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. In the pediatric population, gastroesophageal reflux disease (GERD), infection, eosinophilic esophagitis, and corrosive ingestions account for most cases. (See Pathophysiology and Etiology.)
The clinical presentation depends on the etiology. Bleeding or upper airway obstruction with hemodynamic compromise and perforation of the esophagus or stomach are the most significant immediate complications. Over the long term, all types of esophagitis can be complicated by the development of strictures. (See Clinical Presentation.)
In infants, GER may be difficult to differentiate from colic. Treatment often includes therapy for excessive gas or changing of formulas, especially because parents may note pain and crying, pulling up of legs, and abdominal distention. (See Diagnosis.)
Few laboratory studies are helpful for the diagnosis of esophagitis. Esophagogastroduodenoscopy (EGD) is performed to allow more definitive visualization of the esophageal mucosa. Biopsy samples are always obtained to look for histologic confirmation. An upper gastrointestinal (GI) study should be considered in all patients with persistent emesis and in whom esophagitis is suspected. (See Workup.)
Specific treatment for esophagitis varies with the etiology. Symptomatic treatment may include antacids for mild reflux esophagitis or viral esophagitis in the immunocompetent host. Hospitalization is required if patients have significant bleeding, hemodynamic compromise, obstruction, perforation, or respiratory distress or are unable to feed themselves. (See Treatment and Management, as well as Medication.)
Go to Esophagitis for more complete information on this topic.
The pathophysiology of esophagitis can be categorized according to the etiologic type. These types include chemical esophagitis (ie, esophagitis resulting from gastroesophageal reflux [GER] or from the ingestion of corrosive substances such as certain medications or caustic cleaning products), eosinophilic esophagitis, infectious esophagitis, and radiation esophagitis.
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 affect esophageal clearance time and cause GER. Esophageal inflammation can further induce both mechanisms, creating a vicious circle.
Although decreased LES tone occurs in infantile GER and gastroesophageal reflux disease (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 LES relaxations (TLESRs). Factors that affect 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. The volume of the substance ingested does not necessarily correlate with the degree of tissue injury.
Household and garden materials are alkalis. Crystalline forms of these agents may cause linear burns, whereas liquid forms may lead to circular burns. Lesions vary from mild oral lesions to severe deep liquefaction necrosis with fat and protein digestion that affects all layers of the esophagus.
Acids are less frequently encountered and typically lead to a more superficial coagulation necrosis with eschar formation, which is usually limited to the mucosa and superficial muscle layers. Perforation is less likely to occur.
A pill trapped in the esophagus may cause ulceration and esophageal perforation 24-48 hours after ingestion (so-called pill esophagitis). Corrosive esophagitis induced by direct contact of the mucosa with a medication is seen mainly in patients who have abnormal esophageal motility. Drugs implicated include the following:
The exact pathophysiology of eosinophilic esophagitis is unknown. However, contact of the allergen with the esophageal or intestinal mucosa is thought to be the initiating event.[1, 2, 3]
In contrast to GERD, eosinophilic esophagitis involves the mucosa, the submucosa, and, possibly, the muscularis. Multiple food antigens (eg, milk, eggs, nuts, beef, wheat, fish, shellfish, corn, peanut, soy, chicken) can induce eosinophilic esophagitis; cow’s-milk protein is the most common precipitant.
In recent years, animal models of oral and respiratory eosinophil-associated gastrointestinal (GI) disorders have been developed. 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.[4, 5, 6] In addition, activated mast cells may act through prostaglandin D2 (PGD2) to attract eosinophils to the esophagus.[7] Animal models have shown a role for interleukin-18 (IL-18) overexpression in the induction of eosinophil active cytokines IL-5, IL-13, and intercellular adhesion molecule (ICAM)/vascular cell adhesion molecule (VCAM).[8] Lastly, tissue fibrosis is important in the long-term effects of active eosinophilic esophagitis. Tissue growth factor beta 1 (TGF-β1) is an important cytokine in tissue remodeling and fibrosis in the esophagus of patients with eosinophilic esophagitis. Mouse models suggest a role for resistinlike molecule (Relm)-α in epithelial cell hyperplasia and basal layer thickness in eosinophilic esophagitis.[7, 8, 9, 10]
Radiation Esophagitis
The histologic changes characteristic of radiation esophagitis 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.
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 clinical symptoms of GER (silent GERD). Mild GER is common, with symptoms peaking in infants younger than 6 months.[11, 12]
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 LES 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.
