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  • The oral allergy syndrome (OAS) appears to have become more prevalent in the past decade, but this may be due in large part to increased awareness. It is estimated that OAS affects up to 40% of adults with pollen allergy, especially to birch, ragweed and mugwort pollen. OAS is a form of contact allergy that is confined almost exclusively to the oropharynx and rarely affects other target organs. 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, tightness in the throat, or both. Symptoms are generally short-lived and are most commonly associated with the ingestion of various fresh fruits and vegetables. OAS has also been reported to occur in individuals who are sensitive to house dust mite after ingestion of shell fish.
  • 3
  • 4 The clinical history is paramount in the diagnosis of food allergy. Skin tests and specific IgE levels may provide additional information, especially for decision to performing challenge testing or not.
  • Diagnosing IgE-Mediated food hypersensitivity disorder skin tests
  • Sporik et al (David Hill’s group) from Australia reported that an allergen SPT of ≥ 3mm was a poor predictor of clinically relevant food allergy. However, they found that stronger positive reactions were highly predictive of clinical reactivity to cow’s milk (≥8mm), egg (≥7mm) and peanut (≥8mm) – these were invariably associated with positive challenge tests for these foods. For a subgroup of younger children (≤ 2years) “100% specificity” was achieved with smaller SPT wheal diameters; 6mm for cow’s milk, 5mm for egg and 4mm for peanut. These lower diameters of SPT with “100% specificity” is consistent with previous observations which demonstrate low intrinsic skin reactivity in this age group
  • Sampson and Ho reported that quantification of food-specific IgE provided increased positive predictive accuracies for egg, milk, peanut, and fish hypersensitivity compared with skin prick tests. In individuals with serum food allergen-specific IgE levels in excess of the 95% predictive value may be considered reactive, and the need for an oral food challenge would be obviated. A patient with a food allergen-specific IgE less than the 95% predictive value may be reactive and would require a food challenge to confirm the diagnosis. In addition, recent data suggest that monitoring the allergen-specific IgE values may be useful in predicting when follow-up challenges are likely to be negative (i.e. when patients “outgrow” their food allergies). Based on these data, the patient evaluation may begin with the history, progress to skin testing for the suspected foods, and then provide quantification of the level of serum food-specific IgE to determine the probability that a reaction will occur.
  • .
  • The Atopy Patch Test is performed epi-cutaneously (usually in investigation of contact dermatitis). However, instead of using type IV allergens (such as metals or perfumes) typical immediate-type allergens are used (aeroallergens or foods). The APT has been studied in combination with specific IgE in serum and skin prick testing to determine if the combination is more sensitive for diagnosing food allergy in atopic dermatitis and some gastrointerstinal allergies. It has been touted as being useful in the diagnosis of non-IgE-mediated food reactions. Further studies are necessary to determine its place in the diagnostic armamentarium for food hypersensitivity.
  • This is a commercially available. standardized basophil-based assay (Buhlmann Laboratories, Germany; website address on slide). The CAST-ELISA allows the quantitative determination of sulphidoleukotriene (sLT) release after leukocyte stimulation with an allergen or food additives. A wide variety of allergens and screening assays are commercially available for use in the CAST-ELISA. This test may be useful in evaluation drug allergy and identification of food additives, colourants and preservatives. The main clinical application of this test will possibly be in patients with chronic urticaria, food intolerance and presumed food hypersensitivity with negative standard tests for IgE sensitivity. CAST-ELISA is not currently recommended as a first-line test for allergen-induced IgE-mediated reactions. More studies are required to determine the sensitivity, specificity and predictive value of this test in comparison to DBPCFC testing (Gold Standard)
  • This slide demonstrates cross-reactivity between inhalant allergens and food allergens (generally infrequent and typically allergen – specific)
  • Milk and egg allergies are most frequently “outgrown” in young children. However, allergies to peanut, tree nut, fish and shellfish most commonly remain a life-long issue; peanut allergy and fish allergy may be “outgrown” in a small proportion of patients – but likely to recur (N.B. reports of reactions in patients with a previously negative food challenges following a history of earlier allergy).
  • Transcript

    • 1. GLORIA ™ is supported by unrestricted educational grants from
    • 2. Food Allergy GLORIA Module 6
    • 3. Global Resources in Allergy (GLORIA™) Global Resources In Allergy (GLORIA™) is the flagship program of the World Allergy Organization (WAO). Its curriculum educates medical professionals worldwide through regional and national presentations. GLORIA modules are created from established guidelines and recommendations to address different aspects of allergy-related patient care.
