Iasi,aprilie,2012 ALERGIA ALIMENTARA LA COPIL

(APLV SI INTOLERANTE MULTIPLE)

Prof. Dr. EVELINA MORARU U.M.F. Gr. T. Popa Iasi

Patrel Berceanu

Pe un perete de manastire, Mai caut lumina palmei calde a mamei... Mi-as lipi sufletul de zid s-o mai simt, salvatoare.... Pe o geana de lumina mai sper, Sa vina intaia zi a nelinistii Mai vreau chipul sa ti-l ador in taina Dar taina s-a mutat parasita-n alt cer

Nu ma mai pot intoarce, cum nu mai pot lua Nicio dimineata de la capat.... Mereu pierd geana lunii ce pleaca si pierd invazia soarelui de frica infernului zgomotos pe care lumea noua-l revarsa, peste toate inimile, peste toate soaptele, catre toate tainele.... Totul se grabeste spre uitare, Ceasuri trec, ceasuri vin, ceasuri tac:tic-tac....

CONCEPT VECHI IN ACTUALITATE

1906 pediatrul austriac Clemens von Pirquet (1874-1929) alergie antitoxina D. ser cal alllous (gr.) = altul, diferit + ergon = activitate Alergia alimentara reprezinta modalitatea de raspuns clinic manifestat imediat, intermediar si tardiv dupa ingestie.

Bolile alergice reprezinta a cincea cauza de boli cronice la toate varstele A 3-a cauza de boli cronice la copii sub 18 ani, afectand pana la 1 din 3 copii

Statisticile

indica faptul ca pana in 2015 jumatate din populatia europeana va suferi de o alergie .

ALERGIA ALIMENTARA DE CAND? PANA CAND?

In conceptul marsului alergic alergia alimentara este un

reper initial in disfunctia imuna sistemica.

Predictia asupra duratei variaza intre a fi considerata un

incident trecator sau o manifestare perena.

Confruntarea cu alergia alimentara implicata in boli grave

sustine ideea ca in unele cazuri boala evolueaza si dupa varsta de copil mic (toata viata).

Navarro J, Schmitz, J. Gastroenterologie pediatrique, Flammarion Ed., 2000, 325-354.

MULTI ANI INAINTE

Hipocrate relateaza prima reactie la alimente acum mai bine de 2000 de ani 1919 Sdr. Goodpasture 1921 Prausnitz si Kustner au demonstrat transferul pasiv al sensibilizarii 1950 Loveless a realizat trialuri clinice in alergia alimentara 1960 Sdr. Heiner Anii 1960 Goldman a introdus dietele de eliminare si reintroducere 1975 Kuitunen - APLV

EPIDEMIOLOGIE

Datele epidemiologice sunt controversate Global 1/3 din populaie are o problem de alergie alimentar, nord-americani 10% Diagnostic precizat in 1-2%. La copii variaz n limite mai largi - 0,3 - 7,5% - 0-3 luni - 8% (Franta) - 3 luni-1 an - 2% - 1-2 ani - 2,5% IPLV - prevalen stabil de 2,5% in ultimii 20 de ani si chiar la cei alaptati (2,5%).

Bock, 1992; Crowe, Perdue 1992, Bell 1993, Young 1994

STUDII AMERICANE SI EUROPENE PREVALENTA - ADULTI 1,3 - 2%; - COPII 0,3 - 7,5% PREVALENTA ALERGIEI ALIMENTARE LA COPIL - N PRIMELE 3 LUNI VIATA = 5-8% (FRANTA) - IPLV 2% (STUDIU SCANDINAV) - IPLV SUB VARSTA 2 ANI = 2,5% IN RELATIE CU ORGANUL TINTA - TRACTUL G-I 50-80% - CUTANAT 20-40% - APARAT RESPIRATOR 10-25% - SISTEMIC RAR DIMENSIUNEA PSIHOSOCIAL CONFERA IMPORTANTA

SUBIECTULUI NAVARO 2000, Chandra 1997, Kardinaal 1991

Prevalenta alergiei alimentare

Perceptie de catre public: 20-25% Alergie confirmata (incarcare orala):

Adulti 1-2% Sugari/copii 6-8% (~ milion nasteri)

Alergie la conservanti/coloranti (rara) Alergeni specifici

Dependenti de pattern-ul alimentar Lapte (sugari) 2,5% Arahide/nuci populatia generala 1,1%

REACTII LA ALIMENTE
ADEVARATE ALERGII ALIMENTARE

INTOLERANTE ALIMENTARE

TOXICITATE ALIMENTARA

AVERSIUNE PENTRU ALIMENTE

Reactii alergice la alimente

Reactii toxice Reactii non-toxice

Intoleranta alimentara

Alergie alimentara

IgE / Th2 mediata

Non-IgE mediata

REACII ADVERSE LA ALIMENTE

REACII DE HIPERSENSIBILITATE - ALERGIA ALIMENTAR -

REACII DE INTOLERAN

I. ALERGIA ALIMENTAR (IMUN)

REACTIE IMUNOLOGICA TIP I, III, IV (IgE, CIC, MEDIATA LIMFOCITAR)

RASPUNS IMUN ANORMAL DUP INGESTIA UNUI ALIMENT

II. INTOLERANA ALIMENTAR (NEIMUN)

NEIMUNOLOGIC (CEL MAI FRECVENT) - DEFICIT ENZIMATIC (INTOLERANTA LACTOZ) - DIMINUARE SUPRAFA DE ABSORBIE

- SUBSTANE FARMACOLOGICE ALIMENTARE

- INTOXICAIE, TOXINE - CONTAMINANI CHIMICI, MICROBIENI - REACII IDIOSINCRAZICE - BOLI METABOLICE (FENILCETONURIA)

IMUNOLOGIC (GLUTEN)

REACII ADVERSE LA ALIMENTE

REACII TOXICE

REACII NETOXICE

IMUNE (ALERGICE) SPECIFICE

NEIMUNE (INTOLERAN) NESPECIFICE

MEDIATE IgE

NON IgE
ENZIMATICE FARMACOLOGICE

NEDEFINITE

PSIHOLOGICE

NEUROVEGETATIVE

IMUNOLOGICE? FIZICO-CHIMICE

ou

Lapte arahide

Nuci

8 alergeni
= 90% alergii alimentare Grau Diverse crustacee

Peste

Soia

1,3% >85 toleranti dupa varsta de 3 ani

0,5-0,7% Toleranta clinica la 10-20% din pacienti, cu reactie minora cutanata

2,5% >75%-toleranti dupa varsta de 3 ani

Alergia alimentara
Cei mai obisnuiti alergeni alimentari: Copii

Lapte de vaca, grau, soia, ou, alune Responsabile de peste 90% din reactiile alergice

Adulti

Alune, arahide, peste, crustacee, oua, fructe si legume

Fiziopatologie
Alergenii alimentari glicoproteine hidrosolubile rezistente la incalzire si proteoliza GM 10-70 kDa absorbtie facila prin mucoase Purificate

Alune: Ara h1, Ara h2, Ara h3 Albus ou: Gal d1, Gal d2, Gal d3 Soia: Gly m1 Peste: Gad c1; crab: Pen a1

FIZIOPATOLOGIE
N ALERGIA ALIMENTAR SE CONFRUNTA:

1. ALERGENII ALIMENTARI 2. BARIERA GASTROINTESTINAL 3. SISTEMUL IMUNITAR

Pablo Picasso, Two women running on the beach, 1922

 proteinele laptelui de vac - cazeina - proteine solubile: -lactoglobulina, -lactoglobulina, serum albumina bovin, imunoglobuline bovine proteine din ou - ovomucoid - ovalbumina - lizozim proteine din soia - fraciuni globulinice 2s, 7s, 11s - inhibitori ai tripsinei - lectina

proteine de pete i produi marini - Gad Ch (morun) Met e1, Pen ai Pan 5l (crevete) - Hom Al (langust); Cha/z1 (crab) - fructe de mare proteine din arahide/alune - Ara h1, Ara h2, Ara h3 altele: - vac, porc - fasole - nuci, semine, cacao, ciocolat - citrice, mr, cpuni - gru i alte cereale (atenie, fina de gru!) - condimente, drojdie

Proteine alergenice alimentare

Lapte de vaca Galbenus de ou Alune Soia boabe Peste Mazare verde Orez Rosii

= = = = = = = =

-lactoglobulina,etc Lipoproteina Alune I + altele Glicinina + altele Alergenul M Albumina Gluteina / globuline Glicoproteine

Au fost demonstrate alergii ncruciate (mixte).

