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 Presentation Transcript

  • 1. Food Allergy Update: Overview for SCAFP Suzanne S. Teuber, M.D. [email_address] Professor of Medicine Training Program Director, Allergy and Immunology
  • 2. Sometimes tough to avoid…
  • 3. Definitions
  • 4. Adverse Food Reactions
    • Bacterial food poisoning
    • Heavy metal poisoning
    • Scombroid fish poisoning
    • Caffeine
    • Alcohol
    • Histamine
    Toxic / Pharmacologic Non-Toxic / Intolerance Non-immunologic
    • Lactase deficiency
    • Galactosemia
    • Pancreatic insufficiency
    • Gallbladder / liver disease
    • Hiatal hernia
    • Gustatory rhinitis
    • Anorexia nervosa
    • Idiosyncratic
    Adapted from Sicherer S, Sampson H. J Allergy Clin Immunol 2006;117:S470-475.
  • 5. Adverse Food Reactions
    • Systemic (Anaphylaxis)
    • Oral Allergy Syndrome
    • Immediate gastrointestinal allergy
    • Asthma/rhinitis
    • Urticaria
    • Morbilliform rashes and flushing
    • Contact urticaria
    • Eosinophilic esophagitis
    • Eosinophilic gastritis
    • Eosinophilic gastroenteritis
    • Atopic dermatitis
    IgE-Mediated (most common) Non-IgE Mediated Cell-Mediated Immunologic
    • Protein-Induced Enterocolitis
    • Protein-Induced Enteropathy
    • Eosinophilic proctitis
    • Dermatitis herpetiformis
    • Contact dermatitis
    Sampson H. J Allergy Clin Immunol 2004;113:805-9, Chapman J et al. Ann Allergy Asthma & Immunol 2006;96:S51-68.
  • 6. Pathophysiology
  • 7. Allergens
    • Proteins or glycoproteins (not fat or carbohydrate as primary immunogens)
      • Generally heat resistant, acid stable
    • Major allergenic foods (>85% of allergy)
      • Children: milk, egg, soy, wheat, peanut, tree nuts
      • Adults: peanut, tree nuts, shellfish, fish , fruits and vegetables
      • commonly stated that “ 90% of food allergies are caused by the “Big 8 ””, this was true for children with atopic dermatitis, not the general population with anaphylaxis. ER studies in US: FRUITS and VEGGIES same % as peanut, crustaceans highest
  • 8. Emergency Department Visits for Food Allergy (Clark et al. JACI 2004;113:347) Crustaceans: 19% Peanuts: 12% Fruits and Veggies: 12% Are these counted in food allergy prevalence estimates? -NO
  • 9. CASE: Crustacean Allergy: IgE Towards Protein in the Food, NOT Iodine
    • 79 year old man had anaphylaxis to shrimp at age 20, 25
    • Doctors told him he was allergic to iodine in seafood
    • Avoided seafood, iodized salt for years
    • Age 70: retirement dinner, hostess picked shrimp out of his portion and gave it to him --- ER visit for anaphylaxis
    • At age 79, specific IgE measurement extremely high to shrimp: >100 kU/L
    • On follow-up after education on avoidance, happily consuming foods with iodized salt because he didn’t have to screen salt source any more
  • 10. Pan-allergens
    • Proteins in food, pollen or plants that possess homologous IgE binding epitopes across species
    • Tropomyosins: crustacea, dust mites, cockroach, mollusks
      • Storage mites in flour: anaphylaxis reported!
    • Parvalbumins: fish
    • Bovine IgG: beef, lamb, venison, cow’s milk
    • Lipid transfer protein: fruits (peach, apple), vegetables, peanut, tree nuts
    • Profilin: fruits, vegetables
    • Class 1 chitinases: fruits, wheat, latex
  • 11. Immune Mechanisms IgE-Mediated IgE-receptor Histamine
    • Protein digestion
    • Antigen processing
    • Some Ag enters blood
    Mast cell APC B cell T cell
    • TNF- 
    • IL-5
    Non-IgE Mediated
  • 12. Risk Factors
  • 13. Risk Factors for Development of Food Allergy Chapman J et al. Ann Allergy Asthma & Immunol 2006;96:S51-68.
