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GLORIA Module 6:Food Allergy
Updated: June 2011
Sponsored by an unrestricted educational grant from
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.
World Allergy Organization (WAO)
The World Allergy Organization is an international coalition of 89
regional and national allergy and clinical immunology societies.
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
Food AllergyA GLORIATM Module
Prof. Cassim MotalaUniversity of Cape Town and Red Cross Children's Hospital Cape Town, South Africa
Prof. Joaquín SastreFundación Jimenez Diaz, Department of MedicineUniversidad Autonoma de Madrid Madrid, Spain
Dr. M. Dolores IbáñezHospital Nino JesusMadrid, Spain
Authors
ReviewerProf. Alessandro FiocchiMelloni University HospitalMilan, Italy
Learning objectivesAt the end of this presentation you will be able to:
• Recognise the main pathogenic food allergens in adults and children
• Differentiate between IgE-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
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
•Toxic•Non toxic or hypersensitivity
TOXIC Nontoxic
AllergyIntolerance
Immune-mediated
Non-immune mediated
Enzymatic
Pharmacologic
Undefined
Non-IgE-mediated
IgE-mediated
Adverse Reactions to Food: Position Paper. Allergy 1995; 50:623-635
Adverse reactions to food
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
Food allergy in children: international
USA & UK
Milk
Egg
Peanut
Tree Nuts
Seafood
FRANCE
Egg
Peanuts
Milk
Mustard
ITALY
Milk
Egg
Seafood
ISRAEL
Milk
Egg
Sesame
SINGAPORE
Birds Nest
Seafood
Egg
Milk
AUSTRALIA
Milk
Egg
Peanuts
Sesame
“Second tier” foods
• 10% reactions to foods• 160 foods• Fruits • Vegetables• Seeds (sesame, sunflower, poppy)• Spices
Pathophysiology: allergens
• Proteins (not fat/carbohydrate)- 10-70 kD glycoproteins- Heat resistant, acid stable
• Major allergenic foods (>85% of allergy)- Children: milk, egg, soy, wheat, other depending on geographical
area - Adult: peanut, nuts, shellfish, fish• Single food (or related) > many food allergies • Characterization of epitopes underway
- Linear vs conformational epitopes- B-cell vs T-cell epitopes
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
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
Pathophysiology: immune mechanisms
IgE-Mediated
IgE-receptor
Histamine
Protein digestionAntigen processingSome Ag enters blood
Mast cellAPC
B cell T cell TNF-IL-5
Non-IgE-Mediated
Food allergy: clinical manifestations
IgE IgE/Non-IgE Non-IgE
Urticaria/angioedemaRhinitis /AsthmaAnaphylaxis
Oral allergic syndromeGastrointestinal symptoms (GIT)
Atopic dermatitis
Eosinophilic gastro-intestinaldisorders
Protein-inducedproctocolitis/enterocolitis
Celiac diseaseContact dermatitisHerpetiform dermatitisHeiner´s syndrome
Adapted from J Allergy Clin Immunol. 1999;103:717-728
• 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
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 Urticaria:♦ Food allergy is an infrequent cause of chronic urticaria
and angioedema
Cutaneous food hypersensitivities
IgE mediated: respiratory manifestations
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
Rhinoconjunctivitis• Usually seen during positive controlled challenge tests,
but occasionally reported by patients
IgE Mediated: systemic reaction
anaphylaxis/anaphylaxis syndrome
• Food-induced anaphylaxis- Rapid-onset- Multi-organ system involvement- Potentially fatal- Any food, highest risk: peanut, nut, seafood, milk, egg
• Food-dependent - exercise-induced- Associated with a particular food- Associated with eating any food
Fatal food anaphylaxis
• Frequency: ~ 100 deaths/yr• Risk:
- Underlying asthma - Delayed epinephrine- Symptom denial - Previous severe reaction