Incidenta alergiilor mixte

Sindromul latex-fructe

30-50% din indivizii alergici la latex prezinta hipersensibilitate asociata la unele alimente, in special fructe: avocado, banane, arahide, kiwi, rosii, cartofi. Nu este clar care este alergia primara: la latex sau hipersensibilitatea la fructe???

Factori genetici

Factori de mediu

In aparitia manifestarilor alergice -factori genetici si de mediu

BARIERA INTESTINALA IMUN

MALT (esut limfoid asociat mucoaselor) suprafa de 400 m2

esut limfoid intestinal (GALT)

IgAs

celule efectoare (macrofage, mastocite, plasmocite, limfocite Th, Ts)

Mecanisme imune non inflamatorii mediate de IgA dimeric

Johansen FE, Brandtzaeg P. Transcriptional regulation of the mucosal IgA system. Trends Immunol. 2004, 25:150-57

Corps peint, Picasso

REACTII IMUNE IMPLICATE IN APLV

PREDISPOZIIE GENETIC, FACTORI DE MEDIU

REACIE TIP I:

REAGINIC

Ac IgE, MASTOCITE, MEDIATORI REACIE TIP III: NON REAGINIC

Ac IgG, CIC REACIE TIP IV: NON REAGINIC

IMUNITATE MEDIAT CELULAR, LT, LIMFOKINE

MECANISMELE PATOGENICE ALE ALERGIEI ALIMENTARE

ALERGIA LA UN ALIMENT AR FI UN DEFICIT AL TOLERANEI ORALE IMUNE

ALERGIA ALIMENTAR CONSECINA: - REACII MEDIATE IgE - REACII NON IgE - MEDIATE CELULAR SENSIBILIZAREA ARE LOC LA PRIMA EXPUNERE LA ANTIGEN:

SENSIBILIZARE

DUP MIGRARE PRIN MUCOAS PROTEINELE STRINE CAPTATE DE CELULELE PREZENTATOARE DE ANTIGEN: - MACROFAGE - CELULE DENDRITICE

SUNT PREZENTATE LT CARE PRODUC CITOKINE - MEMORIE CELULAR

REEXPUNERE

O NOU EXPUNERE Ag ELIBERARE DE MEDIATORI LEGAI DE Ac IgE LA RECEPTORI (MASTOCITE, BAZOFILE, MACROFAGE)

PRECOCE

TARDIVA

Nature Reviews Immunology 2, 446-453 (June 2002)

Le Danse (After Matisse) Chris Wake Australian Contemporary Artist - Paintings

Picasso, Guernica

HIPERSENSIBILITATEA DE TIP I ALERGEN IgE + MASTOCITE

FACTORI CHEMOTACTICI DIN MASTOCITE PENTRU NEUTROFILE I EOZINOFILE

HISTAMINA

MEDIATORI ELIBERAI DE NEUTROFILE

REACIE IMEDIAT

REACIE TARDIV

FIZIOPATOLOGIA REACIILOR IMEDIATE I TARDIVE MEDIATE IgE

ALERGIA ALIMENTAR INCLUDE NTOTDEAUNA REACIA MEDIAT IgE DE TIP I DAR NU ESTE LIMITAT NUMAI LA ACEST TIP DE HIPERSENSIBILITATE

patog

Efectele histaminei
Celula T IL-4
Chimiotaxie IL-5

Eozinofil
Cresterea activitatii fosfodiesterazei Scaderea nivelelor celulare de AMPc Cresterea eliberarii de mediatori si citokine Bazofil Celula B

Sinteza IgE

Eliberare de histamina

Monocit

IL-10, TNF, PGE2

Cum ajunge histamina in peste?

Histidina aminoacid esential prezent in mod normal intr-o serie de alimente, in special peste fam. Scombridae Bacteriile produc histidin decarboxilaza, care convertesc histidina in histamina Histamina rezultat al expunerii la temperaturi inalte (>21C) peste mort in navod sau refrigerare tardiva Histamina nu este distrusa de inghetare, prelucrare termica, afumare, conservare

Picasso, Dora Maar au chat

HIPERSENSIBILITATE TIP III

CAUZAT DE CIC - ROL PATOGENIC NECLAR CI - LA INDIVIZI ALERGICI, NON ALERGICI DUP INGESTIE DE ALIMENTE DEPUNERE LOCAL CIC FENOMEN ARTHUS MULI INDIVIZI AU CIC - FR REACII ADVERSE

Faza I: CIC exces Ag

Faza II: depunere CIC vase, leucocite, mediatori (amine vasoactive, leucotriene, PAF)

Faza III: inflamatie mediata CIC

HIPERSENSIBILITATE TIP IV
MEDIAT DE LIMFOCITUL T ASPECTELE CLINICE INCLUD:

- DERMATITA DE CONTACT
- SIMPTOME PULMONARE CRONICE - SIMPTOME GASTROINTESTINALE

PATOGENIA ENTEROPATIEI ALERGICE

ANTIGENE ALIMENTARE

LEZIUNI EPITELIALE

MUCOASA

MEDIATORI CITOKINE
REACII IMUNE I. IgE: MASTOCITE II. IgG, CIC III. LT

GALT

CIRCULAIE SISTEMIC

FACTORI PREDISPOZANI
FACTORI CARE REGLEAZ HIPERSENSIBILITATEA ALIMENTAR LA COPIL I ADULT ALIMENTE SOLIDE

LAPTE

IgA SECRETOR PERMEABILITATE

PREDISPOZIIE GENETIC

NOU NSCUT

ADULT

DE CE COPILUL?

RSPUNSUL IMUN MATUR: BALANA TH1 / TH2

TH0

IFN- IFN-

TH1

IL-2
B
IgA
Imunitate celular

Tr-1 / TH3

TH2

IL-4 IL-5 IL-9 IL-13

IL-10 TGF-

B
IgE

Toleran

Alergie
Dup Spiekermann et al., JPGN 2001; 32:237-55

Reactie imuna
Tip I Tip II

Raspuns imun
IgE IgG, IgM IgG si/sau complement Ly T (Th1) LyT (Th2)

Mecanism efector

Manifestari clinice

Degranulare Anafilaxie, urticarie, astm, mastocitara sdr. Lesoff Citotoxicitate Depuneri de complexe imune

Discrazie sanguina, crioglobulinemie

Vasculita, alveolita alergica Hemosideroza pulmon

Tip III

Tip IVa Tip IVb

Monocite / macrofage
Eozinofile

Eczema, alveolita alergica

Exantem maculo-papular sau bulos, astm

Tip IVc
Tip IVd

LyT (CTL)
LyT

Exantem maculo-papular, Citotoxicitate bulos sau pustulos, eczema Neutrofile Exantem pustulos

Pilette Ch.Tests biologiques dans les maladies allergiques:interets et limites,Louvain Medical, 2005;124:5245-253 Buty JH. Lallergie allimentaire chez le nourisson et lenfant, Louvain Med, 122:S139-S151, 2003

ALERGIA ALIMENTARA DE LA BOALA LA PACIENTI

Entitate clinica Gastroenterita IPLV Varsta 3 luni 2 ani Numar pacienti

87 10
8 3 5 2 1

Gastrita cu eozinofile
Esofagita cu eozinofile Hemosideroza pulmonara Sdr. Heiner Vasculita Henoch-Schnlein Crioglobulinemie Deficit imun complex absenta Rc IL-2

5-16 ani
5-16 ani 14-16 ani 3-10 ani 15-16 ani 6 ani

Fenotipuri ale hipersensibilitatii la alimente si aparitiei bolilor alergice

Studiu suedez 3104 copii evaluati prin chestionare la 2 luni, 1, 2, 4 si 8 ani Hipersensibilitate la alimente si alergie alimentara diagnosticata: 3.1% la 1 an si 7,6% la 8 ani Reactiile alergice la lapte, ou, peste si grau au scazut, in timp ce pentru alune si arahide au crescut Hipersensibilitatea alimentara la varsta mici a crescut riscul pentru astm bronsic, eczema si rinita alergica la varsta de 8 ani, chiar daca au fost luate masuri la acesti copii la varsta mica (<2 ani) Cresterea prevalentei hipersensibilitatii alimentare spre varsta de 8 ani probabil reflecta cresterea alergiei la polen de arbori si a reactiilor la alimente

Ostblom E, Lilja G, Pershagen G, Wickman M. Phenotypes of food hypersensitivity and development of allergic diseases during the first 8 years of life. Clin Exp Allergy. 2008 Aug;38(8):1325-32. Epub 2008 May 8.

