food allergie

GLORIA Module 6:

Food Allergy

Updated: June 2011

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 Allergy A GLORIATM Module

Prof. Cassim Motala

University of Cape Town and

Red Cross Children's Hospital

Cape Town, South Africa

Prof. Joaquín Sastre

Fundación Jimenez Diaz,

Department of Medicine

Universidad Autonoma de Madrid

Madrid, Spain

Dr. M. Dolores Ibáñez

Hospital Nino Jesus

Madrid, Spain

Authors

Reviewer Prof. Alessandro Fiocchi

Melloni University Hospital

Milan, Italy

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 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

Allergy Intolerance

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 digestion

Antigen processing

Some Ag enters blood

Mast cell APC

B cell T cell TNF-

IL-5

Non-IgE-

Mediated

Food allergy: clinical manifestations

IgE IgE/Non-IgE Non-IgE

Urticaria/angioedema

Rhinitis /Asthma

Anaphylaxis

Oral allergic syndrome

Gastrointestinal symptoms

(GIT)

Atopic dermatitis

Eosinophilic

gastro-intestinal

disorders

Protein-induced

proctocolitis/enterocolitis

Celiac disease

Contact dermatitis

Herpetiform dermatitis

Heiner´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

Exercise Wheat

Food-dependent, 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

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


118:1054-9

Dysphagia

Abdominal pain

Poor response to anti - reflux drugs

Biopsy:Eosinophils ++++

>20 eosinophils / HPF

Eotaxin – 3 tissue expression

correlates with eosinophilia –

crucial in pathogenesis of this

disorder

Mixed IgE/non-IgE mediated: GIT

allergic eosinophilic esophagitis (AEE)

Bullock et J Pediatr Gastroenterol Nutr. 2007

Allergic eosinophilic esophagitis

endoscopic findings

Rings White plaques

(eosinophils)

Weight loss, FTT+/_oedema

Vomiting, diarrhoea (post-prandial)

Blood loss

Iron deficiency

Protein/iron- losing enteropathy

↑ TH2 in blood and mucosa

↑ Mast cells, Eosinophils in mucosa

Eotaxin - 3

Persistent food hypersensitivity at 5yr FU.

Mixed IgE/non-IgE mediated: GIT

allergic 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


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 sx Lethargy Diarrhea Eosinophil Diarrhea

# Solid foods implicated: fish, corn, chicken, turkey, vegetables

Nowak-Wegrzyn et al Pediatrics 2003

Zapatero 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


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


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


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


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


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, reproducibility

Acute reactions vs chronic disease

• Diet details / symptom diary

Specific causal food/s

“Hidden” ingredient/s

• Physical examination: Evaluate disease severity

• Identify general approach

Allergy vs intolerance

IgE-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 challenge

Adapted from Adverse Reactions to Foods Committee.


Alergol 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


Spanish Society of Allergy and clinical Immunology


Diagnosing IgE-mediated food

hypersensitivity disorders

Medical 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



Medical 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



Medical history: food






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

Medical history: Patient




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






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)



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)



+

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



Skin 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 ≥14.0

Fish ≥20.0

Tree 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.

Advantages

Multiple determinations with one blood sample

Quantitative and comparable measurements

Use of recombinant allergens

Component-resolved diagnosis

Disadvantages

Cost

Results delayed



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



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: treatment

• Correct diagnosis

• Treatment of reactions

• Avoidance

• Role of dietician

• Tolerance assessment

• Prevention

• Immunotherapeutic strategies



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: 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 diet

Allergen 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 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

– Transgenic foods with new proteins

Parasitized food:

– Mites in flour ( pasta, pizzas)

– Anisakis simplex in fish

READ LABELS IN PREPARED FOOD!!!

Example: milk elimination

Artificial 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 tests

Food IgE level (KUA/l)

Milk 2

Egg 2

Peanut 2

Wheat ?

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

• 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 Secretariat

555 East Wells Street, Suite 1100

Milwaukee, WI 53202

United States

Tel: +1 414 276 1791

Fax: +1 414 276 3349

Email: [email protected]

http://www.worldallergy.org/

mailto:[email protected]

food allergie

Documents