|Jean A. Chapman, MD; I. Leonard Bernstein, MD; Rufus E. Lee, MD;
John Oppenheimer, MD; Associate Editors: Richard A. Nicklas, MD; Jay M. Portnoy, MD; Scott H. Sicherer, MD; Diane E. Schuller, MD; Sheldon L. Spector, MD; David Khan, MD; David Lang, MD; Ronald A. Simon, MD; Stephen A. Tilles, MD; Joann Blessing-Moore, MD; Dana Wallace, MD; and Suzanne S. Teuber, MD
|Food allergy: a practice parameter
|Annals of Allergy, Asthma & Immunology
|Adverse reactions to foods have been reported in up to 25% of the population at some point in their lives, with the highest prevalence observed during infancy and early childhood. Such reactions are generally divided on a basis of the under- lying pathophysiologic changes that produced the reaction, eg, food allergy, food intolerance, pharmacologic reactions, food poisoning, and toxic reactions (see the “Differential Diagnosis of Adverse Reactions to Foods” section). Although adverse reactions to foods are common, food allergy, defined for the purposes of this document as an IgE-mediated response to a food, represents only a small percentage of all adverse reactions to foods. Individuals with atopy appear more likely to develop food allergies compared with the general population. Infants with moderate to severe atopic dermatitis appear to have the highest occurrence (see section “Prevalence and Epidemiology” section). In addition, children who develop an IgE-mediated reaction to one food are at greater risk of developing IgE-mediated reactions to other foods and/or inhalants.
Many studies indicate that the true prevalence of food allergy is much lower than the number of suspected food allergies. Therefore, health care professionals should not perpetuate false assumptions about food allergy. If a patient is incorrectly diagnosed as having a reaction to a food, unnecessary dietary restrictions may adversely affect quality of life, nutritional status, and, in children, growth. Severely restricted diets may lead to the development of eating disorders, especially if they are used for prolonged periods, or may make the patient susceptible to false claims of scientifically unproven and often costly techniques that offer no actual benefit. In addition, unintentional exposure to foods falsely thought to cause adverse reactions can provoke unnecessary panic and use of medications that have potentially potent adverse effects. IgE-mediated reactions to food allergens may occur as a consequence of (1) sensitization through the gastrointestinal tract; (2) sensitization through the respiratory tract to airborne proteins that are either identical (eg, occupational exposure) or homologous to those in particular foods (see “Classification of Major Food Allergens and Clinical Implications” section); or (3) sensitization through epidermis having impaired barrier function. Characteristics of the proteins them- selves and the particular type and degree of immune response that they elicit determine the clinical manifestations of the condition that results from patient exposure. Mucosal adaptive immunity in the gastrointestinal tract is influenced by the nature and the dose of antigen, the immaturity of the host, genetic susceptibility, the rate of absorption of a dietary protein, and the conditions of antigen processing (see “Mucosal Immune Responses Induced by Foods” section). Molecular and immunologic techniques can provide data on which allergens or epitopes of an allergen in a particular food may be responsible for specific clinical outcomes (see “Cross-reactivity of Food Allergens” section). IgE antibodies may be directed to a variety of potential allergenic proteins in foods (eg, casein and whey proteins in cow’s milk, egg white proteins in hen’s eggs, parvalbumin in finned fish, and tropomyosin in shellfish).
Immune responses to a particular allergen can vary, de- pending on the method of exposure and the condition of the food. For example, there are a variety of immune responses to wheat that include (1) acute IgE-mediated reactions, (2) local inhalational reactions (baker’s asthma), (3) systemic reactions that occur when wheat is ingested following exercise, and (4) cell-mediated reactions in atopic dermatitis and celiac disease. Patients who are allergic to egg proteins may be able to tolerate these allergens when eggs are processed as an ingredient in prepared foods. Cooking a food may increase or decrease the patient’s ability to tolerate a food.
Recent studies with molecular biological techniques have characterized a variety of cross-reacting allergens among foods, including tropomyosins, bovine IgG, lipid transfer protein, profilin, and chitinases. Although IgE cross-reactivity to multiple foods is common, clinical correlation is often limited (see “Cross-reactivity of Food Allergens” section).
Although sensitivity to most food allergens, such as milk, wheat, and egg, tend to remit in late childhood, persistence of other food allergies, eg, peanut, tree nut (walnut, cashew, Brazil nut, pistachio), and seafood, are most likely to coninue throughout the patient’s life (see “Natural History of Food Allergy” section). The natural history of specific foods varies substantially. For example, children who have become sensitized to cow’s milk, hen’s egg, wheat, and soybean through the gastrointestinal tract will usually lose this sensitivity as they get older. Peanut allergy, on the other hand, is usually not lost as the patient gets older, with only approximately 20% of children with peanut allergy losing this sensitivity. Peanut allergy affects approximately 0.6% of the general population and is the most common cause of fatal
food-induced anaphylaxis, with those at greatest risk being adolescents with asthma.
