Igemediated Food Allergies

In IgE-mediated food allergies, allergen-specific IgE antibodies are produced in the body in response to exposure to a food allergen, usually a protein. These IgE antibodies are highly specific and will recognize only a specific portion of the protein that they are directed against. Occasionally, IgE antibodies produced against one particular protein in a specific food will confer sensitivity to another food either because the food is closely related or because it shares a common segment with the allergenic protein. Some food proteins are more likely to elicit IgE antibody formation than others. Although exposure to the food is critical to the development of allergen-specific IgE, exposure will not invariably result in the development of IgE antibodies even among susceptible people. Many factors, including the susceptibility of the individual; the immunogenic nature of the food and its constituent proteins; the age of exposure; and the dose, duration, and frequency of exposure, are likely to influence the formation of allergen-specific IgE antibodies.

Allergen-specific IgE antibodies are produced by plasma cells and attach themselves to the outer membrane surfaces of two types of specialized cells: mast cells, which are found in many different tissues, and basophils, which are found in the blood. In this so-called sensitization process, the mast cells and basophils become sensitized and ready to respond to subsequent exposure to that specific food allergen. However, the sensitization process itself does not result in any symptoms. No adverse reactions will occur without subsequent exposure to the specific allergenic protein or some closely related protein. Sensitization to a particular allergen distinguishes allergic individuals from nonallergic individuals.

Once the mast cells and basophils are sensitized, subsequent exposure to the allergen results in the allergen cross-linking two IgE molecules on the surface of the mast cell or basophil membrane. This interaction between the allergen and the allergen-specific IgE triggers the release of a host of mediators of allergic disease, which are either stored or formed by the mast cells and basophils. Several dozen different mediators have been identified, including histamine, prostaglandins, and leukotrienes. Histamine is one of the primary mediators of IgE-mediated allergies. Histamine is responsible for many of the early symptoms associated with allergies. Many of the other mediators are involved in the development of inflammation. The interaction of a small amount of allergen with the allergen-specific IgE antibodies results in the immediate release of comparatively large quantities of the various mediators into the bloodstream and tissues. Thus, exposure to extremely small amounts of allergens can elicit symptoms. This mechanism of IgE-mediated reactions is involved in many different types of allergies to foods, pollens, mold spores, animal danders, bee venom, and pharmaceuticals. Only the source of the allergen is different.

IgE-mediated food allergies are sometimes called immediate hypersensitivity reactions because of the short onset time (a few minutes to a few hours) between the ingestion of the offending food and the onset of symptoms. Since the mediators released from the mast cells and basophils can interact with receptors in a number of different tissues in the body, a rather wide variety of symptoms can be associated with IgE-mediated food allergies (Table 1). The most common symptoms associated with food allergies are those involving the skin and the gastrointestinal tract. Respiratory symptoms are less frequently involved with food allergies than with various inhalant allergies such as pollen and animal dander allergies. However, asthma is a very serious, though uncommon, respiratory manifestation of food allergies. Fortunately, most food-allergic individuals suffer from only a few of the many possible symptoms.

Most of the symptoms of IgE-mediated food allergies are not particularly definitive, which can make clinical diagnosis rather difficult. For example, the gastrointestinal manifestations of food allergies can also be associated with many other foodborne illnesses and a variety of other diseases as well. Additionally, there are millions of asthmatics, but only a few are allergic to foods.

Anaphylactic shock is, by far, the most serious manifestation of food allergies. Anaphylactic shock involves gastrointestinal, cutaneous, and respiratory symptoms in combination with a dramatic fall in blood pressure and cardiovascular complications. Death can ensue within minutes of the onset of anaphylactic shock. Fortunately, very few individuals with food allergies are susceptible to such severe reactions after the ingestion of the offending food.

