Frequently, the term food allergy is used to denote any adverse food reaction, a misnomer that leads to considerable confusion in this field. In addition, the perceived prevalence of food allergy is far greater than actual prevalence. Household surveys indicate that one-third of American families alter their eating patterns in the belief that at least one family member suffers from a food allergy. In Bock’s survey of a general pediatric practice involving 480 babies followed from birth until their third birthday, 28% of the infants were reported to have experienced adverse food reactions. However, symptoms were confirmed by oral food challenge in only 6% to 8% of infants. In four prospective studies from four different countries using appropriately performed milk challenges, 2.2% to 2.5% of infants were found to have cow’s milk allergy in the first 1 to 2 years of life. Follow-up studies indicated that approximately 80% of these milk-allergic infants lost their reactivity to cow’s milk by their fourth to fifth birthday. Similarly, about 1.3% of young children develop egg allergy and 0.8% develop peanut allergy. While approximately 80% of egg-allergic children lose their reactivity to egg by their fifth or sixth birthday, only about 15% to 20% of peanut allergic children “outgrow” their allergy. Adverse reactions to food additives also have been demonstrated in children, although these reactions are fairly rare. Children with atopic disorders tend to have a higher prevalence of food allergy. In a study of children who were referred to a dermatology clinic because of moderate to severe atopic dermatitis, approximately 40% were found to have skin symptoms provoked by food hypersensitivity; the more severe the atopic eczema, the more likely they were to have food allergy. Studies of asthmatic children attending general pulmonary clinics suggest that 8% to 10% of such patients have food-induced wheezing, and surveys of emergency department visits for anaphylaxis indicate that food allergy is the single leading cause of anaphylaxis outside of the hospital in the United States.

The pathogenesis of food allergy involves three main factors: the food (or allergen), the gastrointestinal barrier and its handling of food, and the affected individuals’ genetic predisposition to developing an allergic response. Despite the existence of a widely varied diet, relatively few foods account for the majority of allergic responses. In children, egg, peanut, milk, soy, wheat, and fish account for 85% to 90% of reactions. The allergenic fractions of these foods have several features in common: They are glycoproteins of approximately 10,000 to 60,000 daltons, they are largely heat- and acid-stable, and they are water-soluble.

The gastrointestinal tract uses both nonimmunologic and immunologic mechanisms to prevent intact foreign antigens from gaining access to the body while processing ingested food into forms that can be absorbed and used for energy and cell growth. IgA secreted into the gastrointestinal tract lumen binds foreign antigens, such as food, and impedes their absorption. IgA food antigen complexes become “hung up” in the glycocalyx, where enzymes in the mucosal cell brush border can break down these complex proteins. Food antigen–specific IgA and IgG in the blood may be involved in clearing antigens that enter the circulation. Although more than 98% of ingested protein is blocked by the gastrointestinal barrier, minute amounts of intact food antigens are absorbed and gain access to immune reactive cells. Such factors as decreased stomach acidity (as with antacids) or the ingestion of alcohol or aspirin increases antigen absorption. However, antigenically intact food proteins entering the circulation normally do not cause allergic reactions, because most individuals develop “tolerance” to ingested food antigens.

Oral tolerance in humans has been studied to a very limited extent. Husby demonstrated that feeding keyhole limpet hemocyanin to normal human volunteers resulted in systemic T-cell tolerance but led to B-cell priming, with detection of keyhole limpet hemocyanin antibodies in serum and saliva. The extent of T-cell tolerance depended on the antigen, dosage, and immunization schedule used. The suppression of systemic immunity to foods after oral ingestion does not have a major suppressive effect on human B cells, because antibody production against food proteins is a universal phenomenon in both infants and adults and generally is not associated with hypersensitivity. Most low-level antibodies to foods in clinically tolerant individuals are of the IgG class, with high levels of IgE or IgA antibodies more likely to be an indicator of a pathologic process (e.g., cow’s-milk allergy or celiac disease, respectively).

The increased susceptibility of young infants to food-allergic reactions appears to be the result of immunologic immaturity and, to some extent, immaturity of the gastrointestinal tract. Newborns lack IgA and IgM in exocrine secretions, and salivary secretory IgA (sIgA) is absent at birth and remains low during the early months of life. The relatively low concentration of sIgA in the intestine of young infants, together with the relatively immense quantities of ingested proteins, contributes to the large amount of food antigens confronting gut-associated
lymphoid tissue. In genetically predisposed infants, these antigens may fail to appropriately activate regulatory T cells and may stimulate an excessive production of IgE antibodies or other abnormal immune responses.

Several prospective studies have indicated that exclusive breast-feeding may promote the development of oral tolerance and may prevent some food allergy, atopic dermatitis, and asthma. The protective effect of breast-feeding may be due to several factors: decreased exposure to foreign proteins, breast-milk sIgA that provides passive protection against foreign proteins and pathogens, and soluble factors, such as cytokines, in breast milk that may induce the earlier maturation of the gastrointestinal tract barrier and the infant’s immune response. Resistance of sIgA to proteolytic digestion and decreased proteolytic activity in the infant gastrointestinal tract allows sIgA antibodies to reach sites in the infant’s intestine where foreign antigens and microorganisms may be encountered. In addition to the passive protection provided by sIgA, soluble factors in human milk may stimulate lymphocytes to mature and to produce IgA. The antibacterial activity of human milk is well established, but the ability of breast-milk sIgA to prevent food antigen penetration is less clear.

A variety of food-allergic reactions have been confirmed by controlled trials. These are listed in Box 422.1.