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CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2005;3:1198–1206

RIGINAL ARTICLES

osinophilic Esophagitis: A 10-Year Experience in 381 Children

HRIS A. LIACOURAS,*,‡ JONATHAN M. SPERGEL,‡,§ EDUARDO RUCHELLI,‡,� RITU VERMA,*,‡

ARIA MASCARENHAS,*,‡ EDISIO SEMEAO,*,‡ JONATHAN FLICK,*,‡ JANICE KELLY,*,‡

ERRY BROWN–WHITEHORN,‡,§ PETAR MAMULA,*,‡ and JONATHAN E. MARKOWITZ*,‡

Division of Gastroenterology and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia; §Division of Allergy and Immunology,niversity of Pennsylvania School of Medicine, Philadelphia; �Division of Anatomic Pathology, Clinical Laboratory, University of Pennsylvania

chool of Medicine, Philadelphia; and ‡University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

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ackground & Aims: Eosinophilic esophagitis (EoE) is aisorder characterized by a severe, isolated eosinophilic

nfiltration of the esophagus unresponsive to aggressivecid blockade but responsive to the removal of dietaryntigens. We present information relating to our 10-yearxperience in children diagnosed with EoE. Methods: Weonducted a retrospective study between January 1,994, and January 1, 2004, to evaluate all patientsiagnosed with EoE. Clinical symptoms, demographicata, endoscopic findings, and the results of variousreatment regimens were collected and evaluated.esults: A total of 381 patients (66% male, age 9.1 �.1 years) were diagnosed with EoE: 312 presented withymptoms of gastroesophageal reflux; 69 presentedith dysphagia. Endoscopically, 68% of patients had aisually abnormal esophagus; 32% had a normal-ap-earing esophagus despite a severe histologic esopha-eal eosinophilia. The average number of esophagealosinophils (per 400� high power field) proximally andistally were 23.3 � 10.5 and 38.7 � 13.3, respectively.orticosteroids significantly improved clinical symptomsnd esophageal histology; however, upon their with-rawal, the symptoms and esophageal eosinophilia re-urred. Dietary restriction or complete dietary elimina-ion using an amino acid–based formula significantlymproved both the clinical symptoms and esophagealistology in 75 and 172 patients, respectively.onclusions: Medications such as corticosteroids areffective; however, upon withdrawal, EoE recurs. Theemoval of dietary antigens significantly improved clini-al symptoms and esophageal histology in 98% ofatients.

ver the past 10 years, eosinophilic esophagitis (EoE)has become one of the most discussed diseases

mong pediatric gastroenterologists and allergists in thenited States. EoE is a disease of children and adults

haracterized by a severe, isolated eosinophilic infiltra-ion of the esophagus, unresponsive to acid blockade but

nstead responsive to the removal of dietary food aller-

ens. There is historical evidence that EoE has existed forore than 25 years.Before 1995, patients with symptoms of gastroesoph-

geal reflux or dysphagia who additionally had histologicvidence of esophageal eosinophils were almost alwaysiagnosed as having gastroesophageal reflux diseaseGERD).1 The majority of these patients were misdiag-osed and improperly treated. Since 1995, pediatric gas-roenterologists have recognized that patients presentingith symptoms of GERD and a large number of esoph-

geal eosinophils most commonly have an alternate dis-rder, EoE.2 Additionally, EoE has become increasinglyecognized within the adult population over the past fewears.3

This retrospective study reflects our 10-year experi-nce with regard to the diagnosis, treatment, and man-gement of all patients identified with EoE at The Chil-ren’s Hospital of Philadelphia since 1994.

Patients and MethodsEosinophilic Esophagitis

All patients diagnosed with eosinophilic esoph-gitis from January 1, 1994, to January 1, 2004, in theivision of Gastroenterology and Nutrition at The Chil-ren’s Hospital of Philadelphia, were identified and theirnformation reviewed.

