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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Food allergy &#40;FA&#41; is an important and frequent health problem in our children&#44; and&#44; in Europe&#44; cow&#39;s milk proteins &#40;CMP&#41; and hen&#39;s egg proteins &#40;HEP&#41; are the main offenders&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> The risk of anaphylaxis in IgE-mediated FA is high&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> Its impact on children and on their environmental quality of life&#44; as well as the nutritional aspects&#44; should not be dismissed&#46; Resolution of symptoms during strict avoidance and their reappearance during the double blind placebo control food challenge &#40;DBPCFC&#41; remain the gold standard for the diagnosis of FA&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Until very recently&#44; a single approach was available for the treatment of food allergy&#58; avoidance of the offending food&#46; From our point of view&#44; this approach only represents a lack of treatment and it also leaves the child unprotected from hidden or small amounts of the offending food&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The largest immune organ in the body is the intestine&#46; It is constantly working to protect our body from pathogens and also from external proteins&#46; Oral tolerance is an active immunological process which makes the intestine unresponsive to any food&#44; while FA is the result of its breakdown&#46; The mechanisms involved in the development of oral immune tolerance remain unclear but they seem to depend basically on age and dose of the administered food&#46; The main immunomodulatory cytokines in the gut are IL-10 and TGF-&#946; and in this milieu antigen-specific regulatory cells &#40;CD4<span class="elsevierStyleSup">&#43;</span>CD25<span class="elsevierStyleSup">&#43;</span>FOXP3<span class="elsevierStyleSup">&#43;</span>&#41; are essential&#46; In a genetically predisposed child&#44; those cells and cytokines are not present &#40;or in low numbers&#41; in the gut and the development of FA becomes a fact&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Lately&#44; some protocols on oral immunotherapy &#40;OIT&#41; are being investigated in Reference Centers&#46; OIT has as its first aim to increase the amount of food that the child can tolerate without reacting to it&#44; i&#46;e&#46; preventing anaphylaxis&#46; This is usually achieved with the consumption of small amounts of the allergen&#46; Another aim of this technique is to reach a desensitization state&#44; which allows the child to follow a &#8220;normal&#8221; social life and to achieve an adequate nutritional state&#46; And&#44; finally&#44; the goal of reaching permanent tolerance is of great interest&#46; At this point&#44; it is very important to distinguish between the terms &#8220;desensitization&#8221; and &#8220;tolerance&#8221;&#46; A child is desensitized to a specific food when he&#47;she goes on eating that food daily with the previously recommended amounts&#44; and no reactions are elicited&#46; Moreover&#44; a child becomes tolerant to a specific food when&#44; once the daily intake of the food has been interrupted&#44; he can eat it&#44; whenever he wants&#44; without reactions&#46; So&#44; the ultimate goal of food allergy therapy is permanent oral tolerance&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Before starting OIT&#44; an oral food challenge &#40;OFC&#41; should be performed&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> to assure that the child is still allergic to that food &#40;although skin prick test and s-IgE remain positive&#41;&#46; Parents of all children must sign an informed consent&#44; and the procedure must be approved by the ethics hospital committee&#46; Once allergy is established&#44; the procedure starts with a build-up phase in which small amounts of the diluted food are given to the patient at Hospital&#46; Emergency medications including epinephrine&#44; hydroxyzine&#44; salbutamol and prednisone must be available&#44; and possible symptoms to be evaluated are itching&#44; urticaria&#44; angioedema&#44; exacerbation of eczema&#44; rhinitis or conjunctivitis&#44; dyspnea and wheezing&#44; vomiting&#44; diarrhea and hypotension&#46; Once discharged&#44; the patient must receive the exact amount of the food&#44; daily&#44; at home&#46; The doses are slowly &#40;usually weekly&#41; increased at the out-patient Clinic&#44; until a usual amount of the food is reached &#40;maintenance phase&#41;&#46; The food must be taken daily at home and other amounts of the same protein can be eaten&#44; although always separately from the dose&#46; The dose should never be given on an empty stomach&#46; Patients are recommended