Exposure to Corrosive Substances
Corrosive (caustic) esophagitis 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.
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. The concentrations of base vary from liquid agents (10-25%) to industrial-strength agents (30-35%) to granular agents (50-95%). Alkalis have no taste; thus, a child may ingest a larger amount.
Acid ingestions account for approximately 20% of corrosive ingestions and include hydrochloric, sulfuric, oxalic, and nitric acids. 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. Acids tend to taste bitter, which usually limits the amount a child will ingest.
Although alkalis and acids are encountered most commonly, corrosive esophagitis can also be caused by detergents, disc or button batteries, and overheated food, milk, or formula.
Infection
Infectious esophagitis occurs most often in those who are immunocompromised (eg, as a result of malignancies, acquired immunodeficiency syndrome [AIDS], long-term steroid or immunosuppressive use, long-term proton pump inhibitor (PPI) use, diabetes, congenital immunodeficiencies). However, it can also occur in immunocompetent patients, especially those with preexisting esophageal damage due to chemical or physical causes.
Infectious esophagitis may be viral, fungal, protozoal, or bacterial. Overall, Candida organisms and herpes simplex virus (HSV) are the most commonly encountered agents.[13, 14, 15, 16, 17, 18]
HSV and cytomegalovirus (CMV) are the most common viral pathogens, while varicella-zoster virus and enterovirus are rarely encountered. HSV is the only viral pathogen also commonly found in the immunocompetent host.[14, 17, 18]
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). Go to Cytomegalovirus Esophagitis for more complete information on this topic.
Papillomavirus infection can develop in neonates born to mothers with the infection.
Candida albicans is the most common infective agent in immunocompromised or immunocompetent patients; it can be associated with inhaled steroid therapy and long-term PPI use.[13, 19, 20]
Rare pathogens may include Aspergillus species, Candida glabrata, and Cryptosporidium species in patients with AIDS. Megaesophagus may be a late complication of Chagas disease caused by Trypanosoma cruzi.
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.[21]
Radiation
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 higher 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.
Other 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.
Food allergies and eosinophilic esophagitis can cause esophagitis.[22]
Systemic diseases such as Crohn disease, chronic granulomatous disease, scleroderma, polyarteritis nodosa, graft versus host disease, Behçet disease, and glycogen-storage disease type 1 can cause esophagitis.
Chemotherapy-induced (doxorubicin) esophagitis and esophagitis secondary to epidermolysis bullosa are very rarely encountered in the pediatric population.
Gastroesophageal reflux is the most common esophageal disorder. 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.
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 (ie, GERD). Histologic 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 in the United States. Corrosive esophagitis from unintentional ingestions usually occur in children younger than 5 years, whereas nonaccidental ingestions in adolescents may suggest a suicide attempt.
According to more recent studies, the prevalence of eosinophilic esophagitis is 0.5-1 cases per 1000 persons, and the incidence is 10 cases per 10,000 cases per year. A boy-to-girl ratio of 3:1 is observed in eosinophilic esophagitis.[23, 24] A retrospective study of 558 children with eosinophilic esophagitis found that 22.8% of children with new diagnoses were younger than 5 years.[25]
For patient education information, see eMedicine’s Heartburn/GERD/Reflux Center, Esophagus, Stomach, and Intestine Center, and Yeast and Fungal Infections Center, as well as Reflux Disease (GERD), Heartburn, and Candidiasis (Yeast Infection).
Typically, emesis is effortless and is accompanied by frequent regurgitation in infants. Less commonly, however, 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 (Caustic) Esophagitis
Coughing, crying, and vomiting following ingestion may be initial symptoms of corrosive esophagitis. 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. 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.
Dysphagia and chest pain may occur after ingestion of pill forms of antibiotics (eg, doxycycline, clindamycin, tetracycline) or medications including ferrous sulphate, potassium chloride, quinidine, and anti-inflammatory agents.
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, herpes simplex virus (HSV) infection can present as fever, odynodysphagia, and acute-onset retrosternal pain. Oropharyngeal lesions are usually absent. Rarely, HSV, cytomegalovirus (CMV), and HIV can cause an asymptomatic esophagitis.