On the other hand, allergy to fruits and vegetables, which are the most common food allergies reported by adults, may develop later in life as a consequence of shared homologous proteins with airborne allergens (eg, pollens). Why food allergy persists in some patients and not in others is unclear, although recent studies suggest that this is more likely to occur with foods that contain linear allergenic epitopes.
Risk factors associated with the development of food al- lergy include a personal or family history of atopy or food allergy in particular, possible maternal consumption of major food allergens during either pregnancy or breastfeeding, atopic dermatitis, and transdermal food exposure. An infant at increased risk is a candidate for intervention, which may include breastfeeding and avoidance of highly sensitizing and/or solid foods at a young age, to reduce this risk.
Reactions that occur in individuals after the ingestion, inhalation, or contact with foods or food additives can vary from mild, gradually developing symptoms limited to the gastrointestinal tract to severe, rapidly progressing, life- threatening anaphylactic reactions that may be triggered by even small amounts of food allergen. Immunologic reactions to foods or food additives are characterized by a strong temporal relationship between the onset of the reaction and exposure to a specific food or food additive and may include cutaneous manifestations, gastrointestinal symptoms, respiratory symptoms, hypotension, and laryngeal edema, occurring separately or together.
Anaphylaxis after exposure to foods can include a combination of symptoms that reflect reactions in the respiratory, dermatologic, cardiovascular, and other organ systems. In children, anaphylaxis occurs most frequently after ingestion of peanuts, other legumes, tree nuts, fish, shellfish, milk, and eggs. Most IgE-mediated reactions to foods in adults are caused by peanuts, tree nuts, fish, and shellfish. In highly sensitive patients, inhalation of food allergens may produce anaphylaxis. Anaphylaxis may also occur when foods are ingested before or after exercise (see “Food-Dependent Exercise-Induced Anaphylaxis” section).
Immunologic reactions to foods encompass more than just IgE-mediated reactions. Nevertheless, this monograph will focus primarily on IgE-mediated reactions that have been defined for the purposes of this document as food allergy. An IgE-mediated reaction to foods may be difficult to distinguish from other types of reactions to foods, such as food intolerance, especially if symptoms are primarily or exclusively gastrointestinal (see “Differential Diagnosis of Adverse Re- actions to Foods” section). IgE-mediated reactions can also occur in the upper and lower respiratory tract, usually as part of an anaphylactic reaction that may involve the skin and/or gastrointestinal tract. In IgE-mediated reactions (1) the time from ingestion of the food to symptom onset is usually rapid (eg, within minutes), (2) small amounts of food may elicit severe reactions, and (3) reactions will usually continue to occur with reexposure. IgE-associated food reactions such as those triggering atopic dermatitis are more difficult to discern by history alone and may occur hours after food ingestion.
It is important to recognize that there are a number of other immunologic and nonimmunologic reactions that can pro- duce symptoms after exposure to foods or food additives (see “Differential Diagnosis of Adverse Reactions to Foods” section). These reactions include conditions that are considered to be examples of food intolerance and conditions that are considered to be neither food allergy nor food intolerance, such as scombroid poisoning. Specific clinical and laboratory tests are available for many of these conditions.
The evaluation of food allergy begins with a detailed history, including a list of suspect foods, the quantity of food eliciting a reaction, the reproducibility of the reaction in relationship to food ingestion, the time between exposure and reaction, the clinical manifestations produced, whether there has been resolution of symptoms with elimination of the suspect food, and the overall duration of symptoms and after each exposure. This can be augmented by a written recording of dietary intake.
A clinically relevant physical examination, with particular focus on suspected targeted organ systems (eg, cutaneous, respiratory, and gastrointestinal) should be performed. The presence of atopic disorders such as asthma, atopic dermatitis, and allergic rhinitis implies an increased risk of food allergy. The physical examination may also reveal alternative diagnoses that make food allergy less likely.