The severity of an allergic reaction will depend to some extent on the amount of the offending food that is ingested. Severe reactions are more likely to occur when an allergic individual inadvertently ingests a large amount of the offending food, especially if that individual happens to be

Table 1. Symptoms of IgE-Mediated Food Allergies

Gastrointestinal symptoms Cutaneous symptoms

Vomiting Urticaria (hives)

Diarrhea Dermatitis

Nausea Angioedema

Respiratory symptoms Other symptoms

Rhinitis Anaphylactic shock

Asthma Laryngeal edema exquisitely sensitive. However, exposure to even trace quantities can elicit noticeable reactions due to the large release of mediators.

The most common allergenic foods are peanuts, tree nuts (almonds, walnuts, pecans, cashews, etc), soybeans, cows' milk, eggs, fish, crustacea (shrimp, crab, lobster, etc), and wheat. Peanut allergy is the most common food allergy, especially in the United States where peanuts are a popular dietary item and peanut butter is introduced at an early age. Throughout the world, cows' milk allergy is the most common food allergy among infants due to the widespread ingestion of milk during the first months of life. Any food that contains protein has the potential to elicit an allergic reaction in someone. The most common allergenic foods tend to be foods with high protein content that are frequently consumed. The exceptions are beef, pork, chicken, and turkey, which are uncommonly allergenic despite their frequent consumption and high protein content.

The prevalence of IgE-mediated food allergies is not precisely known. The overall prevalence of food allergies in the developed countries of the world ranges from 4 to 8% in infants to perhaps 1% in adults. Thus, many infants and young children outgrow their IgE-mediated food allergies. The reasons for the development of tolerance to previously allergenic foods are not understood but may involve the development of blocking antibodies of other types, especially IgG and IgA. Allergies to some foods, such as cows' milk and eggs, are more frequently outgrown than allergies to other foods, such as peanuts.

The diagnosis of food allergies is typically approached in a stepwise fashion. The diagnosis of food allergies by an allergist is often critical because parental diagnosis and self-diagnosis are often incorrect, leading to identification of the wrong incorrect foods or the identification of too many foods as allergens. Most individuals with IgE-mediated food allergies are allergic to one or two foods; only on rare occasions do coexistent allergies occur to more than three foods. Thus, the goal of medical diagnosis is to establish a cause-and-effect relationship between one or a few foods and the onset of allergic symptoms. Most physicians begin the diagnosis by taking a careful history of the patient's adverse reactions taking note of the foods eaten immediately before the onset of symptoms, the amount of various foods consumed, the type, severity, and consistency of symptoms, and the time intervals between eating and the onset of symptoms. Sometimes histories are needed from several episodes to reach a probable diagnosis. Challenge tests with the suspected food(s) can be used to establish with certainty the role of a specific food in the reaction. The double-blind, placebo-controlled food challenge (DBPCFC) is considered the most reliable procedure. In the DBPCFC, neither the patient nor the medical personnel know when the food (in capsules or disguised in another food or beverage) is going to be administered and when the placebo is to be administered. Thus, the DBPCFC is free of bias. Single-blind and open challenge tests also have value in some situations. History alone can be sufficient to make the diagnosis in some situations if the cause-and-effect relationship is particularly compelling. Challenge tests are seldom used on individuals who experience life-threatening allergic reactions for rather obvious reasons.

Once the adverse reaction has been clearly linked to the ingestion of a specific food, an assessment of the possible role of IgE must be conducted to determine if the adverse reaction has an allergic mechanism. The diagnosis of an IgE-mediated mechanism can be made with either the skin prick test (SPT) or radioallergosorbent test (RAST). The SPT is the simpler of the two procedures. In the SPT, a small amount of a food extract is applied to the patient's skin, the site is pricked with a needle to allow entry of the allergen, and the site is observed for the development of a wheal-and-flare (basically a hive) response. A wheal-and-flare response at the skin prick site demonstrates that IgE affixed to skin mast cells has reacted with some protein in the food extract releasing histamine into the surrounding tissue and resulting in the formation of the hive. The RAST is an alternative procedure that uses a small sample of the patient's blood serum. In the RAST, the binding of serum IgE to food protein bound to some solid matrix is assessed using radiolabeled or enzyme-linked antihuman IgE. While the RAST is more expensive than the SPT, it is equally reliable and can be conducted in a specialized laboratory in the absence of the patient. The RAST is preferred for patients with extreme sensitivities because of the risk associated with severe reactions to the SPT. It should be emphasized that a positive SPT or RAST in the absence of a history of allergic reactions to that particular food is probably meaningless. The SPT and RAST are the most frequently used and reliable tests to assess the role of IgE in an adverse food reaction.