Eosinophilic Esophagitis
Eosinophilic esophagitis can occur at any age. In infants and young children, eosinophilic esophagitis presents with symptoms similar to those of GERD (including regurgitation, irritability, food refusal, and failure to thrive in infants) but fails to respond to aggressive antireflux therapy. Dysphagia, food impaction, and chest pain may 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.[26]
Radiation Esophagitis
Retrosternal chest pain and dysphagia occur. Strictures that present as dysphagia can occur up to 10 years after the treatment.
Assess vital signs. Patients 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. Oral candidiasis is not predictive of esophageal involvement, except in the immunocompromised child. Nevertheless, extensive esophagitis may be present without oral candidiasis in immunocompromised patients.[13]
Immunosuppressed patients with infectious esophagitis caused by herpes simplex (HSV) typically have vesicular lesions in the oropharynx. However, immunocompetent patients with esophagitis from HSV—the only viral pathogen that commonly causes esophagitis in immunocompetent hosts—usually have no oropharyngeal lesions.
Oral findings may also be absent in corrosive esophagitis, even in patients with more severe esophageal or gastric burns. In one study of patients with a history of caustic ingestion, 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.
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 central nervous system abnormalities can be observed.
Check stools for heme positivity in any child with possible esophagitis.
Bleeding or upper airway obstruction with hemodynamic compromise and perforation of the esophagus or stomach are the most significant immediate complications. Over the long term, all types of esophagitis can be complicated by the development of strictures. After radiation therapy, strictures can occur within 1-10 years after the initial treatment.
Apnea, chronic respiratory illnesses (including asthma), and failure to thrive are not rare complications of reflux esophagitis. 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.
The long-term complications of corrosive esophagitis include perforation, secondary bacterial infections (aspiration pneumonia, peritonitis, mediastinitis, sepsis), altered motility, and obstruction with stricture formation.
Complications of infectious esophagitis include abnormal motility, obstruction, ulceration, perforation, fistula formation, secondary bacterial infections, and hemorrhage.
Long-term complications of eosinophilic esophagitis include progressive fibrostenotic disease. This can, in turn, lead to food impactions and may necessitate the need for endoscopic dilatation, which puts patients at risk for perforation and mediastinitis.[24, 27]
In the patient who is immunocompromised (eg, secondary to cancer, immunodeficiencies, immunomodulating medications), 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. Although fungal and viral causes are usually considered first, chemotherapy, radiation therapy, emesis, acid reflux, and bacterial colonization may be contributors to mucosal injury.
In certain cases, esophagogastroduodenoscopy (EGD) 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.
Endoscopy is the only study used in the diagnosis of eosinophilic esophagitis. Standardized skin-prick testing and radioallergosorbent testing (RAST) are helpful only in immunoglobulin E (IgE)–mediated disorders, including urticaria and anaphylaxis. These tests, patch tests, and IgE levels or serum eosinophil counts are less useful in the diagnosis of eosinophilic esophagitis, though about two thirds of children with eosinophilic esophagitis have an increased peripheral eosinophilic count.
Infiltration of eosinophils in the esophageal epithelium is not pathognomonic for allergic esophagitis, as eosinophilic infiltration is also observed in reflux esophagitis. The severity of the eosinophilic infiltration, the presence of other signs and symptoms suggestive of an allergic etiology (eg, eczema), and the lack of response to aggressive antireflux therapy assist in making the correct diagnosis.
Go to Imaging in Infectious Esophagitis for more complete information on this topic.
Few laboratory studies are helpful for the diagnosis of esophagitis. A complete blood 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. 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 cytomegalovirus (CMV) infection.
EGD allows more definitive visualization of the esophageal mucosa. Biopsy samples at different levels of the esophagus should 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.
Characteristics of Corrosive 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 (including possible perforation). Circumferential ulcers and mucosal sloughing indicate greater severity.
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.
Characteristics of Infectious Esophagitis
With infectious esophagitis in immunocompromised patients, EGD with biopsy may be a valuable tool. Biopsy is the most sensitive and accurate method in diagnosing fungal esophagitis. With Candida esophagitis, the typical finding on endoscopy is a raised, white, adherent lesion with erythematous borders that cannot be washed out or brushed off. The lesions can be localized or can involve the entire esophagus.
In the immunosuppressed patient with herpes esophagitis, ulcers with a characteristic raised yellow border may be observed. The mucosa may also appear normal.
Fungal and viral infections in ulcers tend to occur in particular locations (see the image below).
View Image
Location of fungal and viral infections in ulcers.