The diagnosis of EoE was based on clinical criteria thatncluded chronic symptoms of reflux or dysphagia thatersisted despite a 2-month trial of a proton pumpnhibitor (1 mg/kg; maximum dose, 40 mg/day). Also

Abbreviations used in this paper: EGD, esophagogastroduodenos-opy; EoE, eosinophilic esophagitis; GER, gastroesophageal reflux;ERD, gastroesophageal reflux disease; HPF, high-power field; Ig,

mmunoglobulin; NG, nasogastric.© 2005 by the American Gastroenterological Association

1542-3565/05/$30.00

PII: 10.1053/S1542-3565(05)00885-2

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equired was a lack of demonstrable anatomic abnormal-ty on barium upper GI series (with the exception oftricture, which can be attributable to EoE), and theemonstration of eosinophilic infiltration of esophagealiopsy specimens obtained by esophagogastroduodenos-opy (EGD). At least 2 distal esophageal biopsies (2–4m from the Z-line) and 2 mid-esophageal biopsies7–10 cm from the Z-line) as well as antral and duodenaliopsies were obtained. Whenever eosinophils wereresent, the number of eosinophils in the most denselynvolved 400� microscopic high-power field (HPF)Olympus BX-50 microscope, Olympus, Melville, NY;.23 mm2) were counted. Patients who were identified asaving 20 or more eosinophils in any single 400� HPFlong with normal antral and duodenal biopsies metriteria for EoE.

Age, sex, gastrointestinal and other allergic symp-oms, and family history of allergic disorders were col-ected. Questions relating to allergy included a history ofronchospasm, allergic rhinitis, eczema, and food allergy.uantitative serum immunoglobulin (Ig) E levels and

otal serum eosinophil counts were reviewed when avail-ble. The year of presentation and the age of the childere collected. The study and data collection were ap-roved by The Children’s Hospital of Philadelphia’snternal Review Board.

Pharmacologic Treatment of EosinophilicEsophagitis

We reviewed the effects of several medications onoth clinical symptoms and esophageal histology. Thehoice of pharmacologic therapy was left to the discretionf the treating gastroenterologist. For each medication,ollow-up data were recorded, including symptoms andistology. Treatment success was considered significantf both the esophageal eosinophilia and the patient’slinical symptoms improved.

Dietary Treatment of EosinophilicEsophagitis

Dietary therapy was defined as either “dietaryestriction” with the exclusion of select foods based onllergy testing, or “complete dietary elimination” of alloods with patients being placed strictly on an aminocid–based hypoallergenic formula. All patients withoE were evaluated by a pediatric allergist in an attempto determine specific food allergies. Skin prick and patchesting were performed as previously reported.4 If foodllergies were revealed by either form of allergy testing,hese foods were excluded from the diet, the patient waslaced on “dietary restriction,” and the response was

ased on symptomatic and histologic improvement. c

If no foods were identified by allergy testing, a “com-lete dietary elimination” was begun. A hypoallergenicormula (Neocate, Neocate EO28, Neocate 1�, SHSnternational, Liverpool, UK; or Elecare, RossPediatrics,bbott Laboratories, Abbott Park, IL) was started andatients were monitored for improvement. Completeietary elimination was used in the event patients didot respond to the elimination of certain foods identifiedy allergy testing. If a formula was used, patients werevaluated by a dietitian or nutritionist to estimate nec-ssary calories. For these patients, white grapes and theirure juice or apples and their juice were allowed, assum-ng allergy testing did not reveal allergy to these foods.

henever possible, patients were instructed to drink theormula; however, if they were unable to drink theolution, a nasogastric (NG) tube was inserted so that theormula could be properly administered. In infants,oung children, and some adolescents, the NG tube wasommonly changed every 3–4 weeks; however, mostdolescents inserted the NG tube daily. Repeat EGDith biopsy was performed 4–5 weeks after initiating

he diet.If the esophageal histology normalized, a slow rein-

roduction of foods was begun. Foods were added one attime, every 4–5 days, and continued to be added unless

ymptoms recurred. If symptoms recurred, the impli-ated food was removed. If the patient remained asymp-omatic, a repeat EGD was performed approximately–6 weeks after the fifth new food was added to deter-ine if esophageal eosinophilia recurred. The order of

ood reintroduction was based on consultation from thellergist and previously reported studies.4 Patients in-luded in this group were followed for a minimum of 9onths and a list of allergic foods was compiled.