    • Local Factors (Rodent Models)
    • Pepsin digestion
    • Gastrointestinal infections?
    • Malabsorption
    • Rate of absorption
    • Antigen processing
    • Nature and dose of Ag
    • Transdermal exposure
    • Host Factors
    • Age (esp neonates)
    • Genetic susceptibility
    • FHx of atopy
    • FHx of food allergy
    • Atopic dermatitis
    • Transdermal food exposure (peanut)
  • 14. Food Allergy Disorders
  • 15. Anaphylaxis Syndromes
    • Food-induced anaphylaxis
      • Food allergy = #1 cause of anaphylaxis in the ED
      • Rapid-onset, up to 30% biphasic
      • May be localized (single organ) or generalized
      • Potentially fatal
      • Do DNA Allergy Relief Treatments for these high risk foods:
        • peanut, tree nut, seafood (cow’s milk and egg in young children)
    • Food-dependent, exercise-induced: 2 forms
      • Specific foods (wheat, celery most common)
      • Any food (post-prandial)
  • 16. Fatal Food Anaphylaxis
    • Frequency: ~ 150 deaths / year
    • Clinical features:
      • Biphasic reaction can contribute –initially better, then recurs
      • Cutaneous symptoms may not be present
      • Respiratory symptoms prominent
    • Risk factors :
      • Underlying asthma – Delayed epinephrine
      • Symptom denial – Previous severe reaction
      • Adolescents, young adults
    • History: known food allergen
    • Key foods: peanuts and tree nuts dominate (~90% of fatalities) , fish,crustaceans, few milk, few misc.
    • Most events occurred away from home
    Bock SA, et al. J Allergy Clin Immunol 2001;107:191-3.
  • 17. Cutaneous Reactions
    • Acute urticaria/angioedema – common
    • Contact urticaria - common
    • Food allergy rarely causes chronic urticaria/angioedema
    • 1/3 of kids with moderate to severe atopic dermatitis may have food allergy (especially cow’s milk, egg, soy, wheat). Morbilliform rashes may be seen in these children upon food challenge.
    • Contact dermatitis (food handlers)
  • 18. Respiratory Responses
    • Upper and lower respiratory tract symptoms may be seen (rhinoconjunctivitis, laryngeal edema, asthma)
    • Rarely isolated, usually accompany skin and GI symptoms
    • Inhalational exposure may cause respiratory symptoms that can be severe
        • Occupational
        • Restaurants
        • Kitchen/Home
    Example: crabs to be boiled
  • 19. Pollen-Food Syndrome or Oral Allergy Syndrome
    • Clinical features: rapid onset oral pruritus, rarely progressive
    • Epidemiology: prior sensitization to pollens
    • Key foods: raw fruits and vegetables
    • Allergens: Profilins and pathogenesis–related proteins
      • Heat labile (cooked food usually OK)
    • Cause: cross reactive proteins pollen/food
    Birch Apple, carrot, celery, cherry, pear, hazelnut Ragweed Banana, cucumber, melons Grass Melon, tomato, orange Mugwort Melon, apple, peach, cherry
  • 20. GI Syndromes of Children and Adults:
    • Celiac Disease (Gluten-sensitive enteropathy)
      • In children:
        • FTT, or weight loss
        • Malabsorption, diarrhea, abdominal pain
        • May be subtle
      • In adults, average 10 years of nonspecific symptoms:
        • Diarrhea, abdominal pain
        • GERD
        • Malabsorption
        • May present atypically with osteoporosis, infertility, neurologic sx
    • Pathophysiology: an immune-mediated enteropathy triggered by gluten peptides in genetically predisposed patients (DQ2 or DQ8)
      • Lymphocytic infiltration of small bowel
      • Villus atrophy