Exist cel puin 2 fenotipuri diferite de IAPLV la copii: . De tip I indivizii sunt n cele din urm s poat rezilia rspuns Th2 i reactivitate clinice, rezultate n''''tranzitorii alergii alimentare . De tip II, persoanele fizice nu sunt n msur s downregulate rspuns Th2 i au alimente persistente alergie. Dac se confirm, aceasta ar trebui s ne schimbm abordarea la diagnosticul i managementul de alergie la lapte. Permiterea ingestie de produse lactate nclzite va mbunti dramatic calitatea de via pentru majoritatea subiecilor cu alergie la lapte de mult creterea varietate de produse alimentare pe care le pot consuma. Aceast schimbare dietetice ar facilita ndeplinirea cerinelor nutriionale, reduce anxietatea copilului, reduce disconfortul n situaii sociale, i ofer potenial o strategie eficient de a scurta timp pentru a atinge toleran naturale.

PREOCUPANTE PROBLEME DE DIAGNOSTIC

ALERGIE ALIMENTARA BOALA

RELATIA CAUZALA

EVOLUTIE SI TERAPIE

TABLOU CLINIC

Diateza alergica
Dermatita atopica (Eczema)
Simptome gastrointestinale
Copii: falimentul cresterii

Tulburari de somn Iritabilitate Astenie mentala

Alergie alimentara

Oboseala

Astm: tuse, wheezing Anafilaxie

Rinoconjunctivita alergica (febra de fan)

MANIFESTRI CLINICE I SINDROAME N ALERGIA ALIMENTAR

MANIFESTRI CLINICE

SINDROAME

MANIFESTRI SISTEMICE - ANAFILAXIE

MANIFESTRI GASTROINTESTINALE - EDEM BUZE, PALAT, LIMB - PRURIT ORAL, FARINGIAN - LEZIUNI AFTOASE - COLICI (Ag LAPTE DE VAC) - GREURI, VRSTURI - DIAREE CRONIC I ACUT - MALABSORBIE, MALNUTRIIE - PIERDERI G-I: SANGE, PROTEINE
- DURERI ABDOMINALE, - CONSTIPAIE METEORISM

OC GASTROENTEROPATIA INDUS DE PROTEINE LA SUGAR I COPIL GASTROENTEROPATIE EOZINOFILIC ALERGIC ENTEROPATIA GLUTEN SENSIBIL

MANIFESTRI CLINICE

SINDROAME

MANIFESTRI CUTANATE - TUMEFIERI BUZE, ANGIOEDEM - PRURIT, RASH - URTICARIE, ECZEM - DERMATITA ATOPICA MANIFESTRI RESPIRATORII - STRNUT, RINOREE - WHEEZING, TUSE - BRONHOSPASM, - DISPNEE - LARINGITE

URTICARIE DERMATITA ATOPIC DERMATITA HERPETIFORM SINDROM DE ALERGIE ORALA SINDROM HEINER RINITE ALERGICE OTITE MEDII SEROASE(CONTROVERSE) CONJUNCTIVITE EDEM LARINGIAN BRONITE ASTM (RAR)

ALTE MANIFESTRI - TUMEFIERE ARTICULAR, MIGRENA, CEFALEE, APATIE, IRITABILITATE, HIPERKINEZIE, PROTEINURIE

ARTRITA MIGRENA HIPERACTIVITATE SINDROM NEFROTIC

Clasificarea hipersensibilitatii gastrointestinale la alimente

Ig E
Mediate Ig E, debut acut
-Hipersensibilitate gastrointestinal imediat -Sindromul de alergie oral

Mixte

Non Ig E

AcIgE asociate, mediate celular, debut intarziat/cronic

-Esofagita eozinofilica alergica -Gastrita eozinofilica alergica -Gastroenterocolita eozinofilica alergica

Mediate celular, debut tardiv/cronic

-Enterocolita la proteine alimentare -Proctita la proteine alimentare -Enteropatia la proteine alimentare -Boala celiaca

Tulburari gastrointestinale ale alergiei alimentare la sugar si copil

I. Boli mediate Ig E, cu debut acut
hipersensibilitatea gastrointestinala imediata

sindromul de alergie orala

II. Boli cu Ac IgE asociate cu reactii mediate celular, cu debut tardiv / cronic gastroenteropatia eozinofilica III. Boli mediate celular, cu debut intarziat / cronic
enterocolita la proteinele alimentare proctita la proteinele alimentare enteropatia la proteinele alimentare boala celiaca

HIPERSENSIBILITATE IMEDIAT GASTRO-INTESTINAL PATOGENIE: MEDIATA DE Ig E TRATAMENT: -ELIMINARE PROTEINE GENETICA: -FAMILIAL; -ADES ASOCIATA CU ALTE BOLI ATOPICE. ISTORIA NATURALA:

SINDROM DE ALERGIE ORAL

ANTICORPI Ig E

- ELIMINARE ALERGENI; - PREPARARE.