Statistical AnalysisData were analyzed using the Wilcoxon sign-rank

est and the Mann–Whitney U test for continuous vari-bles, and the �2 test for categorical variables. Statisticalomparisons (mean � standard deviation) were madesing the statistical software package Stata 7.0 (Stata,ollege Station, TX).

ResultsEosinophilic Esophagitis

Three hundred eighty-one patients (66% male)ere diagnosed with EoE. Patients were categorized intoseparate subgroups: a gastroesophageal reflux (GER)

ubgroup and a dysphagia subgroup. The GER subgroup

onsisted of 312 patients (82%) who initially presented

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1200 LIACOURAS ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 3, No. 12

ith symptoms of gastroesophageal reflux; the dysphagiaubgroup contained 69 patients (18%) who presentedrimarily with dysphagia. In the GER subgroup, 21870%) presented with either vomiting and/or regurgita-ion while 190 (61%) had epigastric pain, heartburn,nd/or water brash. Of the 69 patients with dysphagia,4 had evidence of esophageal narrowing by bariumontrast study; however, only 1 patient had a definitivesophageal stricture, as defined by upper endoscopy thatequired esophageal dilatation.

Of the total number of EoE subjects, 202 (53%) wereound to have evidence of another allergic condition suchs asthma, allergic rhinitis, and/or eczema. In addition,64 (43%) patients had a first-degree family memberho had either asthma or specific food allergies; 27 (7%)atients had a parent who either had esophageal stric-ures or histologic evidence of esophageal eosinophils; 19iblings (5%) also were found to have EoE.

Inspection of the esophagus by EGD revealed a normalppearance in 32% of patients, esophageal rings or “tra-healization” in 12%, esophageal furrowing in 41%, andultiple esophageal white plaques in 15% of EoE pa-

ients (Figures 1–4). Greater than 20 eosinophils perPF were present in both the mid and distal esophagus

n 306 of 312 GER patients and in all 69 patients of theysphagia subgroup. Of the remaining 6 patients in theER group, while eosinophils were present in both theid and distal esophagus, 5 had �20 eosinophils per

igure 1. Endoscopic image from a patient with EoE with visuallyormal-appearing esophageal mucosa.

PF only in the distal esophagus and 1 had �20 eosin- a

phils only in the mid esophagus. The number of esoph-geal esoinophils per HPF was significantly greater in theistal esophagus in both subgroups (P � .05). In addi-ion, the dysphagia subgroup had significantly moresophageal eosinophils and was significantly older in agehen compared with the GER subgroup (Table 1). Fig-re 5 depicts the number of new EoE patients diagnosedy year beginning in January 1994 and ending in De-ember 2003. Figure 6 illustrates the age of each EoEatient at the time of the initial diagnosis.

igure 2. Endoscopic image from a patient with EoE with multiplesophageal rings considered to be “trachealization” or a “feline”sophagus.

igure 3. Endoscopic image from a patient with EoE with linear esoph-

geal “furrows” giving a “railroad track” appearance to the esophagus.

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Pharmacologic Therapy

Thirty-nine EoE patients (28 males), mean age.2 � 2.9 years, were treated with oral methylpred-isolone (1.5 mg/kg/day; maximum dose, 40 mg/day).efore treatment, patients had an average of 33.5 � 9.5osinophils per HPF; after 4 weeks of treatment, theumber of esophageal eosinophils was significantly re-uced to 0.9 � 0.6. Six months after discontinuingherapy, the number of esophageal eosinophils returnedo near pretreatment levels of 28.7 � 5.8. Clinically, 27f 29 patients with GER symptoms became completelysymptomatic when placed on oral steroids; the other 2atients showed an improvement in symptoms duringhe third and fourth weeks of therapy. Upon discontinu-ng therapy, clinical symptoms recurred or worsened in4 of the 29 patients within 6 months. With regard toatients who had dysphagia, 10 out of 10 patients be-ame clinically asymptomatic. Upon removal of the med-

igure 4. Endoscopic image from a patient with EoE with multiple,mall, pinpoint, white esophageal lesions representing eosinophilicbscess formation.

able 1. Density and Location of Eosinophils in Patients With

Mid esophagus(eos per HPF)