Characteristics of Eosinophilic Esophagitis
In eosinophilic esophagitis, various patterns of morphological alterations may be seen on endoscopy, including furrowing of the mucosa, presence of white plaques, and mucosal rings. Typically, the gastric mucosa and duodenal mucosa are normal in appearance. Standard biopsy findings reveal severe eosinophilic infiltration; more than 15-20 eosinophils per high-magnification microscopic field are necessary for diagnosis.
An upper gastrointestinal (GI) study should be considered in all patients with persistent emesis and in whom esophagitis is suspected. 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. Additionally, a barium swallow test can be performed to demonstrate swallowing abnormalities. These studies are not helpful in diagnosing gastroesophageal reflux (GER).
In older compliant children, a double-contrast upper GI study may be performed and 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. In addition, lack of patient cooperation can lead to the performance of a suboptimal study.
Go to Imaging in Infectious Esophagitis for more complete information on this topic.
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.
CT scanning may be useful for visualizing paraesophageal abscesses that may extend into the esophagus. CT scanning is also useful in evaluating perforations.
Esophageal pH probe monitoring can be used to document the severity of acid GER on the day of the study. However, the presence of reflux does not necessarily indicate that esophagitis is present.[28]
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.
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.
Corrosive Esophagitis
Biopsy in corrosive 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.
Infectious Esophagitis
In candidal esophagitis, erythema, friability, and adherent white plaques that cover the mucosa are seen macroscopically. 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.[13]
In herpes simplex virus (HSV) esophagitis, shallow ulcers are the typical lesions. 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.
In CMV esophagitis, the viral cytopathic effect 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.
Allergic 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.
Specific treatment for esophagitis varies with the etiology. Symptomatic treatment may include antacids for mild reflux esophagitis or viral esophagitis in the immunocompetent host. Hospitalization is required if patients have significant bleeding, hemodynamic compromise, obstruction, perforation, or respiratory distress or are unable to feed themselves. In particular, be certain to have a low threshold for admitting a child to the hospital after any caustic ingestion.
For mild gastroesophageal reflux (GER), 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 (eg, eliminating tobacco smoke exposure) may be used.
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 reflux esophagitis is diagnosed because the effect of PPIs is more sustained and powerful.[29] A study of healthy children found that erosive esophagitis treated with adequate doses of PPIs for 3 months has a low relapse rate and does not require maintenance with PPIs or H2 -blocker therapy.[30, 31] Emerging research has shown associations of long-term use of acid blocking medications with adverse events in children including increased incidence of necrotizing enterocolitis in preterm infants and increased risk of infections. These infections include clostridium difficile colitis, candida esophagitis, and community-acquired pneumonia. Clearly, risks and benefits of these medications need to be considered alongside the decision to prescribe.[32, 33, 34]
In severe cases of reflux esophagitis that are unresponsive to aggressive medical management, consider surgical referral for Nissen fundoplication. With the availability of PPIs, this 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 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. Endotracheal intubation or tracheostomy may be required if severe upper airway edema is present.
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.
Most children who have ingested a caustic substance 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.
Broad-spectrum antibiotics may be used in severe cases to prevent secondary infection. The use of systemic corticosteroids is controversial, but they may be used in an attempt to decrease stricture formation. Surgical management of perforations and revisions may be required.
Infectious esophagitis requires the appropriate antiviral, antifungal, or antibiotic therapy based on the causative organism. For bacterial esophagitis, drainage of a paraesophageal abscess may be required.
The treatment of eosinophilic esophagitis is still widely debated.[4] Patch testing in combination with skin prick testing can help determine the causative food allergen (most commonly, milk, eggs, wheat, beef, soy, chicken).[35]
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 a higher success rate than testing-based elimination diet.[36, 37]
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 have demonstrated the effectiveness of swallowed topical corticosteroids delivered from a metered dose inhaler (fluticasone) or oral viscous budesonide in treating clinical symptoms and abnormal histology associated with eosinophilic esophagitis.[38, 39, 40] When using swallowed fluticasone, 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. When using oral viscous budesonide, the patient should not eat or drink for at least 30 minutes after taking the medication.
The course of treatment with topical corticosteroids should be 4-12 weeks. However, similar to the effect seen with oral steroid treatment, the disease generally recurs upon discontinuation of treatment.[41]
The use of a topical steroid for maintenance treatment has not been widely studied. The adverse effects with this form of treatment are thought to be significantly less than those with oral steroid therapy because of the much smaller dose and the rapid metabolism by the liver with first-pass effect. In adults, initial studies are not promising that response to swallowed topical steroids is long lasting.[42]
Oral cromolyn sodium and other mast cell stabilizers have not been shown to be effective. Studies have demonstrated benefits from leukotriene-receptor antagonists in adults, and studies of monoclonal antibodies directed against interleukin (IL)–5 are ongoing.[43, 44]
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.