- FAMILIAL; - RINITE ALERGICE FRECVENTE

-80% VINDECARE
PRIN ELIMINARE DIN DIETA

-NECUNOSCUTA

Eveniment declansant - Alergen alimentar +/- IgE areActiv celula T / mastocit

IL-4/IL-13 Eotaxina Chemokine IL-3/IL-5 GM-CSF

Hematopoeza/supravietuire eozinofilica

Activare eozinofilica - Recrutare - Iniltratie gastrica

Citokine CysLT ECP/MBP

GASTRITA CU EOZINOFILE
Leziune mucoasa
Varsaturi/diaree LE P Edeme periferice

Casexie

Perspective for Treatments of Food Allergy Early studies in humans demonstrated the potential risk of severe side-effects of conventional immunotherapy for food allergy.[16, 17]The recent development of animal models for food allergy has greatly enhanced the progress of research for potential treatments. Animal models have facilitated studies on several modalities in the treatment of food allergy (specific immunotherapy with modified antigens/epitopes; regulatory cytokines, e.g. IL-10 or IL-12; immunomodulatory microorganisms; immunomodulatory pharmaceutical agents; anti-IgE antibodies; DNA vaccination; Chinese herbal medicine). They have also been used to study the clinical outcome of specific treatments, and to research potential mechanisms involved in secondary tolerance acquisition. Chinese herbal medicine has provided interesting treatment options for several allergic conditions, including food allergy. The group by Liet al. [18] examined the protective effect of a food-allergy herbal formula called FAHF-1. They administered the formula to mice previously sensitized with peanut antigen in the presence of cholera toxin. Mice treated with FAHF-1 had no signs of anaphylaxis to antigen challenge, while sham treated mice experienced severe anaphylaxis. These results correlated with objective measurement of rectal temperature (which decreases during anaphylaxis). Measurement of biological parameters showed a decreased peanut-specific IgE antibody concentration in FAHF-1-treated mice compared to controls, as well as a decrease in IL-4, IL-5 and IL-13 production by splenocytes after antigen and mitogen activation. Interestingly, antigen-specific T-cell proliferation was maintained in the treated group. These promising results may need to be confirmed for other antigens, and further studies must be carried out to determine the active component(s) of FAHF-1, but, again, such studies show the interesting role of the T cell. As described above, a dysregulation or imbalance of Th1- and Th2-type responses might contribute to the pathogenesis of food allergy. Lee et al. [19] examined IL12 as a potential candidate in the treatment of peanut hypersensitivity. In a mouse model of food allergy, they orally administered liposome-encapsulated recombinant IL-12, either prior to, or following, sensitization of the mice with peanut antigen. They found that primary administration of IL-12 greatly diminished the production of peanut-specific serum IgE, while the same effect was seen to a lesser extent with secondary administration of IL-12. Primary administration of IL-12 also greatly reduced the clinical scores for anaphylaxis. These scores were also reduced to a lesser extent by secondary administration of IL-12. Regarding immunological parameters, peanut-specific IgG1 was greatly reduced in both treatments, while IgG2 levels were not significantly different. Splenocyte proliferation in response to the antigen was maintained in the IL-12-treated groups. However, significantly less peanut-specific fecal IgA was observed in both IL-12-treated groups. This work showed that, by administering a cytokine that shifts the immune response towards Th1, the investigators could either prevent or suppress the Th2-type response. Another potential approach for the treatment of food allergy might involve the immunomodulatory effects of microorganisms that may prevent allergy. Several clinical studies have shown the potential effect of lactobacilli strains in this regard. Shida et al. [20**] administered heat-killed Lactobacillus casei intraperitoneally to ovalbumin T-cell receptor-transgenic mice prior to antigen sensitization.[20**] They found an increased production of IL-12 in the group of mice given lactobacilli. The rise in IL-12 correlated with a decrease in IL-4 and IL-5 and an increase in IFN- production by splenocytes. Upon egg challenge, the clinical anaphylaxis score also decreased in the mice treated with IL-12. These results also correlate well with those of Lee et al. [19] showing a similar effect of orally administered IL-12. However, the administration of an IL-12-promoting bacterial strain might be a much easier approach in further therapeutic trials. The importance of T cells in food allergy is also demonstrated by the observation that infestation by helminths is protective against allergy. Bashir et al. [21**] examined the influence of administering Heligmosomoides polygyruson allergy by using a mouse model similar to the one described above. They found that the group of mice infected with H. polygyrus before sensitization had greatly diminished peanut-specific IgE levels and anaphylactic symptoms upon antigen challenge. Marked reduction of secretion of IL-13 by peanut specific T cells was also observed in the treated group. Furthermore, a role for IL-10 in clinical tolerance was observed. Taken together, these studies indicate a key role for modulation of T cell responses in the treatment of food allergy.

nelegerea noastr de implicare a limfocitelor B i T n alergiialimentare a progresat semnificativ n ultimii ani. Conceptul c unrspuns pur Th2 st la baza mecanismului de alergie alimentara a fost revizuit i nlocuit de teoria c dysregulation imunitar este lalocul de munc i ntr-un fel implic, de asemenea, Th1 i / saucelule TH0. n plus, un rol de citokine de reglementare, cum ar fiIL-10 este puternic sugerat, dar munca suplimentar va finecesare pentru a verifica variabile implicate n achiziionarea de toleran. recirculare a celulelor T este un proces dinamic, puternicinfluenat de prezena receptorii de suprafa, fie indic stareade activare a limfocitelor sau o preferin pentru homing de organe specifice, iar acest proces influeneaz n mod clarexpresia clinic de alergii alimentare. nelegerea noastr deepitop specifice Tcelul sau rspunsuri cu celule B a progresatfoarte mult n ultimii ani i pot contribui n viitorul apropiat lacrearea de teste de diagnostic i abordri mai bune de tratament.n cele din urm, modele de mouse-ul de alergii alimentare sunt un instrument nepreuit i s ofere noi perspective n mecanisme iterapii pentru alergii alimentare, la centrul de care, se pare, esterolul de rspunsuri T-celule.

December 14, 2009 (Buenos Aires, Argentina) Hypoallergenic formulas based on hydrolyzed cow's milk or combinations of amino acids have considerable variation in their biochemical and immunologic characteristics. The degree to which a given formulation is hypoallergenic can be identified and measured with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), mass spectrometry, and the immunoglobulin (Ig)E reactivity of each formula. During their first year, 2% to 3% of infants develop hypersensitivity to cow's milk. This is frequently associated with early exposure to cow's milk. Formulas that lack allergenic activity and do not lead to harmful cytokine production are useful for preventing cow's milk sensitization and allergy in potentially sensitive children, according to Heidrun Hochwallner, a PhD candidate at the Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, in Austria, who presented her team's research here at the World Allergy Organization XXI World Allergy Congress. Scientists have investigated milk proteins for nearly 50 years, and note that sensitivity is more likely to occur in children with early exposure to cow's milk. Because more than half of allergic children have no family history of allergy, an effective way to prevent milk allergies might be to use hydrolyzed milk protein for all children who require breast milk supplements. The current study investigated 16 cow's milk formulas to determine their respective allergenic activity. The IgE reactivity of each formula was tested in sera from 22 patients with a cow's milk allergy; T-cell proliferation and cytokine secretion were examined in cultures of peripheral blood mononuclear cells from patients with cow's milk allergy and from people with IgG antibodies specific to cow's milk. Among the 16 formulas tested, "the amino acid formulations showed the lowest IgE-binding activity, low T-cell reactivity, and low allergenic activity," Ms. Hochwallner told Medscape Allergy and Immunology. In contrast, "the formulas with intact proteins, complete proteins, showed high levels of IgE-binding activity, Tcell reactivity, and allergenic activity," she said. "We could also see a difference in the induction of cytokine levels, so we could kind of identify formulas that induce lower levels than others of interferon-, interferon-, and [interleukin] IL-6. . . . And we could see formulas that induced lower levels of the Th2-driving cytokines IL-5 and IL-13," said Ms. Hochwallner. As summarized in the meeting abstract: "We could rank the various formulas regarding allergenic activity. Most interestingly, we could demonstrate that certain formulas did not stimulate a potential detrimental cytokine pattern, indicating that these formulas not only lack IgE-related inflammatory and sensitizing activity, but also do not induce harmful cytokine production." Is it odd that the standards for "hypoallergenic cow's milk formulas" are so varied? It is "somewhat surprising, but not really, because the manufacturing process varies from one manufacturer to another," session comoderator Sami Bahna, MD, DrPH, professor of pediatrics and medicine, chief of allergy and immunology, and director of the Allergy and Immunology Training Program, Louisiana State University Health Sciences Center, in Shreveport, toldMedscape Allergy and Immunology. "The molecules or the peptides that are remaining can vary widely for example, the extensively hydrolyzed whey. You may find casein in it, because the whey came from the whole milk," said Dr. Bahna. "Casein-derived formulas can have whey in them, but generally, they are hypoallergenic. Only about 3% to 5% of children who are allergic to cow's milk are allergic to the extensively hydrolyzed formula." "On the other hand, partially hydrolyzed formulas have larger peptides and can cause allergy. So although they are useful as . . . prophylaxis, they are not indicated. In fact, they are contraindicated for children who are already allergic," Dr. Bahna said. A person who is truly allergic to cow's milk or milk formula has to go to extensively hydrolyzed formula, and probably more than 95% of the formula on the market would be tolerated well. "If it's not tolerated, then they go to amino acid formulas," added Dr. Bahna. "Also, it depends on the availability, the society, the community, and the prices," explained Dr. Bahna. "The majority of cow's-milk-allergic children would tolerate soy formula, which is similar in price, and it's easily available and the taste is reasonable also. We have to individualize," Dr. Bahna said. "If a person is highly allergic, we may have to go to the very expensive or the amino acid formulas . . . so the individualization will be good for the family." In closing, the presenters noted that some formulas lack IgE-related inflammatory and sensitizing activity and do not induce production of harmful cytokines. The authors suggest that other types of inflammatory disease inflammatory bowel disease, for example might benefit from these noninflammatory milk formulations. Ms. Hochwallner and Dr. Bahna have disclosed no relevant financial relationships. World Allergy Organization XXI World Allergy Congress (WAC): Abstract 471. Presented December 7, 2009.