  • 21. Celiac Disease (Gluten-sensitive enteropathy) Cont’d:
    • Diagnosis
      • ~1/133 people in US have celiac disease – many are currently undiagnosed
      • IgA anti-tissue transglutaminase (IgG if IgA-deficient), anti-endomysial Ab, little role for anti-gliadin Ab currently due to poor specificity
      • Upper endoscopy with biopsy;
    • Management
      • Strict, lifelong, gluten avoidance (wheat, barley, rye)
      • Rare risk of GI lymphoma
      • Oats almost always OK
      • Link with resources: dietician, local support groups, national organizations (listed at www.celiac.nih.gov)
  • 22. GI Syndromes of Children and Adults
    • Gastrointestinal Anaphylaxis or Immediate Gastrointestinal Allergy
      • IgE-mediated
      • Acute emesis/diarrhea/abdominal pain
      • Can present without other signs or symptoms of an allergic reaction to food
  • 23. GI Syndromes of Children and Adults
    • Eosinophilic Gastrointestinal Disorders: eosinophilic esophagitis/gastritis/gastroenteritis
    • Prevalence increasing, eosinophilic esophagitis is the most common syndrome, all rare in adults
    • Symptoms
      • Post-prandial N/V/D/abdominal pain, weight loss
      • FTT in infants and young children, irritability, sleep disturbance
      • GER, often refractory, may be seen
      • In teens/adults: dysphagia, food impaction
  • 24.
    • Eosinophilic Gastrointestinal Disorders: eosinophilic esophagitis/gastritis/gastroenteritis cont’d:
    • Diagnosis
      • Biopsy: eos infiltration (mucosa  serosa): >15/HPF
      • Presence of eos doesn’t necessarily invoke food allergy
      • May affect esophagus to rectum
    • Response to specific food elimination found in a subset of patients (especially eosinophilic esophagitis): can screen for food allergy with prick/in vitro IgE, patch testing with food is currently under investigation
  • 25. Disorders Not Proven to be Related to Food Allergy
    • Migraines
    • Behavioral / Developmental disorders
    • Arthritis
    • Seizures
    • Inflammatory bowel disease
  • 26. Prevalence and Natural History
  • 27. Prevalence of Food Allergy
    • Perception by public: 20-25%
    • Confirmed allergy (oral challenge)
      • Adults: 3-4%
      • Infants/young children: 6-8%
    • Specific Allergens
      • Dependent upon societal eating and cooking patterns
    • Prevalence higher in those with:
      • Atopic dermatitis
      • Certain pollen allergies
      • Latex allergy
    • Prevalence seems to be increasing
  • 28. Estimated Prevalence of Food Allergy Sampson H. J Allergy Clin Immunol;113:805-19. Food Children (%) Adults (%) Cow’s milk 2.5 0.3 Egg 1.3 0.2 Soy 0.3-0.4 0.04 Peanut 0.8 0.6 Tree nut 0.2 0.5 Crustaceans Fish 0.1 0.1 2.0 0.4
  • 29. Prevalence of Clinical Cross Reactivity Among Food “Families” Food Allergy Prevalence of Allergy to > 1 Food in Family Fish 30% -100% Tree Nut 15% - 40% Grain 25% Legume 5% Any 11% Sicherer SH. J Allergy Clin Immunol. 2001 Dec;108(6):881-90.
  • 30. Natural History
    • Dependent on food & immunopathogenesis
    • ~ 85% of cases of cow milk, soy, egg and wheat allergy remit by age 3 yrs – numbers may be worse now for milk and egg
      • Declining/low levels of specific-IgE favorable
      • IgE binding to conformational epitopes favorable
    • Non-IgE-mediated GI allergy
      • Infant forms resolve in 1-3 years
      • Toddler / adult forms more persistent
  • 31. Natural History (cont’d)
    • Allergies to peanuts, tree nuts, seafoods, and seeds typically persist
    • ~20% of cases of peanut allergy resolve by age 5 years.
