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Food Allergy Seminar.Lecture.Class
 

Food Allergy Seminar.Lecture.Class

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  • Food Allergy: Diagnosis and Management This slide set was created on behalf of the Adverse Reactions to Foods Committee by Hugh Sampson M.D., FAAAAI Scott Sicherer M.D. Robert S. Zeiger, MD, PhD., FAAAAI
  • Adverse reactions to foods can be divided among those which are toxic and those that are non-toxic reactions 1 . Toxic reactions do not depend upon host factors and can be elicited by virtually anyone who ingests a sufficient quantity of the tainted food. Causes include bacterial food poisoning but can also include pharmacologic effects such as jitteriness from caffeine or itching and flushing from ingested histamine exemplified by scromboid poisoning. In contrast to the toxic reactions, nontoxic reactions are dependent upon host factors and can be divided among food intolerance and food allergy. Food intolerance is not mediated by the immune system. Examples include symptoms elicited from disaccharidase deficiency (lactose intolerance), metabolic disorders (galactosemia), pancreatic insufficiency, gallbladder or liver disease, anatomic defects (hiatal hernia), neuronally mediated illness (gustatory rhinitis-rhinorrhea from spicy or hot foods) and psychiatric disorders (anorexia nervosa). Examples of these are listed.
  • In contrast to food intolerance, food allergy defines adverse reactions to food protein mediated by the immune system. Food allergy can be further divided into those allergies that are mediated by IgE antibody and those which are not IgE mediated. The IgE mediated food allergies are typically acute in onset and examples include anaphylaxis or urticaria. The non-IgE mediated food allergies are generally slower in onset and primarily are gastrointestinal reactions.
  • The immunologic reactions in food allergy are directed toward the proteins in foods, not to fat or carbohydrate. Allergenic proteins are typically small glycoproteins which are heat resistant and acid stable. The foods which account for the majority of significant allergy in adults are peanuts, tree nuts, shellfish and fish while children have allergy to these but also to milk, egg, soy, and wheat 2-5 . It should be appreciated that a single food is composed of many proteins and that these proteins may have multiple areas to which the immune system can respond, termed epitopes. Epitopes which are dependent upon the folding of the proteins are termed conformational epitopes while those that are not dependent upon folding are termed linear epitopes. The identification of these epitopes are underway for a large number of foods, and these studies are aimed at determining both the epitopes recognized by B and T-cells.
  • The immunologic reactions in food allergy are directed toward the proteins in foods, not to fat or carbohydrate. Allergenic proteins are typically small glycoproteins which are heat resistant and acid stable. The foods which account for the majority of significant allergy in adults are peanuts, tree nuts, shellfish and fish while children have allergy to these but also to milk, egg, soy, and wheat 2-5 . It should be appreciated that a single food is composed of many proteins and that these proteins may have multiple areas to which the immune system can respond, termed epitopes. Epitopes which are dependent upon the folding of the proteins are termed conformational epitopes while those that are not dependent upon folding are termed linear epitopes. The identification of these epitopes are underway for a large number of foods, and these studies are aimed at determining both the epitopes recognized by B and T-cells.
  • When food is ingested, intestinal and pancreatic enzymes break proteins into amino acids and small peptides. Specialized cells in the gastrointestinal tract selectively absorb these peptide s and amino acids. Secretary IgA molecules in the gut lumen bind foreign proteins and block absorption. Despite this barrier, some allergenic proteins enter the circulation intact 6 . Antigen presenting cells is the gut lumen and elsewhere in the body present the potentially allergenic proteins to T-cells which, in the genetically predisposed individual, result in Th-2 allergic responses. For non-IgE mediated allergic reactions, mediators released by T-cells and other effector cells, such as eosinophils, result in the inflammation or vascular leakage characterized by these non-IgE mediated reactions. For IgE mediated allergy, B cells produce specific IgE antibody which bind to high affinity IgE receptors on mast cells and basophils. When these cells are exposed to the specific proteins, cross-linking of IgE occurs and mediators such as histamine are released resulting in the classic signs of symptoms of IgE-mediated food allergy 7 .
  • We will now discuss several specific food allergic disorders. Anaphylaxis represents a rapid multisystem IgE-mediated food allergic reaction which can potentially be fatal. Any food proteins can potentially cause anaphylaxis, but the foods responsible for 80-90% of life threatening anaphylactic reactions are peanuts, tree nuts and seafood. 8,9 Food-associated, exercise-induced anaphylaxis is a disorder in which either eating a particular food or, more rarely, eating any food prior to exercising results in anaphylaxis. Individuals with this disorder are able to eat the incriminated food or are able to exercise without a problem when each is done separately but develop anaphylaxis when they are done in combination 10 .