PREVALENTA ALERGIEI ALIMENTARE IN ALTE PATOLOGII

Astm bronsic 6%

Eczema atopica 35-40%

Urticarie acuta 20%

ASPECTE DE MARE SEVERITATE!!!

Anafilaxia

Mecanisme:
Eliberarea IgE mediata a produsilor mastocitari Hymenoptera, alimente, penicilina, latex

Alergia alimentara
Aliment declansator, anafilaxie indusa de efort Rara Apare la 2-4 ore dupa ingestia anumitor alimente Apare la adolescenti decada 4 de viata M:F = 1:2 Alimente incriminate: grau, telina, crustacee, peste, fructe, lapte

Anafilaxia indusa de efort (Exercise-induced anaphylaxis)

Exercitiu fizic precedat sau urmat de ingestie de alimente specifice:

Crustacee, piersici, telina, grau

Mecanism incomplet elucidat raspunsuri exagerate din partea mastocitelor

Anafilaxie

Reactii anafilactice la alimente fatale sau aproape fatale la copii si adolescenti

13 copii cu anafilaxie la alimente Toti cunoscuti cu alergie alimentara 6 decedati 7 intubati

Sampson, NEJM 1992;327:360-4

DIAGNOSTICUL ALERGIILOR ALIMENTARE

FRANZ INGELFINGER - INTERNIST - 1949:
"ALERGIA GASTROINTESTINAL ESTE UN DIAGNOSTIC SUSPECTAT FRECVENT, OCAZIONAL EVALUAT I RAR CONFIRMAT CU PRECIZIE" BOAL SUBDIAGNOSTICAT I SUBTRATAT FRECVENT DATORIT COOPERRII NTRE ALERGOLOG PEDIATRU I GASTROENTEROLOG ; S-AU FCUT PROGRESE IMPORTANTE PRIVIND STANDARDIZAREA METODELOR DE DIAGNOSTIC N ALERGIA ALIMENTAR DIAGNOSTICUL PRESUPUNE: ARGUMENTE CLINICE ARGUMENTE DE LABORATOR

DIAGNOSTIC CLINIC ISTORIC - INTEROGATORIU

- VRSTA DE DEBUT - FACTORI PRECIPITANTI POSIBILI - RELAIE TEMPORAL NTRE INGESTIE SI APARIIA SIMPTOMELOR - CANTITATEA DE ALIMENT INGERAT I CARACTERISTICI ALE ALIMENTULUI - REPRODUCTIBILITATEA RSPUNSULUI ALERGIC APARENT

EXAMEN FIZIC COMPLET

- PRECIZAREA MANIFESTARILOR DE ORGAN

ALERGIE ALIMENTAR SUSPECTAT

PROBA EXCLUDERE: SELECTIV DIET OLIGOANTIGENIC

SIMPTOME - DIMINUAREDISPAR N CTEVA ZILE

PROBA NCRCARE: LIBER DUBLU ORB-PLACEBO-CONTROL REACIE IMUN RECDERE ACELEASI SIMPTOME

ALERGIE ALIMENTAR CONFIRMAT

Definitie Ingestia in cantitati crescande a alimentului incriminat, la intervale fixe, sub observatie stricta

Skin-prick test (SPT) Cel mai rapid si cel mai ieftin Prag de sensibilitate mai mic decat CAP CAP IgE specifice mai mici de 0,1 sunt sugestive pentru test de incarcare negativ la majoritatea pacientilor 4 alimente: ou, lapte, alune, grau Simplu orb placebo controlat

Pre-teste

TESTUL DE INCARCARE ALIMENTARA

3 tipuri de teste de incarcare alimentara

Dublu-orb placebo controlat Gold standard Preferat pentru protocoale stiintifice

Deschis Cel mai obisnuit

DIAGNOSTIC DE LABORATOR
TESTE

1)

ELIMINARE I NCRCARE

STANDARD DE AUR

TEST DE NCRCARE ORAL DUBLU ORB CONTRA PLACEBO

Testul de incarcare orala Testul de incarcare dublu orb, placebo controlat gold standard pentru diagnosticul alergiei alimentare

Se elimina alimentele suspectate 7-14 zile inaintea testarii Se opresc antihistaminicele

STANDARDIZAREA TESTULUI DE NCRCARE ORAL DUBLU ORB CONTRA PLACEBO

PRIMA ZI in spital
Se incepe testul prin utilizarea preparatului de testat (PT) sau a preparatului placebo (PP); acelasi aspect si gust Preparat de testat: 200 ml = 10 g NEOCATE + 20 g l.p. degresat + 180 ml a.f. Preparat placebo: 200 ml = 30 g NEOCATE + 180 ml a.f. Administrate la intervale de 30 min.:

8:00 8:30 9:30 10:00 10:30 16:00

1 ml pe brat, apoi pe coapsa ingestie 5 ml ingestie 10 ml ingestie 50 ml ingestie 100 ml etc. pana la doza zilnica necesara pentru varsta

dupa Erika ISOLAURI

STANDARDIZAREA TESTULUI DE NCRCARE ORAL DUBLU ORB CONTRA PLACEBO

PRIMA SAPTAMANA
A 2-a zi
A 3-a zi A 4-a zi A 5-a zi

LA DOMICILIU, CU EVIDENTA DOZELOR DE PREPARAT INGERATE SI COMPLETAREA FORMULARULUI DE SUPRAVEGHERE

A 6-a zi
A 7-a zi

COPILUL ESTE REINTERNAT

Daca se produc reactii adverse, copilul este internat imediat si investigat; testul de incarcare este oprit.
dupa Erika ISOLAURI

STANDARDIZAREA TESTULUI DE NCRCARE ORAL DUBLU ORB CONTRA PLACEBO

A DOUA SAPTAMANA
A 8-a zi
A 9-a zi A 10-a zi COPILUL RAMANE IN SPITAL

A 11-a zi
A 12-a zi A 13-a zi A 14-a zi

LA DOMICILIU, INCEPEREA PROBEI DE INCARCARE CU AL DOILEA PREPARAT (PT/PP) DUPA MODELUL ANTERIOR

COPILUL ESTE REINTERNAT

dupa Erika ISOLAURI

TESTE IMUNOLOGICE
2) A) IN VIVO TESTE CUTANATE ALERGOLOGICE

- prima etapa a diagnosticului

TESTE CUTANATE ALERGOLOGICE TESTE PRIN INTEPATURA -SKIN PRICK TEST (SPT) CU ANTIGEN DEFINIT TESTE PRIN ZGARIETURA SCRATCH TEST

TESTE INTRADERMICE folosite pentru alergiile cutanate

TESTE EPICUTANATE PATCH TEST

TESTE PRIN INTEPATURA -SKIN PRICK TEST (SPT) - CU ANTIGEN DEFINIT

FOLOSESC EXTRACTE ALIMENTARE 1/70 -1/20 ALESE FUNCTIE DE ANAMNEZA SI ALIMENTELE CELE MAI FRECVENT UTILIZATE
TEHNICA 2 MARTORI - NEGATIV DILUTII SOL. DE ANTIGEN
- POZITIV (DEGRANULANTI MASTOCITARI) IMUNOLOGICI HISTAMINA 10 mg/ml NONIMUNOLOGICI FOSFAT DE CODEINA 9%

REZULTATUL SE CITESTE LA 15-20 MIN REZULTAT POZITIV PAPULA DE CEL PUTIN 3 mm LA SUGAR 8 mm DATORITA PARTICULARITATII MASTOCITELOR CUTANATE NR REDUS, NIVELE IgE LIPSA EXTRACTELOR ANTIGENICE IMAGINAREA UNEI VARIANTE A TESTULUI PRICK PRICK TEST

VP NEG 95% - REZULTATELE NEGATIVE INFIRMA AA VP - POZITIVA 50% - REZULTATE POZITIVE POSIBIL SENSIBILIZARE

TESTE PRIN ZGARIETURA SCRATCH TEST

LIMITATE DIN CAUZA - REACTII SISTEMICE - DISCONFORT - CICATRICI DEPIGMENTARE

In aceste cazuri exista o mare dificultate in interpretarea reactiilor IgE, mai ales atunci cand simptomele apar dupa cateva zile de la ingestia alimentului. In aceste cazuri de reactii alergice complexe singura metoda de diagnostic este testul de provocare dublu orb-placebo.