    • Prognostic factors include :
      • PST <6mm
      • ≥ 2 years avoidance
      • History of mild reaction
      • Few other atopic diseases
      • Low levels of peanut-specific IgE
      • Rarely re-develop allergy: role for regular ingestion?
  • 32. Diagnosis and Management
  • 33. Evaluation: History & Physical Exam
    • History: most important
      • Symptoms, timing, reproducibility, treatment and outcome
      • Concurrent exercise, NSAIDs, EtOH
    • Diet details / symptom diary
      • Subject to recall
      • “ Hidden” ingredient(s) may be overlooked
    • Physical exam: assess for other allergic and alternative disorders
    • Identify general mechanism
      • Allergy vs intolerance
      • IgE versus non-IgE mediated
  • 34. Evaluation of Food Allergy
    • Suspect IgE-mediated
      • Panels/broad screening should NOT be done without supporting history because of high rate of false positives.
      • Prick skin tests (prick-prick with fresh food if pollen-food syndrome)
      • In vitro tests for food-specific IgE
    • Suspect non-IgE-mediated
      • Consider biopsy of gut, skin
    • Suspect non-immune, consider:
      • Breath hydrogen
      • Sweat test
      • Endoscopy
  • 35. Interpretation of Laboratory Tests
    • Positive prick test or specific IgE
      • Indicates presence of IgE antibody NOT clinical reactivity
      • ~90% sensitivity
      • ~50% specificity
      • ~ 50% false positives
      • Larger skin tests/higher IgE correlates with likelihood of reaction but not severity
    • Negative prick test or specific IgE
      • Essentially excludes IgE antibody (>95% specific)
  • 36. Unproven/Experimental Tests
    • Intradermal skin test with food
      • Risk of systemic reactions and death
      • Not predictive (high false positive rate)
    • Provocation/neutralization, cytotoxic tests, applied kinesiology (muscle response testing), hair analysis, electrodermal testing, food-specific IgG or IgG4 (IgG “RAST”)
    • Note: industry/restaurants have no way of ascertaining whether a consumer was “diagnosed” by these methods or has a true food allergy. Science does not enter until a lawsuit is filed….
  • 37. Diagnosis: Elimination Diets & Food Challenges
    • Elimination diets (1 - 6 weeks) most useful for chronic disease ( eg. AD, GI syndromes)
      • Eliminate suspected food(s) or
      • Prescribe limited “eat only” diet or
      • Elemental diet
    • Oral challenge testing (MD supervised, emergency meds available)
      • Open
      • Single-blind
      • Double-blind, placebo-controlled (DBPCFC)
  • 38. Diagnostic Approach: IgE-Mediated Allergy
    • If test for specific-IgE antibody is
      • Negative: reintroduce food*
      • Positive: start elimination diet
    • If elimination diet is associated with
      • No resolution: reintroduce food*
      • Resolution
        • Open / single-blind challenges to “screen”
        • DBPCFC for equivocal open challenges
    * Unless convincing history warrants supervised challenge
  • 39. Treatment of Food Allergy
    • Complete avoidance of specific food trigger
    • Ensure nutritional needs are being met
    • Education
    • Anaphylaxis Emergency Action Plan if applicable
      • most accidental exposures occur away from home
    This frozen dessert could have peanut, tree nut, cow’s milk, egg, wheat
  • 40. Peanut allergen exposure through saliva: assessment and interventions to reduce exposure. Maloney JM et al. JACI 2006:118:719-24 .
    • In our UC Davis group of patients with severe tree nut or peanut allergy, 5.3% volunteered that they had a reaction from kissing, sometimes several hours after partner had eaten food. 1/3 in dating situation .
    • This study: Waiting 60 min, then brushing still did not remove peanut allergen completely
    • Authors suggest waiting several hours and ingesting a peanut-free meal to be more effective than tooth-brushing or gum-chewing.