    • 4. World Allergy Organization (WAO) The World Allergy Organization is an international coalition of 74 regional and national allergy and clinical immunology societies.
    • 5. WAO’s Mission
      • WAO’s mission is to be a global resource and advocate in the field of allergy, advancing excellence in clinical care, education, research and training through a world-wide alliance of allergy and clinical immunology societies
    • 6.  
    • 7. Food Allergy A GLORIA TM Module Cassim Motala University of Cape Town and Red Cross Children's Hospital Cape Town, South Africa Joaquín Sastre Fundación Jimenez Diaz, Department of Medicine Universidad Autonoma de Madrid Madrid, Spain M. Dolores Ibáñez Hospital. NiÑo Jesus Madrid, Spain Contributors:
    • 8. Learning objectives
      • At the end of this presentation you will be able to:
      • Recognise the main pathogenic food allergens in adults and children
      • Differentiate between Ig-E mediated, cell-mediated and mixed IgE- and cell-mediated food-related diseases in different organ systems
      • Discuss the diagnosis of food allergy and the limitations of diagnostic techniques
      • Review the treatment of food allergy
    • 9. Adverse reactions to food: Definition
      • Any abnormal clinical response attributed to ingestion, contact or inhalation of any food, a food derivative or a food additive.
    • 10. TOXIC Nontoxic Allergy Intolerance Immune-mediated Non immune mediated Enzymatic Pharmacologic Undefined Non IgE mediated IgE mediated Adverse reaction to food: Position paper. Allergy 1995; 50:623-635 Adverse reactions to food
    • 11.
      • Precise prevalence is unknown, but estimates are:
      • Adults: 1.4% - 2.4%
      • Children < 3 years: ~ 6%
      • Atopic dermatitis (mild/severe): ~35%
      • Asthmatic children: 6 - 8%
      • Prevalence depends on: Genetic factors, age, dietary habits, geography and diagnostic procedures
      Prevalence of food allergy Adapted from Sampson HA. Adverse Reactions to foods. Allergy Principles and Practice. 2003
    • 12.
      • Children
      • Cow’s milk
      • Egg
      • Fish
      • Peanut
      • Fruits
      • Legumes
      • Wheat
      • Adults
      • Fruits
      • Peanuts
      • Tree nuts
      • Fish
      • Shellfish
      Foods more frequently implicated in food allergy
    • 13. Food allergens
      • Major class 1 food allergens:
        • Primary sensitizers
        • Sensitization may occur in the gastrointestinal tract
        • Water-soluble glycoproteins
        • Molecular weights ranging from 10 to 70 kD
        • Stable to heat, acid and proteases
      • Class 2 food allergens (cross-reactive):
        • Generally plant-derived proteins
        • Highly heat-labile
        • Difficult to isolate
        • No good, standardized, extracts are available for diagnostic purposes.
      Adapted from Sampson HA. Adverse Reactions to foods. Allergy Principles and Practice. 2003
    • 14. Ma j or class 1 food allergens
      • Cow's milk:
      • Caseins (  ,  ,  ),  -lactoalbumin,  -lactoglobulin, serum albumin
      • Chicken egg:
      • Ovomucoid, ovalbumin, ovotransferrin
      • Peanut:
      • Vicillin, conglutin, glycinin
      • Soybean:
      • Glycinin, profilin, trypsin inhibitor
      • Shrimp:
      • Tropomyosin
      • Lipid transfer proteins (LTPs):
      • Apple, apricot, peach, plum, corn
    • 15. Class 2 food allergens (Cross-reactive and associated with oral allergy syndrome, latex-fruit syndrome)
      • Pathogen-related protein 2 group (glucanase):
      • Latex, avocado, banana, chestnut, fig
      • Pathogen-related protein 3 group (chitinase):
      • Latex (Hev b6), avocado
      • Pathogen-related protein 5 (thaumatin-like):
      • Cherry, apple, kiwi
      • Birch Bet 1 homologues (pathogen-related proteins 10):
      • Apple, cherry, apricot, peach, pear, carrot, celery, parsley, hazelnut
      • Birch Bet 2 homologues (celery-mugwort-spice syndrome) profilin:
      • Latex, celery, potato, pear, peanut, soybean
    • 16. Pathogenesis of food hypersensitivity: Gut barrier
      • The immune system associated with this barrier is capable of discriminating among harmless foreign proteins or commensal organisms and dangerous pathogens.
      • Food allergy is an abnormal response of the mucosal immune system to antigens delivered through the oral route.
      • The immature state of the mucosal barrier and immune system might play a role in the increased prevalence of gastrointestinal infections and food allergy in the first few years of life.