TESTE INTRADERMICE folosite pentru alergiile

cutanate si nu pentru cele alimentare

TESTE EPICUTANATE PATCH TEST

EXPLOREAZA HIPERREACTIVITATEA INTARZIATA ALERGENUL PLASAT INTR-UN GODEU SE FIXEAZA CU AJUTORUL UNUI PETEC ADEZIV PE TEGUMENTUL SANATOS PARAVERTEBRAL REZULTATUL SE CITESTE DUPA 72 ORE, LA 20 MIN DUPA RIDICAREA PETECULUI

IN COMBINATIE CU SPT CRESTE ACURATETEA DIAGNOSTICULUI

IN VITRO

IgE TOTALE NU AU VALOARE DIAGN. - 20-30 DINTRE ATOPICI AU VN

ANTICORPI SPECIFICI IgE - RAST - CAP-RAST - ELISA - RIA ANTICORPI SPECIFICI IgG (IgA, IgM) - SPECIFIC ALIMENTARI - SE IGNOR
CIC, C1Q TESTUL TROFOTOP HISTAMINA PLASMATIC, TEST ELIBERARE A HISTAMINEI BAZOFILE (DETECIE INDIRECT A HISTAMINEI LEGATE DE BAZOFILE) - NU ESTE DE RUTIN, DOZAREA PROTEINELOR EOZINOFILE

The levels of IL-4 and IL-13, characteristic Th2-type cytokines, have been reported to show a tendency to be higher in the milk of allergic mothers than in that of nonallergic mothers [15], in contrast to the earlier finding by Rudloff et al. [133]. The reports on the levels of IL-8 [131] and IL-10 [133] showed similar results. Most recently, two papers have reported an association between low levels of TGF-b in mother's milk and development of IgE-mediated CMA or atopic eczema in breast-fed infants [134,135]. The levels of TGF-b were shown to correlate positively with the total number of IgA-producing cells in the peripheral blood of the infants [134] and with specific IgA antibodies to BLG and specific IgG antibodies to a-casein and whole formula, but negatively with the diameter of a SPT response to cow's milk and with lymphocyte indices to a-casein and BLG [135]. Based on their findings

RAST
Considerat mai putin sensibil decat testarea cutanata Recomandat: Pharmacia CAP-RAST Utilizat cand testele cutanate sunt contraindicate

Dermatografism Dermatita severa Imposibilitatea opririi antihistaminicelor Risc crescut de anafilaxie

3) TESTE SPECIFICE GASTROINTESTINALE

BIOPSIA GASTRIC

BIOPSIA INTESTINAL
RECTOSIGMOIDOSCOPIE-BIOPSIE STUDIUL ABSORBIEI ZAHARURI - D-XILOZ ANALIZ SCAUN : - 1 ANTITRIPSIN - SNGE - GRSIMI CAROTEN SERIC

PRECIZARI PRACTICE
Testele cutanate nu detecteaza reactiile imunologice tardive, ci doar pe cele de tip IgE. Testele cutanate pozitive nu certifica o reactivitate simptomatica. Prick testul este edificator dupa prima luna de viata, dar depinde de puritatea alergenelor utilizate (trusa utilizata) Patch testul deceleaza reactiile tardive (dermatita atopica) Utilizarea combinata prick test si patch test creste semnificatia diagnostica in alergii Nici un test nu este perfect fiabil in APLV si criteriile clinice sunt infailibile

Valoare diagnostica in protocoale standardizate au testele de provocare la laptele de vaca dublu orb controlat placebo
Testele de provocare se efectueaza copiilor fara antecedente de anafilaxie Alergia alimentara impune supravegherea de catre pediatri experimentati, dieteticieni, iar introducerea unui nou aliment trebuie facuta cu prudenta, de obicei in spital.

Noi teste pentru detectarea riscului de alergie la nou-nascuti

Profesorul Tony Ferrante, imunolog la Children's Research Centre la University of Adelaide: test sanguin simplu care prezice daca nounascutii au risc crescut de dezvoltare a alergiilor pe masura ce

cresc

Protein kinaza C zeta proteina cu rol in semnalizarea celulara

nivele scazute la copiii cu risc de alergii ulterioare
Mai eficienta decat alti indicatori: istoric familial, nivele IgE alergen-induse
Initial descoperita impreuna cu Profesor Susan Prescott de la University of Western
Australia in 2007, dar Prof. Ferrante a realizat testul simplu sanguin de aplicat la nou-nascut

Alte domenii de interes: daca suplimentarea cu ulei de peste la gravide si imediat dupa nastere scade riscul alergiei ulterioare la copil

DIAGNOSTIC DIFERENIAL

NOU NSCUT ALERGIA ALIMENTAR PREMATUR I ERONAT SUSPECTAT

ASPIRAIA ALIMENTAR (TUSE, WHEEZING)

ANOMALII STRUCTURALE (VRSTURI): - HERNIA HIATAL CU RGE - STENOZA PILORIC - STENOZA DUODENALA BOALA HIRSCHSPRUNG

COPII

ULCER PEPTIC COLECISTITA, COLELITIAZA DEFECTE ENZIMATICE (LACTAZA) FIBROZA CHISTIC, SDR. MALABSORBIE INFECII CRONICE: BACTERII, FUNGI, ALGETOXINETLBURRI GASTROINTESTINALE SEVERE; SIMPTOME NEUROLOGICE: - CL. BOTULINIC, STAFILOCOC AURIU, SALMONELLA, SHIGELLA, E. COLI, CAMPYLOBACTER

COPII
GIARDIAZA, TRICHINELOZA
REACII LA AGENI FARMACOLOGICI DIN ALIMENTE: - COFEIN; TEOBROMIN; HISTAMIN; TIRAMIN; SEROTONIN; FENILETILAMIN; ALCOOL ALIMENTE CONTAMINATE, ADITIVI ALIMENTARI: - TARTRAZINE; METABISULFIT DE Na - NITRII, NITRAI; BENZOAI - HIDROXITOLUEN BUTILAT - CONSERVANTE-SULFII - GLUTAMAT MONOSODIC ("CHINESE RESTAURANT SYNDROME)

DIAGNOSTIC DIFERENIAL
DERMATITA ATOPIC; TULBURRI CUTANATE

DERMATITA SEBOREIC ENTEROPATIA GLUTEN SENSIBIL ALTE CAUZE DE ECZEM: - SDR. WISKOTT-ALDRICH - AGAMAGLOBULINEMIA BRUTON - BOALA LEINER - HISTIOCITOZA X - ACRODERMATITA ENTEROPATICA - BOLI METABOLICE
MANIFESTRI ALERGICE SINO-PULMONARE

SINDROMUL DEFICITULUI DE ANTICORPI FIBROZA CHISTIC SINDROMUL CILILOR IMOBILI

PROFILAXIE

Picasso Le reve, 1932

PREVENTIA
IDENTIFICAREA SUGARILOR CU RISC ISTORIC FAMILIAL DE ATOPIE IgE CRESCUT N SNGELE CORDONULUI OMBILICAL

UN SINGUR PRINTE ATOPIC - RISC 25-35% AMBII PRINI ATOPICI - RISC 40-60% AMBII PRINI ATOPICI CU ACELEAI MANIFESTRI - RISC 50-80%

Picasso Alaptare

Bunic

Bunica

Bunic

Bunica

Tata

Mama

Copil

Copil

Copil

Copil

Factori de risc ereditari

(manifestari clinice, de ex. rinita alergica, eczema atopica)