• History: known allergic food• Biphasic reaction• Lack of cutaneous symptoms
Gastrin
ExerciseWheat
Food-dependent, exercise-induced anaphylaxis
Mediator release- Histamine
- Others (LTD4,PAF, etc)
Temperature
ANAPHYLAXISAdapted from Adverse Reactions to Foods Committee. Spanish Society of Allergy and Clinical Immunology
IgE-mediated: GIT manifestation
oral allergy syndrome (OAS)• Elicited by a variety of plant proteins that cross-
react with airborne allergens• Pollen allergic patients may develop symptoms
following the ingestion of vegetable 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 reduce/eliminate oral allergy symptoms
Adapted from J Allergy Clin Immunol. 2004;113:808-809
Food allergy prevalence in specific disorders
Disorder Food Allergy Prevalence
Anaphylaxis 35 - 55 %
Oral allergy syndrome 25 - 75% in pollen allergic patients
Atopic dermatitis 35% in children(rare in adults)
Urticaria 20% in acute(rare in chronic)
Asthma 5 - 6% in asthmatic or food allergic children
Chronic rhinitis Rare
• 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 can occur in children and adults. Increasing yearly incidence (23/100.000 population in Switzerland)
• In children symptoms similar to gastroesophageal reflux and in adults dysphagia and impaction is common
• Almost 50% of patients have other atopic diseases• Diagnosis is based on endoscopic findings and biopsy
(>15-20 eosinophils per High Power Field)
Mixed IgE/Non-IgE mediated: GIT
allergic eosinophilic disorders
Adapted from J Allergy Clin Immunol. 2006;118:1054-9
DysphagiaAbdominal painPoor response to anti -
reflux drugsBiopsy:Eosinophils ++++
>20 eosinophils / HPF Eotaxin – 3 tissue
expression correlates with eosinophilia – crucial in pathogenesis of this disorder
Mixed IgE/non-IgE mediated: GITallergic eosinophilic esophagitis (AEE)
Bullock et J Pediatr Gastroenterol Nutr. 2007
Allergic eosinophilic esophagitis endoscopic
findings
Rings White plaques (eosinophils)
Weight loss, FTT+/_oedemaVomiting, diarrhoea (post-prandial)Blood lossIron deficiencyProtein/iron- losing enteropathy↑ TH2 in blood and mucosa ↑ Mast cells, Eosinophils in mucosaEotaxin - 3Persistent food hypersensitivity at 5yr FU.
Mixed IgE/non-IgE mediated: GITallergic eosinophilic gastroenteritis
(AEG)
Chehade M et al JPGN 2006;42;516-521
• Food antigens have been implicated as one of the main etiologies
• Skin prick test and atopy patch tests can be useful for food allergy diagnosis
• Elimination diets or even amino-acid formula can be instituted on the basis of allergy testing, clinical history, biopsy and treatment response
• Pharmacologic treatment: oral steroids and/or swallowed aerosolized fluticasone
• ? Anti-IL-5 therapy
AEE and AEG
Adapted from J Allergy Clin Immunol. 2006;118:1054-9
Non-IgE mediated: GIT food protein induced syndromes (typically milk
and soy induced)
Enterocolitis # Enteropathy Proctocolitis
Age Onset: Infant Infant/Toddler Newborn
Duration: 12-24 mo ? 12-24 mo < 12mo
Characteristics: Failure to thrive Malabsorption Bloody stools
Shock Villous atrophy No systemic sxLethargy Diarrhea Eosinophil
Diarrhea
# Solid foods implicated: fish, corn, chicken, turkey, vegetables
Nowak-Wegrzyn et al Pediatrics 2003Zapatero Remon L et al. Allergol Immunopathol 2005
• Occurs in infants prior to 8-12 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 and older children, fish, shellfish and cereals hypersensitivity may provoke a similar syndrome with delayed onset of severe nausea, abdominal cramps and protracted vomiting
• Resolved: 50% at 18 months, 90% at 36 months
Non IgE mediated: GIT food protein-induced enterocolitis
syndrome
Adapted from J Allergy Clin Immunol. 2004;113:808-809