to avoid exercise for 3<span class="elsevierStyleHsp" style=""></span>h after the food intake&#46; If there is an intercurrent illness&#44; the dose is not increased&#44; and the previous dose is repeated&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> This is a time-consuming procedure in which the commitment and compliance of the child and the families are crucial&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In many countries OIT protocols have been developed and research on this area is becoming an important feature in pediatric allergy&#46; Milk and egg allergies are the most frequently treated allergies regarding this approach&#46; Most of the international publications show successful desensitization rates which range from 60&#37; to 100&#37; in different studies&#46; But the acquisition of real tolerance remains unknown as there are only a few studies which evaluate the outcome after the discontinuation of the daily intake of the food&#46; Peanut has also been lately a target for OIT and some encouraging results have been published&#44; although the safety is a big concern&#46; Other foods are under research with no results available yet&#46; The main problem regarding OIT is the possibility of adverse events&#46; These are frequent and sometimes severe&#46; During the last two years&#44; two publications<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">3&#44;4</span></a> gave a view on egg &#40;study on 51 patients&#41; and milk &#40;study on 81 patients&#41; OIT adverse events&#58; most of the patients suffered adverse events &#40;95&#37; in cow&#39;s milk allergy and 90&#37; in egg allergy&#41;&#44; although frequency was low in relation with the administered doses &#40;6&#46;6&#37; and 7&#46;6&#37;&#44; respectively&#41;&#46; Most of the OIT reactions were mild &#40;grades 1 and 2&#41; although some patients suffered grade 4 reactions&#46; Respiratory adverse events were more frequent during cow&#39;s milk OIT&#44; while gastrointestinal reactions were more frequent during egg OIT&#46; These results emphasize the need for well-trained medical personnel and adequate hospital facilities &#40;intensive care unit&#41; available if this treatment is to be followed&#46; On the other hand&#44; for the subgroup of anaphylactic patients&#44; the odds of ever outgrowing the allergy are small and the risk of future severe reactions high&#46; Under these circumstances&#44; this approach would be justified&#58; the more severe the food allergy is and the more common the implicated food&#44; the better the cost&#47;benefit ratio is for OIT approach&#44; including anaphylactic patients&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The use of concomitant treatments such as omalizumab &#40;anti-IgE monoclonal antibody&#41; has also been studied&#44; the results being encouraging&#46; But some questions arise&#58; when should omalizumab be discontinued once desensitization&#47;tolerance has been reached&#63; Can the health system afford the expense&#63; Other approaches are sublingual &#40;peach and hazelnut&#41; and epicutaneous &#40;still under development&#41; immunotherapy&#46; And&#44; finally&#44; the use of heated allergens seems to be a valuable method of specific food desensitization&#46; Traditionally&#44; food allergic children are advised to avoid all forms of specific treated proteins in their diets&#46; Lately&#44; some studies encourage the ingestion of baked egg and milk in allergic patients&#44; under the hypothesis that the heating of proteins on a cereal matrix destroys conformational epitopes decreasing allergenicity&#46; This is an invigorating new pathway as it has been shown that these treated foods can hasten the acquisition of desensitization&#47;tolerance to that specific food&#44; measured by clinical responses and immunological changes&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> Nevertheless&#44; patients should be chosen carefully&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion&#44; food allergy is a frequent and important problem in our children&#46; Avoidance of the specific food represents only a lack of treatment which leaves the child exposed to hidden proteins with the potential risk of anaphylaxis&#44; as well as nutritional deficiency and social exclusion&#46; OIT methods are being investigated with promising results which encourage the researchers to find the correct pathway&#44; although adverse events should not be dismissed&#46; Common protocols between Reference Centers should be designed&#46;</p></span>"
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Editorial
Oral immunotherapy in food allergy: Present and future
Inmunoterapia oral en la alergia a alimentos: presente y futuro
M. Alvaroa,
Corresponding author
malvaro@hsjdbcn.org

Corresponding author.
