GLORIA Module 6: Food Allergy Updated: June 2011

GLORIA Module 6:Food Allergy

Updated: June 2011

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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


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


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


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


• 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


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


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


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


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


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


disordersMedical history: food

Adapted from Adverse Reactions to Foods Committee.Spanish Society of Allergy and clinical ImmunologyAlergol Inmunol Clin 1999; 14: 50-62.


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.


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)


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)


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


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


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


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]

http://www.worldallergy.org/

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GLORIA Module 6: Food Allergy Updated: June 2011