  • 41. Treatment: Dietary Elimination
    • Education
    • Hidden ingredients in restaurants/homes (peanut in sauces,egg rolls)
    • Labeling issues (“spices”, changes, errors)
    • Cross contact (shared equipment)
    • Seeking assistance
      • Food allergy specialist
      • Registered dietitian: (www.eatright.org)
      • Food Allergy & Anaphylaxis Network (www.foodallergy.org; 800-929-4040) and local support groups
  • 42. Treatment: Dietary Elimination
    • Education
    • Hidden ingredients in restaurants/homes (peanut in sauces,egg rolls)
      • International products
      • Restaurants: outsourced dressings/desserts a problem
        • Woman with near-fatal reaction after patisserie cake
      • Secret ingredients
  • 43. FALCPA won’t help this: “No Nuts in It!” swore the chef
    • -- Meal served. Told specifically that there were no nuts in it
    36 yr old woman with tree nut allergy – peanuts OK Upscale bistro; chef in charge Told waitress of life-threatening allergy – asked to check with chef to make sure dishes she was ordering were safe. Was told, “No problem.” Highly Educated Expert Chef
  • 44.
    • Ate a few bites and started to have tingling in the mouth
    Called the waitress over and asked if there was any way there were nuts in the dish – was told “No” Reaction progressed over minutes, trouble breathing and speaking, used her Epi-Pen, 911 called Hospitalized Jambalaya
  • 45.
    • After discharge, she spoke to the chef, who repeatedly denied to her that there were nuts in the dish
    • Important to find out the cause, because if it was a new allergy she would have to track it down to avoid it in future along with tree nuts
    • Threatened a lawsuit
    Chef only then disclosed ground cashews were used as a secret ingredient
  • 46.
    • “ Didn’t know it could be so serious”
    • The chef maintained that he had been residing on planet earth despite an address in San Francisco
  • 47. Hospitality literature
    • Wait staff: majority thought it was OK to pick an allergen off a dish and serve it to the customer
    • 80% of managers said they were familiar with food allergy but only about 50% could define it. Others gave examples of things like spoiled food.
  • 48. Treatment: Dietary Elimination
    • Education
    • Hidden ingredients in restaurants/homes (peanut in sauces,egg rolls)
    • Labeling issues (“spices”, changes, errors)
    • Cross contact (shared equipment)
    • Seeking assistance
      • Food allergy specialist
      • Registered dietitian: (www.eatright.org)
      • Food Allergy & Anaphylaxis Network (www.foodallergy.org; 800-929-4040) and local support groups
  • 49.
    • Contain cow’s milk: Artificial butter flavor, butter, butter fat, buttermilk, casein, caseinates (sodium, calcium, etc.), cheese, cream, cottage cheese, curds, custard, Half&Half ® , hydrolysates (casein, milk, whey), lactalbumin, lactose, milk (derivatives, protein, solids, malted, condensed, evaporated, dry, whole, low-fat, non-fat, skim), nougat, pudding, rennet casein, sour cream, sour cream solids, sour milk solids, whey (delactosed, demineralized, protein concentrate), yogurt. MAY contain milk : brown sugar flavoring, natural flavoring, chocolate, caramel flavoring, high protein flour, margarine, Simplesse ® .
    • AS of January 1, 2006, all food containing “Big Eight Allergens” (cow’s milk, peanut, tree nut, hen’s egg, soy, wheat, fish, crustacean) in the U.S. MUST declare the ingredient on the label in COMMON language. Does NOT apply to non-Big 8 allergens (e.g., sesame).
    Label reading used to be very challenging Example: Cow’s Milk Food Allergen Labeling and Consumer Protection Act of 2004 (P.L. 108-282) (FALCPA)
  • 50. Geographic Unit United States (U.S. Public Law 2004) European Union (European Commission 2003) Australia-New Zealand (Australia New Zealand Food Authority 2001) Canada (pending law, Health Canada 2008) Japan (Ministry of Health 2001) Cow’s milk √ √ √ √ √ Hen’s egg √ √ √ √ √ Wheat √ √ √ √ √ Soy √ √ √ √ Peanut √ √ √ √ √ Tree nuts √ √ √ √ Fish √ √ √ √ Crustacean √ √ √ √ Molluscs √ √ Sesame √ √ √ Mustard seed √ celery √ buckwheat √
  • 51. Undeclared food (allergens)
    • Current laws don’t help people with allergy to less common food allergens that are present in small amounts.