ER subgroup (312) 19.7 � 10.5ysphagia subgroup (69) 39.7 � 10.0value �.05

OTE. Table represents the average age and the average number ofm above LES) esophagus in patients with EoE. Two subgroups of paastroesophageal reflux (GER subgroup) and those who presented primlder and had higher mucosal eosinophil counts.

os, eosinophils.

cation, dysphagia recurred in all 10 patients within 4onths.Seventeen patients (13 males), mean age 8.7 � 2.6

ears, were treated with swallowed aerosolized flutica-one propionate from a metered dose inhaler at a dose of10 mcg twice daily for children �8 years of age and20 mcg twice daily for children �8 years of age.atients were instructed to spray the metered dose in theack of their mouth and swallow the medication. Beforereatment, patients had an average of 27.7 � 5.0 eosin-phils per HPF. After 4 weeks of treatment, the numberf esophageal eosinophils was significantly reduced to1.2 � 2.7; however, 6 months after discontinuingherapy, the number of esophageal eosinophils returnedo near pretreatment levels of 23.5 � 2.9. Clinically, 7 of4 patients with GER symptoms became completelysymptomatic; 4 patients demonstrated an improvementn symptoms during the third and fourth weeks of ther-py; and 3 patients showed no improvement in symp-oms. Upon discontinuing therapy, clinical symptomsecurred or worsened in all but 1 patient within 6onths. With regard to the 3 patients who had dyspha-

ia, 2 showed moderate clinical improvement, whereas

igure 5. Graph representing the number of new EoE patients diag-osed from January 1 to December 31 each year for the years 1994o 2003.

inophilic Esophagitis

Distal esophagus(eos per HPF) Age (y)

34.9 � 10.2 8.1 � 2.956.2 � 18.7 12.8 � 2.2

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hageal eosinophils in the distal (2–4 cm above LES) and mid (6–10s were identified: patents who presented primarily with symptoms ofwith dysphagia (Dysphagia subgroup). Note that the latter group was

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he other patient had no change in symptoms. Uponemoval of the medication, dysphagia recurred in bothatients within 3 months. Two patients receiving fluti-asone redeveloped reflux symptoms while being treatednd were found to have esophageal candidiasis. Theyere successfully treated with antifungal agents.Fourteen patients (10 males), mean age 7.8 � 3.1

ears, were treated with cromolyn sodium (100 mg fourimes daily). Before treatment, patients had an average of8.3 � 6.4 eosinophils per HPF; after 4 weeks of treat-ent, the number of esophageal eosinophils remained

nchanged at 25.4 � 4.3 eosinophils per HPF. Thesendings persisted 6 months after discontinuing therapy27.6 � 4.4 eosinophils per HPF). Clinically, not aingle patient demonstrated any improvement in symp-oms. No significant complications occurred.

These results represent initial therapy for each patient.comparison of these outcomes is depicted in Figure 7.

ll patients whose symptoms relapsed were again foundo have EoE on biopsy, considered to be treatment fail-res, and were candidates for dietary therapy.

Dietary Therapy

Two hundred forty-seven patients underwent ahange in their dietary regimen. Sixty-three had previ-usly failed pharmacologic therapy. One hundred thirty-wo patients attempted “dietary restriction” using theesults of skin prick and patch testing.4 Based on signif-

igure 6. Age of presentation of new patients when first diagnosedith EoE.

cant improvement of their esophageal eosinophilia, 75 o

atients (51 males; average age, 10.4 � 5.2) were suc-essfully treated with removal of specific foods. For theseatients, 6.1 � 2.7 allergic foods were discovered by aombination of pin prick and patch testing. Of the 75atients who eliminated the responsible foods, 54 pre-ented with GER symptoms while 21 presented withysphagia. In both groups, clinical symptoms and his-ologic resolution significantly improved (Figure 8). Fol-ow-up was conducted for at least 9 months and duringhat time, no reintroduction of the implicated foods wasttempted. For those 57 patients who either did notespond clinically or continued to have severe EoE byiopsy, complete dietary elimination using an aminocid–based formula was initiated.

