg PO qd
Pediatric Dose	3.3-6.6 mg/kg/d PO qd
Contraindications	Documented hypersensitivity; fungal meningitis; cardiac dysrhythmias may occur when used with cisapride, terfenadine, or astemizole
Interactions	Inhibits CYP450 3A3/4 and 3A5-7; may increase levels of phenytoin, cyclosporine, digoxin, theophylline, corticosteroids, protease inhibitors, and warfarin; levels of ketoconazole may be decreased by phenobarbital, rifampin, and isoniazid; because gastric acidity is required for absorption, H2 antagonists, antacids, and omeprazole may decrease absorption
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Hepatotoxicity may occur; may reversibly decrease corticosteroid serum levels (adverse effects avoided with dose of 200-400 mg/d); administer antacid, anticholinergics, or H2 blockers at least 2 h after taking ketoconazole; GI disturbance, rash, pruritus, hepatotoxicity, headache, fever, and bone marrow suppression

Drug Name	Itraconazole (Sporanox)
Description	Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome CYP450-dependent synthesis of ergosterol, a vital component of fungal cell membranes.
Adult Dose	200 mg PO/IV qd; not to exceed 400 mg/d
Pediatric Dose	5-10 mg/kg/d PO/IV divided q12h
Contraindications	Documented hypersensitivity; cardiac dysrhythmias may occur when used with cisapride, terfenadine, or astemizole
Interactions	Antacids may reduce absorption of itraconazole; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; CYP450 3A4 inhibitor; may increase tacrolimus and cyclosporine plasma concentrations when high doses are used; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (lovastatin, simvastatin); coadministration with cisapride can cause cardiac rhythm abnormalities and death May increase digoxin levels; coadministration may increase plasma levels of midazolam or triazolam; phenytoin and rifampin may reduce itraconazole levels (phenytoin metabolism may be altered)
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Caution with liver disease; phlebitis, rash, GI disturbance, fever, headache, fatigue, hepatotoxicity, and bone marrow suppression

Drug Name	Amphotericin B (Amphocin, Fungizone)
Description	Produced by a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak, with subsequent fungal cell death.
Adult Dose	0.25-1.5 mg/kg/d IV infused over 2-3 h
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Antineoplastic agents may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity is increased with cyclosporine
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Monitor renal function, serum electrolytes such as magnesium and potassium, liver function, CBC count, and hemoglobin concentrations; resume therapy at lowest level (eg, 0.25 mg/kg) when therapy is interrupted for >7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion)

Drug Category: Corticosteroids

The use of corticosteroids is controversial, but they may be helpful in patients with severe caustic esophageal mucosal injury (second- or third-degree burns) to decrease inflammation, edema, fibrosis, and, possibly, help decrease the incidence of stricture formation.

Drug Name	Prednisone (Deltasone, Orasone)
Description	Beneficial for allergic esophagitis that is unresponsive to antireflux therapy. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Adult Dose	20-60 mg/d PO for 4 wk for allergic esophagitis
Pediatric Dose	1-2 mg/kg/d PO for 4 wk for allergic esophagitis
Contraindications	Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI ulceration
Interactions	Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use

Drug Name	Fluticasone propionate (Flovent)
Description	The HFA product is PO-inhaled corticosteroid and is available as 44, 110, and 220 mcg per actuation.
Adult Dose	880-1760 mcg/d (4-8 actuations/d of 220 mcg per actuation) via PO inhalation divided 2-4 times/d
Pediatric Dose	<4 years: Not established 440-880 mcg/d via PO inhalation divided 2-4 times/d
Contraindications	Documented hypersensitivity; bronchospasm, status asthmaticus, and other types of acute episodes of asthma
Interactions	Coadministration with CYP450 3A4 isoenzyme inhibitors (eg, amprenavir, atazanavir, darunavir, delavirdine, fosamprenavir, indinavir, ketoconazole, nelfinavir, ritonavir, tipranavir) decreases fluticasone elimination and increases plasma fluticasone levels, case reports of iatrogenic Cushingoid symptoms have been reported
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Avoid using higher than recommended doses; suppression of HPA function, suppression of linear growth (ie, reduction of growth velocity), reduced bone mineral density, hypercorticism (Cushing syndrome), hyperglycemia, or glucosuria may occur; these adverse effects (as well as intracranial hypertension) may occur with topical use and have been reported in pediatric patients; use with extreme caution in patients with respiratory tuberculosis, untreated systemic infections, or ocular herpes simplex; use with caution and monitor patients closely with hepatic dysfunction Eosinophilic conditions (eosinophilia, vasculitic rash, cardiac complications, worsening pulmonary symptoms, and/or neuropathy) may occur and are usually associated with withdrawal or decrease of PO corticosteroids after the initiation of fluticasone (PO inhalation); a causal relationship by fluticasone has not been established

Drug Category: Antiviral agents

These agents are used to treat infectious esophagitis. Patients with immunocompetency may not require specific antiviral therapy.

