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During the past half century, allergies of all kinds have become much more common within the developed world. Dietary allergies are no exception, and up to 5% of children develop allergy to cow's milk and other proteins (reviewed by Walker-Smith and Murch1 and Wood2). There has also been a change in patterns of presentation. As dietary exposures in infancy and early childhood have altered, previously unusual reactions to antigens such as peanut and sesame have become much more common.3-5 There are important geographical differences, with different incidence of specific allergies varying from country to country.5 This may relate to genetic differences in immune responses amongst different ethnic groups, or to local dietary customs - exemplified most strikingly by reports of anaphylaxis to birds' nest soup in Singaporean infants.6 However, a broader context is provided by recent evidence from the direction of basic science, which highlights the importance of infectious exposures of the innate immune system in early life in inducing tolerance to dietary antigens (oral tolerance). This chapter attempts to encompass both the clinical aspects of food allergy and some of the relevant scientific background.

Early life exposures, possibly even prenatal exposures, have changed substantially within countries of the developed world, in the past two generations. Birth in disadvantaged conditions within the developing world is protective against most forms of allergy, and predisposition to allergy may manifest only once a certain threshold of improved material conditions is passed.7,8 Allergies occur because of breakdown of immunological tolerance. The immune system must differentiate between all foreign molecules, reacting only to potentially harmful pathogens while remaining unresponsive (tolerant) to the commensal bacterial flora and to foods. The role of the bacterial flora in establishing immune tolerance has only recently become apparent, and will be discussed in more detail later, together with evidence that manipulation of the bacterial flora may provide a novel approach to the management of dietary and other allergies.8-11

First, however, it is important to clarify the difference between food intolerance and food allergy (Table 22.1). As there may however be an overlap in the symptomatology, an accurate history and

Table 22.1 Food intolerance reactions which may be confused with true allergy

Direct toxic effects

Bacterial contamination; heavy metals or toxins; some food additives Intolerance due to enzyme deficiency

Inborn metabolic abnormalities (e.g. phenylketonuria, tyrosinemia, galactosemia) inducing adverse responses to specific dietary components. Enterocyte gene deficiencies (lactase deficiency, sucrase-isomaltase deficiency or glucose-galactose malabsorption) inducing diarrhea after ingestion of relevant sugars. Enteropathy causing down-regulated expression of lactase and sucrase

Symptoms due to pharmacological properties of foods

For example tyramine contained in cheese or red wine; histamine in strawberries supportive investigations are needed for secure diagnosis of true food allergy.

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