cleveland clinic journal of medicine 2010 hong 51 9

7/29/2019 Cleveland Clinic Journal of Medicine 2010 HONG 51 9

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Sandra Hong, MdRespiratory Institute,Cleveland Clinic

Food allergy and eosinophilicesophagitis: Learning what to avoid

ABSTRACT

Food allergies have increased in prevalence signicantly

in the past decade and so, apparently, has eosino-philic esophagitis. Although the cause o eosinophilicesophagitis is unknown, allergic responses includingood allergies have been implicated. This article reviewsboth conditions, ocusing on how to detect and managethem.

KEY POINTS

Food allergies can be classied as mediated by immuno-globulin E (IgE-mediated), non-IgE-mediated, or mixed.Their clinical presentation can vary rom lie-threateninganaphylaxis in IgE-mediated reactions to chronic, de-layed symptoms as seen in eosinophilic esophagitis (amixed reaction).

The diagnosis o an IgE-mediated ood allergy is madeby taking a complete history and perorming directedtestingskin-prick testing or measurement o ood-specic IgE levels in the serum, or both.

Despite promising developments, ood allergies continue

to be treated primarily by telling patients to avoid aller-gens and to initiate therapy i ingestion occurs.

Because most patients with eosinophilic esophagitishave a strong history o atopic disease and respond toallergen-ree diets, a complete evaluation by a specialistin allergy and immunology is recommended.

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 77 NUMBER 1 JANUARY 2010 51

More children a v auts sm tb ag t vaus s ts ays

ta t past. As appaty t s s

a k t, sp spagts.T as ts ass s t a.Ts at s ts t wat w kwabut t masms ags a -sp spagts, w t ags tm,a w t tat tm.

FOOD ALLERGIES ARE COmmOn,AnD mORE pREvALEnt thAn EvER

F agsabma mmu spsst pts1at a stmat 6% t8% yug a 3% t 4% auts t Ut Stats,2,3 a t pvaappas t b sg vp uts.Stus US a Bts attat paut agy as ub t past -a.4

Ay a pvk a at, but ya w s aut mst t sgatag ats: ws mk, sy, wat, ggs,pauts, t uts, s, a ss.

T pva agy s gatst

t st w yas (Table 1

).

2

Agst mk, gg, a pauts a m mm , w ags t t uts, s, ass a m mm auts.2,5

Appxmaty 80% ags t mk,gg, wat, a sy sv by t tm t pa-tt as ay as.6 Fw asssv wt t ut ags (ap-pxmaty 9%) paut agy (20%),7,8a ags t s a ss t vp psst aut.

A amy sty a atp sas su

as astma, ag ts, zma, a-

REVIEW

doi:10.3949/ccjm.77a.09018

nicola M. Vogel, MdAllergy Associates o New Hampshire,Portsmouth

EDUCATIONAL OBJECTIVE: Readers will be amiliar with the mechanisms, diagnosis, and current treatmento ood allergiesCREDIT

CME


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52 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 77 NUMBER 1 JANUARY 2010

FOOD ALLERGY AND EOSINOPHILIC ESOPHAGITIS

gy s a sk at vpg a a-gy.3 Csg tat t at paut agyas ub v t past 10 yas,vmta ats may as pay a .3

how we olerae oodsor ecoe allergic o eT gut, t agst musa ga tby, s xps t ag quatts gpts ay. Mst pt s bk w bystma a a gstv zyms t ss-atg ppts s bu by stymmugbu A (IgA), w pvts tm bg absb. Fut, t ptas g t gut t aw ag m-us t pass asy, avg tgt tauajuts a bg v wt muus.

F ts ass, ss ta 2% t p-t s absb a ag m.9T as ags a m pvat s mst ky tat ava mmatu gut ba, w IgA vs, ag gast pH, a w ptyt -zym vs.

W tay pts ss t gutba, t mmu systm may suppss-s t ag sps. Rguaty T s,t s, a a mmu spsspay ta s t vpmt t-a. Sva typs guaty T s, suas T1 s (w st tuk 10),TH3 s (w st tasmg gwt

at bta), CD4+CD25+ guaty T s,

gamma-ta T s, a CD8+ suppsss a a tbut t suppssg agspss.10 Dt s as p uta by stmuatg CD4+ T s t s-

t tasmg gwt at bta, was t t put tuk 10 aata tasmg gwt at bta.11

Facors a coriue o ood allergyMay ats may tbut t wt aps bms tat t sstz t asp pt. The dose o antigen. Ta a v-p at t g w ss atgs,but by t masms. The antigen structure.Sub atgs a

ss sstzg ta patuat atgs.12,13 Processing o oods. Dy-ast pautsa m ag ta aw b pa-uts, paty baus ty a ss sub.13