      Adapted from J Allergy Clin Immunol 2004;113:808-809
    • 17. Pathogenesis of food hypersensitivity: Gut barrier
      • About 2 % of ingested food antigens are absorbed and transported throughout the body in an immunologically intact form, even through the immature gut.
      • The underlying immunologic mechanisms involved in oral tolerance induction have not been fully elucidated.
      Adapted from J Allergy Clin Immunol 2004;113:808-809
    • 18.
      • IgE mediated:
      • Gastrointestinal: Oral allergy syndrome, gastrointestinal, anaphylaxis
      • Cutaneous: Uriticaria, angioedema, morbilliform rashes, flushing
      • Respiratory: Rhinoconjunctivitis, bronchospasm, wheezing, anaphylactic shock
      • Generalized: Any or all of the above
      Food allergy: Clinical manifestations Adapted from J Allergy Clin Immunol 2004;113:808-809
    • 19. Food Allergy: Clincal manifestations
      • Cell mediated
      • Gastrointestinal: Food protein-induced: Enterocolitis/proctocolitis/enteropathy syndromes, celiac disease
      • Cutaneous: Contact dermatitis, herpetiformis dermatitis
      • Respiratory: Food-induced pulmonary hemosiderosis (Heiner’s syndrome)
      Adapted from J Allergy Clin Immunol. 2004; 113:808-809
    • 20. Food Allergy: Clinical manifestations
      • Mixed IgE and cell mediated:
      • Gastrointestinal: Allergic eosinophilic esophagitis/gastritis/gastroenteritis
      • Cutaneous: Atopic eczema
      • Respiratory: Asthma
    • 21. Gastrointestinal food hypersensitivities: Oral allergy syndrome (OAS) or pollen-food allergy syndrome
      • Elicited by a variety of plant proteins that cross-react with airborne allergens
      • Pollen allergic patients may develop symptoms following the ingestion of vegetables foods:
        • - Ragweed allergic patients: Fresh melons and bananas
        • - Birch pollen allergic patients: Raw potatoes,
        • carrots, celery, apples, pears, hazelnuts and kiwi
      • Immunotherapy for treating the pollen-induced rhinitis may eliminate oral allergy symptoms
      Adapted from J Allergy Clin Immunol. 2004; 113:808-809
    • 22.
      • Characterized by infiltration of the esophagus, stomach and/or intestinal walls with eosinophils, basal zone hyperplasia, papillary elongation, absence of vasculitis and peripheral eosinophilia in about 50 % of patients
      • AEE is seen most frequently during infancy through adolescence and typically presents with chronic gastroesophageal reflux
      • Responsible food allergens may need to be eliminated from the diet for up 8 weeks to bring about resolution of symptoms and up to 12 weeks to bring about normalization of intestinal histology
      Gastrointestinal food hypersensitivities: Allergic eosinophilic esophagitis (AEE) and gastroenteritis Adapted from J Allergy Clin Immunol. 2004; 113:808-809
    • 23.
      • Usually presents in the first few months of life and is thought to be due to food proteins passed to the infant in maternal breast milk, or to milk or soy-based formulas
      Gastrointestinal food hypersensitivities: Food protein-induced protocolitis Adapted from J Allergy Clin Immunol. 2004; 113:808-809
    • 24.
      • Occurs in infants prior to 3 months of age, but may be delayed in breast-fed babies (milk or soy protein-based formulas are implicated)
      • Symptoms may include irritability, protracted vomiting 1-3 hours after feeding, bloody diarrhoea (leading to dehydration), anaemia, abdominal distension, failure to thrive
      • In adults, shellfish hypersensitivity may provoke a similar syndrome with delayed onset of severe nausea, abdominal cramps and protracted vomiting
      Gastrointestinal food hypersensitivities: Food protein-induced enterocolitis syndrome Adapted from J Allergy Clin Immunol. 2004; 113:808-809
    • 25.
      • Occurs in first few months of life
      • Diarrhoea (mild to moderate steatorrhea in about 80 % of cases)
      • Poor weight gain
      • Biopsy shows patchy villous atrophy with prominent mononuclear round cell infiltrate, few eosinophil s
      Gastrointestinal food hypersensitivities: Dietary protein-induced enteropathy (excluding celiac disease) Adapted from J Allergy Clin Immunol. 2004; 113:808-809
    • 26. Gastrointestinal food hypersensitivities: Celiac disease
      • Extensive enteropathy leading to malabsorption
      • Associated with sensitivity to gliadin (wheat, rye and barley)
      • Highly associated with HLA-DQ2  1 *0501.  1 *0201)
      • Serology: Anti-gliadin IgA, anti-transglutaminase IgA
      • Treatment: Elimination of gluten-containing foods
      Adapted from J Allergy Clin Immunol. 2004; 113:808-809
    • 27. Gastrointestinal food hypersensitivities: Infantile colic
      • Syndrome of paroxysmal fussiness characterized by inconsolable, agonized crying
      • Generally develops in the first 2 to 4 weeks of life and persists through the third to fourth months
      • Diagnosis can be established by the implementation of several brief trials of hypoallergenic formula
      Adapted from J Allergy Clin Immunol. 2004; 113:808-809
    • 28.
