GLORIA Module 6:
Food Allergy
Updated: June 2011
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(GLORIA™)
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Food Allergy
A GLORIATM Module
Authors
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
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
Adverse reactions to food
TOXIC
Nontoxic
Immune-mediated
Allergy
Non-IgE-mediated
IgE-mediated
Adverse Reactions to Food: Position Paper. Allergy 1995;
50:623-635
Non-immune
mediated
Intolerance
Enzymatic
Pharmacologic
Undefined
Prevalence of food allergy
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
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
Protein digestion
Antigen processing
Some Ag enters blood
IgE-Mediated
IgE-receptor
APC
Mast cell
Non-IgEMediated
Histamine
B cell
T cell
TNF-
IL-5
Food allergy: clinical manifestations
IgE
IgE/Non-IgE
Non-IgE
Urticaria/angioedema
Rhinitis /Asthma
Anaphylaxis
Atopic dermatitis
Protein-induced
proctocolitis/enterocolitis
Oral allergic syndrome
Gastrointestinal symptoms
(GIT)
Eosinophilic
gastro-intestinal
disorders
Celiac disease
Contact dermatitis
Herpetiform dermatitis
Heiner´s syndrome
Adapted from J Allergy Clin Immunol. 1999;103:717-728
Cutaneous food hypersensitivities:
atopic eczema
• 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
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
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
Food-dependent, exercise-induced anaphylaxis
Exercise
Wheat
Temperature
Gastrin
Mediator release
- Histamine
- Others (LTD4,PAF, etc)
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
Mixed IgE/Non-IgE mediated: GIT
allergic eosinophilic disorders
• 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 (>1520 eosinophils per High Power Field)
Adapted from J Allergy Clin Immunol. 2006;
118:1054-9
Mixed IgE/non-IgE mediated: GIT
allergic eosinophilic esophagitis (AEE)
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




Bullock et J Pediatr Gastroenterol Nutr. 2007
Allergic eosinophilic esophagitis
endoscopic findings
Rings
White plaques
(eosinophils)
Mixed IgE/non-IgE mediated: GIT
allergic eosinophilic gastroenteritis (AEG)
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.
Chehade M et al JPGN 2006;42;516-521
AEE and AEG
• 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
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
Malabsorption
Villous atrophy
Diarrhea
Bloody stools
No systemic sx
Eosinophil
Characteristics: Failure to thrive
Shock
Lethargy
Diarrhea
# Solid foods implicated: fish, corn, chicken, turkey, vegetables
Nowak-Wegrzyn et al Pediatrics 2003
Zapatero Remon L et al. Allergol Immunopathol 2005
Non IgE mediated: GIT food protein-induced
enterocolitis syndrome
• 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
Adapted from J Allergy Clin Immunol. 2004;
113:808-809
Non-IgE Mediated: GIT food protein-induced
enteropathy (excluding celiac disease)
• 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 proteininduced protocolitis
• 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
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, 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
Diagnosing food hypersensitivity
disorders: 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.
Spanish Society of Allergy and Clinical Immunology
Alergol Inmunol Clin 1999; 14: 50-62.
Diagnosing IgE-mediated food
hypersensitivity disorders
Medical history: Symptoms
 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
Alergol Inmunol Clin 1999; 14: 50-62.
Diagnosing IgE-mediated food
hypersensitivity disorders
Medical history: Timing of reaction
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
Adapted from Adverse Reactions to Foods Committee, Spanish Society of Allergy and
Clinical Immunology Alergol Inmunol Clin 1999; 14: 50-62.
Diagnosing IgE-mediated food
hypersensitivity disorders
Medical history: food






Identification of food
How food was prepared
Quantity ingested
Previous tolerance
Cross-reactions with other food
Hidden foods, additives, contaminants
Adapted from Adverse Reactions to Foods Committee.
Spanish Society of Allergy and clinical Immunology
Alergol Inmunol Clin 1999; 14: 50-62.
Diagnosing IgE-mediated food
hypersensitivity disorders
Medical history: Patient





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
Adapted from Adverse Reactions to Foods Committee.
Spanish Society of Allergy and clinical Immunology
Alergol Inmunol Clin 1999; 14: 50-62.
Diagnosing IgE-mediated food
hypersensitivity disorders
 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
Alergol Inmunol Clin 1999; 14: 50-62.
Diagnosing IgE-mediated food
hypersensitivity disorders
Skin tests
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 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
Diagnosing IgE-mediated food
hypersensitivity disorders
Skin tests
Intradermal:
Not indicated
 Atopy Patch test (APT):
Atopic dermatitis, delayed
reactions
Fresh food or dry food
recommended
Non-standardized
Difficult to interpret
Specific IgE to food
(CAP / Radioallergosorbent 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




Diagnostic food-specific IgE values (CAPsystem fluorescent enzyme immunoassay)
of greater than 95% positive predictive value
Food
Egg
≤ 2 yr old
Milk
≤ 2 yrs old
Peanut
Fish
Tree nuts
Serum IgE Value (kU/L)
≥7.0
≥2.0*
≥15.0
≥5.0**
≥14.0
≥20.0
≥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.
Diagnosing IgE-mediated food
hypersensitivity disorders
Serum specific IgE (CAP / RAST)
Advantages
 Multiple determinations with one blood sample
 Quantitative and comparable measurements
 Use of recombinant allergens
 Component-resolved diagnosis
Disadvantages
 Cost
 Results delayed
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:
OAS = Oral Allergy Syndrome
clinical relevance
CMA = Cow’s Milk Allergy
Scott H. Sicherer. AAAAI San Francisco 2004:Seminar 3508.
Diagnosing IgE-mediated food
hypersensitivity disorders
Other Techniques
 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
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
Controlled food challenges: doubleblind, placebo-controlled (DBPCFC)
• 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
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
Controlled food challenges:
open challenge
• 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
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
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: 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
Milk
Egg
Peanut
Wheat
Soy
Perry et al. JACI 2004
IgE level (KUA/l)
2
2
2
?
?
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: info@worldallergy.org