Prevention of accidental ingestion is critical, because of 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.
Consult a gastroenterologist, especially if endoscopy or biopsy is required for definitive diagnosis.[45]
For corrosive ingestions, always notify a local Poison Control Center. Their staff can help 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.
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.
Depending on the etiology of the esophagitis, medications directed at treating gastroesophageal reflux (GER), treating or preventing infection, and decreasing inflammation may be required.
Clinical Context:
Famotidine competitively inhibits histamine at H2 receptors of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentrations.
These agents decrease the secretion and volume of gastric acid by competitively blocking histamine-2 (H2) receptors in gastric cells. Gastroesophageal reflux disease (GERD) may be initially treated with H2 -receptor antagonists; however, tachyphylaxis may quickly develop.
Clinical Context:
For patients with GER, metoclopramide may mildly increase resting pressure of the lower esophageal sphincter and increase rates of gastric emptying.
Clinical Context:
Erythromycin is a macrolide antibiotic that duplicates the action of motilin and is responsible for the migrating motor complex activity, by binding to and activating motilin receptors. Intravenous administration of this drug enhances the emptying rate of both liquids and solids. The effect can be seen with oral erythromycin. Substitution of the enteric-coated form may be tolerated better by the patient.
These agents augment cholinergic activity and improve motility in the gastrointestinal (GI) tract. However, no evidence-based efficacy in gastroesophageal reflux disease (GERD) is available.
Clinical Context:
Omeprazole inhibits gastric acid secretion. It decreases gastric acid secretion by inhibiting the parietal cell H+/K+ -ATPase pump. Give this agent with or before the first meal of the day.
Clinical Context:
Lansoprazole inhibits gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells. Give this agent with or before the first meal of the day.
These drugs inhibit the H+/K+/-ATPase pump in gastric parietal cells, thus inhibiting gastric acid secretion. Proton pump inhibitors (PPIs) should be used when reflux esophagitis is diagnosed because the effect of PPIs is more sustained and powerful.
Clinical Context:
Clotrimazole is a broad-spectrum synthetic antifungal agent that inhibits growth of yeasts by altering cell membrane permeability. Therapy is directed at the underlying condition, with the goal of minimizing symptoms and preventing complications.
Clinical Context:
Fluconazole has fungistatic activity. It is a synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P450 (CYP450) and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. It may be the preferred initial regimen for candidal esophagitis, with fewer adverse effects.
Clinical Context:
There is potential for development of resistance with ketoconazole. It has fungistatic activity. It is an imidazole broad-spectrum antifungal agent; it inhibits synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.
Clinical Context:
Itraconazole is a synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP450-dependent synthesis of ergosterol, a vital component of fungal cell membranes.
Clinical Context:
Amphotericin B is produced by a strain of Streptomyces nodosus; it can be fungistatic or fungicidal. It binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak, with subsequent fungal cell death.
Clinical Context:
Nonabsorbable polyene antifungal agent obtained from Streptomyces noursei. Binds to sterols in cell membrane of susceptible fungi, with resulting change in membrane permeability allowing leakage of intracellular components. Indicated for treatment of PO candidiasis.
Therapy is directed at the underlying condition, with the goal of minimizing symptoms and preventing complications.
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.
Clinical Context:
Prednisone is beneficial for allergic esophagitis that is unresponsive to antireflux therapy. It may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Clinical Context:
The HFA product is an oral-inhaled corticosteroid and is available as 44, 110, and 220 mcg per actuation. Several studies have demonstrated the effectiveness of swallowed topical corticosteroids delivered from a metered-dose inhaler in treating clinical symptoms and abnormal histology associated with eosinophilic esophagitis.
Clinical Context:
Studies are showing effectiveness of the swallowed topical steroid mixed with sucralose in treating abnormal histology associated with eosinophilic esophagitis. It is available in a 0.5 mg/2 mL dosage.
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, and fibrosis and, possibly, to help decrease the incidence of stricture formation.
