European Journal of Clinical Nutrition (2000) 54, Suppl 1, S75±S78 ß 2000 Macmillan Publishers Ltd All rights reserved 0954±3007/00 $15.00 www.nature.com/ejcn Food allergy and intolerance in children and adolescents, an update CY Pascual1*, JF Crespo2, PG Perez1 and MM Esteban1 1Hospital Universitario `La Paz', Madrid, Spain; and 2Hospital 12 de Octubre, Madrid, Spain Epidemiological surveys demonstrate that rapid increase in allergic diseases is a real phenomenon. In developed countries they are about the commonest chronic diseases, reaching between 15% and 30% of the population. Adverse reaction to food can be divided into toxic reaction and non-toxic reactions. The non-toxic reactions are divided into non-immune mediated and immune mediated, these are considered food allergic reactions. We showed our experience in a 4 y survey, individualized by food allergens during the ®rst two years of life. In Spain egg white protein is the most common allergen followed by cow's milk and peanuts. These three food items represent half of the sensitizations in children under 2 y of age. After 4 y sensitivities to vegetable allergens such as nuts, fruits and legumes are most frequent. The diagnosis of food allergy is still problematic, even in the case of atopy or IgE mediated hypersensitivity. There is a lack of standardized diagnostic procedures; the only test accepted as `gold standard' for con®rmation of food allergy and in general for food intolerance, is a properly performed double blind placebo-controlled oral food challenge. Negative results should be always followed by an open food challenge. This test should only be conducted in patients with a good medical condition and in a clinic or hospital setting, and only if trained personal and equipment for treating systemic anaphylaxis are present. Contraindications to a challenge test are limited to those situations that can be hazardous for the patient in relationship to the studied food. The treatment of food allergy and intolerance is avoiding the implicated food as long as necessary, until tolerance appears. Prevention of food allergy is the ®rst goal of every pediatric allergologist. Controlled trials of food allergy prevention have been performed only in high allergic risk children. Descriptors: food allergy; children; adolescents; food allergens European Journal of Clinical Nutrition (2000) 54, Suppl 1, S75±S78 Food allergy and intolerance Food allergy can be IgE mediated, also called atopy, and non-IgE mediated. The only well known and proven Epidemiological surveys demonstrate that rapid increase immunologic mechanism in food allergy is the IgE in allergic diseases is a real phenomenon. Interactions of mediated, the other immune mechanisms are suspected various factors are involved, such as changes in feeding but none of them have proven yet to be certain (Bruijn- habits, housing and environment. In developed countries zeel-Koomen et al, 1995). they are about the commonest chronic diseases, affecting The magnitude of IgE mediated immune response to between 15% and 30% of the population (European Allergy allergens is determined by the equilibrium balance between White Paper, 1997). the Th1 and Th2 populations of T-helper cells (Holt et al, Adverse reactions to food are frequently suspected due 1998). The Th1 population is dominant in strains of IgE in to increasing public awareness of the relationship between low responders and the Th2 phenotype IgE in high respon- diet and health. Twenty percent of the population report ders, on an experimental basis in rat pups. The Th2 some type of food adverse reaction (Young et al, 1994). response in the high responder can be suppressed by Reports from the USA claim a prevalence in food allergy of exposure to infection concomitantly with the allergen in 13% for children and 7% for adults, in Europe the claimed high doses. Switching to a Th2 response can be induced in prevalence is 0.3 ± 7% for children and 2% for adults. The low responders by exposing them to allergen and tobacco prevalence is higher, 10%, among atopic people (Kajosaari, smoke in a simultaneous way. It can only happen in 1982, Crespo et al, 1995a ± d). immunologically naive rat pups. These experimental data Adverse reaction to food can be divided into toxic are re¯ected in the enhancing factors of food allergy reactions and non-toxic reactions. Toxic reactions can (BjoÈrksten, 1997). appears in any exposed individual, and the toxicity can We used our experience in a 4 y survey and individua- be naturally induced during food processing or by external lized by food allergens during the ®rst 2 y of life (Table 1, contamination. The non-toxic allergic reactions are divided Figure 1). All food allergens are potentially sensitizing; into non-immune mediated (food intolerance) and immune their prevalence is in relationship to the feeding habits of mediated, these are considered food allergic reactions. the community. In Spain egg white protein is the most common allergen followed by cow's milk and ®sh (Crespo *Correspondence: CY Pascual, Servicio de Alergia PediaÂtrica, Laboratorio