Complete dietary elimination using an amino acid–ased formula (including at least a 9-month follow-uperiod) was performed in 172 patients (112 males) whoad a mean age of 8.1 � 4.3 years; 137 were fed by anG tube while 35 (20%) ingested the formula orally. Of

he total number of patients, 8 (5%) patients were non-

igure 7. Graph representing the effect of oral corticosteroids, swal-owed topical corticosteroids, and a mast cell stabilizer on the maxi-al number of esophageal eosinophils (per most involved 400� HPF)

n individual patients before initiating therapy, 4–5 weeks after begin-ing therapy, and 6 months after discontinuing therapy.

igure 8. Graph representing the effect of using a specific foodlimination diet based on skin prick and patch testing on the number

f esophageal eosinophils, GERD symptoms, and dysphagia.

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ompliant with the dietary regimen including 5 of the5 (14%) who attempted to orally ingest the formula andof 137 (2%) patients who received the formula by anG tube. Of the remaining 164 patients, 160 (97%)

emonstrated a significant improvement in clinicalymptoms and esophageal eosinophilia (Figures 9, 10,nd 11). In the dysphagia subgroup, barium studiesemonstrated normalization of the esophagus in 21 of 22atients who initially had evidence of esophageal nar-owing and who complied with the diet. Four of 164atients (2.4%) had no significant change in esophagealosinophils or clinical symptoms despite adhering to theiet.Although both dietary treatments showed significant

mprovement, Table 2 depicts the residual number ofsophageal eosinophils after treatment was lower in themino acid–based diet group compared with the selec-

igure 9. Graph representing the effect of using a strict amino acid–ased formula on the number of esophageal eosinophils, GER symp-oms, and dysphagia.

igure 10. Esophageal histology of a patient with severe EoE beforehe initiation of dietary therapy with an amino acid–based formula.ote the large number of eosinophils and the hypertrophied basal cell

ayer. H&E stain, original magnification 400�. m

ive food elimination group (1.1 � 0.6 vs 5.3 � 2.7; P.05). Following the normalization of the esophageal

iopsies of patients who were on a complete dietarylimination, individual foods were reintroduced. A newood was reintroduced approximately every 5 days. Pa-ients were subsequently followed for clinical symptomsnd the recurrence of esophageal eosinophilia. EGD withiopsy was performed in all cases approximately 4–8eeks after the reintroduction of the last food. Theseatients were followed for an average of 14 � 3.6onths. Table 3 reveals the foods most commonly found

s allergens in patients with EoE. An average of 5.6 �.9 allergic foods per patient were directly linked to theevelopment of esophageal eosinophilia. However, alloods have yet to be tested in this group. At present, only

patients have been able to reintroduce previouslynown allergenic foods (31, 38, and 46 months afternitial food removal) without recurrence of esophagitis.

There was no significant weight loss, electrolyte ab-ormality, or alteration of growth parameters (height,eight, head circumference) in patients who underwentietary therapy. Only 5 patients were considered to haveailure to thrive (weight � 5th percentile based on theppropriate growth curve), and all 5 patients had aignificant increase in weight after initiating the com-lete elimination diet.To date, of the 247 patients who underwent dietary

herapy, there have been no significant nutritional, proce-ural, or mechanical complications. Of the 160 patientsequiring a complete elimination diet, 26 (16%) continueo require the amino acid formula as the mainstay of theiriet because of the severity of their food allergy. In contrast,

igure 11. Esophageal histology of the same patient 1 month afterreatment with an amino acid–based formula, water, white grapes,nd a natural white grape juice. Note complete resolution of esoph-geal eosinophils and a normal basal cell layer. H&E stain, original

agnification 200�.

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34 were able to discontinue the amino acid–based formularom 3 to 18 months (average time 5.24 � 2.73 months)fter its initiation. For these patients, only 3 have beeneported to ingest a food previously known to cause EoE,5, 46, and 63 months after the time of their initialsophageal histologic resolution.