      • Acute Urticaria and Angioedema:
      • The most common symptoms of food allergic reactions.
      • The exact prevalence of these reactions is unknown.
      • Acute urticaria due to contact with food is also common.
      • Chronic Urticar i a:
      • Food allergy is an infrequent cause of chronic urticaria and angioedema.
      Cutaneous food hypersensitivities
    • 29.
      • Generally begins in early infancy
      • Characterized by typical distribution, extreme pruritus, and chronically relapsing course
      • Allergen-specific IgE antibodies bound to Langerhans cells play a unique role as “non-traditional” receptors
      • Double blind, placebo-controlled food challenges generally provoke a markedly pruritic, erythematous, morbilliform rash
      • Food allergy plays a pathogenic role in about 35 % of moderate-to-severe atopic dermatitis in children
      Cutaneous food hypersensitivities: Atopic eczema
    • 30. Respiratory food hypersensitivities: Asthma
      • An uncommon manifestation of food allergy
      • Usually seen with other food-induced symptoms
      • Vapors or steam emitted from cooking food may induced asthmatic reactions
      • Food-induced asthmatic symptoms should be suspected in patients with refractory asthma and history of atopic dermatitis, gastroesophageal reflux, food allergy or feeding problems as an infant, or history of positive skin tests or reactions to food
    • 31. Respiratory food hypersensitivities
      • Rhinoconjunctivitis
      • Usually seen during positive controlled challenge tests, but occasionally reported by patients
      • Heiner´s Syndrome
      • A rare form of food-induced pulmonary hemosiderosis, typically due to cow's milk
    • 32. Anaphylaxis
      • Food allergies are the cause of at least one-third of anaphylaxis cases seen in hospital emergency
      • Variable expression of cutaneous, respiratory and gastrointestinal symptoms, and cardiovascular symptoms including hypotension, vascular collapse and cardiac dysrhythmias
      • Serum  -tryptase is rarely elevated in food-induced anaphylaxis
      Adapted from J Allergy Clin Immunol. 2004;113:808-809
    • 33. Gastrin Exercise Food Food allergy: Exercise-induced anaphylaxis Mediator release - Histamine - Others (LTD4,PAF, etc) Temperature ANAPHYLAXIS Adapted from Adverse Reactions to Foods Committee. Spanish Society of Allergy and Clinical Immunology
    • 34. 1) Identification and relationship with the food: Medical history 2) To identify specific IgE: Skin tests/serum specific IgE 3) To demonstrate that IgE sensitization is responsible for the clinical reaction : Controlled challenge tests Diagnosis is based on the medical history, supported by identification of specific IgE antibodies to the incriminated food allergen. Adapted from Adverse Reactions to Foods Committee. Spanish Society of Allergy and Clinical Immunology Diagnosing food hypersensitivity disorders: IgE-mediated
    • 35.
      • The diagnosis of food allergy cannot be performed on the basis of a non-compatible medical history
      • No diagnostic analysis (skin tests, specific IgE in serum, etc) is of value if it is interpreted without reference to medical history
      Adapted from Adverse Reactions to Foods Committee. Spanish Society of Allergy and Clinical Immunology Diagnosing IgE-mediated food hypersensitivity disorders
    • 36.
      • Symptoms described by patient
      • Length of time between ingestion and development of symptoms
      • Severity of symptoms
      • Frequency of symptoms
      • Time from last episode
      Adapted from Adverse Reactions to Foods Committee. Spanish Society of Allergy and clinical Immunology Diagnosing IgE-mediated food hypersensitivity disorders Medical history: Symptoms
    • 37.
      • An immediate reaction ( 1-2 hours) is suggestive of an IgE mediated reaction to foods.
        • It may be preceded by previous tolerance of minimal symptoms
        • It may occur apparently after the first contact
      Diagnosing IgE-mediated food hypersensitivity disorders Medical history: Timing of reaction
    • 38.