Drug Name	Foscarnet (Foscavir)
Description	Organic analogue of inorganic pyrophosphate that inhibits replication of HSV, including CMV. Selectively inhibits at pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular polymerases. Unlike ganciclovir, does not require activation by a kinase and is active in vitro.
Adult Dose	CMV: Induction: 90 mg/kg IV q12h for 14-21 d Maintenance: 90-120 mg/kg/d IV HSV resistant to acyclovir: 40 mg/kg IV bid/tid until infection resolves Adjust dose with renal impairment
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Avoid administration with potentially nephrotoxic drugs (eg, aminoglycosides, amphotericin B, IV pentamidine) may increase nephrotoxicity (do not administer unless potential benefits outweigh risks); coadministration with IV pentamidine may cause hypocalcemia
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	May cause decline in renal function; for correct dosing, obtain 24-h serum creatinine at baseline and continue to monitor (discontinue if serum creatinine <0.4 mL/min/kg); hydration may reduce nephrotoxicity Carefully monitor electrolytes (eg, calcium, magnesium); assess for electrolyte and mineral level abnormalities if mild perioral numbness, paresthesias symptoms, or seizures; granulocytopenia and anemia may occur (regularly monitor CBC count) Infuse foscarnet solutions into veins with adequate blood flow to avoid local irritation; to avoid toxicity do not administer by rapid or bolus IV injection

Drug Name	Ganciclovir (Cytovene)
Description	Acyclic nucleoside analogue of 2'deoxyguanasine. Phosphorylates first to monophosphate form by CMV-encoded protein kinase homologue, then to diphosphate and triphosphate forms by cellular kinases, allowing for a 100-fold greater concentration of ganciclovir in CMV-infected cells, possibly due to preferential phosphorylation of ganciclovir in virus-infected cells. Thought to inhibit CMV replication by competitive inhibition of viral DNA polymerases and by incorporating itself into viral DNA, causing termination of viral DNA elongation. Like acyclovir, ganciclovir is virostatic and only exerts its effect on replicating virus.
Adult Dose	Induction: 5 mg/kg IV q12h for 14-21 d Maintenance: 6 mg/kg IV 5 times/wk Role of PO ganciclovir maintenance at doses of 1 g tid is uncertain Adjust dose for renal impairment
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Concomitant administration with cytotoxic drugs such as dapsone, vinblastine, doxorubicin, pentamidine, flucytosine, vincristine, amphotericin B, trimethoprim/sulfamethoxazole combinations or other nucleoside analogs may result in additive toxicity in bone marrow, spermatogonia, and germinal layers of skin and GI mucosa (coadminister only if potential benefits outweigh risks); coadministration with imipenem-cilastatin may cause generalized seizures (use only if potential benefits outweigh risks); serum creatinine may increase following concurrent use of ganciclovir with either cyclosporine or amphotericin B; in presence of probenecid, ganciclovir renal clearance is reduced; bioavailability may increase when didanosine is administered either 2 h prior to or simultaneously with ganciclovir; bioavailability of ganciclovir may decrease in presence of zidovudine, while bioavailability of zidovudine is increased in presence of ganciclovir
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	May cause granulocytopenia, anemia, and thrombocytopenia; since PO is associated with higher rate of CMV retinitis progression, compared to IV formulation, use only when benefits outweigh risks (advanced HIV disease); half-life and plasma/serum concentrations may be increased as a result of reduced renal clearance; dosages >6 mg/kg IV may result in increased toxicity; rapid infusions may result in increased toxicity; initially, reconstituted IV solutions have a high pH (11); phlebitis or pain may occur at site of IV infusion despite further dilution in IV fluids; adequate hydration must accompany administration; photosensitization (photoallergy or phototoxicity) may occur

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Hospitalization is required if patients have significant bleeding, hemodynamic compromise, obstruction, perforation, or respiratory distress or are unable to feed themselves.
• Following a caustic ingestion, most children need to be admitted at least for observation to keep them on nothing by mouth (NPO) status, provide intravenous hydration until endoscopy, and monitor vital signs and respiratory distress.
• If no mucosal burns are detected, a patient may be discharged home after tolerating a normal diet. For patients with first-degree burns only, observe for at least 48-96 hours and until tolerating a normal diet. Patients with second- and third-degree burns require prolonged hospitalization.

Further Outpatient Care

• Close monitoring with the primary physician after caustic ingestion is important in the early detection and intervention of stricture formation. Among patients who develop strictures, 50% develop them in 1 month, 80% develop them in 2 months, and all patients develop them by 8 months.
• Late esophageal squamous carcinoma is rare.

In/Out Patient Meds

• H2-receptor antagonists and PPIs may be used for the ongoing management of reflux esophagitis. The duration of treatment depends on severity of esophagitis and response to therapy.
• Antibiotic, antiviral, or antifungal therapy may be indicated for infectious esophagitis.
• Corticosteroid use may be considered in patients with severe inflammation to possibly decrease the incidence of (but not prevent) stricture formation. The use of corticosteroids in allergic esophagitis may also be beneficial, but only after an unsuccessful trial with an adequate elimination diet.

