Food allergy: a winding road to the present

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Around 25 yrs ago, Bengt Bjorksten came to me and said that he would like to start a journal to highlight pediatric allergy and immunology. While I was fully supportive, it was really the hard work, determination, and foresight of Bengt, along with help from Sten Dreborg, that launched the first issue of Pediatric Allergy and Immunology (PAI) in 1990. Although the field was small, Bengt, together with a cadre of friends from around the world, nurtured the new journal, which helped highlight the specialty of allergy and immunology in pediatrics and which today has become a show place for our subspecialty. Much has changed since that first issue in October 1990, and nowhere has there been greater change than in my special area of interest, food allergy.

At the time PAI was founded, the field of food allergy was just coming out of its scientific infancy. There were few investigators in the USA and Europe focusing on food allergy and most physician scientists looked at it as a dubious area of investigation and a minor nuisance for patients, with 0.1–0.5% of children being affected. May and Bock had published their findings of the double-blind placebo-controlled oral food challenge (DBPCFC) as a diagnostic test for food allergy over a decade earlier [1], and subsequent studies affirmed that it was the ‘gold standard’ for diagnosing food allergies [2]. While the DBPCFC was accepted as ‘diagnostic’ for food allergy, it bolstered the arguments of ‘food allergy agnostics’ that skin tests and radioallergosorbent tests [(RASTs) used at that time] were of little use in diagnosing clinical reactivity to food. By this time, most allergists recognized the association between food allergy and flares of atopic dermatitis, and some pediatric allergists were using the DBPCFC to accurately diagnose food allergy and implement appropriate food elimination diets in children with food allergies. Allergic reactions to egg and milk far outstripped allergies to other foods at the time, food allergies were thought to play little role in other allergic disorders, and food-induced anaphylaxis and non-IgE-mediated food allergies were rarely discussed. A number of epidemiologic studies suggested that young infants from atopic families were at increased risk for food allergies and that exclusive breast feeding or use of hypoallergenic diets in conjunction with elimination of major food allergens in the maternal and newborn diets was useful in preventing atopic dermatitis and some food allergies [3, 4]. Management of food allergies consisted solely of implementing strict elimination of the causative allergens from the diet.

Much has changed in the field of food allergy over the past 25 yrs, and many of our earlier practices have not stood the test of time. While the prick skin test is still used in the evaluation of food allergy, it is now recognized that the mean wheal diameter directly correlates with the likelihood that the child will react to a food [5], providing a more predictive measure of food allergy. With the demonstration that food-specific IgE levels also correlate directly with the likelihood of clinical reactivity to foods [6], the RAST has largely disappeared and has been replaced by quantitative tests of serum food-specific IgE antibody levels. Much has been learned in the past 25 yr about the major allergenic proteins within foods, and today, measurement of food allergen component proteins, for example, Ara h 2, is beginning to provide even more accurate means of predicting clinically relevant food allergy [7]; food allergenic epitope-based assays show promise of providing even more specific information [8]. As shown in Table 1, a variety of IgE-mediated and non-IgE-mediated disorders are now recognized to be secondary to food allergies. Along with this recognition of more food allergic disorders, the prevalence of food allergies has increased dramatically in developed countries around the world, especially peanut and tree nut allergy, which have tripled over the first decade of this century in the USA [9] and several other countries. Food allergy is now believed to affect up to 4–5% of children in some countries. Perhaps, most alarming, however, is the apparent increase in fatal food-induced allergic reactions, [10] especially in adolescents and young adults, which were rarely seen 25 yrs ago. In retrospect, it appears that several of our previous practices may have contributed to the increase in food allergy. Several studies in the past 25 yrs have failed to support the prophylactic value of allergen-restricted diets in pregnant mothers and their offspring, and some more recent studies even suggest that delayed introduction of foods to young, high-risk infants actually increases the likelihood of their developing food allergy [11, 12]. In addition, over the past two decades, it appears that many children are taking longer to ‘outgrow’ their milk and egg allergy, a period of time that corresponds to the increasing utilization of strict allergen elimination diets for the treatment of children with these allergies. Recent studies indicate that about 80% of young children with milk and egg allergy can tolerate these foods in baked forms, that is, extensively heated proteins that have become denatured, and that the addition of heat-denatured proteins into the diet actually leads to more rapid development of tolerance to all forms of milk and egg [13, 14].

Table 1. Food-induced allergic disorders
IgE-mediated reactionsMixed IgE- and Non-IgE reactionsNon-IgE-mediated reactions

Skin:

Urticaria; angioedema; generalized flushing

Atopic dermatitisContact dermatitis; dermatitis herpetiformis

Respiratory:

Allergic rhinoconjunctivitis; laryngeal edema; bronchospasm

AsthmaHeiner's syndrome (food-induced pulmonary hemosiderosis)

GI:

Oral allergy syndrome; acute colic, vomiting and diarrhea

Eosinophilic esophagitis

Eosinophilic gastroenteritis

Food protein-induced

 Enterocolitis syndrome

 Proctocolitis syndrome

 Enteropathy syndrome

Celiac disease

Generalized:

Anaphylaxis

  

Twenty-five yrs ago, management of food allergy consisted solely of educating patients and their families on how to avoid allergenic foods, and about 15 yrs ago, the strategy of arming food allergic patients with epinephrine auto-injectors to treat accidental ingestions began to take hold. Virtually, no one was attempting to utilize immunotherapeutic approaches to treat patients with food allergies, even though the first use of oral immunotherapy had been published in 1908 [15]. Today, many studies on oral, sublingual, and epicutaneous immunotherapy have appeared in the scientific literature and show considerable promise for desensitizing food allergic patients. In addition, a number of novel therapies are in the pipeline, which should lead to safer and more effective treatments for food allergy [16].

During the life of PAI, the field of food allergy has gone from the ‘poor stepchild’ of allergy to one of the most attractive and rapidly growing areas of our specialty, and pediatricians have largely led the way. Many young investigators have entered the field, and the generation of new information has increased exponentially, as witnessed by the numbers of abstracts presented at international meetings and the hundreds of articles published yearly in peer-reviewed scientific journals. While a great deal has been learned about the allergenic properties of foods and the basic immunologic mechanisms underlying food allergy over the past 25 yrs, much remains to be discovered about the optimal way to prevent, diagnose, and manage food allergies in our patients. The investigational era of immunotherapy for treating food allergy is off to a strong start and new areas, such as the microbiome, which affect how we respond to our food and environment (as proposed by PAI's first editor more than a decade ago) may dramatically alter the way we approach prevention and treatment for allergic disease. With an ever-expanding pool of talented young investigators focusing on food allergy and our knowledge-base and technological capabilities continuing to increase exponentially, I see a very bright future for PAI as it continues to document the exciting new advances in food allergy and other areas of our specialty.

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