  • It is estimated that about 100-200 individuals in the US die each year from food-allergic reactions. Based on a few reports, individuals at increased risk for fatal anaphylaxis include those who delay treatment with epinephrine, have asthma, have experienced prior severe food allergic reactions, or who deny ongoing symptoms. 8,9 Teenagers appear to be at particular risk. Usually these deaths are caused by a known food allergy while away from home and the fatal flaw is the failure to promptly administer epinephrine. Many of the children reported with fatal reactions had a biphasic reaction. They had initial mild symptoms within 30 minutes of ingesting the food that resolved only to have a recurrence of severe symptoms 1-2 hours following the ingestion. Thus, it is vitally important to observe patients with an acute anaphylactic reaction for at least 4 hours prior to discharge from the emergency room. Additionally, fifteen percent of those with severe reactions and 80% with fatal reactions had no skin symptoms. Thus, the absence of skin symptoms does not exclude the possibility of anaphylaxis.
  • Oral allergy syndrome describes a disorder of rapid onset of mouth itching, burning, and swelling caused by particular fresh fruits and vegetables typically occurring in individuals with allergic rhinitis due to pollen allergy 11 . This IgE-mediated reaction is rarely progressive. The underlying cause is cross-reactive proteins found in the particular fresh fruits or vegetables which possess conserved homologous proteins that are immunologically similar to those in certain pollens. Because the incriminated proteins are generally heat labile, cooking the food usually allows for ingestion without reactions. Examples of the particular pollen allergy and its associated foods are listed 12 .
  • Oral allergy syndrome describes a disorder of rapid onset of mouth itching, burning, and swelling caused by particular fresh fruits and vegetables typically occurring in individuals with allergic rhinitis due to pollen allergy 11 . This IgE-mediated reaction is rarely progressive. The underlying cause is cross-reactive proteins found in the particular fresh fruits or vegetables which possess conserved homologous proteins that are immunologically similar to those in certain pollens. Because the incriminated proteins are generally heat labile, cooking the food usually allows for ingestion without reactions. Examples of the particular pollen allergy and its associated foods are listed 12 .
  • Oral allergy syndrome describes a disorder of rapid onset of mouth itching, burning, and swelling caused by particular fresh fruits and vegetables typically occurring in individuals with allergic rhinitis due to pollen allergy 11 . This IgE-mediated reaction is rarely progressive. The underlying cause is cross-reactive proteins found in the particular fresh fruits or vegetables which possess conserved homologous proteins that are immunologically similar to those in certain pollens. Because the incriminated proteins are generally heat labile, cooking the food usually allows for ingestion without reactions. Examples of the particular pollen allergy and its associated foods are listed 12 .
  • Celiac disease, or gluten-sensitive enteropathy, is characterized by malabsorption and abdominal pain with villus atrophy. There is an increased risk for malignancy. Patients, while on a gluten-containing diet, typically have anti-gliadin IgA antibody and anti-endomysial IgG and IgA antibody. Removal of gluten from the diet results in resolution of gastrointestinal symptoms. Eosinophilic gastroenteritis is a disorder characterized histologically by eosinophilic infiltration of the gut 18,19 . Patients may experience poor growth, early satiety, abdominal pain, vomiting, diarrhea and symptoms of reflux. Particular areas of the gut may be affected, for example primarily the esophagus or stomach, and the degree and depth of inflammation is variable. Severe inflammation can result in obstruction. This disorder is typically caused by multiple food allergies and there are both IgE and non-IgE associated subtypes. Lastly, gastrointestinal anaphylaxis describes a syndrome of acute vomiting and diarrhea caused by IgE mediated food hypersensitivity 7 .  
  • A number of disorders have been unscientifically linked to food allergy or to adverse reactions to foods. These disorders include migraines, behavioral or developmental disorders, arthritis, seizures, and inflammatory bowel disease among others. No studies have conclusively identified food allergy as a cause for these disorders.
  • Although 20-25 percent of the general public believes that they have a food allergy 21,22 , population studies employing oral food challenges have indicated that 1-2 percent of adults 22 and 6 to 8 percent of children 2 have food allergy. Adverse reactions to food dyes or preservatives are much less common (<1%) 23 . The prevalence of allergy to a specific food proteins is dependent upon societal eating patterns. For example, fish allergy is more common in Scandanavian countries. Population studies have determined that milk allergy effects 2.5 percent of infants 24,25 and 1.1 percent of the general population of the United States has peanut or tree nut allergy 26 .  