et al, 1995a ± d). In USA the triad is egg, cow's milk and de Inmunoalergia, Hospital Universitario `la Paz', Castellana 261, 28046 peanuts (Bock, 1987). These three food items represent half Madrid, Spain. E-mail: [email protected] of the sensitizations in children under 2 y of age. After 4 y, Guarantor: National Institute of Health (INSALUD). sensitivities to vegetal allergens as nuts, fruits and legumes Food allergy and intolerance CY Pascual et al S76 Table 1 Food allergens: prevalence; 3205 patients under 15 y (1994 ± food intake and its relation to clinical symptoms, quantity 1998) of food, elapsing interval, family history of atopic or related Cases (%) symptoms, calendar of food introduction in children etc. The differential diagnosis of IgE mediated food allergy Egg 1017 31.7 should be done with entities which present similar symp- Nuts 474 14.8 toms but are not related to food: diseases with vomiting and Cow's milk 450 14.0 Fish 408 12.7 diarrhea in children. Differential diagnosis should also Fresh fruits 322 10.0 include other reactions to food of possible immunological Legumes 252 7.9 mechanism, but not mediated by IgE, such as cow's milk Crustaceans and molluscs 208 6.5 enteropaty due to protein hypersensitivity. The differential Vegetables 204 6.4 diagnosis also needs to include non-immunological food Meats 170 5.3 Cereal grains 35 1.1 intolerance syndromes and reactions by toxic agents which Others 3 0.1 contaminate or were generated during food processing (Burks & Sampson, 1992). The pathogenic diagnosis is based on the presence of speci®c IgE antibodies in vivo or in vitro to the suspected food. The search in vivo is done by skin prick-test Intracu- taneous tests are not recommended because of its lack of speci®city and the danger of systemic reaction in highly sensitized patients. Fresh food may be used, with the puncture of food with a prick-test needle and immediately pricking the skin; this is called the Prick-by-Prick method and many times is more sensitive than using commercial extracts (Bruijnzeel-Koomen et al, 1995). The prick-test done with high quality allergens, if performed correctly, for practical reasons is the choice method to con®rm diagnosis of IgE mediated food hypersensitivity (Bock, 1987). Although its positive predictive value is lower than 50%, a negative skin prick test practically excludes the possibi- Figure 1 Food allergen prevalence. Allergy outpatient setting 1994 ± lity of a positive challenge test, unless we are dealing with a 1998. Predominant sensitizations at different ages Ð milk in the ®rst year non-IgE mediated reaction. The interpretation of a prick of life, egg during the second. test should be done according to EAACI guidelines. The alternative to cutaneous test is the search for in vitro IgE speci®c antibodies. The advantage is the number of aller- are more frequent and also sensitization to pollen is very gens that can be tested with a single blood sample, but the often found in these patients (Crespo et al, 1995a ± d). cost is high. The sensitivity is similar to the skin prick test The clinical symptoms elicited by food involve different and both share the problems with non-standardized aller- organs and systems, but those that correspond to the classic gens and the quality of commercial sources of allergenic allergic symptoms are the only ones clearly identi®ed with material. Other tests such as histamine release from baso- food allergy, i.e. (systemic anaphylaxis, exercise-induced phils or from duodenal mast cells, or measurement of anaphylaxis, urticaria and angioedema, oral allergy syn- histamine in gastric lavage ¯uid after challenge, are con- drome, atopic dermatitis, rhinitis, asthma, vomiting and sidered as experimental procedures. Immunoassays for diarrhea. Other manifestations such as coeliac disease, mast cell tryptase and cosinophil derived protein as eosi- dermatitis herpetiformis, eosinophilic gastroenteritis, nophil peroxidase (EPX) or eosinophilic cationic protein ulcerative colitis and allergic vasculitis are supposed to (ECP) are promising but their clinical usefulness has not be associated with an immunological mechanism, but clear been completely documented (Bruijnzeel-Koomen et al, demonstration of this relationship is still missing. The signs 1995; Crespo et al, 1998). and symptoms due to immediate hypersensitivity appear A positive DBPCFC, properly performed, is the only rapidly, even immediately, usually within 1 h of the intake conclusive evidence of a food allergy. Negative results of related food (Bruijnzeel-Koomen et al, 1995). Mucocu- should be always followed by an open food challenge. taneous (urticaria, angioedema and OAS) and acute diges- The challenge test should only be conducted in patients tive symptoms predominate (Crespo et al, 1995a ± d). In with a good medical condition and in a clinic or hospital strongly sensitized individuals respiratory symptoms some- setting, and only if trained personnel and equipment for times appear (rhinitis and asthma) and are usually accom- treating systemic anaphylaxis are present.