The route o initial exposure. Sst-zat t pts a u tytug t gut t sk. Atatvy, ta u ty va t spaty tat.Sk xpsu may b spay sstzg wt atp matts.14,15

The gut fora. W m a as agm- vmt, ty a t vpma ta.16 Ty a as m kyt bm sstz ty a tat wtatbts ty ak t-k ptstat gz bata ppysaas.17Futm, uma stus suggst tat p-bts pmt ta, spay p-vtg atp matts, atug t stu-s av a ftg suts.1821 The gastric pH. Mu a uma stu-s va tat ata mats ast sk agy.22,23

Genetic susceptibility. A wt a sb-g w s ag t pauts s appxmat-y 10 tms m ky t b ag t pa-uts ta pt by t at t gappuat. Atug sk-g gas b t, a stuy tws swa paut agy 64.3% ta tws vs 6.8% ata tws.24

tree yes o iue resoses o oodAbut 20% a pp at t t b-aus s abut avs ats t

s.3

Ts avs ats u mta-

Most common

ood allergens:

cows milk,

soy, wheat,

eggs, peanuts,

tree nuts, fsh,

shellfsh

tAbLE 1

Prevalence o ood allergiesin the United States

FOOD ChILDREn ADULtS

milk 2.5% 0.3%

Egg 1.3% 0.2%

peau 0.8% 0.6%

tree us 0.2% 0.5%

Fis 0.1% 0.4%

Sellfs 0.1% 2.0%

Oerall 6% 3.7%

FROM SAMpSON HA. UpDAtE ON FOOD ALLERgY. J ALLERgY CLIN

IMMUNOL 2004; 113:805819; WItH pERMISSION FROM ELSEVIER,WWW.SCIENCEDIRECt.COM/SCIENCE/JOURNAL/00916749


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b ss (g, ats ta), a -at t a pamag mpt su asa a tx tamat a (g,bata psg), psyga -

ats (g, avs), a umtmmug spss t a (g, a-gy) (Table 2).2,3,25

Immug ats t s a b -v t t atgs: mat by m-mugbu E (IgE), -IgE-mat, amx. T, ts ss a pstas a aut, pttay -tatg a-t as a sas su as s-p gasttpaty. IgE-mediated reactions a mmat y-psstvty spss. I mst patts, a

IgE-mat masm a b m bya pstv sk tst a tst -spIgE t sum. I ts at, t tm agy s t a IgE-mat at t a, uss tws at. Non-IgE-mediated reactions av a -ay st a symptms. Cm-my, ty a t t gasttst-a tat; xamps a -pt-utts, ptts, a ptts aa sas.3,26,27 Hwv, t sasssu as tat matts, matts pt-ms, a -u pumay ms-ss (H sym) a as s-IgE-mat ags. Mixed-reaction disorders a au t sp gasttpats,, sp ptts, spgasttts, a sp spagts.28T patpysgy ts sass s p-y ust. May patts av v ag sstvts t t v-mta ags, bt, but wt tssstvts av a ausa ts s-s s t a.

Atp matts, at mpatsas pss, may b assat wt mx-at agy, as appxmaty 35% yug wt mat t sv atpmatts av ags.29

Diagosis o IgE-ediaed ood allergies A thorough history and physical exami-nation a ky t agsg a IgE-mat agy.

T sty su u ptta u-

pt s, t quatty at, t tmg t st symptms, a at atssu as xs, a tak, ma-t us. Symptms a IgE-mat a-t a gay ap st but may bay up t a w us, w -IgE m-at symptms may pst sva us tays at. Food challenge. A ub-b, pab-t a ag s t g sta-

a t agss ags. (T

tAbLE 2

Classifcation o adverse reactions to oods

Iolerace (oallergeic)Lactose intoleranceGalactosemiaAlcohol

paracologicCaeineTyramine in aged cheesesAlcohol

toxicBacterial ood poisoning

Food allergyMediated by immunoglobulin E (IgE) (acute onset)Urticaria, angioedemaRhinitis, asthmaAnaphylaxisFood-associated exercise-induced anaphylaxisPollen-ood allergy syndrome(oral allergy syndrome)

Non-IgE-mediated (delayed-onset, chronic symptoms)Celiac disease, dermatitis herpetiormisContact dermatitisDietary protein enterocolitisDietary protein proctitis and proctocolitisHeiner syndrome (ood-induced pulmonary hemosiderosis)

Mixed (IgE-mediated and non-IgE-mediated)Eosinophilic gastroenteropathies(including eosinophilic esophagitis)

Atopic dermatitis

Syos siilar o ood allergyAuriculotemporal syndromeScombroid sh poisoning

ADAptED FROM SICHERER SH, SAMpSON HA. FOOD ALLERgY.