Nu exista alergie 10-20%

1 parinte alergic 20-40%

1 frate sau 1 sora alergici 30%

2 parinti alergici 40-60%

2 parinti cu aceeasi alergie 72%

Beta-lactoglobulina

I. HIDROLIZATE PARIALE

- sunt denumite lapte hipoalergenic (HA) - conin lactoz i sunt potenial contaminate de proteinele laptelui - la rndul lor sunt de trei tipuri: Hidrolizate pariale ale proteinelor lactoserului (PLS): - Bleidilait HA - Gallia HA - Guigoz HA - Milumec HA - Modilac HA - Novalac HA 1 i 2 - Nidal HA 1 i 2 - Humana HA 1 i 2 Hidrolizate pariale mixte de PLS i cazein - Enfamil HA Hidrolizate pariale de PLS care nu poart meniunea HA: - Omneo 1 i 2 - Conformil 1 i 2 - Hidrolizat de soia i colagen de porc, dar care conine lactoz - Lactopregomin

II. FORMULE EXTENSIV HIDROLIZATE

- conin puin sau deloc lactoz (2% din zaharuri) - excepie: Lactopregomin care conine 80% din total zahr Hidrolizate din PLS: - Alfar - Pepti Junior Hidrolizate de cazein: - Galliagen Progress - Nutramigen - Pregestimil - Hidrolizat de soia i colagen de porc fr lactoz - Pregomin proteine de colagen de porc i soia Soluii de aminoacizi: - Neocate Nutrijunior - Pregomin AS

MSURI PREVENTIVE DIETETICE LA POPULAIA CU RISC

EFECTE SIGURE: ALIMENTAIE EXCLUSIV LA SN 4-6 LUNI CU DIET RESTRICTIV A MAMEI PENTRU: - LAPTE DE VAC - OU (ALBUS) - ALUNE - PETE ALTERNATIVA: FORMULE CU HIDROLIZAT DE PROTEINE (PARIAL SAU TOTAL HIDROLIZAT) DUP 4-6 LUNI FORMULE DE LAPTE SUPLIMENTATE CU PROBIOTICE SI PREBIOTICE INTRODUCERE TARDIV A ALIMENTELOR SOLIDE (PESTE 6 LUNI) ELIMINAREA LAPTELUI DE VAC, OU (12-24 LUNI) FR EFECT: DIET MATERN DE EXCLUDERE N TIMPUL SARCINII ALI FACTORI EPIDEMIOLOGICI FUMATUL PARENTAL ANIMALE DE CAS INFECII RESPIRATORII (ELIMINARE CRE)

RISCUL ALIMENTATIEI ARTIFICIALE PREVENTIA NECESITA OPTIUNI SPECIALE

ALGORITM EVALUARE IN SUSPICIUNE DE ALERGIE ALIMENTARA

ANAMNEZA SUGESTIVA

SUSPECT ALERGIE MEDIATA IgE SKIN TEST

ALERGIE NON IgE MEDIATA ENDOSCOPIE SUPERIOARA

+ + SANGERARE

NEEVALUARE VIITOARE

NEEVALUARE

CONSILIERE RISC ANAFILAXIE EPINEFRINA

TRATAMENTUL SOCULUI ANAFILACTIC URGENTA MEDICALA

ADRENALINA INTRAMUSCULAR 0,15-0,25 mg COPIL 0,3-1 mg ADULT ABORDARE VENOASA TRAT. COLAPS

CORTICOIZI
ANTIHISTAMINICE PERSPECTIVE ATC. ANTI IgE

Tratament
Eliminarea completa a agentului incriminat Plan de urgenta

Algoritm clar in anafilaxie Epinefrina injectabila Bratara Medic alert

Control anual la specialistul alergolog

Adrenalina

Doza
Adulti 0,3 0,5 ml IM 1:1000 repetata in 520 min daca e necesar Copii 0,01 mg/kg IM

Epinephrine (Adrenaline, EpiPen, TwinJect) DOC for treating anaphylaxis. Helps decrease symptoms of anaphylaxis by increasing systemic vascular resistance, elevating diastolic pressure, producing bronchodilation, and increasing inotropic and chronotropic cardiac activity. In addition, helps reduce urticaria, angioedema, laryngeal edema, and other systemic manifestations of anaphylaxis. Dosing Interactions Contraindications Precautions Adult 0.3 mL IM (also traditionally given SC) of 1:1000 aqueous injected (usual range is 0.2-0.5 mL) q10-15min, not to exceed 3 doses; may need to decrease dose to 0.2 mL in elderly persons or those with known cardiac conditions 0.3 mL IM of 1:1000 dilution q10-15min; IV route (1:10,000) seldom used; not to exceed 0.25 mg; given very slowly and with extreme caution 0.3-mg self-injectable devices (EpiPen, Twinject 0.3 mg)

Pediatric IM dosing in children based on weight or 0.01 mL/kg IM of 1:1000 dilution; not to exceed 0.3 mL IM 1:2000 dilution q1015min 0.15-mg self-injectable devices (EpiPen Jr, Twinject 0.15 mg)

Anafilaxie
Tratament agenti de linia a doua Antihistaminice

Blocante H1 Blocante H2

Corticosteroizi (?? previn faza tardiva 6-8 ore)

Anafilaxie

Daca este pe beta blocant, glucagon (1 mg bolus cu infuzie continua 1-5 mg/ora)

TRATAMENT - PRECIZARI

La sugari formula alternativa; In APLV severa:

Mediata Ig E 86 % tolereaza formule pe baza de soia; Non mediata Ig E rata tolerantei este doar 50 %.

In IPLV se descriu doua categorii:

A) Sugari care nu tolereaza: Formule hidrolizate partial; Formule lactate delactozate; Laptele altor mamifere (oaie,capra) ele nu reprezinta o buna alternativa. B) Sugari care tolereaza 95 % sugari care tolereaza formule extensiv hidrolizate (alergeni reziduali); 5 %,putini,necesita formule pe baza de aminoacizi(tip NEOCATE).

DURATA TRATAMENTULUI

IPLV forme digestive vindecare inainte de 2 ani:

77 % studiul Hst; 84 % studiul Bock (la 3 ani). Copii atopici Ig E; IPLV:

IPLV evolutie mai putin favorabila:

Alergie alimentara multipla; Vindecare la 2 ani sub 22 % (Hill).

IPLV Indusa de alimentatia la san:

Vindecare cazuri; La 1 an si 6 luni test de provocare; Testul negativ scoasa restrictia.

DURATA TRATAMENTULUI CU NEOCATE

Forme digestive:
Tratament scurt 15 zile; Tolereaza formula cu lactoza 29 %.

Anafilaxie 1 an.

Alergie alimentara multipla 24 luni (2 ani).

PREVENTIE De ales !!!

Un parinte alergic Doi parinti alergici Aceleasi simptome

H I P O A

Diversificare corecta!

SIMPTOMATIC=FORMULE EXTENSIV HIDROLIZATE!

PREVENTIA ALTOR ALERGII ALIMENTARELA COPILUL CU IPLV

Va evita:
Carne,nuci Faina de grau Ou si peste Arahide

inainte de 6 luni; inainte de 8 luni; inainte de 1 an; inainte de 2-3 ani.