  • Symptomatic allergy to multiple members of particular families of foods is uncommon, although positive tests for specific IgE among foods in the family are not uncommon. Only 11 percent of individuals are allergic to more than one food and these multiple food allergies usually cross food families. 30-100% percent of fish allergic individuals react to more than one species of fish 12 . Approximately one-third of individuals with tree nut allergy react to more than one tree nut. Twenty-five percent of individuals with grain allergy react to more than one grain. Although almost half of individuals with peanut allergy have positive tests for specific IgE to other members of the legumes family, only five percent have clinical reactivity to more than one legume 36,37 Taking this information together, it is generally unwarranted to limit all members of a particular family of foods because of clinical reactions to one member. However, consideration for removal of all members of a food family can be considered when the food family is not a major part of the diet, for example with tree nuts.
  • The clinical course and natural history of food allergy is dependent both on the food proteins in question and the mechanism of reactivity. Approximately 85 percent of children with milk, egg, wheat and soy allergy will outgrow the sensitivity by three years of age 38-40 . Declining concentrates of specific IgE 41,42 and lack of IgE directed to linear epitopes of these proteins correlate with early loss of clinical reactivity. In contrast, allergy to peanuts, tree nuts, and seafood are more persistent 43,44 . For non-IgE mediated gastrointestinal allergy, infantile forms generally resolve in one to three years, while syndromes affecting toddlers and adults are more persistent.  
  • The clinical course and natural history of food allergy is dependent both on the food proteins in question and the mechanism of reactivity. Approximately 85 percent of children with milk, egg, wheat and soy allergy will outgrow the sensitivity by three years of age 38-40 . Declining concentrates of specific IgE 41,42 and lack of IgE directed to linear epitopes of these proteins correlate with early loss of clinical reactivity. In contrast, allergy to peanuts, tree nuts, and seafood are more persistent 43,44 . For non-IgE mediated gastrointestinal allergy, infantile forms generally resolve in one to three years, while syndromes affecting toddlers and adults are more persistent.  
  • As is the case for all medical illnesses, diagnosis rests upon a careful history and physical examination. The history, as it pertains to food allergic reactions, must focus upon the symptoms elicited, the timing of the symptoms in relation to food ingestion, and reproducibility of reactions. Acute reactions to isolated ingestions should be differentiated from chronic disease related to food. Dietary details are key and a symptom diary may be helpful. The physical examination focuses on the exclusion of non-allergic causes of food-induced symptoms. The physician should be able to conclude the history and physical examination with an idea of whether an allergy or food intolerance is on the differential diagnosis and whether IgE or non-IgE mediated mechanisms are playing a role.
  • A directed laboratory evaluation is helpful in identifying particular causative foods. If IgE mediated reactivity is under consideration, prick skin testing or RAST is performed. Ancillary laboratory testing for non-IgE mediated reactions are dependent upon the particular syndrome and biopsies may be indicated. If food intolerance is a likely cause, particular tests such as breath hydrogen or sweat tests to rule out particular disorders may be indicated as determined by the history and physical examination.
  • Laboratory tests must be interpreted in the context of the history and physical examination. Positive prick skin test or RAST indicates the presence of IgE antibody but does not indicate symptomatic clinical reactivity. That is, the false positive rate associated with the test is high (~ 50 percent). However, a negative prick skin test or RAST essentially excludes IgE mediated reactivity. Intradermal skin testing with food results in an increased false positive rate and a risk for systemic reactions to the test and is not indicated 45 . A number of tests are unproven or experimental for the diagnosis of food allergy and should not be used 46 . These tests include provocation-neutralization, cytotoxic tests, applied kinesiology, hair analysis, and IgG4 testing among others.
  • Laboratory tests must be interpreted in the context of the history and physical examination. Positive prick skin test or RAST indicates the presence of IgE antibody but does not indicate symptomatic clinical reactivity. That is, the false positive rate associated with the test is high (~ 50 percent). However, a negative prick skin test or RAST essentially excludes IgE mediated reactivity. Intradermal skin testing with food results in an increased false positive rate and a risk for systemic reactions to the test and is not indicated 45 . A number of tests are unproven or experimental for the diagnosis of food allergy and should not be used 46 . These tests include provocation-neutralization, cytotoxic tests, applied kinesiology, hair analysis, and IgG4 testing among others.
