IgE-mediated or immediate hypersensitivity reactions are associated with the rapid onset of symptoms, usually within minutes to a few hours, after the ingestion of the offending food. Immediate hypersensitivity reactions are mediated by an allergen-specific IgE antibody, as depicted in Figure 102.1 (4). Food allergens are typically naturally occurring proteins in foods (7). In IgE-mediated food allergies, exposure to the allergen stimulates the production of allergen-specific IgE antibodies in susceptible individuals (5, 6). The allergen-specific IgE attaches itself to the surface of mast cells in various tissues and basophils in the blood. This process is known as sensitization.

During the sensitization phase, the susceptible individual may form allergen-specific IgE antibodies on exposure to a specific food protein. However, even among susceptible individuals, exposure to food proteins does not usually result in the formation of IgE antibodies. In normal individuals, exposure to a food protein in the gastrointestinal tract results in oral tolerance through either the formation of protein-specific IgG, IgM, or IgA antibodies or no immunologic response whatsoever (clonal anergy) (8, 9). Heredity and other physiologic factors are important in predisposing individuals to the development of IgE-mediated allergies, including food allergies (10). Monozygotic and dizygotic twins demonstrate that genetics is an extremely important parameter, and identical twins may inherit the likelihood of responding to the same allergenic food, such as peanuts (11, 12). Approximately 65% of patients with clinically documented allergy have first-degree relatives with allergic disease (10). Conditions that
increase the permeability of the small intestinal mucosa to proteins such as viral gastroenteritis, premature birth, and cystic fibrosis also seem to increase the risk of development of food allergy.

Although no symptoms occur during the sensitization process, the affected individual is now primed for an allergic reaction. On subsequent exposure to the allergenic food, the allergen cross-links IgE molecules on the surface of the mast cell or basophil membrane, causing these cells to release various mediators of the allergic reaction into the bloodstream and tissues. Dozens of physiologically active mediators of the allergic reaction have been identified (13). Histamine is one of the most important mediators of the immediate hypersensitivity reaction and can elicit inflammation, pruritus, and contraction of the smooth muscles in the blood vessels, gastrointestinal tract, and respiratory tract (6). Other important mediators include various leukotrienes and prostaglandins (6, 13). The released mediators interact with receptors in various tissues, eliciting a wide range of physiologic responses. Because the mediators are released into the bloodstream, systemic reactions involving multiple tissues and organs can ensue.

Allergies to pollens, mold spores, animal danders, dust mites, certain drugs (e.g., penicillin), and bee venom also occur through this same IgE-mediated mechanism. Susceptible individuals may form allergen-specific IgE to one or several substances, including food allergens. Occupational food allergies are also known to occur where individuals are affected by contact with or inhalation of the offending food rather than its ingestion (14).

The Food and Agriculture Organization (FAO) of the United Nations has established that peanuts, soybeans, fish, crustacea, milk, eggs, tree nuts, and wheat are the most common allergenic foods on a worldwide basis (21). Perhaps 90% of all IgE-mediated food allergies are caused by these eight foods or food groups, sometimes referred to as the big eight. The big eight actually involves many more than eight foods because several food groups are included. Fish refers to all species of finfish, although some species of fish such as cod and salmon are more commonly allergenic than others (22, 23). Shrimp, prawns, crab, lobster, and crayfish are included in the category of crustacea; most individuals with crustacean allergy are sensitive to all species (24). Egg-allergic individuals are allergic to the eggs of all avian species (25). Furthermore, both egg white and egg yolk contain allergens (26), although egg white is considered to be the more potent sensitizing fraction. Milk-allergic individuals are primarily sensitized to cows’ milk, but typically are also reactive to the milk of other species, including goat and sheep (27). The commonly allergenic tree nuts include almonds, walnuts, pecans, cashews, Brazil nuts, macadamias, pistachios, hazelnuts (filberts), hickory nuts, chestnuts, and pine (pinyon) nuts (2). Although sometimes included in the tree nut category, coconuts, kola nuts, and shea nuts are rarely, if ever, allergenic. Cross-reactions do not inevitably occur with closely related foods. Although there are several hundred species of edible legumes, peanuts and soybeans account for the vast majority of legume-related food allergies. However, several other legumes, including lentils, beans, and garbanzo beans (chickpeas), occasionally have caused serious allergic reactions (28, 29).

Although the eight most commonly allergenic foods and food groups account for more than 90% of all IgE-mediated food allergies on a global basis, more than
160 other foods have been documented in the medical literature on one or more occasions to elicit food allergies (30). Any food that contains protein has the potential to elicit allergic sensitization. Generally, foods that are major sources of protein and that are frequently consumed in the diet are most likely to cause allergic reactions. However, certain foods that are considered to be good sources of protein, such as beef, pork, chicken, and turkey, are rarely allergenic (30).

Although the FAO list of the eight most commonly allergenic foods or food groups is reasonably well accepted, various regulatory jurisdictions have established their own list of commonly allergenic foods (Table 102.3). These lists are used for food labeling regulations in these areas. The lists partially reflect the fact that unique cultural dietary patterns may affect the comparative prevalence of specific allergenic foods. For example, lists in Canada, the European Union, and Australia/New Zealand include sesame seed, a common allergenic food among certain Asian and Middle Eastern cultures (31). By contrast, sesame seed allergy appears to be comparatively uncommon in the United States. Although the earliest European lists included sesame seed, mustard, and celery (uniquely allergenic in central Europe, where celeriac is a more common food ingredient), the development of a scientific approach to construction of such lists in Europe (32) led to a decision to add molluscan shellfish and an emerging allergenic food, lupine (33), to the European Union list. Molluscan shellfish are also on the list in Canada. Mustard is on the list of commonly allergenic foods in the European Union and Canada, even though the prevalence of mustard allergy is not very well established; mustard allergy has principally been reported in France and Spain for unexplained reasons (34). Buckwheat is included on the list of commonly allergenic foods in Japan and Korea and appears to be a commonly allergenic food in those countries, probably because of frequent exposure to soba noodles (35).

