Food Allergy and Intolerance in Children and Adolescents, an Update

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. Whenever one panied by generalized reaction or as consequence of may expect that the challenge might elicit acute and easily inhalation of volatile food allergens (Crespo et al, 1995a ± observed symptoms, such as happens in most cases of d; Dominiguez et al, 1996). immediate-type reaction to foods in the infant and young The diagnosis of food allergy is still problematic even in child, it is suf®cient to perform the challenge by an open- the case of atopy or IgE mediated hypersensitivity. There is label or single-blinded method. Whenever symptoms are a lack of standardized diagnostic procedures; the only test atypical, without a direct relationship to the intake of the accepted as `gold standard' for con®rmation of food allergy food item or it is dif®cult to be objective about them, and in general for food intolerance, is a properly performed particularly in older children and adults, it may be prefer- double-blind placebo-controlled oral food challenge able to perform the challenge in a double-blind manner so (DBPCFC) (Bock, 1997). The diagnosis of food adverse that results can be better trusted (Bock, 1987; Crespo et al, reactions begins with a careful medical history, recording 1998).

European Journal of Clinical Nutrition Food allergy and intolerance CY Pascual et al S77 Contraindications to a challenge test are limited to those deep freezing (Pascual & Crespo, 1995). The prevalence of situations that can be hazardous for the patient (history of Anisakis spp.-speci®c IgE in the general population is about anaphylactic shock, edema of the glottis, recurrent general- 15%, while in atopic children with crustacean sensitization ized urticaria) in relationship to the studied food, or there is and urticaria the prevalence is 81% (Pascual et al, 1996a, b; a recent evidence of symptoms related to the ingestion of 1997a, b). that food, together with the presence of speci®c IgE. In Heating and long storage can also modify the food infants sensitized to a food that had never previously been allergenicity, creating new epitopes recognized by some ingested, the challenge test will be delayed until that food is patients (Malanin et al, 1995). The modi®cation of soy to be introduced in his=her diet (Bock, 1997). beans through biotechnology, adding brazil nut genes to Prevalence of food allergy is higher in children than in ameliorate its amino acid composition, made them aller- adults; in prospective studies of adverse food reactions in genic for patients sensitized to brazil nuts (Nordlee et al, small children, about 80% outgrow their problem after the 1996). third year of life (Bock, 1987). One-third of food allergic The transfer of symptomatic peanut allergy to the patients lose their sensitivity after 2 y of an avoiding diet recipient of a combined liver and kidney transplant is a (Sampson & Scanlon, 1989). The lasting of clinical sensi- new method of transfer of food allergy brought by the tization depends on the sensitizing allergen Ð patients with progress of medical sciences that will be found more milk allergy are more prone to loosing their sensitization in frequently in the future (Legendre et al, 1997) 1 or 2 y than those who are allergic to eggs. Patients The treatment of food allergy and intolerance is avoid- sensitized to ®sh, nuts, shell®sh or legumes will rarely ing the implicated food as long as necessary, until tolerance tolerate the incriminated food (Crespo et al, 1995a ± d). appears. Immunotherapy is not yet well documented. The Some allergens have peculiasities that need to be known EAACI position paper on food adverse reactions points out for a better understanding of the clinical aspects of food some indications for dietary management (Bruijnzeel- allergy. Although the vast majority of IgE mediated allergic Koomen et al): reactions to ®sh come from ingestion, a few cases of unexpected allergic reactions to ®sh could take place (1) Correct identi®cation of the offending foods and addi- through the exposure to airborne ®sh particles. The steam tives. acrosols from salmon share IgE-binding components with (2) Knowledge of potential hidden sources of the food raw and boiled salmon, which corroborate the risk of items. allergic reactions in ®sh-allergic patients being caused by (3) Awareness of possible cross-reactivities between foods exposure to airborne ®sh particles (Crespo et al, 1995a ± d; and inhalants. Pascual et al, 1996). (4) Proper supervision of elimination diets with regards Latex allergy also has been reported to be associated to nutritional requirements, particularly in growing with allergy to certain foods such as chestnut, avocado, children.' banana, kiwi, potatoes and tomatoes. Up to 70% of adult Prevention of food allergy is the ®rst goal of every latex allergic patients react with a positive skin prick test to pediatric allergologist. Controlled trials of food allergy at least one food, but the majority of positive skin prick prevention have been performed only in high allergic risk tests to foods were not associate with symptomatic allergy. children (BjoÈrksten, 1994; Zeiger, 1994). There can be The reason for cross-reaction between rubber latex and considered to be three steps in preventive measures, pri- fruits is also not completely known, but some of the latex mary (children at risk without disease), secondary (patients allergenic proteins have homologies with fruit and other with early indicators of disease), and tertiary (patients with vegetable allergens (Breitenender & Scheine; 1998. Blanco evidence of chronic disease) Holt et al, 1998). The mea- et al, 1994; Beezhold et al, 1996). sures of primary prevention are directed towards diminish- Recently, several publications have described the occur- ing the number of allergens to which infants are exposed rence of cross-reactivity among crustaceans and molluscs early in life. The successful results of this preventive with aeroallergens from arthropods. Food allergy caused by strategy is based on cooperation between health profes- snails seems to prevail in patients sensitized to mites. sionals, including allergologists, and motivated parents. Cross-reactivity exists between larvae of chironomids (non-biting midges) and shrimp and also between shrimp and cockroach (Van Ree et al, 1996; Shanti et al, 1993). References In a recent study, we used a serum pool from children Baldwin JL, Chou AH & Solomon WR (1997): Popsicle induced anaphy- sensitized to German cockroach and boiled Atlantic shrimp laxis due to carmine dye allergy. Ann. 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