Transfer

• Consider transferring patients with hemodynamic instability, severe bleeding, or respiratory distress to a facility with intensive care monitoring. Specialists experienced in pediatric endoscopy and surgery are also required.

Deterrence/Prevention

• Prevention of accidental ingestion is critical to prevent the potentially high associated morbidity and mortality. Corrosive agents should be locked up and kept out of reach of young children and maintained in their closed original containers.

Complications

• Bleeding or upper airway obstruction with hemodynamic compromise and perforation of the esophagus or stomach are the most significant immediate complications.
• Apnea, chronic respiratory illnesses including asthma, and failure to thrive are not rare complications of reflux esophagitis. Barrett esophagus or adenocarcinoma is rare.
• Abnormal motility, obstruction, perforation, strictures, fistula formation, secondary bacterial infections, and hemorrhage are complications of infectious esophagitis.
• The long-term complications of corrosive esophagitis include perforation, secondary bacterial infections (aspiration pneumonia, peritonitis, mediastinitis, sepsis), altered motility, and obstruction with stricture formation.

Prognosis

• The prognosis for esophagitis depends on the etiology and any underlying medical conditions.

Patient Education

• Reflux precautions, such as maintaining upright and prone positioning, following feeding guidelines, elevating the head of the bed, thickening formula, and eliminating tobacco smoke exposure, may help in gastroesophageal reflux (GER).
• When talking with patients, stress poisoning prevention measures and proper childproofing of the home.
• For excellent patient education resources, visit eMedicine's Heartburn/GERD/Reflux Center, Esophagus, Stomach, and Intestine Center, and Yeast and Fungal Infections Center. Also, see eMedicine's patient education articles Reflux Disease (GERD), Heartburn, and Candidiasis (Yeast Infection).

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Reflux esophagitis
• • The frequency of reflux esophagitis is somewhat debatable because irritability could be the presenting symptom in an infant with gastroesophageal reflux (GER). This condition may be difficult to differentiate from colic. Treatment often includes therapy for excessive gas or changing formulas, especially because parents may note pain and crying, pulling up of legs, and abdominal distention.
  • Although most cases of colic self-resolve and require only conservative measures, a minority of infants may benefit from reflux therapy, specifically antacids or H2 antagonists. This is true especially if a history of frequent regurgitation or other characteristic posturing is noted by the parent or physician.
  • Before beginning motility agents (eg, Reglan), be certain to document that upper GI anatomy is normal.
• Corrosive esophagitis
• • Be certain to have a low threshold for admitting a child to the hospital, even if just for observation, following any caustic ingestion.
  • Do not be falsely reassured by the quantity of the ingestion. Significant burns have followed minimal exposures, such as licking the bottle cap of a container that holds an alkali and eating from an unwashed spoon that had been used to measure liquid lye.
  • Esophageal burns do not always correlate with the presence of oral lesions or burns. In one study, almost 50% of patients with no oral lesions had esophageal burns, whereas only slightly more than 50% of patients with oral lesions also had esophageal lesions.

Special Concerns

• Infectious esophagitis
• • For the patient with cancer (immunocompromised), esophagitis may have multiple etiologies. Clinically, noninfectious and infectious causes may be difficult to distinguish. Consequently, antireflux, antifungal, antiviral, and antibiotic therapies are often instituted.
  • Chemotherapy, radiation therapy, emesis, acid reflux, and bacterial colonization may be contributors to mucosal injury, although fungal and viral causes are usually considered first.
  • In certain cases, esophagoscopy with biopsy may assist in the management of infectious esophagitis. The absolute neutrophil count (ANC) or presence of oropharyngeal colonization does not necessarily predict the cause of the esophagitis.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Gold BD. Gastroesophageal reflux disease: could intervention in childhood reduce the risk of later complications?. Am J Med. Sep 6 2004;117 Suppl 5A:23S-29S. [Medline].
2. Boccia G, Manguso F, Miele E et el. Maintenance therapy for erosive esophagitis in children after healing by Omeprazole: is it advisable?. Am J Gastroenterol. Jun 2007;102(6):1291-7. [Medline].
3. Spergel JM. Eosinophilic esophagitis in adults and children: evidence for a food allergy component in many patients. Curr Opin Allergy Clin Immunol. June 2007;7(3):274-8. [Medline].
4. Liacouras CA, Wenner WJ, Brown K, Ruchelli E. Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids. J Pediatr Gastroenterol Nutr. Apr 1998;26(4):380-5. [Medline].
5. Noel RJ, Rothenberg ME. Eosinophilic esophagitis. Curr Opin Pediatr. Dec 2005;17(6):690-4. [Medline].
6. Arnold L, Liacouras CA. Foreign bodies and caustic ingestions. In: Altschuler SM, Liacouras CA, eds. Clinical Pediatric Gastroenterology. Philadelphia, Pa: Churchill Livingstone; 1998:25-9.
7. Azimi PH, Willert J, Petru A. Severe esophagitis in a newborn infant. Pediatr Infect Dis J. Apr 1996;15(4):385. [Medline].
8. Berezin S