The specific avoidance diet is the primary means of treatment for IgE-mediated food allergies. For example, if allergic to peanuts, don't eat peanuts. With IgE-mediated food allergies, very low amounts of the offending food can be tolerated by most allergic individuals. Thus, the construction of a safe and effective avoidance diet can be quite difficult. Food-allergic patients must have considerable knowledge of food composition. For example, casein, whey, and lactose are common food ingredients that are derived from cows' milk. These milk ingredients would likely be hazardous for milk-allergic individuals. The ingredient must contain the specific allergenic protein to be hazardous to the allergic consumer. For example, peanut oil and soybean oil, despite being derived from allergenic sources, do not contain protein and would not be hazardous for peanut-allergic or soy-allergic individuals unless the oils had become contaminated during use. The careful reading and complete understanding of food labels is critical to the implementation of a safe and effective avoidance diets. Of course, the manufacturers of packaged foods have the responsibility to ensure that the label statements on packages are accurate. Occasionally, errors are made by food processors that result in the presence of undeclared residues of allergenic foods in a packaged food. The contamination of one food with another from the use of shared food processing equipment is one of the most common errors occurring in food manufacturing. However, restaurant and other food service meals can present an even bigger challenge for food-allergic individuals. Residues of allergenic foods can arise from the use of shared food preparation equipment (utensils, cooking surfaces, pots and pans, etc). Additionally, the accurate identification of all of the ingredients in food service and restaurant meals can sometimes be quite difficult, and such foods are not labeled. As a result, many inadvertent exposures occur among allergic consumers who are attempting to avoid their offending food(s).

Cross-reactions are another perplexing issue for food-allergic consumers as they attempt to develop effective avoidance diets. Cross-reactions can occur but do not inevitably occur between closely related foods. For example, many individuals are allergic to peanuts, but most of these individuals are not allergic to other legumes such as soybeans, peas, green beans, and so on. A few of these individuals are cross-reactive with one or more other legumes. Alternatively, cross-reactions frequently occur among the various crustacea (shrimp, crab, lobster, and crayfish). Cows' milk and goats' milk invariably cross-react as do the eggs of various avian species. Cross-reactions can also occur between foods and other environmental allergens. The most common examples are the cross-reactions that occur between some fresh fruits and vegetables and certain pollen allergies in some individuals and the cross-reaction that occurs in a few individuals with allergies to natural rubber latex with several foods, including bananas and kiwis. The basis for such cross-reactions is frequently not known.

Infants born to parents with histories of allergic disease are much more likely than other infants to develop food allergies. Prevention of the development of food allergies in such infants is quite difficult. The avoidance of commonly allergenic foods such as cows' milk, eggs, and peanuts primarily through breast feeding appears to delay but not prevent the development of food allergies.

A few specialized hypoallergenic foods are available in the marketplace. These foods are intended for infants who have developed allergies to infant formula made with cows' milk. The most effective hypoallergenic infant formulae are based on extensively hydrolyzed casein. Although casein is a common milk protein and a major milk allergen, the hydrolysis of its peptide bonds renders it safe for cows' milk-allergic infants.

Other approaches to the treatment of food allergies are considered controversial. Immunotherapy (eg, allergy shots), sublingual food drops, and the use of rotation diets would be examples of such controversial approaches.

Pharmacological approaches can be used to treat the symptoms of allergic reactions. In particular, epinephrine (also known as adrenalin) is prescribed for individuals who experience life-threatening food allergies. The early administration of epinephrine after inadvertent exposure to the offending food can be life-saving for such patients. Antihistamines can also be used to treat the less-serious symptoms of food allergies.

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