      • Identification of food
      • How food was prepared
      • Quantity ingested
      • Previous tolerance
      • Cross-reactions with other food
      • Hidden foods, additives, contaminants
      Diagnosing IgE-mediated Food Hypersensitivity Disorders
    • 39. Diagnosing IgE-mediated Food Hypersensitivity Disorders
      • Age at onset of symptoms
      • Other factors (eg, brought on by exercise)
      • Personal and family history of atopic diseases
      • Risk factors
      • Physical examination: Atopic dermatitis, dermographism, nutritional status
    • 40. Clinical symptoms compatible with allergic reaction to food Immediate reactions ( from minutes to 1-2 hours) after ingestion/contact/inhalation with food Late gastrointestinal or atopic dermatitis reactions (>2 hours) Any age After last reaction, patient could not tolerate the food Early correct positive diagnosis allows a suitable diet to be followed and avoids the risks of inappropriate dietary restrictions. Negative diagnosis avoids unnecessary dietary restrictions. Allergy Assessment
    • 41.
      • Prick: Reproducible, sensitive, not irritant
      • Prick-prick: Use raw or cooked food. Highly recommended for fruits and vegetables (commercially prepared extracts are generally inadequate because of the lability of the allergens, so the fresh food must be used for skin testing)
      Diagnosing IgE-mediated food hypersensitivity disorders Skin tests
    • 42.
      • Prick: Reproducible, sensitive, not irritant
      • Prick-prick: Use raw or cooked food. Highly recommended for fruits and vegetables (commercially prepared extracts are generally inadequate because of the lability of the allergens, so the fresh food must be used for skin testing)
      • Intradermal: Not indicated.
      • Atopy Patch test (APT): Atopic dermatitis, delayed reactions, fresh food is recommended
      Diagnosing IgE-mediated food hypersensitivity disorders Skin tests
    • 43.
      • Skin Prick Tests are used to screen patients for sensitivity to specific foods
      • Allergens eliciting a wheal of at least 3 mm greater than the negative control are considered positive
      • Overall positive predictive accuracy is < 50 %
      • Negative predictive accuracy > 95 % (negative skin test results essentially confirm the absence of IgE-mediated reactions)
      Diagnosing IgE-mediated food hypersensitivity disorders
    • 44.
      • In infants younger than 2 years, skin prick tests to milk, egg, or peanut with wheal diameters of at least 8 mm are more than 95 % predictive of reactivity.
      • In general, negative skin prick test results are extremely useful for excluding IgE-mediated food allergies, but positive skin test results are only suggestive of presence of clinical food allergies.
      • There is no correlation between the size of wheal and the clinical sensitivity in individual patients
      Diagnosing IgE-mediated food hypersensitivity disorders
    • 45. Diagnosis of IgE-mediated food allergy: Skin prick testing Sporik et al. Clin Exp Allergy 2000; 30: 1540-6
    • 46.
      • Sensitivity similar to skin prick tests
      • Good correlation with other procedures
      • Efficiency: Depends on the allergen
      • Indicated if SPT are contraindicated (eg, skin disease, medications)
      • Useful if discrepancy exists between history and SPT
      • The use of quantitative measurements has shown to be predictive, for some allergens, of symptomatic IgE-mediated food allergy
      Diagnosing IgE-mediated food hypersensitivity disorders Serum specific IgE (CAP/Radioallergosorbent tests)
    • 47. Diagnostic Food-Specific IgE Values (CAP-System Fluorescent Enzyme Immunoassay) of Greater than 95% Positive Predictive Value
      • Food Serum IgE Value (kU/L)
      • Egg ≥7.0
      • ≤ 2 yr old ≥2.0*
      • Milk ≥15.0
      • ≤ 2 yrs old ≥5.0**
      • Peanut ≥14.0
      • Fish ≥20.0
      • Tree nuts ≥15.0
      • From Sampson HA: JACI 107:891-896,2001 .
      • Note: Patients with food-specific IgE values less than the listed diagnostic values may experience an allergic reaction following challenge. Unless history strongly suggests tolerance, a physician-supervised food challenge should be performed to determine if the child can ingest the food safely.
      • Boyano-Martinez T, Garcia-Ara C, Diaz-Pena JM, et al: Clin Exp Allergy 31:1464-1469,2001
      • ** Garcia-Ara C, Boyano-Martinez T, Diaz-Pena JM, et al: JACI 107:185-190,2001
    • 48.