, A. Murarob
a Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Esplugues, Universitat de Barcelona, Spain
b Food Allergy Referral Centre for Diagnosis and Treatment, Veneto Region, Department of Women and Child Health, Padua University Hospital, Padua, Italy
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Food allergy &#40;FA&#41; is an important and frequent health problem in our children&#44; and&#44; in Europe&#44; cow&#39;s milk proteins &#40;CMP&#41; and hen&#39;s egg proteins &#40;HEP&#41; are the main offenders&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> The risk of anaphylaxis in IgE-mediated FA is high&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> Its impact on children and on their environmental quality of life&#44; as well as the nutritional aspects&#44; should not be dismissed&#46; Resolution of symptoms during strict avoidance and their reappearance during the double blind placebo control food challenge &#40;DBPCFC&#41; remain the gold standard for the diagnosis of FA&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Until very recently&#44; a single approach was available for the treatment of food allergy&#58; avoidance of the offending food&#46; From our point of view&#44; this approach only represents a lack of treatment and it also leaves the child unprotected from hidden or small amounts of the offending food&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The largest immune organ in the body is the intestine&#46; It is constantly working to protect our body from pathogens and also from external proteins&#46; Oral tolerance is an active immunological process which makes the intestine unresponsive to any food&#44; while FA is the result of its breakdown&#46; The mechanisms involved in the development of oral immune tolerance remain unclear but they seem to depend basically on age and dose of the administered food&#46; The main immunomodulatory cytokines in the gut are IL-10 and TGF-&#946; and in this milieu antigen-specific regulatory cells &#40;CD4<span class="elsevierStyleSup">&#43;</span>CD25<span class="elsevierStyleSup">&#43;</span>FOXP3<span class="elsevierStyleSup">&#43;</span>&#41; are essential&#46; In a genetically predisposed child&#44; those cells and cytokines are not present &#40;or in low numbers&#41; in the gut and the development of FA becomes a fact&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Lately&#44; some protocols on oral immunotherapy &#40;OIT&#41; are being investigated in Reference Centers&#46; OIT has as its first aim to increase the amount of food that the child can tolerate without reacting to it&#44; i&#46;e&#46; preventing anaphylaxis&#46; This is usually achieved with the consumption of small amounts of the allergen&#46; Another aim of this technique is to reach a desensitization state&#44; which allows the child to follow a &#8220;normal&#8221; social life and to achieve an adequate nutritional state&#46; And&#44; finally&#44; the goal of reaching permanent tolerance is of great interest&#46; At this point&#44; it is very important to distinguish between the terms &#8220;desensitization&#8221; and &#8220;tolerance&#8221;&#46; A child is desensitized to a specific food when he&#47;she goes on eating that food daily with the previously recommended amounts&#44; and no reactions are elicited&#46; Moreover&#44; a child becomes tolerant to a specific food when&#44; once the daily intake of the food has been interrupted&#44; he can eat it&#44; whenever he wants&#44; without reactions&#46; So&#44; the ultimate goal of food allergy therapy is permanent oral tolerance&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Before starting OIT&#44; an oral food challenge &#40;OFC&#41; should be performed&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> to assure that the child is still allergic to that food &#40;although skin prick test and s-IgE remain positive&#41;&#46; Parents of all children must sign an informed consent&#44; and the procedure must be approved by the ethics hospital committee&#46; Once allergy is established&#44; the procedure starts with a build-up phase in which small amounts of the diluted food are given to the patient at Hospital&#46; Emergency medications including epinephrine&#44; hydroxyzine&#44; salbutamol and prednisone must be available&#44; and possible symptoms to be evaluated are itching&#44; urticaria&#44; angioedema&#44; exacerbation of eczema&#44; rhinitis or conjunctivitis&#44; dyspnea and wheezing&#44; vomiting&#44; diarrhea and hypotension&#46; Once discharged&#44; the patient must receive the exact amount of the food&#44; daily&#44; at home&#46; The doses are slowly &#40;usually weekly&#41; increased at the out-patient Clinic&#44; until a usual amount of the food is reached &#40;maintenance phase&#41;&#46; The food must be taken daily at home and other amounts of the same protein can be eaten&#44; although always separately