Determinants of systemic manifestations of food allergy

The myriad of systemic manifestations induced by food hypersensitivity responses is testament to the ability of localized exposure to foods in the gastrointestinal tract to result in symptoms in distal target organs. Cow's milk protein, for example, may induce hives (urticaria), atopic dermatitis, isolated gastrointestinal symptoms, or severe generalized anaphylaxis in different individuals or in the same person at different times. These diverse manifestations are the result of complex interactions among the causal food protein, gut, immune system, and target organs. The dynamic state of these interactions is demonstrated by the development of food tolerance in most subjects and by the ability to experience the development of new allergies in some subjects. This review explores the variety of clinical manifestations of food hypersensitivity disorders in the context of the question: What determines the local or systemic expression of food allergy in a given individual at a particular time? Evidence is provided for both systemic and local immune activation. The role of food-protein chemistry, absorption and processing of ingested allergen, immune responses (type, degree, and specificity), and target organ hyperreactivity are considered as determinants in the expression of food allergic disorders.