J ALLERgY CLIN IMMUNOL 2006; 117:S470S475;

WItH pERMISSION FROM ELSEVIER, WWW.SCIENCEDIRECt.COM/SCIENCE/JOURNAL/00916749.

HONG AND VOGEL


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t b tst s t apsus.) Hwv, ts tst pss sgatsks, a t agst mts a mpata sg. Skin-prick tests wt mmay ava-ab xtats a a ap a sstv mt sg agy t sva s.

Ngatv sk-pk tsts av a st-mat gatv ptv vau m ta95% a a t xu IgE-mat ags.

A pstv tst ats t ps IgEagast a sp ag a suggsts aa agy, atug t spty t tst s y abut 50%, makg a ps-tv sut ut t tpt. Atug tsz t sk-tst sps s t s-say at wt t ptta svty a at, a sps ag ta 3 mm sat a gat k a a-tvty. A pstv tst s mst pu -

mg t agss IgE-mat a-gy w mb wt a a sty -u symptms.

T pts mmay bas x-tats mst uts a vgtabs a tab; t, sk tstg wt s utsa vgtabs may b at.30

Immunoassays. Raagsbt tsts(RASTs) a fust zym mmu-assays a us t tty -sp IgEatbs t sum. T mmayavaab tsts t us aatvty, but t

tm RAST s st mmy us.

Immuassays a gay ss sstva m sty ta sk-pk tsts, at suts a t mmaty avaab,uk ts sk-pk tstg. Hwv,

ts vt tsts a t at by at-stam us a a usu patts wtsv matg ts sv aa-pyaxs, wm sk-pk tstg wut b apppat.

As wt t sps sz t sk-pk tst, t g t tat a-sp IgE, t g t k a a at.29 Ts vaus -sp IgE av b stabsabv w t k tat t pattw xp a ag at s gat

ta 95% (Table 3).3,29,31Hwv, uk a gatv sk-pk

tst, a uttab sum -sp IgEv as a w gatv ptv vau, aa uttab v may b assat wtsymptms a ag at 10% t25% patts.29 T, susptsa ag at but -sp IgEa b tt t sum, mg tabs a a agy must b wta sk-pk tst wt a pysa-supvsa ag, bt.

maagig ood allergyy aoidig e allergeF ags a maag by stty avg ags a by takg mats suas s-jtab pp aapyatsymptms.

Patts a agvs must b uatabut ag abs, avg g-skstuats su as atg at buts a tstauats wt g sk ss-tam-

at, wag a ma-at bat, -gzg a maagg ay symptms aag at, a ag mgysvs ty a avg a ag at.S Jauay 2006, t US F a DugAmstat as qu maua-tus t st mm ags abs (ws mk, sy, wat, gg, paut,t uts, s, a ss), a t abgmust us smp, asy ust tms, suas mk sta wy. Hwv, t s stput t a a gts st t

ab.

IgE-mediated

reactions are

usually

immediate;

non-IgE and

mixed reactions

are delayed

or chronic

tAbLE 3

Predictive values o specifc immunoglobulin Eor selected ood allergens

ALLERGEn ImmUnOGLObULIn E (kIU/L) a

mEAn AGE 5 YEARS,50% REACt

mEAn AGE 5 YEARS,95% REACt

AGE 2 YEARS,95% REACt

Egg 2 7 2

milk 2 15 5

peau 2 (convincing history)5 (unconvincing history)

14

a Measured by Pharmacia CAP system fuorescent enzyme immunoassay

FROM SICHERER SH, SAMpSON HA. FOOD ALLERgY.J ALLERgY CLIN IMMUNOL 2006; 117:S470S475,

WItH pERMISSION FROM ELSEVIER; WWW.SCIENCEDIRECt.COM/SCIENCE/JOURNAL/00916749.