  • Elimination diets are an essential component for diagnosing food allergy. An elimination diet is carried on for one to six weeks depending upon the underlying suspected disorder. In some cases, elimination of one or several particular suspected foods is adequate. However, when multiple foods are suspected it may be useful to prescribe a limited "eat only" diet where the physician indicates exactly what foods are to be included. In complicated cases, an elemental diet using a hydrolyzed or amino-acid based formula usually is necessary. Another essential component to diagnosing food allergy is the oral challenge test 47 . The food in question is fed to the patient in gradually increasing amounts over a specified period of time with evaluation for development of symptom. If there is any risk of a significant reaction, these tests must be performed under physician supervision with emergency medications immediately available. Oral challenge testing can be performed openly by feeding the patient with the suspected food in its common form. However, an open challenge is prone to both observer and subject bias so while a negative test is good indication that the food is not a problem, a positive should only be accepted if objective symptoms develop. Testing can be done single blind to remove subject bias but the “gold standard” for diagnosing food allergy is the double-blind, placebo-controlled oral food challenge. In this test, neither the patient nor physician is aware whether the feeding is placebo or the food since both are masked in a capsule or food carrier to which the subject tolerates.
  • Following the history and physical examination, the diagnostic approach to IgE mediated food allergy is based upon specific tests for IgE antibody. If tests are negative, the food may be reintroduced to the diet unless there is a convincing history warranting physician-supervised challenge. If tests are positive, an elimination diet is undertaken. If the elimination diet fails to show resolution of the underlying disorder, the food can be reintroduced to the diet unless, again, a convincing history warrants a supervised food challenge. If the elimination diet results in resolution of symptoms, open or single blind challenges can be used to screen for reactivity while double-blind, placebo-controlled food challenge is more appropriate if multiple foods are involved or clarification of open challenges is necessary. Oral challenges would not be appropriate for severe reactions to isolated food ingestion with a positive test for specific IgE antibody.
  • After causal foods are identified, the first step in treatment is dietary elimination. Dietary elimination is not a simple procedure 48 . For example, particular foods may be hidden ingredients as is the case for peanut butter in some sauces or in egg rolls. A number of issues surrounding labeling of processed foods must be addressed. Manufacturers can be contacted when ambiguous labeling such as "spices" or "may contain peanuts" are on the label. Another issue is cross contamination. This can occur in the home because of shared utensils or in industry because of shared processing equipment. Food allergic patients and their families must be taught words on labels that could indicate the presence of particular foods. For example, "natural flavor" could indicate cow’s milk protein. It is very helpful to seek assistance from a registered dietitian to address these issues and also to ensure that the diet is nutritionally adequate. The Food Allergy Network (800-929-4040) is a lay organization that is very helpful in issues concerning food allergy and dietary management.
  • After causal foods are identified, the first step in treatment is dietary elimination. Dietary elimination is not a simple procedure 48 . For example, particular foods may be hidden ingredients as is the case for peanut butter in some sauces or in egg rolls. A number of issues surrounding labeling of processed foods must be addressed. Manufacturers can be contacted when ambiguous labeling such as "spices" or "may contain peanuts" are on the label. Another issue is cross contamination. This can occur in the home because of shared utensils or in industry because of shared processing equipment. Food allergic patients and their families must be taught words on labels that could indicate the presence of particular foods. For example, "natural flavor" could indicate cow’s milk protein. It is very helpful to seek assistance from a registered dietitian to address these issues and also to ensure that the diet is nutritionally adequate. The Food Allergy Network (800-929-4040) is a lay organization that is very helpful in issues concerning food allergy and dietary management.
  • After causal foods are identified, the first step in treatment is dietary elimination. Dietary elimination is not a simple procedure 48 . For example, particular foods may be hidden ingredients as is the case for peanut butter in some sauces or in egg rolls. A number of issues surrounding labeling of processed foods must be addressed. Manufacturers can be contacted when ambiguous labeling such as "spices" or "may contain peanuts" are on the label. Another issue is cross contamination. This can occur in the home because of shared utensils or in industry because of shared processing equipment. Food allergic patients and their families must be taught words on labels that could indicate the presence of particular foods. For example, "natural flavor" could indicate cow’s milk protein. It is very helpful to seek assistance from a registered dietitian to address these issues and also to ensure that the diet is nutritionally adequate. The Food Allergy Network (800-929-4040) is a lay organization that is very helpful in issues concerning food allergy and dietary management.
