Up to 45% of the population report adverse reactions to food (572). Various enteric antigens play a role in the pathogenesis of conditions loosely termed food allergic diseases; many conditions associate with food allergies (Table 6.42). Milk and other dairy products are more commonly allergenic among children than among adults. Other common offending agents include nuts, eggs, and soy products (573). The increased susceptibility of young infants to food allergies results from their general immunologic immaturity and the
overall immaturity of the GI tract (244). There is also a variant of the IPEX syndrome that results in autoimmune enteropathy, hyper-IgE, and severe food allergies that become manifest after weaning. It results from a deletion in the FOXP3 gene (574). Food allergies affect up to 8% of children. Tissue damage results from either the primary pathologic event or from unavoidable side effects of protective immune responses. A definitive diagnosis of a food allergy requires (a) the demonstration of an unequivocal clinical reaction after a controlled food challenge and (b) elimination of the symptom complex subsequent to removal of the offending food. Thus, one can accept the diagnosis of milk allergy only if (a) symptoms subside with elimination of milk from the diet, (b) symptoms occur within 48 hours after refeeding, (c) three sequential challenges are positive, and (d) symptoms abate after each challenge.

The clinical features of food allergy are extensive and vary in location, severity, and time of onset (575). Clinical findings correlate with the site and extent of mast cell degranulation. The principal organs affected by allergic food reactions are the intestinal tract, skin, and lungs. In some patients, the signs and symptoms of an immediate reaction remain limited to the GI tract, with cramping, bloating, nausea, vomiting, diarrhea, growth failure in children, and weight loss in the adult. Any disease that disrupts mucosal integrity promotes the development of a food allergy by allowing allergens into the lamina propria, facilitating their interaction with immune cells.

Histologically, biopsies show partial villous atrophy with vacuolated cytoplasm, particularly at the surface, and mucosal eosinophilic infiltrates. The eosinophils may aggregate in the lamina propria or extend into the epithelium (Fig. 6.205). Since these infiltrates are usually focal, multiple biopsies are often required to make the diagnosis (576). Also, lymphonodular hyperplasia of the duodenal bulb is present in more than 50% of cases.