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Exerieal reaes or ood allergies Humanized monoclonal anti-IgE antibod-ies su as tazumab (as kw as TNX-901) a mazumab (Xa) av b -

vp, but t us agy as bmt. I a stuy patts wt pautagy, jts tazumab as tts sstvty t pauts mstpatts, but 25% t patts t avay mpvmt.32 A stuy mazumab patts wt paut agy was stpp atavs ats vp ug a pa-ut ags.33

Oral immunotherapy. Rt stussuggst t may b pssb t u ata patts wt IgE-mat

agy. Pt stus av sw tatqut, asg ss a-gs (gg, mk, a paut) may as tts at w symptms u.3436Tug ts stus suggst tat a m-mutapy may ptt sm pattsagast a at ty atay gsta ty a ag t, sm pattsu t a t ga ss baus a-g symptms w pvk.

At ts ay stag, ts statgs must bs vstgata, a m am-z, pab-t stus a .Fut stus w as b t asssswt a mmutapy us yst-tm sstzat ( w as tag s t b gst ay t pvtats) susta ta ( was t atg pt a b gstwtut symptms spt ps abst-).

thE ROLE OF FOOD ALLERGY

In EOSInOphILIC ESOphAGItISEsp spagts as b gzwt asg quy bt a auts v t past sva yas. Symp-tms a u uty g, au ttv, vmtg, pgast st pa, ys-paga, a mpat.

Dagst ta sp spag-ts a37:

Ca symptms spaga ysu-t

At ast 15 sps p g-pw

at ast spaga bpsyspm

N sps t a pt-pump b-t g ss (up t 2 mg/kg/ay)

1 t 2 mts, ma suts pHpb mtg t spagus (tas ts t s tat pattswt gastspaga fux sas aas av ag umbs sps t spagusm ta 100 p g-pw 38)Exus t auss.Tug t aus sp spa-

gts s t mpty ust, atpy asb stgy mpat as a at. Mta 50% patts wt sp

spagts as av a atp t (g,atp matts, ag ts, astma), asw as pstv suts sk-pk tstg masumt atg-sp IgE tsum.3941 As, s mst patts mpvwt t tay stt mtats, sstzat appas t pay a -sab .

As wt atp ts su as ast-ma, atp matts, ag ts, a agy, sp spagts asb k wt mmu spss vv-g p T 2 (TH2). Auts a - wt sp spagts av bu t av vat sp utsa tta IgE vs ppa b.37I t spagus, patts av vatvs t TH2 ytks t s atp patts (g, tuks 4, 5, a13) a mast s.42,43 I m, spspagts a b u by ag xp-su a vxpss TH2 ytks.

44,45Expss tax-3, a ptt spmattatat, was t t b g wt sp spagts ta ts.46

O tst, sm patts wt s-p spagts say t symptms vaywt t sass, atg wt sasaags spaga sp vs.47,48

Sudies likig eosioilic esoagiisad ood allergy i cildreA k btw agy a spspagts was tay suggst w pa-

tts w a sp spagts m-

Skin-prick plus

patch testing

may be more

eective than

skin-prick

testing alone

in identiying

potential ood

triggers

HONG AND VOGEL


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It may be

possible to

induce oral

tolerance

in patients with

IgE-mediated

ood allergy

pv w put a mta ag- t (Table 4).39,4953 Mst t stuskg agy a sp spag-ts av b .

Ky t a49 pt tat 10 wt symptmat gastspaga fuxa sp spagts a a pata mpt sut symptms a -mta t.

Makwtz t a50 u tat symptms fux sas a spspagts mpv 49 51 a mta t, a t umb s-ps t sta spagus as sg-aty.

Lauas t a39 pt sma gs a 10-ya xp. O 132 wa sp spagts, 75 mpvwt tay stt bas suts sk-pk a pat tstg. T 57 pattsw t sp a 115 ts wstat a mta t. O t 164 pa-tts w mp wt t mta t,160 a sgat mpvmt symptmsa a sgat as t umb sps t spagus. Ivua sw tu appxmaty vy 5 ays,a spaggastuspy wt bp-

ss was pm 4 t 8 wks at t ast

was tu t t t.I a tsptv stuy, Kagawaa t a51

pt tat 60 wt spspagts w tat wt t a -mta t a sx- mat t (mk, sy, wat, gg, paut, sa). Ttw gups sw sma a a st-g mpvmts.

Ctvy, ts stus pat pa-tts mpy tat agy s a sgatat t patgss spspagts.

Sudies i adulsFw stus t k btw agya sp spagts av b

auts.I a pmay stuy, 18 auts wt sx- mat t. Symptms m-pv 17 (94%), a stg gsmpv 14 (78%).52

O t t a, sx aut pattswt sp spagts, Sm t a53u tat y a mpvmt symp-tms at matg wat a y m tt, a a sgat ags tumb sps t spagus.