  • After causal foods are identified, the first step in treatment is dietary elimination. Dietary elimination is not a simple procedure 48 . For example, particular foods may be hidden ingredients as is the case for peanut butter in some sauces or in egg rolls. A number of issues surrounding labeling of processed foods must be addressed. Manufacturers can be contacted when ambiguous labeling such as "spices" or "may contain peanuts" are on the label. Another issue is cross contamination. This can occur in the home because of shared utensils or in industry because of shared processing equipment. Food allergic patients and their families must be taught words on labels that could indicate the presence of particular foods. For example, "natural flavor" could indicate cow’s milk protein. It is very helpful to seek assistance from a registered dietitian to address these issues and also to ensure that the diet is nutritionally adequate. The Food Allergy Network (800-929-4040) is a lay organization that is very helpful in issues concerning food allergy and dietary management.
  • This is an example of words and ingredients found on product labels that indicate or may indicate the presence of milk. As can be imagined, it is not a simple process to avoid common food allergens. A great deal of education is mandatory to assist the patient toward successful avoidance. The difficulties in strict avoidance should also be kept in mind when evaluating a patient with a known allergy to a common food such as milk or soy. It is much more common to have a reaction to a hidden ingredient to which there is a known allergy rather than to experience an allergic reaction to a previously tolerated food.
  • After causal foods are identified, the first step in treatment is dietary elimination. Dietary elimination is not a simple procedure 48 . For example, particular foods may be hidden ingredients as is the case for peanut butter in some sauces or in egg rolls. A number of issues surrounding labeling of processed foods must be addressed. Manufacturers can be contacted when ambiguous labeling such as "spices" or "may contain peanuts" are on the label. Another issue is cross contamination. This can occur in the home because of shared utensils or in industry because of shared processing equipment. Food allergic patients and their families must be taught words on labels that could indicate the presence of particular foods. For example, "natural flavor" could indicate cow’s milk protein. It is very helpful to seek assistance from a registered dietitian to address these issues and also to ensure that the diet is nutritionally adequate. The Food Allergy Network (800-929-4040) is a lay organization that is very helpful in issues concerning food allergy and dietary management.
  • After causal foods are identified, the first step in treatment is dietary elimination. Dietary elimination is not a simple procedure 48 . For example, particular foods may be hidden ingredients as is the case for peanut butter in some sauces or in egg rolls. A number of issues surrounding labeling of processed foods must be addressed. Manufacturers can be contacted when ambiguous labeling such as "spices" or "may contain peanuts" are on the label. Another issue is cross contamination. This can occur in the home because of shared utensils or in industry because of shared processing equipment. Food allergic patients and their families must be taught words on labels that could indicate the presence of particular foods. For example, "natural flavor" could indicate cow’s milk protein. It is very helpful to seek assistance from a registered dietitian to address these issues and also to ensure that the diet is nutritionally adequate. The Food Allergy Network (800-929-4040) is a lay organization that is very helpful in issues concerning food allergy and dietary management.
  • For patients with IgE-mediated food allergy, emergency medications are an important aspect of management. Epinephrine is the drug of choice for severe allergic reactions. Patients must be prescribed self-administered epinephrine and have this readily available. It is essential that the patient (family) be taught the indications and also the technique of use for these medications. Antihistamines must also be readily available to treat milder reactions and are ancillary secondary treatment with epinephrine for severe reactions. It is helpful to have an emergency care plan in writing for schools, caregivers, and others. Emergency identification bracelets are also recommended.
  • Another widely held belief is that the severity of previous anaphylactic reactions will predict future episodes or that each consecutive episode will become progressively more severe. To be accurate, there is no predictable pattern with regard to the severity of future anaphylactic reactions. The severity of any reaction depends on the individual’s degree of hypersensitivity and the dose of the allergen, neither of which is constant or predictable. In addition, a patient’s response to a particular allergen may be exacerbated by poorly controlled asthma, exercise, or the consumption of alcohol. Wood RA. Identifying patients at risk for serious allergic reactions: an introduction to anaphylaxis. Presented at: Anaphylaxis: Safely Managing Your Patients at Risk for Severe Allergic Reactions. Postgraduate Institute for Medicine; October 8, 1999; Washington, DC. Dey, L.P. Fact file on anaphylaxis: acute allergic reactions to food, medication, insect stings, latex. Napa, Calif: Dey, L.P.; 2000.
  • A number of therapies are under investigation and development for treatment of food allergic disorders. Anti- IgE antibody, through its ability to scour IgE, may prove beneficial for treatment of food allergy without consideration for the specific allergen. Food-specific therapies utilizing injection of genes encoding allergenic proteins, engineered proteins with site-directed mutation of IgE-binding epitopes, and fragments of allergenic proteins (peptide immunotherapy) are under development. In addition, immune- modulating adjuvents to produce Th-1 rather than Th-2 responses may be helpful.

Food Allergy Seminar.Lecture.Class Food Allergy Seminar.Lecture.Class Presentation Transcript