Clinical Context:
Acyclovir is a prodrug activated by phosphorylation by virus-specific thymidine kinase that inhibits viral replication. Herpes virus thymidine kinase (TK), but not host cell TK, uses acyclovir as a purine nucleoside, converting it into acyclovir monophosphate, a nucleotide analogue. Guanylate kinase converts the monophosphate form into diphosphate and triphosphate analogues that inhibit viral DNA replication.
Acyclovir has affinity for viral thymidine kinase and, once phosphorylated, causes DNA chain termination when acted on by DNA polymerase. It inhibits activity of both herpes simplex virus (HSV)-1 and HSV-2. Patients experience less pain and faster resolution of cutaneous lesions when used within 48 hours from rash onset. It may prevent recurrent outbreaks. Early initiation of therapy is imperative. Acyclovir is used for HSV esophagitis.
Clinical Context:
Foscarnet is an organic analogue of inorganic pyrophosphate that inhibits replication of HSV, including cytomegalovirus (CMV). It selectively inhibits at pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular polymerases. Unlike ganciclovir, foscarnet does not require activation by a kinase and is active in vitro.
Clinical Context:
Ganciclovir is an acyclic nucleoside analogue of 2'deoxyguanasine. It 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.
Ganciclovir is 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 exerts its effect on replicating virus only.
Gayle H Diamond, MD, Assistant Professor of Pediatrics, Perelman School of Medicine, University of Pennsylvania; Attending Physician, Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia
Disclosure: Nothing to disclose.
Coauthor(s)
Maria Rebello Mascarenhas, MBBS, Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania; Section Chief of Nutrition, Division of Gastroenterology and Nutrition, Director, Nutrition Support Service, Medical Director, Integrative Health Program, Children's Hospital of Philadelphia
Disclosure: Received research grant from: Kabi Fesinius<br/>Faculty member, DIGEST and member DSMB for: Cystic Fibrosis Foundation.
Specialty Editors
Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Stefano Guandalini, MD, Founder and Medical Director, Celiac Disease Center, Chief, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Chicago Medical Center; Professor, Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Division of the Biological Sciences, The Pritzker School of Medicine
Disclosure: Nothing to disclose.
Chief Editor
Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine
Disclosure: Received honoraria from Prometheus Laboratories for speaking and teaching; Received honoraria from Abbott Nutritionals for speaking and teaching. for: Abbott Nutritional, Abbvie, speakers' bureau.
Acknowledgements
Andrew S Chu, MD Medical Director, CHOP Connection at Grand View Hospital, Children's Hospital of Philadelphia; Clinical Assistant Professor, Division of General Pediatrics, Department of Pediatrics, University of Pennsylvania School of Medicine
Andrew S Chu, MD is a member of the following medical societies: American Academy of Pediatrics and Society of Hospital Medicine
Disclosure: Nothing to disclose.
Vera De Matos, MD Fellow in Pediatric Gastroenterology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine
Vera De Matos is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.
Jayant Deodhar, MD Associate Professor in Pediatrics, BJ Medical College, India; Honorary Consultant, Departments of Pediatrics and Neonatology, King Edward Memorial Hospital, India
Disclosure: Nothing to disclose.
Jessica Wen, MD Clinical Fellow, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia
Jessica Wen, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Study of Liver Diseases, American Medical Association, and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition
Esophageal reflux. Walker WA, Goulet O, Kleinman RE, et al, eds. Pediatric Gastrointestinal Disease. 4th ed. Lewiston, NY: BC Decker; 2004. 400-24.
Ruchelli ED, Liacouras CA. Esophageal disorders in childhood. Russo P, Ruchelli E, Piccoli DA, eds. Pathology of Pediatric Gastrointestinal and Liver Disease. New York, NY: Springer-Verlag; 2004. 37-46.
Committee on Infectious Diseases. Candidiasis. 2006 Red Book: Report of the Committee on Infectious Diseases. American Academy of Pediatrics; 2006. 242-6.
Committee on Infectious Diseases. Cytomegalovirus infection. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. American Academy of Pediatrics; 2006. 273-7.
Committee on Infectious Diseases. Antifungal drugs for systemic fungal infection. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. American Academy of Pediatrics; 2006. 774-6.
Committee on Infectious Diseases. Antiviral drugs for non-human immunodeficiency virus infections. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. American Academy of Pediatrics; 2006. 785-9.
Committee on Infectious Diseases. Herpes simplex. In: 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. American Academy of Pediatrics; 2006. 361-71.
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