FOODALLERGY€¦ · Fish Parvalbumin (Gad c 1) Lipid transfer proteins (PR-14) Apple (Mal d 3) Corn...
Transcript of FOODALLERGY€¦ · Fish Parvalbumin (Gad c 1) Lipid transfer proteins (PR-14) Apple (Mal d 3) Corn...
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FOOD ALLERGY JACEK GOCKI
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FOOD HYPERSENSITIVITY
Objectively reproducible symptoms or signs initiated by exposure to a food at a dose tolerated by healthy persons
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Food hypersensitivity
Immunological mediated (Allergy)
Non immunological mediated
IgE mediated Non IgE mediated
Toxic Metabolic Pharmacologic
toxic contaminants (e.g., histamine in scombroid fish poisoning, toxins secreted by Salmonella, Shigella, and Campylobacter) pharmacologic properties of the food (e.g., caffeine in coffee, tyramine in aged cheeses) metabolic disorders (e.g., lactase deficiency)
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FOOD ALLERGY
Hypersensitivity reaction to a food, initiated by specific immunologic mechanisms
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PREVALENCE
Food allergy affects about 6% of the US population less than 5 years of age and about 3.5 4% of the general population Most important food allergens in Europe: Children: cow milk, egg, wheat, soy, fish, peanut Adults: hazelnut, apple, peach, kiwi, carrot
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When sensitized person eat a simple meal, in fact they eat a mixture of several allergens. Some of them can be hidden allergens, and some could be cross reactive. It is difficult sometimes to recognize wchich allergen provoced symtoms
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FOOD ALLERGEN
Food allergens are proteins (15-40 kDa) or glikoproteins (10-70 kDa), wchich are good tolerated by helthy person, in atopic patients provoke allergic disorders
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SOURCE OF ALLERGENS
ANIMAL ALLERGENS Most important in childrens
PLANT ALLERGENS Most importants in adults
A. Cod
B. Milk ( -laktoglogulin)
C. Corn
D. Birch
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TERMINOLOGY OF FOOD ALLERGENS
Most fruts, vegetables, milk, eg, fish has a several allergens For example: apple has a 3 main allergens: Mal d 1, Mal d 2, Mal d 3 International names of this proteins is made by using the latin name of their sourse (e.g. apple Malus domestica ) The international names consist of 3 parts First: 3 letters of genus (e.g. Malus Mal) Second: one or two letters of species (e.g. domestica d) Third: numeral (e.g. 1 ) Example: main allergen of apple: Mal d 1
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FEATURE OF FOOD ALLERGENS (Clinical important)
Resistance to heating, chemical and enzymatic proteolysis Cross reactive with other allergens This features are important for division all food allergens in two clasess:
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Class 1 C lass 2
Cow milk Caseins (Bos d 8) Whey - -laktoglobulin (Bos d 5) Egg Owoalbumin (Gal d 2) Owomukoid (Gal d 1) Peanuts Vicilin (Ara h 1) Conglutin (Ara h 2) Glicinin (Ara h 3) F ish Parvalbumin (Gad c 1) L ipid transfer proteins (PR-14) Apple (Mal d 3) Corn (Zea m 14)
C ross reactive proteins latex-fruits PR-2 proteins Latex (Hev b 2) Banana Kiwi PR-3 proteins Latex (Hev b 6.02) Avocado (Pers a 1) PR-5 proteins Apple (Mal d 2) Cherry (Pru av 2) Birch (Bet v 1) homologus allergens (PR-10) Apple (Mal d 1) Carrot (Dau c 1) Celery (Api g 1) Birch (Bet v 2) homologus proteins Latex (Hev b 8) Celery (Api g 4)
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COW MILK (Bos d)
Cow's milk generally represents the first foreign proteins introduced into an infant's diet. It is the most common food allergy in young children. Cow's milk contains at least 20 protein components, which may lead to antibody production in humans. The milk protein fractions are subdivided into casein and whey proteins. The caseins constitute 76 86% of the protein in cow's milk. The casein fraction is composed of four basic caseins ( s1, s2, , and ). The non-casein fraction, or whey, consists of -lactoglobulin, -lactalbumin, bovine immunoglobulins, and bovine serum albumin. Extensive heating will destroy several of the whey proteins (bovine serum albumin, bovine -globulin, and -lactalbumin). However, routine pasteurization is not sufficient to denature these proteins, but may increase the allergenicity of some milk proteins, such as -lactoglobulin.
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HEN EGG(Gal d)
Hen egg is the most common IgE-mediated food allergy in children. The yolk is considered less allergenic than the white, although IgE antibodies to chicken gamma globulin, apovitellenin I, and contaminating egg white proteins can be demonstrated. The egg white contains 23 different glycoproteins;; however, ovomucoid, ovalbumin, and ovotransferin have been identified as the major allergens. Although ovalbumin comprises the majority of the protein in egg white, ovomucoid has been shown to be the dominant allergen when highly purified egg white proteins are utilized. Ovomucoid is responsible for clinical reactivity in the vast majority of egg allergic children. In addition, it was shown that about 70% of egg allergic children may be able to ingest small amounts of egg protein in extensively heated (baked) products, e.g., breads, cakes, and cookies.