from the dose&#46; The dose should never be given on an empty stomach&#46; Patients are recommended to avoid exercise for 3<span class="elsevierStyleHsp" style=""></span>h after the food intake&#46; If there is an intercurrent illness&#44; the dose is not increased&#44; and the previous dose is repeated&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> This is a time-consuming procedure in which the commitment and compliance of the child and the families are crucial&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In many countries OIT protocols have been developed and research on this area is becoming an important feature in pediatric allergy&#46; Milk and egg allergies are the most frequently treated allergies regarding this approach&#46; Most of the international publications show successful desensitization rates which range from 60&#37; to 100&#37; in different studies&#46; But the acquisition of real tolerance remains unknown as there are only a few studies which evaluate the outcome after the discontinuation of the daily intake of the food&#46; Peanut has also been lately a target for OIT and some encouraging results have been published&#44; although the safety is a big concern&#46; Other foods are under research with no results available yet&#46; The main problem regarding OIT is the possibility of adverse events&#46; These are frequent and sometimes severe&#46; During the last two years&#44; two publications<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">3&#44;4</span></a> gave a view on egg &#40;study on 51 patients&#41; and milk &#40;study on 81 patients&#41; OIT adverse events&#58; most of the patients suffered adverse events &#40;95&#37; in cow&#39;s milk allergy and 90&#37; in egg allergy&#41;&#44; although frequency was low in relation with the administered doses &#40;6&#46;6&#37; and 7&#46;6&#37;&#44; respectively&#41;&#46; Most of the OIT reactions were mild &#40;grades 1 and 2&#41; although some patients suffered grade 4 reactions&#46; Respiratory adverse events were more frequent during cow&#39;s milk OIT&#44; while gastrointestinal reactions were more frequent during egg OIT&#46; These results emphasize the need for well-trained medical personnel and adequate hospital facilities &#40;intensive care unit&#41; available if this treatment is to be followed&#46; On the other hand&#44; for the subgroup of anaphylactic patients&#44; the odds of ever outgrowing the allergy are small and the risk of future severe reactions high&#46; Under these circumstances&#44; this approach would be justified&#58; the more severe the food allergy is and the more common the implicated food&#44; the better the cost&#47;benefit ratio is for OIT approach&#44; including anaphylactic patients&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The use of concomitant treatments such as omalizumab &#40;anti-IgE monoclonal antibody&#41; has also been studied&#44; the results being encouraging&#46; But some questions arise&#58; when should omalizumab be discontinued once desensitization&#47;tolerance has been reached&#63; Can the health system afford the expense&#63; Other approaches are sublingual &#40;peach and hazelnut&#41; and epicutaneous &#40;still under development&#41; immunotherapy&#46; And&#44; finally&#44; the use of heated allergens seems to be a valuable method of specific food desensitization&#46; Traditionally&#44; food allergic children are advised to avoid all forms of specific treated proteins in their diets&#46; Lately&#44; some studies encourage the ingestion of baked egg and milk in allergic patients&#44; under the hypothesis that the heating of proteins on a cereal matrix destroys conformational epitopes decreasing allergenicity&#46; This is an invigorating new pathway as it has been shown that these treated foods can hasten the acquisition of desensitization&#47;tolerance to that specific food&#44; measured by clinical responses and immunological changes&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> Nevertheless&#44; patients should be chosen carefully&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion&#44; food allergy is a frequent and important problem in our children&#46; Avoidance of the specific food represents only a lack of treatment which leaves the child exposed to hidden proteins with the potential risk of anaphylaxis&#44; as well as nutritional deficiency and social exclusion&#46; OIT methods are being investigated with promising results which encourage the researchers to find the correct pathway&#44; although adverse events should not be dismissed&#46; Common protocols between Reference Centers should be designed&#46;</p></span>"
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Article information
ISSN: 23412879
Original language: English
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Idiomas
Anales de Pediatría (English Edition)
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