      • Example: spices. UCD: personally have patients with oregano, cumin, garlic allergy. Virtually any food can be an allergen
        • Prefer not to experiment with finding a threshold in an uncontrolled setting!
      • FULL disclosure of all ingredients would be helpful
      • Gets back to fact that we need more data on meaningful thresholds for a reaction
        • E.g., soy lecithin
  • 52. May Contain..
    • FDA mandated to publish results of follow-up studies on utility and consumer preferences for “may contain” labeling.
    • Should be available soon.
    • Consumers “hate it”
    • As detection kits improve, can the use of these terms decrease? Need thresholds
  • 53. Treatment: Dietary Elimination
    • Education
    • Hidden ingredients in restaurants/homes (peanut in sauces,egg rolls)
    • Labeling issues (“spices”, changes, errors)
    • Cross contact (shared equipment)
    • Seeking assistance
      • Food allergy specialist
      • Registered dietitian: (www.eatright.org)
      • Food Allergy & Anaphylaxis Network (www.foodallergy.org; 800-929-4040) and local support groups
  • 54. Cross-Contact
    • We need to do a better job teaching patients
    • And restaurant staff
      • Utensils
      • Surfaces
      • Pans/pots
      • Deep fryers
      • Scatter
    • No need to “eliminate” allergens when there is a “safe” area for all and knowledgeable staff.
  • 55. Treatment: Dietary Elimination
    • Education
    • Hidden ingredients in restaurants/homes (peanut in sauces,egg rolls)
    • Labeling issues (“spices”, changes, errors)
    • Cross contact (shared equipment)
    • Seeking assistance
      • Food allergy specialist
      • Registered dietitian: (www.eatright.org)
      • Food Allergy & Anaphylaxis Network (www.foodallergy.org; 800-929-4040) and local support groups
  • 56. Emergency Treatment: Anaphylaxis
    • Epinephrine: drug of choice
      • Self-administered epinephrine readily available at all times
      • If administered, seek medical care IMMEDIATELY
      • Train patients, parents, contacts: indications/technique
    • Anti-histamines: secondary therapy only: WILL NOT STOP ANAPHYLXAXIS
    • Written Anaphylaxis Emergency Action Plan
      • Schools, spouses, caregivers, mature sibs / friends
    • Emergency identification bracelet
  • 57. MYTH: Prior Episodes Predict Future Reactions
    • No predictable pattern
    • Severity depends on:
      • Sensitivity of the individual
      • Dose of the allergen
      • Other factors (e.g., food matrix effects, exercise, concurrent medications, airway hyperresponsiveness)
    • Must always be prepared for an emergency
    .
  • 58. Patients with severe food allergy may not receive education on avoidance, self-injectable epinephrine or referral to an allergist at emergency department visits. It is imperative for primary care doctors and allergists to recognize the risks and help patients avoid a future accident. Emergency Department Management of Food Allergy Clark S, et al. J Allergy Clin Immunol 2004;113:347-352.
  • 59. Future Immunomodulatory Therapies
    • Recombinant anti-IgE antibody
    • Mutated B-cell epitopes
    • Minimal T-cell epitopes
    • Immune-modulating adjuvants (ISS)
    • Probiotics
    • T lymphocyte manipulation to induce tolerance
    • Heat-killed E. coli encoding mutated allergens
    • Chinese herbal remedies (Food Allergy Herbal Formula)
    • Oral tolerance induction
  • 60. Induction of tolerance after establishment of peanut allergy by the food allergy herbal formula-2 is associated with up-regulation of IFN- γ . Qu et al. CEA 2007;37:846 .