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FISH
Fish are one of the most common causes of food allergic reactions in adults, and a common cause in children as well. The major allergen in cod, Gad c 1, is a parvalbumin that has been isolated from the myogen fraction of the white meat. A similar protein, Sal s 1, has been isolated from salmon. It is heat-stable and resistant to proteolytic digestion, has a molecular weight of 12 kDa. Immunoblot analyses, 10 common fish species were shown to have a protein that is similar to Gad c 1. Unlike many other food allergens, the fish protein fraction(s) responsible for clinical symptoms in some patients appear to be more susceptible to manipulation (e.g., heating, lyophilization) than other foods. Furthermore, it was found that most patients allergic to fresh cooked salmon or tuna could ingest canned salmon or tuna without difficulty, indicating that preparation led to destruction of the major allergens. Nevertheless, allergic reactions following exposure to airborne allergen emitted during cooking are not uncommon.
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SHELLFISH
Shellfish allergens are considered a major cause of food allergic reactions in adults, affecting up to 2.3% of the US adult population. This group consists of a wide variety of mollusks (snails, mussels, oysters, scallops, clams, squid, and octopus) and crustacea (lobsters, crabs, prawns, crawfish, and shrimp). Shrimp allergens have been most extensively studied. Eighteen precipitating antigens have been detected. Tropomyosin, a protein found both in muscle and elsewhere, has been identified as the major allergen in shrimp. Considerable cross-reactivity among crustacea has been demonstrated by skin test Invertebrate tropomyosins are highly homologous and tend to be allergenic those from crustaceans (e.g., shrimp, crab, crawfish, and lobster), arachnids (house dust mites), insects (cockroaches), and mollusks (squid, snails) whereas vertebrate tropomyosin tends to be non-allergenic.
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PEANUTS (Ara h)
Peanuts are the most common food allergy in the pediatric population beyond the age of 4 years. Peanut proteins are traditionally classified as albumins (water-soluble) and globulins. Thirty-two protein bands have been identified, however, three with molecular weights of 63.5 kDa (Ara h 1), 17 kDa (Ara h 2), and 64 kDa (Ara h 3) have been identified as major allergens. Ara h 4 through 8 have been identified. A wide variety of peanut products including flour and reprocessed peanuts have been shown to retain their allergenicity.
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SOYBEANS
Soybeans are a second member of the legume family that provokes a significant number of hypersensitivity reactions, predominantly in infants and young children. Since soybeans provide an inexpensive source of high-quality protein, soybean protein is used in many commercial foods. Approximately 10% of the seed proteins are water-soluble albumins and the remainder are salt-soluble globulins. Four major protein fractions have been separated
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TREE NUTS
Tree nut allergies affect about 0.6% of the American population. Walnuts were the nut provoking the most allergic reactions (34%), followed by cashews (20%), almonds (15%), pecan (9%), pistachio (7%), and hazel nut, Brazil nut, pine nut, and macadamia nut, all less than 5%. I Europe most allergic reactions are provoking by hazel nut (4,8% of overall population), and it is a major food allergen in adults. Skin testing reveals extensive cross-reactivity among tree nuts.
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PROFILINS
Profilin is an actin-binding protein that was first identified in birch pollen (Bet v 2) and is now recognized as an allergenic protein in a number of fruits and vegetables. Profilins are responsible for the celery-mugwort-spice syndrome and are responsible for oral allergy syndrome (OAS) to apple, pear, carrot, celery (Api g 4), and potato in birch pollen-allergic patients. Profilins have also been identified in tomato, peanut (Ara h 5), and soybean (Gly m 3), but whether these proteins cause allergic reactions remains to be established
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PRs
Pathogen-related proteins (PRs) have been shown to comprise a large number of class 2 allergenic proteins found in various vegetables and fruits. These proteins are induced when pathogens, wounding or certain environmental stresses, such as drought, heat, etc., stress the plant. PRs have been classified into 14 families, although six PR families account for the majority of cross-reactivity among plant proteins.