• Occurs from 0 - 24 months• Diarrhea (mild to moderate steatorrhea in
about 80% of cases)• Food implicated: milk, cereals, egg, fish• Poor weight gain • Diagnosis:
-Biopsy shows patchy villous atrophy with prominent mononuclear round cell infiltrate, few eosinophils, -Response to exclusion diet, -Challenge test
• Resolved at 2 - 3 years old
Adapted from J Allergy Clin Immunol. 2004;113:808-809
Non-IgE Mediated: GIT food protein-induced enteropathy (excluding
celiac disease)
• 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
• Rectal bleeding is common • Diagnosis: endoscopy and colonic biopsy
(eosinophils in epithelium and lamina propia)• Good response to extensively hydrolized
formulas. Diet without dairy product in mother if lactating
• Good prognosis with resolution at 12 months of life
Non-IgE Mediated: GIT food protein-induced protocolitis
Adapted from J Allergy Clin Immunol. 2004;113:808-809
Non-Ige Mediated: GIT celiac disease
• Extensive enteropathy leading to malabsorption• Associated with an immune reaction to gliadin
peptides (wheat, rye and barley)• Highly associated with HLA-DQ2 1 *0501. 1
*0201)• Serology: anti-transglutaminase IgA, Anti-gliadin
IgA (asymptomatic and +ve serology is common)
• Treatment: Elimination of gluten-containing foods
Adapted from J Allergy Clin Immunol. 2004;113:808-809
Non-IgE-mediated syndromes affecting the skin and lung
• Dermatitis Herpetiformis- Vesicular, pruritic eruption- Gluten-sensitive- Associated with Celiac Disease
• Heiner’s Syndrome- Infantile pulmonary hemosideroisis- Anemia, failure to thrive- Cow’s milk-associated- Precipitating antibodies to cow’s milk
Gastrointestinal food hypersensitivity?
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
Disorders not proven to be related to food allergy
• Migraines• Behavioral/Developmental disorders• Arthritis• Seizures• Inflammatory bowel disease
Diagnosis: history / examination
• History: symptoms, timing, reproducibilityAcute reactions vs chronic disease
• Diet details / symptom diarySpecific causal food/s“Hidden” ingredient/s
• Physical examination: Evaluate disease severity• Identify general approach
Allergy vs intoleranceIgE-mediated vs non-IgE mediated
Identification and relationship with the food: Medical history
To identify specific IgE: Skin tests/serum specific IgE
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 and confirmed by challengeAdapted from Adverse Reactions to Foods Committee.
Spanish Society of Allergy and Clinical ImmunologyAlergol Inmunol Clin 1999; 14: 50-62.
Diagnosing food hypersensitivity disorders:
IgE-mediated
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 ImmunologyAlergol Inmunol Clin 1999; 14: 50-62.
Diagnosing IgE-mediated food hypersensitivity
disordersMedical history: Symptoms
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
disordersMedical history: Timing of reaction
Adapted from Adverse Reactions to Foods Committee, Spanish Society of Allergy and Clinical Immunology Alergol Inmunol Clin 1999; 14: 50-62.
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
disordersMedical history: food
Adapted from Adverse Reactions to Foods Committee.Spanish Society of Allergy and clinical ImmunologyAlergol Inmunol Clin 1999; 14: 50-62.
Diagnosing IgE-mediated food hypersensitivity
disorders
Age at onset of symptomsOther factors (eg, brought on by exercise)Personal and family history of atopic diseasesRisk factorsPhysical examination: Atopic dermatitis,
dermographism, nutritional status
Medical history: Patient
Adapted from Adverse Reactions to Foods Committee. Spanish Society of Allergy and clinical ImmunologyAlergol Inmunol Clin 1999; 14: 50-62.
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 ImmunologyAlergol Inmunol Clin 1999; 14: 50-62.
