Food Allergies

Food Allergies

Hugh A. Sampson

Adverse food reactions may be divided into toxic and nontoxic reactions. Toxic reactions may occur in anyone, provided a sufficient dose is ingested (e.g., histamine in scombroid fish poisoning, toxins secreted by Salmonella, Shigella, and Campylobacter). Nontoxic reactions depend on individual susceptibilities and may be the result of immune mechanisms (allergy or hypersensitivity) or nonimmune mechanisms (intolerances). Food intolerance makes up the majority of adverse food reactions and may be secondary to pharmacologic substances found in some foods, chemical or microbial contaminants, or metabolic disorders of the host (e.g., lactose intolerance). Although IgE-mediated mechanisms are the most well-characterized forms of hypersensitivity response, other less well-defined immunologic mechanisms are responsible for such disorders as food-induced enterocolitis syndrome, benign eosinophilic proctocolitis, allergic eosinophilic esophagitis and gastroenteritis, and celiac disease.


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.

Gastrointestinal Food Hypersensitivity

A number of gastrointestinal syndromes are associated with both IgE-mediated and non–IgE-mediated food allergies.

Oral Allergy Syndrome

Pruritus and edema of the lips, tongue, palate, and throat may be the first symptoms of a generalized food-allergic reaction or may be the sole manifestations of ingesting a food allergen. The oral allergy syndrome occurs in patients with allergic pollenosis and is associated with the ingestion of various fresh fruits and raw vegetables. Symptoms are due to “conserved homologous proteins” in plant pollens and certain fruits and vegetables and are isolated to a contact reaction in the oropharynx. Oral symptoms developing during the ingestion of raw potatoes, carrots, celery, apples, and hazelnuts are associated with birch pollen allergy; and symptoms secondary to bananas and melons (e.g., watermelon, cantaloupe, honeydew) are associated with ragweed sensitivity. In addition, many children will experience symptoms when ingesting raw, pitted fruit (e.g., cherries, peaches, plums). No symptoms occur when such fruits and vegetables have been cooked, because these conserved proteins are not heat-stable.

Gastrointestinal Anaphylaxis

Nausea, abdominal pain, cramps, vomiting, and (less frequently) diarrhea develop within minutes to 2 hours of ingesting a food allergen in IgE-mediated gastrointestinal allergy. However, repeated ingestion of a food allergen in allergic infants may result in the partial desensitization of gastrointestinal mast cells and subclinical symptoms, such as poor appetite, periodic abdominal pain, and poor weight gain. Malabsorption has been demonstrated using various absorption markers (e.g., lactulose, rhamnose, mannitol, polyethylene glycol). Improved appetite and catch-up weight gain may follow the elimination of the responsible food allergen.

Eosinophilic Esophagitis and Gastroenteritis

Non–IgE-mediated food hypersensitivity appears to be responsible for symptoms in most patients with allergic eosinophilic esophagitis and gastroenteritis but, in a subset, IgE-mediated food allergy is responsible for symptoms. Typically, patients present with postprandial nausea and vomiting (or “spitting up”), gastroesophageal reflux, abdominal pain, diarrhea, and weight loss (in older children) or failure to thrive (in infants). Approximately one-half of patients will have peripheral blood eosinophilia and, less commonly, iron-deficiency anemia and hypoalbuminemia. Generally, patients with IgE-mediated food-induced symptoms have other atopic symptoms, elevated serum IgE levels, and positive skin-prick tests to a variety of foods and inhalants. In one study, approximately 40% of referred infants younger than 1 year of age experiencing gastroesophageal reflux were found to have milk-induced allergic eosinophilic esophagitis and reflux. The elimination of cow’s-milk formula led to a resolution of symptoms, with normalization of biopsy findings. Blinded challenge with cow’s milk provoked symptoms and abnormal biopsy findings. In rare infants, generalized edema develops secondary to marked protein-losing enteropathy and hypoalbuminemia, often in the presence of minimal gastrointestinal symptoms. Rarely, allergic eosinophilic gastroenteritis presents in infants as pyloric stenosis with outlet obstruction. Elimination of the responsible food allergen from the diet for 6 to 8 weeks may be necessary to bring about a resolution of symptoms and a normalization of intestinal histology.

Food-Induced Proctocolitis

Unlike the other eosinophilic gastroenteropathies, food-induced proctocolitis presents in the first few months of life and is generally secondary to cow’s-milk or soy-protein hypersensitivity. The majority of affected infants presenting with this disorder are breast-fed and reacting to antigens passed in maternal breast milk. Typically, such infants appear healthy, and their disorder is discovered because of the presence of gross or occult blood in their stool. Mucosal lesions are confined to the distal large bowel. Sigmoidoscopic findings are variable but range from areas of patchy mucosal injection to severe friability, with small aphthoid ulcerations and bleeding. Biopsies reveal mucosal edema and a prominent eosinophilic infiltrate in the surface and crypt epithelium and lamina propria. Generally, gross hematochezia resolves within 72 hours of appropriate food-allergen elimination (or, in the case of a breast-fed infant, elimination of the food allergen from the mother’s diet), but resolution of the mucosal lesions may take several weeks. Reintroduction of the responsible food leads to resumption of symptoms within several hours to days. Often, food-induced proctocolitis resolves after 6 months to 2 years of allergen avoidance.

Food-Induced Enterocolitis Syndrome

Young infants who are between ages 1 week and 3 months and have food hypersensitivity may present with protracted vomiting and diarrhea, resulting frequently in dehydration. Most often, cow’s milk or soy proteins are responsible, but rice- and cereal grain–induced enterocolitis are being reported more frequently. Some infants appear to be sensitized by exposure to food proteins passed in maternal breast milk, but do not react until ingesting the actual food. Generally, the stools of affected infants contain occult blood, eosinophils, and polymorphonuclear neutrophils. IgE food-specific antibodies are absent. Jejunal biopsies reveal flattened villi, edema, and increased numbers of lymphocytes, eosinophils, and mast cells. Generally, the elimination of the responsible food leads to a resolution of symptoms within 72 hours. The diagnosis is established by oral food challenge, which consists of administering up to 0.3 to 0.6 g/kg body weight of the suspected protein allergen. A positive challenge results in vomiting and diarrhea within 1 to 6 hours, and occasionally it may be accompanied by shock. Monitoring the peripheral blood cell count reveals a rise in the absolute neutrophil count (greater than 3,500 cells per cubic millimeter) 4 to 6 hours after symptoms develop. Neutrophils, eosinophils, and occasionally red blood cells may be found in the stools. Once their disorder is diagnosed, children with cow’s-milk sensitivity should be placed on a hypoallergenic formula (Alimentum, Nutramigen, or Pregestimil) until approximately 9 to 12 months of age, because as many as 50% may develop a similar sensitivity to soy if placed on a soy-based formula. Exposure to other foods probably should be limited until after 6 months of age. The majority of these children appear to outgrow their hypersensitivity in 1 to 3 years.

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Jul 24, 2016 | Posted by in ORTHOPEDIC | Comments Off on Food Allergies
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