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Food Allergy

Vicky Wee Eng-Biñas, M.D.


Allergologist
Definitio
n

Adverse food reaction


 Any abnormal response after
ingestion of a food

American Academy of Allergy, Asthma &


Immunology
Current Nomenclature
Adverse Food Reaction

Toxic Non-toxic
(Staphylococcal Poisoning)

Non-immunologic
Immunologic
(pharmacologic effect, metabolic disorder)

IgE mediated Non-IgE mediated


(Food protein induced enterocoliltis)
( Food protein induced proctocolitis)
American Academy of Allergy, Asthma &
Immunology
Epidemiology

 Food allergy is more common in


infants/children (6% <3 y.o.) than
in adult (3.5%)

Bock SA
Pediatrics
1987;79:683-8
Pathogenesi
s

Host Environment
Gene Food allergens
Mucosal barrier
Oral tolerance
Pathogenesi
s
Mucus

M Enzymes
U Bile
salts
C Low pH
O sIgA
S Epithelium w/ tight
junction
A Trefoil factors
L
B
A NK cells

R Macrophage
R
PMN
I
E Serum IgG IgA

Lymphocytes
R
Pathogenesi
s

 2% of ingested food antigen


absorbed & transported
throughout the body in an
immunologically intact form

Host A
Pediatr Allergy Immunol 5:5-36,
1994
Pathogenesi
s
 Oral tolerance

 Intestinal epithelial cells


 Dendritic cells
 Regulatory T cells
Pathogenesi
s

Host
Gene S
E
Environment
predisposition N
S Food allergens
Mucosal barrier I
T
breakdown I
Z

Failure to develop A
T
Oral tolerance
I
O

Food Allergy
Pathogenesi
s
Family history of atopy as risk
factor of atopy in the child
Family history of atopy Child risk of
atopy
Biparental (same 40-60%
allergy) 40-50
Sibling 20-40
Uniparental
Pathogenesi
s
 Infants
 Low basal acid output
 Suboptimal enzymatic activity
 Increase intestinal permeability
(tight junctions are less “tight”)
 sIgA system is not fully mature till
4 yrs old
 Oral tolerance cannot be induced
yet due to immature MALT
Pathogenesi
s

 Early introduction of numerous


food antigens stimulate
excessive production of IgE
antibodies or other adverse
immune response in genetically
predisposed infants
Sbothill JF, Strokes CR, Turner
MW et al Clin Allergy 6:305-319,
1976
Pathogenesi
s
Common foods associated with allergy:
Children Adults
Cow’s milk (2.5%) Shellfish (2%)
Egg (1.3%) Peanut (0.6%)
Peanut (0.8%) Tree nuts (0.5%)
Wheat (0.4%) Fish (0.4%)
Soy (0.4%)
Tree nuts (0.2%)
Fish, shellfish (0.1%)
Wood RA, Pediatrics 2003
Pathogenesi
s
Major food allergens

 Water soluble glycoproteins


 MW of 10-70 kD
 Stable to heat, acid & proteases
(some are heat labile)
Pathogenesi
s
Major food allergens isolated &
characterized

 Cow milk
 Casein α-caseins
β-casein
κ-casein
 Whey β-Lactoglobulin
α-Lactalbumin
Pathogenesi
s
Major food allergens isolated
& characterized

 Chicken egg white Ovomucoid


Ovalbumin
Ovotransferrin
 Peanut Vicilin
Conglutin
Glycinin
 Soybean Vicilin
Conglycinin
Pathogenes
is
Major food allergens isolated
& characterized

 Fish Parvalbumin
 Shrimp Tropomyosin
 Wheat α-Amylase inhibitor
 Celery Pathogenesis related
protein
 Potato Patatin
 Carrots Pathogenesis related protein
 Apple Pathogenesis related protein
Profilin
Clinical
Manifestations
 IgE mediated
 Cutaneous
 Urticaria
 Angioedema
 Gastrointestinal
 Oral allergy
syndrome
 GI anaphylaxis
 Respiratory
 Rhinitis
 Asthma
 Systemic
 Anaphylaxis
Clinical
Manifestations
 Mixed
 Gastrointestinal
 Allergic
eosinophilic
esophagitis
 Allergic
eosinophilic
gastroenteritis
 Cutaneous
 Atopic dermatitis
 Respiratory
 Asthma
Clinical
Manifestations
 Non-IgE mediated
 Gastrointestinal
 Food-protein induced
enterocolitis
 Food protein induced
proctatitis
 Food- protein
induced enteropathy
 Celiac disease
 Cutaneous
 Contact dermatitis
 Dermatitis
herpetiformis
 Respiratory
 Food induced
pulmonary
Clinical
Manifestations
Presumed mechanisms in food
allergies
Immunologi IgE mediated Non-IgE Mixed
c Reaction mediated
Onset of Minutes to 24 to 72 hours Minutes to
symptoms few hours several hours
Usual Minutes to Several days Hours to days
duration few hours
Predominat Anaphylaxis Celiac disease AD
e Urticaria Protein Asthma
Angioedema induced Allergic
Rhinitis enteropathy eosinophilic
GI Heiner enterocolitis
anaphylaxis syndrome
Clinical
Manifestations