      • Advantages
      • Multiple determinations with one blood sample
      • Quantitative and comparable measurements
      • Use of recombinant allergens
      • Disadvantages
      • Cost
      • Results delayed
      Diagnosing IgE-mediated food hypersensitivity disorders Serum specific IgE (CAP/RAST)
    • 49. Diagnosing IgE-mediated food hypersensitivity disorders
      • Histamine release with foods:
      • Similar sensitivity and specificity to serum specific IgE
      • Sulphidoleukotrienes released from basophils with food: Not well studied
      • For monitoring food challenges:
      • Plasma and urinary histamine : High sensitivity, low specificity
      • Serum tryptase : High specificity, low sensitivity
      Other Techniques
    • 50. Diagnosis of non-IgE mediated food allergy
      • Reaction: Slower onset
      • Difficult to distinguish from food intolerance
      • Elimination - challenge testing
      • In-vitro and in-vivo tests: Little progress
      • Atopy Patch Test (APT)
      • Cellular Allergen Stimulation Test (CAST)
    • 51. Atopy Patch Test (APT)
    • 52. Cellular allergen stimulation test (CAST  -ELISA)
      • Commercially available
      • Basophil-based assay, sulphidoleukotriene (SLT) release
      • Non-IgE-mediated reactions, food intolerance, IgE mediated reactions
      Crockard et al. Clin Exp Allergy 2001; 31:345-350
    • 53.
      • Challenge should be performed either for establishment or exclusion of the diagnosis, for scientific reasons in clinical trials, or for enabling determination of the sensitivity of the actual patient (threshold value) or for determining the allergenicity of food.
      • The determination of the sensitivity enables tailor-made guidelines for the patient, and opens the possibility of following sensitivity by repeated challenges, especially in children w ith food allergies which are normally outgrown during childhood (cow´s milk or hen´s egg).
      Controlled food challenges: Selection of patients for challenge (IgE-mediated Type I allergy) E AACI Position Paper, Allergy 2004: 59: 690-697
    • 54.
      • Patients of any age with history of adverse reaction to a food :
      • For establishment or exclusion of the diagnosis of food intolerance/allergy;
      • For scientific reasons in clinical studies;
      • For determination of the threshold value or degree of sensitivity;
      • For asse s sment of tolerance. Once diagnosed, when a patient is suspected to have outgrown clinical allergy -especially in children, whose food allergies are normally outgrown during childhood (eg, milk or hen’s egg allergies).
      Controlled food challenges: Inclusion criteria (IgE-mediated allergy) EAACI Position Paper, Allergy 2004; 59: 690-697
    • 55.
      • Patients without specific history of adverse reaction to a food :
      • If any chronic symptom is suspected by the patient or the physician to be food-related
      • If a patient is on an inappropriate elimination diet, without a documented history of adverse food reaction. If the food has to be reintroduced into the diet, and there are reas o ns to suspect that an adverse reaction is possible
      • If a sensitization to a food is diagnosed and tolerance is not known – for example, sensitization to cross-reactive foods that have not been eaten after the adverse reaction
      Controlled food challenges: Inclusion criteria (IgE-mediated Type I allergy) EAACI Position Paper, Allergy 2004; 59: 690-697
    • 56.
      • When a controlled food challenge is not necessary for diagnosing food allergy
      • Repetitive reactions with minimal quantities of food with positive SPT/CAP-RAST
      • Recent (children) severe systemic reaction or anaphylaxis (adults)
      • In selected cases where positive test results makes challenge unnecessary ( e.g. Children with atopic eczema and positive SPT to egg and specific IgE (CAP) <= 17.5 Ku/L)
      Controlled food challenges : exclusion criteria
    • 57. Controlled food challenges
      • Diseases where epinephrine is contraindicated
      • Patients treated with beta-blockers
      • Patients with ongoing disease should not be challenged e.g., patients with acute infection, unstable angina pectoris or patients with seasonal allergy during the season
      Relative Contraindications
    • 58. Controlled food challenges
      • Pregnant women
      • Patients taking medication which may enhance, mask, delay or prevent evaluation of a reaction or interfere with treatment of a reaction
      • Patients with chronic atopic disease such as asthma or atopic eczema should only be challenged when disease activity is at a stable and low level
      Relative Contraindications
    • 59. Controlled food challenges
      • Trained medical personal
      • Emergency treatment available
      • Patient information and informed consent
      • Early treatment of reactions
      • Observation for at least 2- 4 hours
    • 60. Controlled food challenges
      • Patient without symptoms, and fasting
      • The quantity of food to start the challenge may depend upon the quantity of food that induced the last reaction
      • Is highly recommended to start with minimal doses, with a slight increase at intervals superior to the latency period that the patient has experienced in previous reactions
    • 61. Controlled food challenges
      • The quantity of the last challenge dose will be related to the age of the patient (normal amount)
      • Challenge with different foods on different days
      • In asthma ensure long wash-out periods, FEV1 ≥ 80%, and follow-up with FEV 1 or peak expiratory flow (PEF) hourly for 6 hours
      • Atopic eczema and chronic urticaria: If partial improvement after exclusion diet and on minimal treatment
    • 62. Types of challenge testing
      • Double -blind
      • Single-Blind
      • Open
      • Double-blind placebo controlled (DBPCFC)
      • Exercise + oral challenge
      • Inhalation challenge
    • 63.