Initial evaluation may be enhanced by certain testing procedures (see “Diagnosis of Food Allergy” section). Skin prick or puncture tests are often useful in screening patients with suspected food allergy. Commercial food extracts from foods with stable proteins (eg, peanut, milk, egg, tree nuts, fish, shellfish) are reliable to detect specific IgE antibodies in most patients, whereas extracts from foods that contain labile proteins (eg, many fruits and vegetables) are less reliable. Under these conditions, pricking the food and then the patient may be useful. It is important to recognize that skin or in vitro test results may remain positive even though the patient’s skin is no longer clinically sensitive. Intracutaneous (intradermal) skin tests are not recommended because they are potentially dangerous. In addition, they are overly sensitive and are associated with an unacceptable rate of false-positive reactions. A positive skin test result may indicate food allergy (positive predictive value 50%), but a negative skin test result virtually rules out an IgE-mediated mechanism (negative predictive value 95%). If done, skin testing should be performed selectively for suspected foods, because allergy to multiple foods is not common. From an epidemiologic stand- point, generally larger wheal-flare reactions on prick or puncture tests and higher concentrations of food-specific IgE measured by in vitro tests correlate with a greater likelihood of a reaction.
In vitro tests may also provide useful information to evaluate possible IgE-mediated reactions. Situations in which these tests may be particularly valuable include but are not limited to (1) patients with a history of a life-threatening
reaction to the suspected food; (2) patients who have medical conditions (eg, extensive atopic dermatitis or dermatographism that could interfere with interpretation of skin test results); (3) patients with a nonreactive histamine control (eg, due to medications that suppress skin test response); or (4) women known to be pregnant (see Practice Parameters for Allergy Diagnostic Testing). If the patient has a history of an anaphylactic reaction and test results for specific IgE anti- bodies are positive, no further evaluation is usually required. A number of other diagnostic tests (eg, atopy patch tests) are currently under investigation for IgE-mediated reactions to foods. Provocation-neutralization is considered disproved as a diagnostic method in allergy, whereas hair analysis, food specific IgG or immune complex assays, and newer versions of the previously disproved cytotoxic tests are considered unproven or experimental.
The rational selection, application, and interpretation of tests for food-specific IgE antibodies requires the following: (1) consideration of the epidemiology and underlying immunopathophysiology of the disorder under investigation; (2) the importance of making a definitive diagnosis; (3) estimation of prior probability that a disorder or reaction is attributable to a particular food; and (4) an understanding of the utility of the diagnostic tests being used.
Challenge with a suspected food may help to determine if the test results were either falsely negative or falsely positive. Initial challenge can be performed in an open or single- blinded fashion. When such challenges are performed, the physician must recognize the potential for bias that is introduced if both the patient and the physician are not blinded. Double-blind, placebo-controlled food challenge is most likely to provide the physician with a valid evaluation of the patient’s capacity to react to a given food and has the highest positive predictive value. In most patients, a diagnosis of an IgE-mediated reaction to a particular food or food additive can be best made by obtaining a detailed history in conjunction with a positive test result for specific IgE antibodies to the food and a positive challenge result with the food, especially if the challenge is performed in a double-blind, placebo-controlled manner. Patients who have a history of reactions to foods that could be IgE-mediated benefit from consultation with an allergist-immunologist.
The management of food allergy relies primarily on avoid- ance of exposure to suspected or proven foods (see “General Management of Food Allergy” section). This can best be done if the specific foods responsible for the patient’s symptoms are identified by history and appropriate tests. If this is not possible, patients with chronic symptoms may benefit from an elimination diet, remembering that patients have an increased risk of unintentional food allergen exposure in a number of special circumstances, such as schools and restaurants (see “Management in Special Settings and Circumstances” section). Because of the potential for inadvertent exposure to foods, education of the patient and/or the patient’s advocate is essential. This includes reading labels and recognition that unfamiliar terms may indicate the presence of a clinically relevant food. Vague or inaccurate labeling and cross-contamination of packaged foods or foods eaten in restaurants are potential hazards. Avoidance of the implicated food may encourage future tolerance, especially with cow’s milk, egg, and soy. Patient outcomes may be improved when avoidance measures are maintained over time. This has been shown to be associated with loss of symptomatic reactivity in both children and adults to specific food allergens.
Currently, there is no known oral or parenteral agent that has been shown consistently to prevent IgE-mediated reactions to foods. Reliance on such treatment can lead to tragic consequences. Immunotherapy to food proteins is currently experimental.
Injectable epinephrine is the treatment of choice for an anaphylactic reaction, regardless of the cause (see Anaphylaxis and Stinging Insect Hypersensitivity Practice Parameters). For this reason, patients who have experienced IgE- mediated reactions to a food or their caregivers should be educated and provided with injectable epinephrine to carry with them. Because anaphylactic reactions may be prolonged or biphasic, it is reasonable to instruct the patient to carry more than one epinephrine injector, to seek immediate med- ical care after a reaction, and to be monitored for an appropriate period (see “General Management of Food Allergy” section).