Angioedema
Urticaria
Clinical
Manifestations
Angioedema of the
lip
Clinical
Manifestations

Infantile atopic dermatitis


Clinical
Manifestations
AD: Older children & adult
Clinical
Manifestations
Anaphylaxi
s
Diagnosis

Overdiagnosis of food allergy


 Malnutrition
 Eating disorders
 Psychosocial problems
 Family disruption
Underdiagnosis of food
allergy
 Unnecessary suffering from symptoms of
food allergy
 growth failure
 Permanent physical impairment
Diagnosis

Historical details to be
ascertained
 Description of symptoms & signs
 Timing from ingestion to onset of
symptoms
 Whether the ingestion of suspected food
produced similar symptoms on other
occasions
 Frequency with which reactions have
occurred
 Time of most recent occurrence
Diagnosis

SKIN PRICK TEST  Positive result: Any food


allergen elicit a wheal at least 3-
mm greater than the negative
control

 Positive result - indicates the


possibility that the patient has
symptomatic reactivity to the
specific food (PPV <50%)

 Negative result - confirms the


absence of IgE mediated
reaction (NPV >95%)
Bock
Diagnosis

 Prick & prick test


 For fruit & vegetable allergy
 Using fresh fruits or vegetables
Diagnosis

 RASTs
 Significant dermatographism
 Severe skin disease with limited
skin surface areas for testing
 Difficulty to discontinue
antihistamine
 Suspected exquisite sensitivity to
certain foods
Diagnosis

 CAP system FEIA/ Pharmacia-


upjohn Diagnostics
 Quantitative measurements of food
specific IgE antibodies
 More predictive of symptomatic IgE
mediated food allergies
Diagnosis
Predictive value of food
allergen-specific IgE levels
Allergen kU/L PPV
Egg 7 98
infants <2yrs 2 95
Milk 15 95
infants <2 yrs 5 95
Peanut 14 100
Fish 20 100
Tree nuts 15 95
Soybean 30 73
Wheat 26 74
Sampson H, et al
Diagnosis

 Other tests
 Atopy patch test
 Basophil histamine release assays
 Intestinal Mast cell histamine release
assays
Diagnosis
 Elimination diets
 Use alternate formula: soy, extensively
hydrolyzed milk formula, amino acid
formula
 Eliminate specific foods or restrict to the
following diet:
 Rice or corn
 Fresh lamb, beef & pork
 2-3 vegetables (except cabbage, beans, spinach,
tomato)
 2-3 fruits (except citrus fruits)
 Water (apple juice)
 Salt, sugar, honey, olive oil, vegetable oil,
Diagnosis

 Food challenges
 Open food challenge
 Single blind food challenge
 DBPCFC
 Gold standard test
Treatmen
t
 STRICT ELIMINATION of the
offending allergen is the
only proven therapy
Treatmen
t
Food allergen avoidance
 Avoid high risk situation (buffet)
 Take note of hidden allergens
Treatmen
t
Treatmen
t
Treatmen
t
Accidental ingestion
 Auto-injectable epinephrine
 Diphenhydramine tablet or syrup
 Written emergency plan describing
their allergy, their potential
symptoms, medications to be given
& emergency phone numbers to
call
Treatmen
t
Medications
 H1 & H2 blockers
 Corticosteroid
 To reverse severe inflammatory
symptoms
 Leukotriene inhibitors
(Montelukast), cromolyn Na
Treatmen
t
Future approaches to food
allergy:
 Conventional IT
 Probiotics
 Traditional Chinese Medicine
 Mutated allergens
 Anti-IgE antibodies (TNX-901, omalizumab)
 Immunostimulatory sequence (CpG motifs)
 Peptides
 Bacterial adjuvants
Prognosis
Natural history
Usually Usually not
“outgrown” “outgrown”
Cow’s milk Peanut
Egg Tree nut
Soy Fish
Shellfish
Prognosis

Clinical tolerance (Cow’s milk):