      • DB is the procedure generally recommended, especially if a positive challenge outcome is expected
      • DB is the method of choice for scientific protocols
      • DB is the method of choice when s tudying late reactions or chronic symptoms, such as atopic eczema, isolated digestive late reactions, or chronic urticaria
      • DB is the only way to conveniently study subjective food-induced complaints, such as acute subjective adverse reactions, chronic fatigue syndrome, multiple chemical sensitivities, migraine or joint complaints
      Controlled food challenges: Double-blind, placebo-controlled (DBPCFC) EAACI Position Paper. Allergy 2004; 59: 690-697
    • 64. Controlled food challenges: Eligible patients for DBPCFC include:
      • 1. All patients with suspicion of an immediate, systemic allergic reaction to a food for establishment or exclusion of the diagnosis
      • 2. Infants and children  three years: An open challenge controlled and evaluated by a physician is most often sufficient
      • 3. Patients with pollen related oral allergy syndrome as their only symptom should only undergo DBPCFC in selected cases, eg, in cases with discrepancy between the case history and the outcome of in vivo and/or in vitro tests
      EAACI Position Paper. Allergy 2004; 59: 690-697
    • 65. Controlled food challenges: Double-blind, placebo-controlled (DBPCFC)
      • An open challenge may precede DBPCFC in older children and adults because a negative result renders DBPCFC unnecessary
      • Open challenges should not be applied in cases with a high probability of a positive outcome, or in cases with subjective and/or controversial symptoms only
      EAACI Position Paper. Allergy 2004; 59: 690-697
    • 66. Placebo controlled food challenges Intercalate food and placebo Active and placebo should have identical characteristics and ensure allergenicity Masking of food: Appearance, colour, flavor, texture Placebos: Dextrose, liquids Vehicles: Capsules (lyophilized) Liquids (placebo) There are many recipes published for masking foods. Capsules: Limit quantity (cereals, dry fruits) Avoid contact with oral mucosa (not used in oral allergy syndrome)
    • 67. Double-blind, placebo-controlled food challenge testing: Limitations
      • Tedious
      • Time-consuming
      • Potential risk
      • Requires specialist unit (research)
      • IgE-mediated or non-IgE-mediated?
    • 68. Controlled food challenges: Single-blind challenge
      • Single-blind challenge carries the same difficulties for blinding foods as for double-blind, and introduces subjective bias of the observer
      • It needs additional work (cross-over by an external technician)
      • The recommendation of the European Academy of Allergology and Clinical Immunology is to always perform double-blind food challenge
      EAACI Position Paper. Allergy 2004; 59: 690-697
    • 69.
      • A negative double-blind challenge should always be followed by an open challenge
      • A positive open challenge could be sufficient when dealing with IgE-mediated acute reactions manifesting with objective signs
      • For practical reasons, an open challenge can be the first approach when the probability of a negative outcome is estimated to be very high
      Controlled food challenges: Open challenge EAACI Position Paper. Allergy 2004: 59: 690-697
    • 70.
      • In infants and children  3 years, an open, physician-controlled challenge is often sufficient for suspected immediate type reactions (unless a psychological reaction of the mother is expected)
      • For patients with pollen-related oral allergy syndrome as their only symptom, an open challenge could be sufficient as regular procedure. However, double-blind challenge is recommended for scientific protocols and other selected cases for example, discrepancies between the clinical history and the outcome of diagnostic tests
      Controlled food challenges: Open challenge EAACI Position paper Allergy 2004: 59: 690-697
    • 71. Cross-reactivity among foods
      • Patients often have positive SPTs or RAST results to other members of a plant family or animal species ( immunological reactivity ) – does not always correlate with clinical reactivity
      • Cross reactions caused primarily by “Type 1” sensitization
        • Legumes, tree nuts, fish, shellfish, cereal grains, mammalian and avian food products
      • Cross reactions caused by “Type 2” sensitization
          • Pollen-food allergy syndrome (oral allergy syndrome)
          • latexfood syndrome
      • Proper clinical evaluation (ideally by double-blind placebo-controlled challenge testing) is necessary in patients who demonstrate immunological cross-reactivity to foods (to avoid unnecessary restriction of certain foods).