COPIL ALERGIC

FAMILIE SCOALA COMUNITATE PREDISPOZITIE GENETICA

SOLUTII

PEDIATRU IMUNOLOG

ALERGENI

CAUZE

RASPUNS IMUN ANORMAL AL TUBULUI DIGESTIV

ALGORITM DECIZIONAL TERAPEUTIC SUGARI

MASURI IN POPULATIA GENERALA

COPII CU RISC ATOPIE

ALIMENTATIA NATURALA

LAPTE HIPOALERGENIC NU PREPARATE DIN SOIA

GRAVIDA (TGF2 crescut in lapte) PREMATUR SUGARI CU DIAREE, ATB, etc

DIVERSIFICARE TARDIVA > 6 LUNI

NOU! GOOD FOOD GOOD LIFE

PROBIOTICE

BUSINCO 1987, AROST 1988, KAJOSARRI 1995, ODDY 1999, BOTTCHER

PROBIOTICE

FAO/OMS: MICROORGANISME VII EFECTE BENEFICE (FULLER, 1989) ELIE METCHNIKOFF = PREMIUL NOBEL PENTRU CONTRACARAREA FLOREI PATOGENE EFECTE DEMONSTRATE:

AMELIORAREA SEMNELOR DE ECZEMA ATOPICA LA COPIL MODULAREA ECHILIBRULUI MICROFLOREI INTESTINALE PRIN PROBIOTICE (COX2, PGE2, ACTIVITATE PROTEOLITICA)

STRATEGIE ACTUALA DE PREVENTIE A ALERGIEI ALIMENTARE INDUCEREA SI MENTINEREA TOLERANTEI ORALE LA BETALACTOGLOBULINA LACTOBACILLOS PARACASEI NCC 2461, BIFIDOBACTERIUM LACTIS NCC 362, LACTOBACILLUS JOHNSONII CONCEPT ACTUAL : PREBIOTICE PROBIOTICE - SINBIOTICE

PREBIOTICE
OLIGOZAHARIDE CARE CONTRIBUIE LA STIMULAREA NATURALA A CRESTERII BIFIDOBACTERIILOR SI BACILILOR LACTICI DIN INTESTIN CONTRIBUIE LA INTARIREA CAPACITATII DE APARARE SPECIFICA A ORGANISMULUI PRODUC ACIZI GRASI CU AJUTORUL BIFIDOBACTERIILOR

SI LACTOBACILILOR

IMBUNATATESC ABSORBTIA CALCIULUI

AMELIOREAZA TRANZITUL INTESTINAL PREBIOTICE:
FRUCTOOLIGOZAHARIDE (FOS), INULINE, LACTILOL, LACTOSUCROZA, LACTULOZA, OLIGOFRUCTOZA ETC.

Terapii imunomodulatoare viitoare

Anticorpi monoclonali umanizati anti-IgE Imunoterapie cu alergeni proteici mutanti (inginerie genetica) Imunoterapie modulata de secventa antigen-imunostimulatorie (CpG) Imunoterapie peptidica Imunoterapie ADN-plasmidica Imunoterapie citokin-modulata Inducerea tolerantei sau imunoterapiei orale (lapte, ou, alune)

TERAPII DE VIITOR
Vaccinarea anti IgE
Tinte terapeutice: molecula IgE citokineTh2: IL-4, -5, -13, -33, -18 si limfopoietina stromala timica

Therapeutic vaccines against IgE-mediated allergies Lars Hellman Expert Review of Vaccines, March 2008, Vol. 7, No. 2, Pages 193-208

PROGNOSTIC
ACHIZIIA TOLERANEI CU VARSTA

ALERGIA ALIMENTAR LA COPIL ESTE DE OBICEI TRANZITORIE

ISTORIA NATURAL MULI COPII PIERD ACEAST SENSIBILITATE CLINIC N TIMP TOLERANA LA ANTIGENUL ALIMENTAR ESTE DOBNDIT DUP 1-4 ANI DE LA ELIMINAREA ALERGENULUI ISTORIA NATURAL ESTE INFLUENAT DE : - VALOAREA INIIAL A Ac IgE ALIMENTARI - ELIMINAREA ALERGENULUI (GRAD DE ELIMINARE) - SPECIFICITATEA ANTIGENULUI ALIMENTAR - PARTICULARITATI GENETICE

PROGNOSTIC

TESTELE DE NCRCARE PENTRU ALERGIA ALIMENTAR SE VOR FACE: - DUP 12-18 LUNI PENTRU LAPTE VAC, OU, GRU - DUP 2-3 ANI PENTRU NUCI - DUP 3 ANI PENTRU ALUNE, PETE DUP 3 ANI 80% DIN SIMPTOMELE DE ALERGIE ALIMENTAR DISPAR ALERGIA LA LAPTE DISPARE DUP VRSTA DE 3 ANI LA 87% COPII ALERGIA LA ANUMITE ALERGENE POATE PERSISTA TOAT VIAA (NUCI, ALUNE, PETE)

CONCLUZII
ALERGIA ALIMENTARA ARE INCIDENTA IN CRESTERE, DEVINE O PREOCUPANTA PROBLEMA DE SANATATE PUBLICA

MANIFESTARILE CLINICE AU MARE VARIABILITATE (DISCRETE, SEVERE) RAR PROVOACA MALNUTRITIE

ELUCIDARILE PATOGENICE AU PERMIS ACHIZITII TERAPEUTICE IMPLICATIILE SOCIALE SUNT MAJORE: ALIMENTATIA NATURALA, FORMULE HIPOALERGENICE, DIVERSIFICARE TARDIVA, UTILIZAREA PROBIOTICELOR

ALERGIA ALIMENTARA NECESITA CUNOASTERE, ABORDARE IN ECHIPA, TRATAMENT IN URGENTA (SOCUL ANAFILACTIC)
ASISTENTA COPILULUI SI A FAMILIEI ESTE ESENTIALA PENTRU SUCCESUL TERAPIEI

here are no surveys of population and geographical trends in food allergy in adults or children (though the situation is different in pediatric asthma and rhinitis) and this unmet need is particularly felt for CMA. The perception of milk allergy is far more frequent than confirmed CMA. Patient reports of CMA range between 1 and 17.5%, 1 and 13.5%, and 1 to 4% in preschoolers, at children 5 to 16 years of age and adults respectively. Cow's milkspecific IgE sensitization point prevalence progressively decreased from about 4% at 2 years to less than 1% at 10 years of age in the German Multi-Centre Allergy Study. The most reliable data in epidemiology are those from birth cohorts that are free from selection bias. There are 5 such challenge-confirmed studies. The CMA prevalence during infancy ranged from 1.9% in a Finnish study, 2.16% in the Isle of Wight, 2.22% in a study from Denmark, 2.24% in the Netherlands, and up to 4.9% in Norway. Patients with CMA develop gastrointestinal symptoms in 32 to 60% of cases, skin symptoms in 5 to 90%, and anaphylaxis in 0.8 to 9% of cases. This frequency of anaphylaxis is the main concern pointed out in many CMA studies. In a review, nearly one third of children with atopic dermatitis (AD) received a diagnosis of CMA after an elimination diet and an oral food challenge, and about 40 to 50% of children less than a year of age with CMA also had AD. Finally, with actual population and geographical trends remaining unknown, allergists are primarily in need of more detailed epidemiological surveys on a global scale. One large such epidemiological study supported by the European Commission is ongoing and aims to furnish the first prevalence data regarding the suspicion of CMA, sensitization to cow's milk, and oral food challenge-confirmed diagnosis in 10 European birth cohorts. Back to Top | Article Outline

n general, food allergy is more frequent in the pediatric, rather than the adult, population. According to a recent Japanese multicenter trial, the prevalence of CMA is 0.21% in newborns and 0.35% amid extremely premature babies (<1000 g).14 Food allergies are a cause of particular concern for children. Incidence is estimated to be greater in toddlers (58%) than it is in adults (12%).1517 Earlier prospective challenge-based studies have shown that in a population of 480 newborns followed up in the setting of a U.S. general pediatric practice through their third birthday, a parental report of 28% food allergy translates into a challenge-confirmed CMA rate of 8%,18,19 with 2.27 to 2.5% occurring in the first 2 years of life.

The number of studies on CM sensitization in unselected populations is limited. The meta-analysis carried out by Rona and colleagues23 identified 7 studies reporting a sensitization rate of 0.5 to 2% of preschoolers, of 0.5% at 5 to 16 years of age, and in less than 0.5% of adults.23,2533 In a later cohort of 543 children from the Isle of Wight followed-up from birth and tested at 1, 2, and 3 years of age, a positive milk sensitization test was found in 2 infants at 12 months (0.37%), in 5 at 2 years (0.92%), and in 3 at 3 years (0.55%).49 In the German Multicenter Allergy Study, 1314 children initially recruited were followed from birth for 13 years. The longitudinal data were analyzed for 273 children testing positive for serum cow's milk specific IgE antibody and were obtained at age 2, 5, 7, and 10. The point prevalence of sensitization to cow's milk progressively decreased from about 4% at 2 years to less than 1% at 10 years.50

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