 50% by 1 year of age
 70% by 2 years of age
 85% by 3 years of age

Host A
Pediatr Allergy Immunol 5:5-36,
1994
Food: Essential for life
Food: Major source of
pleasure
Epidemiolog
y
 35% of children with moderate
to severe atopic dermatitis have
IgE mediated food allergy

Eigenmann PA, et al

Pediatrics 101: e8, 1998


Epidemiolog
y

 6%-8% of asthmatic children


have food-induced wheezing

Novembre E, de Martino M,
Vierucci A JACI 81: 1059, 1988
Pathogenesi
s

 There is a direct linear relationship


between the number of solid foods
introduced into the diet by 4 months
of age to the development of atopic
dermatitis

Ferguson DM, Horwood LJ, Shanon


FT et al Pediatric 86:541-546, 1990
Pathogenesi
s
Factors affecting allergenicity
of a food allergen
 Heat promotes protein denaturation,
make foods less reactive, more
reactive (cereals) or create new
allergens
 Dry roasting of peanuts at higher
heat (1800C) increases peanut
allergen allergenicity
 Maturation & curing increase
allergenicity of food allergen
Chung Sy et al
J Agri Food Chem
2003;51:4273-7
Pathogenesi
s
Factors affecting allergenicity
of a protein
 Pressure makes protein less reactive
(canned tuna)
 Pasteurization, sterilization & deep
freezing have little effect on food
allergenicity
 Airborne food particles induces
allergic reaction in highly sensitized
individual (cooking fish, opening a
Chung Sy et al
peanut sack pack)2003;51:4273-7
J Agri Food Chem
Treatmen
t
Try the offending food in
small increments

 Potential for serious reactions


 Desensitization - not proven to be
of benefit in the treatment of food
allergy
Treatmen
t

No food already tolerated


would be restricted.

S. Cherer
JACI 2005
Taking antihistamine prior
to intake of offending food
 Modify the milder symptoms
 Minimal efficacy
 Mask early cutaneous symptoms
but can not block systemic
symptoms
Prevention
AAP recommendations for high
risk infants & infants with cow
milk allergy
 Cow milk allergy infants
 Exclusive breastfeeding (maternal
restriction of cow milk, egg, fish,
peanuts & tree nuts) & if this is
unsuccessful,

Pediatrics 2000;106:346-
349
Prevention
AAP recommendations for high
risk infants & infants with cow
milk
 Cowallergy
milk allergy infants
 Alternative to breastfeeding
 Extensively hydrolyzed milk
formula
 Free amino acid based formula
 Soy formula

Pediatrics 2000;106:346-
Prevention
AAP recommendations for high
risk infants & infants with cow
milk allergy
 High risk infants
 Exclusive breastfeeding (maternal
restriction of peanuts, tree nuts, egg,
cow milk & fish)
 Hypoallergenic formula or partially
hydrolyzed formula
 No solid foods till 6 months of age with
dairy products delayed until 1 year, eggs
until 2 years, peanut, nuts & fish until 3
years Pediatrics 2000;106:346-
349
Prevention
AAP recommendations for high risk
infants & infants with cow milk
allergy
 No maternal dietary restrictions
during pregnancy are necessary
except peanuts
 Breastfeeding mothers on restriction
diet should use supplement minerals
(calcium) & vitamins
Pediatrics 2000;106:346-
349
Food Allergy Reactions

Non-IgE mediated rxn IgE mediated rxn

Prick S.T.
+ -
Laboratory studies -
&/or endoscopy,
biopsy Strong hx of anaphylaxis? Open feeding
+ -

Restrict food CAP-FEIA

> Dx value < Dx


value

Elimination diet

Ssx improved?
* Up to 2 wks for IgE mediated rxs; up to 8 wks + -
for non-IgE-mediated food hypersensitivity.

Algorithm Diagnosing Food Hypersensitivity. Open challenge Suspect other


Adopted from: Bock SA, Sampson, HA. Evaluation of Food Allergy. In condition
Leung, DYM & Sampson, SA (ed). Pediatric Allergy: Principles &
Practice, 2003. Mosby.
Open challenge

For Non-IgE mediated rxn For IgE mediated rxn

(+) (-)
(+) Equivocal (-)

Restrict food Continue feeding Restrict food Add to diet


up to 5 days

DBPCFC

Symptoms
Recurred?
(+) (-)
+ -

Add to diet
Algorithm Diagnosing Food Hypersensitivity.
Adopted from: Bock SA, Sampson, HA. Evaluation of Food Allergy. In Leung, DYM & Sampson, SA (ed).
Pediatric Allergy: Principles & Practice, 2003. Mosby.