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CLINICAL MANIFESTATIONS - IgE mediated - Non IgE mediated - Mixed, IgE and non IgE mediated
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IgE mediated diorders
Skin: Urticaria, angioedema, flushing, acute morbilliform rash, acute contact urticaria
Gastrointestinal:Oral allergy syndrome, gastrointestinal anaphylaxis
Respiratory:Acute rhinoconjunctivitis, acute bronchospasm
Generalized: Anaphylaxis, food-dependent exercise-induced anaphylaxis
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Non IgE mediated disorders
Skin : Contact dermatitis,dermatitis herpetiformis Gastrointestinal: Allergic proctocolitis, food protein-induced enterocolitis syndrome, celiac disease, infantile colic
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Mixed, IgE and non IgE mediated
Skin: Atopic dermatitis, contact dermatitis Gastrointestinal: Allergic eosinophilic esophagitis, allergic eosinophilic gastroenteritis
Respiratory: Asthma
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Oral allergy syndrome (OAS)
Pollen-food allergy syndrome (oral allergy syndrome [OAS]) is elicited by a variety of plant proteins, especially PRs, cross-reacting with airborne allergens. Symptoms are provoked almost exclusively in the oropharynx and rarely involve other target organs. It is estimated that OAS affects up to 50 70% of adults suffering from pollen allergy, especially to birch, ragweed, and mugwort pollens. Local IgE-mediated mast cell activation provokes the rapid onset of pruritus, tingling, and angioedema of the lips, tongue, palate, and throat, and occasionally a sensation of pruritus in the ears and/or tightness in the throat. Symptoms are generally short-lived and are most commonly associated with the ingestion of various fresh fruits and vegetables.
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DIAGNOSIS
Medical history Diet diaries Elimination diets Prick skin tests In vitro allergen-specific IgE tests Intragastral provocation under endoscopy Oral food challenges
OPEN SINGLE BLIND DOUBLE BLIND
The double-blind, placebo-controlled food challenge (DBPCFC)
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DBPCFC
The double-blind, placebo-controlled food challenge (DBPCFC) has been labeled the for the diagnosis of food allergies. Many investigators have utilized DBPCFCs successfully in children and adults to examine a variety of food-related complaints. The selection of foods to be tested in DBPCFCs is generally based upon history, skin test, and/or in vitro IgE results. Foods unlikely to provoke food allergic reactions may be screened by open or single-blind challenges. However, for research studies positive reactions by these methods should be confirmed by DBPCFC, except perhaps in very young infants.
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DBPCFC
Prior to undertaking DBPCFC, several factors need to be taken into consideration. Suspect foods should be eliminated for 714 days prior to challenge, longer in some non-IgE-mediated gastrointestinal disorders. Antihistamines should be discontinued long enough to establish a normal histamine skin test, and other medications should be minimized to levels sufficient to prevent breakthrough of acute symptoms. In some asthmatic patients, short bursts of corticosteroids may be necessary to insure adequate pulmonary reserve for testing (FEV1 >70% predicted).
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Food Challange
Concerns about bias No Yes
Objective symptoms Subjective or difficult to interpret symptoms or research study
Open OFC blinded OFC
DBPC FC SB OFC
With/Without Placebo
Patient and observer bias reduced
Patient bias reduced
No symptoms or convincing objective symptoms
Subjective symptoms
Accurate diagnosis food allergy
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THERAPY OF FOOD ALLERGIC DISORDERS
strict elimination of the offending allergen In accidental ingestions and exposures will occur, so food-allergic patients must be educated and prepared to recognize symptoms and initiate treatment of food allergic reactions should be prescribed an epinephrine autoinjector
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THERAPY OF FOOD ALLERGIC DISORDERS
Some medications such as H1 and H2 antihistamines, ketotifin, corticosteroids, and leukotriene inhibitors have been utilized in an attempt to modify symptoms of food allergic disorders. Antihistamines may partially mask symptoms of oral allergy syndrome and IgE-mediated skin symptoms, but overall they have minimal efficacy in blocking systemic reactions. Oral corticosteroids are generally effective in treating chronic IgE-mediated disorders, e.g., atopic dermatitis or asthma, or non-IgE-mediated gastrointestinal disorders, e.g., allergic eosinophilic esophagitis or gastroenteritis, and dietary-induced enteropathy, but the steroid side effects are generally unacceptable. Oral cromolyn sodium has not been shown to be effective in preventing or treating IgE-mediated food allergies or allergic eosinophilic gastroenteritis in appropriately controlled studies.
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THERAPY OF FOOD ALLERGIC DISORDERS
Anti-IgE antibody in the treatment Chinese herbal medication
recombinant food proteins are currently under development
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SUMMARY
Food allergy affects about 6% of the US population less than 5 years of age and about 3.5 4% of the general population Sensitization to specific proteins within food allergens may occur in the gastrointestinal tract,
egg, milk or peanut, or as a consequence of an allergic sensitization to inhalant allergens, considered class 2 food allergy, e.g., raw carrots and apples or melons, secondary to birch or ragweed pollen sensitivity, respectively
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SUMMARY
Food reactions may be due to IgE-mediated, non-IgE-mediated, or a combination of IgE- and non-IgE-mediated reactions involving the skin, gastrointestinal tract, respiratory tract, and/or cardiovascular system Increasing levels of food-specific serum IgE antibodies or prick skin test mean wheal diameters correlate with increasing probabilities of clinical reactivity, although the double-blind, placebo-for diagnosing food allergy Strict food allergen avoidance remains the only proven therapy for treating food allergy, although a number of promising immunomodulatory approaches are now in clinical trials
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Thank you and good appetite