    • 72. Some Cross-Reactions Between Inhalant Allergens and Food Allergens Dr N. Eriksson et al (1947) Crustaceans Chironomids Banana, chestnut, kiwi, avocado Latex Tomato, peanut, pea, wheat, rye Grass pollen Melon, banana Ragweed pollen Nuts, apple, pear, peach, plum, cherry, carrot Birch pollen Food allergy Inhalant allergy
    • 73. Cross reactivity in food allergy: Clinical relevance Scott H. Sicherer.AAAAI San Francisco 2004:Seminar 3508 OAS = Oral Allergy Syndrome CMA = Cow’s Milk Allergy
    • 74. Cross reactions with foods: Clinical implications
      • If the patient is diagnosed with allergy to a food, assessment of clinical sensitization to foods with known cross reactivity is recommended
      • If the patient is diagnosed with allergy to a food with known cross reactivity with another food which he/she is not eating (unknown tolerance), that food must be challenged to assess tolerance
    • 75. Food allergy: Treatment
      • Correct diagnosis
      • Treatment of reactions
      • Avoidance
      • Role of dietician
      • Tolerance assessment
      • Immunotherapeutic strategies
      • Prevention
      Adapted from Adverse Reactions to Foods Committee. Spanish Society of Allergy and Clinical Immunology
    • 76. Treatment of reactions
      • Epinephrine: 1/1000 w/v, 0,01mg/ kg ( Epi-pen®, Adreject®) intramuscularly
      • Emergency ward treatment
      • Oral/parenteral antihistamines
      • Corticosteroids
    • 77. Dietary avoidance
      • Mainstay of treatment
      • Must be considered as a therapeutic approach
      • Risk-benefit must be assessed
        • Correct diagnosis is essential
        • Very restrictive diets can lead to malnutrition
    • 78. Vitamins and minerals which will be affected by restricted diet Vitamin E, niacin, magnesium, manganese, & chromium Peanut Thiamin, riboflavin, niacin, iron, & folate if fortified Wheat Thiamin, riboflavin, pyridoxine, folate, calcium, phosphorus, magnesium, iron, & zinc Soy Vitamin B12, riboflavin, pantothenic acid, biotin, & selenium. Egg Vitamin A, vitamin D, riboflavin, pantothenic acid, vitamin B 12 , calcium, & phosphorus Milk Vitamin and Minerals Allergen
    • 79. Hidden foods
      • Some foods (allergens) are masked and may be taken un-noticed during diagnostic procedure:
        • Spices: Mustard, pepper, sesame.
        • Legumes and tree nuts: Peanut, soy.
        • Milk protein (protein supplements): Caseine, caseinates.
        • Vaccines
        • Kitchen tools, volatile allergens.
      • Parasitized food:
        • Mites in flour ( pasta, pizzas)
        • Anisakis simplex in fish.
        • Transgenic foods with new proteins.
    • 80. Immunotherapeutic strategies
      • Humanized anti-IgE monoclonal antibody therapy (TNX-901)
      • “ Engineered (mutated) allergen protein immunotherapy
      • Antigen-immunostimulatory sequence (CpG)-modulated immunotherapy
      • Peptide immunotherapy
      • Plasmid-DNA immunotherapy
      • Cytokine-modulated immunotherapy
    • 81.
      • In adults the natural history of food allergy is unknown
      • In children tolerance is frequent after dietary avoidance
      • Milk allergy is “outgrown” at 1 yr (50-60%); 2 yrs (70-75%); 3 yrs (85%)
      • Egg allergy is “outgrown” : > 6 yrs (55%)
      • Allergy to peanut, tree nuts, fish and shellfish:
      • − more likely to continue into adulthood (lifelong).
      • − may be ‘outgrown” (rare)
      • − recurrences may occur after allergy to these foods outgrown
      Food allergy: Natural history
    • 82. Prevention of food allergy
      • Identify patients at risk (difficult):
        • There is no reliable or genetic immunological marker
        • Atopic background in parents, siblings
      • Dietary restriction (milk, egg, fish, nut)
        • In pregnancy: No benefit
        • Adverse events on maternal-fetus nutrition
        • During lactation: Variable effect
      • Prolonged breast feeding?
      • Probiotics??
      Adapted from Adverse Reactions to Foods Committee. Spanish Society of Allergy and Clinical Immunology
    • 83. World Allergy Organization (WAO) For more information on the World Allergy Organization (WAO), please visit or contact the: WAO Secretariat 555 East Wells Street, Suite 1100 Milwaukee, WI 53202 United States Tel: +1 414 276 1791 Fax: +1 414 276 3349 Email:
    • 84.