    • Murine model of peanut anaphylaxis
    • Treatment by gavage bid x 6 weeks started AFTER mice allergic completely blocks reactions
    • Still blocked reactions to peanut 4 weeks after treatment stopped
    • IL-4, IL-5, IL-13 significantly decreased in mesenteric lymph nodes of treated mice
    • IFN- γ significantly increased in mesenteric lymph nodes of treated mice
    • An apparently synergistic combination of phytochemicals is present
  • 61. Phamacological and immunological effects of individual herbs in the Food Allergy Herbal Formula-2 (FAHF-2) on peanut allergy. Kattan JD et al. Phytotherapy Res 2008;epub ahead of print 4/08
    • The nine separate “herbs” were individually tested as in the previous studies in the murine model
    • No single herb offered full protection
    • One offered statistically signif (but only 4 mice) protection (only ¼ mice had a reaction to peanut): Huang Bai: Phellodendron bark
    • Huang Bai also reduced plasma histamine levels, but no change in IgE or specific IgG2a levels, whereas FAHF-2 results in decreased IgE and increased IgG2a
    • Tried a simplified formula with only Huang Bai and 2 other “herbs”, but 2/5 mice had anaphylactic reactions to peanut
    • Best results with full formula
  • 62. Food Allergy Initiative and NIH-NIAID Food Allergy Consortium
    • Funding to Xiu-Min Li and Hugh Sampson at Mt. Sinai.
    • Food Allergy Herbal Formula 2 is a bitter-tasting decoction/tea. Now, a tablet form has been developed (12 small tablets tid is the human dose). Phase I trial scheduled to start now – announced that patients were now being enrolled at 2008 AAAAI meeting: just tolerability/safety.
    • They plan to seek FDA approval via Phase II, III trials.
  • 63.
    • If the safety profile is good, since it is an herbal supplement, it could be available OTC with no health claims by the end of 2008 according to a recent Food Allergy Initiative mailer.
      • This needs to be thought through very carefully though
      • Knock-offs could proliferate with claims for all kinds of allergies
        • Lead, arsenic, cadmium, adulteration (remember Zencor/sildenafil??)
        • Takes time for FTC to catch up with those who illegally make claims
  • 64. A randomized, double-blind, placebo-controlled study of Milk Oral Immunotherapy (MOIT) for cow’s milk allergy. Skripak JM et al. JACI 2008;S137
    • 20 randomized to milk or placebo (2:1 ratio) after baseline studies
    • Build up day: started with 0.4 mg milk protein, final dose 50 mg
    • Daily dosing with eight weekly dose increases to maintenance of 500 mg
    • Continued daily for 3-4 mo
    • 11 completed, 5 active, 6 placebo
    • Baseline OFC: all 11 reacted to 40 mg milk protein (the initial dose)
  • 65. Cont’d: MOIT
    • Post OFC active group: cumulative median dose to elicit reaction in active group: 5,140 mg (range 2,540 – 6,140)
      • 1 patient tolerated final dose of 8,140 mg with no symptoms.
    • Post OFC placebo group: still reactive at 40 mg
    • 968 total active MOIT doses: 9.9% local reactions, 3.8% systemic, epi given in 2 reactions
    • 994 placebo doses: 11.3% local reactions, 1.2% systemic, no epi given.
  • 66. Rush specific oral tolerance induction in peanut allergic patients at high risk of anaphylactic reactions. Blumchen K et al. JACI 2008:S136 .
    • 6 children, ages 3-10
    • Peanut ImmunoCAP range 85->100 kU/l, median >100
    • All asthmatic, all “high risk”
    • DBPCFC median provoking dose 470 mg peanut
    • Inpatient rush protocol, allergic symptoms appeared at 96 mg to 480 mg, 3/6 had lower respiratory symptoms, multiple reactions requiring treatment
    • Discharged after 6 days: on maintenance doses from 24 mg to 160 mg of peanut
    • NOT protective doses!
    • Conclusion: not a good approach for this type of pt.