DiscussionOver the past 5 years, EoE has become a world-

ide phenomenon with reports originating from thenited States, Canada, Europe, Australia, and Southmerica.5–8 Pediatric gastroenterologists now recognize

hat children who present either with chronic symptomsf GERD or dysphagia (frequent or intermittent) unre-ponsive to aggressive acid blockade may have EoE. Noelt al reported on a specific population of children diag-osed with EoE between the years 2000 and 2003, andalculated a disease incidence of 1 in 10,000 per year andprevalence of 4 in 10,000.9

As our data indicate, the number of new cases seen atur institution has doubled in the last 4 years. Severalactors may contribute to this finding. First, because ofncreased awareness, EoE is now more easily recognizedy both gastroenterologists and pathologists. Presently,t is strongly suggested that mucosal biopsies should beollected in all patients even when the mucosal tissueppears normal.10 In addition, when biopsies were ob-ained in the past, pathologists may have assumed thathe presence of esophageal eosinophils represented gas-roesophageal reflux and simply reported “reflux esoph-gitis.” On further investigation, a significant number ofatients with unresponsive GERD, who were previously

able 2. Effect of Dietary Therapy on EsophagealEosinophils and Clinical Symptoms in PatientsWith EoE

Pre-diet Post-diet P value

mino Acid formula (160)Eosinophils per 40� HPF 38.7 � 10.3 1.1 � 0.6 �.001GER symptoms (134) 134 3 �.01Dysphagia symptoms (30) 30 1 �.01

ood elimination diet (75)Eosinophils per 40� HPF 47.5 � 12.1 5.3 � 2.7 �.001GER symptoms (54) 54 2 �.01Dysphagia symptoms (21) 21 1 �.01

OTE. Table depicts the average number of esophageal eosinophilsnd the number of patients complaining of clinical symptoms beforend 1 month after the initiation of dietary therapy. Two groups ofatients are represented: patients who were treated with a strictmino acid–based formula; and patients in whom foods were elimi-ated based on the use of a combination of skin prick and skin patchesting.

hought to have reflux esophagitis, had large numbers of P

sophageal eosinophils. Thus, pathologists are now be-inning to describe the esophageal inflammation by re-orting the number of eosinophils observed in the bi-psy. This enables the clinician to consider EoE in theifferential diagnosis of patients who present with refluxymptoms or dysphagia.

Clinically, EoE presents in a variety of ways. As ourtudies indicate, young children and school-aged childrenommonly present with symptoms indistinguishable fromhildren who have gastroesophageal reflux.11,12 In contrast,lder children typically present with either heartburn orymptoms of dysphagia.8,13,14 More specifically, many ad-lescents often come to the attention after they experiencen esophageal food impaction.15 Although there have beeno reports in children regarding the long-term effects ofntreated EoE, we believe the apparent change in symp-omatology from toddlers to adolescents to adults representsull thickness tissue involvement of eosinophils as previ-usly suggested by Fox.16 Thus, left untreated, the long-erm effects of patients with EoE may lead to esophagealtricture formation.

While the diagnosis of EoE rests upon the use of upperndoscopy, obtaining biopsies of the esophagus is crucial.s our study indicates, one third of children have visuallyormal esophageal tissue despite having a severe histologicvidence of EoE. In addition, while the visual findings ofultiple, small, white, raised specks on the esophagealucosa, trachealization or ring-like formation of the esoph-

gus, or the presence of esophageal linear furrows or “rail-oad tracks” are very suggestive of EoE, without a biopsy,hese findings could represent esophageal candidiasis, con-ective tissue disease, or gastroesophageal reflux, respective-y.11,17–24 It has been hypothesized that the lack of reportsf EoE in adults reflects the tendency for adult gastroenter-

able 3. Proportion of Patients With EoE Who Are Allergic toFoods

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logists not to biopsy the esophageal mucosa and to rely onts visual appearance.

The location of esophageal eosinophils in patients withoE has also been debated. It is well known that patientsith esophagitis secondary to GERD typically have evi-ence of histologic disease in the distal esophagus.25 How-ver, over the past 5 years, investigators have reported thatatients with EoE have a large number of eosinophilshroughout the esophagus.26 Our study confirms these find-ngs. Whereas EoE patients who present primarily withysphagia have significantly more esophageal eosinophilshan those who present with symptoms of GER, bothroups show a significantly greater number of eosinophils inhe distal esophagus as compared to the mid esophagus. Inither location, more than 20 eosinophils per single HPF,uring therapy with a proton pump inhibitor, is required tostablish the diagnosis of EoE.