Virtually all of the allergens in foods are naturally occurring proteins (7). However, foods contain millions of proteins and relatively few are known to be allergens. Allergenicity does not appear to be an inherent property of proteins, although all proteins are capable of provoking immune reactions under selected circumstances. Some commonly allergenic foods, including peanuts, eggs, milk, and soybeans, contain multiple allergens (7). Other commonly allergenic foods appear to contain only a single major allergen, including cod and Brazil nut (7). Major allergens are generally defined as proteins for which 50% or more of the allergic patients have specific IgE (7). Plant food allergens tend to fall into certain functional categories, such as some of the pathogenesis-related proteins or certain classes of storage proteins (36). For example, the 2S albumins, storage proteins rich in sulfur-containing amino acids, are major allergens in peanuts, Brazil nuts, sesame seeds, walnuts, sunflower seeds, and mustard (37). Similarly, several pan-allergens appear to exist in allergenic animal species, such as the parvalbumin in fish (38) and tropomyosin in crustaceans (39).

Allergic diseases are estimated to affect 10% to 25% of the general population (4). The prevalence of IgE-mediated food allergies in the United States can be estimated at 3.5% to 4.0% of the population, based on surveys indicating that the prevalence of shrimp, peanut, tree nut, and fish allergies as 1.9%, 0.76%, 0.62%, and 0.4% of the overall population (40, 41). IgE-mediated food allergies are more common among infants and young children than among adults; the prevalence in children under the age of 3 is in the range of 5% to 8% (42). Although food allergies develop most commonly in early childhood, they can develop later in life. For example, crustacea are among the most common allergenic foods among adults (41), but that
food allergy is rarely seen among young children, probably because of their infrequent ingestion of crustacea.

The prevalence of IgE-mediated food allergies to specific foods has been evaluated primarily on the basis of random digit-dial telephone surveys (40, 41). For certain types of food allergies, including immediate hypersensitivity reactions associated with noteworthy symptoms, these telephone surveys are arguably reasonably accurate. However, clinical confirmation of these estimates has not been obtained, making prevalence estimates uncertain (43). A large effort is being completed in Europe, through a project called EuroPrevall, to prepare a more reliable estimate of prevalence based on clinical confirmation. As noted, there is general agreement that eight foods or food groups comprise the majority of IgE-mediated food allergies (21). This is based primarily on comparative prevalence studies conducted in allergy clinics with groups of patients (44).

Fewer studies have attempted to determine the prevalence of specific food allergies among the general population. The prevalence of adverse reactions to foods, as confirmed by double blind, placebo-controlled food challenge (DBPCFC) during the first 3 years of life among 480 consecutively born infants in a community in Colorado, was 8% (45). Of these children, 25 (5.2%) were suspected to be allergic to cows’ milk, but DBPCFC confirmed sensitivity to cows’ milk in only 11 (2.3%) (45). In a prospective study of 1,749 newborns in a single hospital in Denmark during 1985, 39 (2.2%) were found to have adverse reactions to cows’ milk (46). Similarly, Jakobsson and Lindberg (47) followed a cohort of 1079 Swedish newborns and found that 1.9% developed sensitivity to cows’ milk. A prevalence rate of 2.8% was observed in challenge studies conducted on a group of Dutch infants (48). The overall prevalence of food allergies among a birth cohort in Australia was estimated at about 8.5%, with 3.2% for egg, 2.0% for milk, 1.9% for peanut, and 0.42% for sesame seed (49).

Many young children outgrow their food allergies within a few months to several years after the onset of the hypersensitivity (6, 50). As many as 80% to 87% of children identified with food allergies are able to tolerate the offending food by 3 years of age (50). Allergies to certain foods, such as cows’ milk, are more commonly outgrown than are allergies to other foods, such as peanut (50). Exceptions do exist, as perhaps 20% of peanut-allergic individuals ultimately become tolerant (51), and a subpopulation of milk-allergic children fail to achieve tolerance over time (50). The mechanisms involved in the loss of sensitivity to specific foods are not precisely known, but the development of immunologic tolerance is definitely involved (9). The emergence of tolerance has been examined closely in children with milk and egg allergy, showing that those milk- and egg-allergic children who are destined to achieve tolerance first are able to tolerate these foods in baked form (52, 53). Presumably these patients are reactive to conformational epitopes on the milk and egg proteins that are more likely to be disrupted by the high temperature conditions of baking. In contrast, the children who fail to reach tolerance tend to be reactive to linear sequences of amino acids on the milk and egg allergens that would be unaffected by food processing.

Treatment or management of IgE-mediated food allergies can be approached in two different ways. Allergic reactions can be treated to resolve the symptoms or, preferably, the avoidance of the allergenic foods will prevent the occurrence of allergic reactions.

Antihistamines are useful for treatment of most mild-to-moderate allergic reactions, and function by blocking histamine receptors in the tissues (71). Epinephrine or adrenaline is a much more powerful drug that has the ability to resolve severe anaphylactic reactions in many cases. Those patients with a history of life-threatening reactions to foods are advised to carry an epinephrine-filled syringe with them at all times (72).