I a 37-ya- ma wt sp

spagts, symptms mpv at m-

tAbLE 4

Response to dietary manipulationin patients with eosinophilic esophagitis

StUDY n AGE DIEt SYmptOmSImpROvED ORRESOLvED (%)

DECREASE InEOSInOphILS (%)

Kelly et al (1995)49 10 8 mo12.5 yr Elemental 100 100

Markowitz et al (2003)50 51 8.3 3.1 yr Elemental 96 96

Liacouras et al (2005)39 247 10.4 5.2 yr8.1 4.3 yr

RestrictedElemental

57 a

975797

Kagalwalla et al (2006)51 60 6.3 yr (mean) Six-ood eliminationbElemental

97100

7488

Gonsalves et al (2008)52 18 1970 yr Six-ood elimination 94 78

Simon et al (2006)53 6 25.8 9.0 yr No wheat or rye 17 0

a O 132 patients, 75 improved with dietary restriction; 57 patients who did not respond were included in the 172 patients started

on an elemental diet; 160 o the 164 patients compliant with the elemental diet had signicant improvement o symptoms and a

signicant decrease in the number o eosinophils in the esophagus.b Six-ood elimination: milk, soy, wheat, egg, peanut, and seaood


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atg gg m s t.54

Yamazak t a55 masu xpss tuk 5 a tuk 13 15 autpatts wt sp spagts. F

a aags tat u mk, sy,ust mt, agw, a Aspergillus usgaty m tuk 5 put ts patts ta atp ts, sug-gstg tat bt s a aags mayav a t patgss spspagts auts.

how o ideiy oeial ood riggerso eosioilic esoagiisTug mta ts av b assatwt a as symptms a spaga

spa, mta muas a xp-sv a upaatab a ps a sk u-tta pvat. Ityg sp ags t mat m t t patts wt sp spagts may bss xpsv a m sab ta a vymt mta t.

Hwv, ptta tggs av ba t ty sp spagts. At ssus pt t mm vt agy tstg,37 wg t a ak pstv gatv ptv vaus -sp IgE v tstg spspagts. Futm, t abs IgEs t mat a as a ptta tgg,s -IgE masms may pay a . Skin-prick testing s t utyvaat agst mts. Sva stu-s av us sk-pk tstg s patts wt sp spagts. Its stus, appxmaty tw-ts pa-tts a pstv tst ats t at ast , mst t t mm a-

gs su as ws mk, gg, sy, wat, apaut, but as t y, b, a ba.37 Ia t at,56 81% aut patts wtsp spagts a m a-gs t by sk-pk tstg, a50% t patts tst pstv m ags.

Atopy patch testing. T mbat sk-pk tstg a atpy pat tstgmay b m tv ta sk-pk tst-g a tyg ptta tg-

gs. Atpy pat tstg as b us tagss -IgE -mat (ay)mmu spss, w T s may paya sgat .

Atpy pat tstg s sma t pattstg tat matts. It vvspag a sma quatty t ska vauatg a a ay atat a st tm.

I tw stus,50,57 146 wt bp-sy-pv sp spagts a smat m t t t bass ps-

tv sk-pk tsts a atpy pat tsts.Appxmaty 77% t a sg-at ut spaga sps bpsy spms (m 20 p g-pw t 1.1). T s mst mmy m-pat by sk-pk tstg w ws mk,gg, wat, paut, ss, pas, b, s,y, a tmat; ts t by atpypat tstg w ws mk, gg, wat,, b, mk, sy, y, k, ats, aptat. T mbat bt typs tstg a a gatv ptv vau 88% t 100% a s xpt mk, wt pstv ptv vau was gat ta74% t mst mm s ausg -sp spagts.58

Tug atpy pat tstg sws smususs tyg s tat may t-IgE-mat ats, uty tststs a t vaat a av b vauat- y a sma umb stus. Cuty, staaz tstg matas, mts appat, tptat suts xst,

a stus av u a t ppu-at t vaat atpy pat tstg. Mstus a t vaat atpy pat tst-g as a ab agst t b t a bmm as a mpt ut ag-st vauat patts wt spspagts.

More studies

are needed

to validate

atopy patch

testing in

patients with

eosinophilic

esophagitis

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ADDRESS: Sandra Hong, MD, Respiratory Institute, ST10,Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195;e-mail [email protected].

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