The treatment for EoE remains controversial. Severalherapeutic options exist including: (1) the dietary elim-nation of the offending antigen(s); (2) the use of sys-emic corticosteroids; (3) the use of a topical steroidreparation (fluticasone); and (4) the use of a leukotrieneeceptor antagonist.34,35 There are advantages and dis-dvantages to each of the treatments rendered.

Several reports have shown the efficacy of using sys-emic corticosteroids.27,28 Our study confirms those re-ults. However, when the medication is discontinued,he symptoms and esophageal eosinophilia return.20 Weypically reserve systemic steroid use to patients whoresent with severe clinical symptoms such as dysphagia,sophageal strictures, or severe symptoms of GER caus-ng an alteration in lifestyle. We generally do not advo-ate the long-term use of systemic steroids.

As an alternative, several investigators have reporteduccess using swallowed aerosolized fluticasone.29,30 Inur study, we demonstrated both clinical and histologi-al improvement with this type of medication. Althoughhis treatment improves patient symptoms, many reportsemonstrate incomplete resolution of esophageal dis-ase.30,31 A recent report suggests almost completesophageal healing with higher dose therapy.29 However,ecent reports have documented a 20%–40% occurrencef oral and esophageal candidiasis with the chronic use oferosolized fluticasone.32,33

Dietary therapy is the mainstay of our treatment. Re-oval of the offending food agents results in symptom

esolution, histologic normalization of the esophagus, ando need for the chronic use of medication for patients withoE. Thus, aggressive dietary restriction should be at-empted whenever possible. An amino acid–based formula

s frequently required, which often necessitates the use of a

asogastric tube in children. This type of feeding may beeeded for several months. Additionally, because both clin-cal symptoms and noninvasive allergy testing do not al-ays accurately depict the severity of the esophageal eosin-philia, serial EGDs must be performed in all patients toocument the effects of diet therapy. Our protocol uses aepeat endoscopy approximately 4–8 weeks after the rein-roduction of the last new food. In our study, more than5% of patients with EoE put their disease into remissiony either avoiding the identified allergenic foods or byeing maintained on a hypoallergenic diet.

Because pharmacologic therapy for EoE must be usedhronically, has significant side effects, and does not alwaysesult in complete healing of the esophagus, we believe thatggressive dietary intervention should be attempted in allatients with EoE. The patients treated with dietary ther-py improved both clinically and histologically. Our studyemonstrated no significant side effects to the prolonged usen elemental formula either administered orally or by NGube. In most cases, within 6 months, we were able toetermine the specific foods causing the allergy. Unfortu-ately, unlike infants who present with a protocolitis frommilk or soy allergy and in whom the allergy generally

esolves when the offending antigen is removed from theiet, to date, only 3 of 247 patients with EoE demonstratedresolution in their food allergy despite long-term with-

rawal of the allergens.Alterations of the immune system and its relationship to

llergic disorders continue to be thought of as the mainathophysiologic link to the diagnosis of EoE.36–41 Al-hough some suggest that aeroallergens contribute to EoE,ood allergy has been well documented to causeoE.4,20,42–45 As evidenced by our data, the strict use of anlemental diet is very effective. When used, both the clin-cal symptoms and esophageal histology completely resolve.n contrast, while the management of a food eliminationiet based on the use of skin prick and patch tests providesignificant improvement in esophageal histology and isasier to administer, it often does not provide completedentification of all possible allergic foods. Our study re-ealed a difference between the number of residual esoph-geal eosinophils after a food elimination diet comparedith patients given a strict elemental (amino acid–based)iet. In the rare cases when the esophageal biopsy remainsbnormal despite the use of an amino acid–based formula,oncompliance, environmental allergens, and eosinophilicastroenteritis should be strongly considered.

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Address requests for reprints to: Chris A. Liacouras, MD, Associaterofessor of Pediatrics, University of Pennsylvania School of Medicine,ivision of Gastroenterology and Nutrition, The Children’s Hospital ofhiladelphia, 34th and Civic Center Boulevard, Philadelphia, Pennsyl-

ania 19104. e-mail: liacouras@email.chop.edu; fax: (215) 590-3606.