Diagnosing IgE-mediated food hypersensitivity
disorders
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
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+
Diameter 3 mm
Intradermal: Not indicated
Atopy Patch test (APT): Atopic dermatitis, delayed reactions
Fresh food or dry food recommended
Non-standardized
Difficult to interpret
Diagnosing IgE-mediated food hypersensitivity
disordersSkin tests
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
Possibility to perform component-resolved diagnosis very useful in cross-reactivity reactions: profilins (Bet v2, Phl p12), polcalcins (Bet v4, Phl p7), LPT (Pru p3, Cor a8), Gly m4, Cross-reactive Carbohydrate Determinants or CCDs
Specific IgE to food (CAP / Radioallergosorbent
tests)
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 ≥14.0Fish ≥20.0Tree nuts ≥15.0
From Sampson HA: JACI 107:891-896,2001.
* 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.
AdvantagesMultiple determinations with one blood sampleQuantitative and comparable measurementsUse of recombinant allergensComponent-resolved diagnosisDisadvantagesCostResults delayed
Diagnosing IgE-mediated food hypersensitivity
disorders
Serum specific IgE (CAP / RAST)
Interpretation of laboratory tests
• Positive prick test or RAST / CAP - Indicates presence of IgE antibody NOT clinical
reactivity (~50% false positive)
• Negative prick test or RAST- Essentially excludes IgE antibody (>95%)
• Intradermal skin test with food
• - Risk of systemic reaction & not predictive
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),
- Latex- food syndrome • Proper clinical evaluation (ideally by double-blind placebo-
controlled challenge testing) is necessary in patients who demonstrate immunological cross-reactivity to foods and when tolerance to food is unknown (to avoid unnecessary restriction of certain foods)
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
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
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
Unproven / experimental tests (useless)
• Provocation / neutralization• Cytotoxic tests• Applied kinesiology• Hair analysis
• IgG4
Diagnosis: elimination diets and food challenges
• Elimination diets (1 - 6 weeks):- Eliminate suspected food/s, or- Prescribe limited “eat only” diet, or- Elemental diet
• Oral challenge testing:- Physician supervised- Emergency room medications must be available
Basic elimination diet: ALLOWED foods
• Rice• Fruit: Pear, Apple, Grape• Meat: Lamb, Chicken• Vegetables: Asparagus, Beetroot, Carrots, Lettuce,
Sweet potatoes, Butternut Squash• Other: Black Tea, Rooibos• Olive oil, Sunflower oil, Sugar, Salts
NB: No Preservatives, no tinned or packet foods
Types of challenge testing• Double -blind
• Single-Blind
• Open
• Exercise + oral challenge
• Inhalation challenge
• 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 studying 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
Double-blind, placebo-controlled food challenge
testing: limitations
• Tedious
• Time-consuming and expensive
• Potential risk requires specialist unit (research)
• IgE-mediated or non-IgE-mediated?
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
• 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
EAACI Position Paper. Allergy 2004: 59: 690-697
Controlled food challenges:
open challenge
Diagnostic approach:non-IgE-mediated disease • Includes disease with unknown mechanisms
- Food additive intolerance
• Elimination Diets (may need elemental diet)
• Oral Challenges- Timing / dose / approach individualized for disorder - Enterocolitis syndrome can elicit shock- Enteropathy / eosinophilic gastroenteritis-prolonged feedings to develop symptoms
• May require ancillary testing (endoscopy / biopsy)
Food allergy: treatmentFood allergy: treatment
• Correct diagnosis• Treatment of reactions• Avoidance• Role of dietician• Tolerance assessment• Prevention• Immunotherapeutic strategies
Adapted from Adverse Reactions to Foods Committee. Spanish Society of Allergy and Clinical Immunology
Treatment emergency medicines
• Epinephrine: drug of choice for reactions- Self-administered epinephrine readily available- Train patients: Indications / technique
• Antihistamines: Secondary therapy
• Emergency plan in writing- Schools, spouses, caregivers, mature siblings / friends
• Emergency identification bracelet
Treatment: avoidanceTreatment: 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
• Dietician’s role is crucial
Vitamins and minerals which will be affected by
restricted dietAllergen Vitamin and Minerals
Milk Vitamin A, vitamin D, riboflavin, pantothenic acid, vitamin B12, calcium, & phosphorus
Egg Vitamin B12, riboflavin, pantothenic acid, biotin, & selenium
Soy Thiamin, riboflavin, pyridoxine, folate, calcium, phosphorus, magnesium, iron, & zinc
Wheat Thiamin, riboflavin, niacin, iron, & folate if fortified
Peanut Vitamin E, niacin, magnesium, manganese, & chromium
Treatment: dietary elimination
• Hidden ingredients • Labelling issues • Cross contamination (shared equipment)• “Code words” (“Natural flavor” may be cow’s
milk)• Seeking assistance
Registered dietician: (www.eatright.org) • Food Allergy Network (www.foodallergy.org)
(800-929-4040)
Hidden foodsSome 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– Transgenic foods with new proteins
Parasitized food:– Mites in flour ( pasta, pizzas)– Anisakis simplex in fishREAD LABELS IN PREPARED FOOD!!!
Example: milk eliminationArtificial butter flavor, butter fat, buttermilk, casein, caseinates (sodium, calcium, etc), cheese, cream, cottage cheese, curds, custard, Half&Half®, hydrolysates (sasein, 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®
Substitute infant formulas
• Soy (confirm soy IgE negative)<15% soy allergy among IgE-cow’s milk allergy~50% soy allergy among non-IgE cow’s milk allergy
• Cow’s milk protein hydrolysates:90% tolerance in IgE-cow’s milk allergy
• Partial hydrolysates: Not hypoallergenic!
• Amino acid-based formulas: Lack allergenicity
Natural history• Dependent on food & immunopathogenesis• IgE-mediated allergy:
- CM 85% remit by 8 yrs Saarinen et al JACI 2005- Egg 66% remit after 5 yrs Bovano-Martinez et al JACI 2002- Peanut 20% may remit (8% may recur) Fleischer et al JACI 2004- Treenut, seafood typically persist
• Declining/low levels of specific-IgE predictive• Non-IgE-associated GI allergy
- Infant forms resolve 1- 3 years- Toddler/adult forms more persistent
Treatment: follow-up
• Re-evaluate for tolerance periodically
• Interval and decision to re-challenge:- Type of food allergy- Severity of previous symptoms- Allergen
• Ancillary testing- Skin prick test/RAST/CAP may remain positive- Reduced concentration specific-IgE encouraging
Food specific IgE cut off levels which predict 50% pass rate
for challenge testsFood IgE level (KUA/l)Milk 2Egg 2Peanut 2Wheat ?Soy ?
Perry et al. JACI 2004
Prevention of food allergy / allergic disease
• 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 effects on maternal-fetus nutrition– Hydrolyzed formula (HF): Variable effect (Cochrane
Database Syst Rev. 2006 Oct 18); GINI Study, JACI Mar 2007; extensively HF & partially HF reduce incidence of AD, but not that of asthma
– Delayed introduction of solid food: Variable effect (Ann Allergy Asthma Immunol. 2006;97:10-20)
• Prolonged breast feeding?• Probiotics??
Future immunomodulatory therapies
Future immunomodulatory therapies
• Humanized anti-IgE monoclonal antibody therapy
• “Engineered (mutated) allergen protein immunotherapy
• Antigen-immunostimulatory sequence (CpG)-modulated immunotherapy
• Peptide immunotherapy• Plasmid-DNA immunotherapy• Cytokine-modulated immunotherapy• Induction of tolerance or oral immunotherapy
(milk, egg, hazelnut…….)
Summary• IgE & non-IgE mediated food allergy conditions exist
• History and examination paramount
• Diagnosis is by elimination and challenge testing
• Avoidance / education / preparation for emergencies are current therapies
• Periodic re-challenge to monitor tolerance as indicated by history, allergen, and level of food specific-IgE
World Allergy Organization (WAO)For more information on the
World Allergy Organization (WAO), please visit www.worldallergy.org or contact:
WAO Secretariat555 East Wells Street, Suite 1100
Milwaukee, WI 53202United States
Tel: +1 414 276 1791Fax: +1 414 276 3349
Email: [email protected]