Pedia - Food Allergy

Food Allergy Vicky Wee Eng-Biñas, M.D. Allergologist

Definitio n Adverse food reaction 

Any abnormal response ingestion of a food

after

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 Gene Mucosal barrier Oral tolerance

Environment Food allergens

Pathogenesi s Mucus

M U C O S A L B A R R I E R

Enzymes Bile salts Low pH sIgA Epithelium w/ tight junction Trefoil factors

NK cells Macrophage PMN Serum IgG IgA

Lymphocytes

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 predisposition

S E N S

Mucosal barrier breakdown Failure to develop Oral tolerance

Environment Food allergens

I T I Z A T I O N

Food Allergy

Pathogenesi s Family history of atopy as risk factor of atopy in the child Family history of atopy Biparental (same allergy) Sibling Uniparental

Child risk of atopy 40-60% 40-50 20-40

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

 Whey

α-caseins β-casein κ-casein β-Lactoglobulin α-Lactalbumin

Pathogenesi s Major food allergens isolated & characterized 

Chicken egg white



Peanut



Soybean

Ovomucoid Ovalbumin Ovotransferrin Vicilin Conglutin Glycinin Vicilin Conglycinin

Pathogenes is Major food allergens isolated & characterized       

Fish Shrimp Wheat Celery protein Potato Carrots Apple

Parvalbumin Tropomyosin α-Amylase inhibitor Pathogenesis related Patatin Pathogenesis related protein 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 c Reaction

Non-IgE mediated

Onset of symptoms

Minutes to few hours

24 to 72 hours Minutes to several hours

Usual duration

Minutes to few hours

Several days

Hours to days

Celiac disease Protein induced enteropathy Heiner syndrome

AD Asthma Allergic eosinophilic enterocolitis

Predominat Anaphylaxis e Urticaria Angioedema Rhinitis GI anaphylaxis

Mixed

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 allergy   

of

food

Unnecessary suffering from symptoms of food allergy growth failure Permanent physical impairment

Diagnosis Historical ascertained  







details

to

be

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 3mm greater than the negative control

 Positive

result - indicates possibility that the patient symptomatic reactivity to specific food (PPV <50%)

 Negative

the has the

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/ Pharmaciaupjohn 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 Egg infants <2yrs Milk infants <2 yrs Peanut Fish Tree nuts Soybean Wheat

kU/L 7 2 15 5 14 20 15 30 26

PPV 98 95 95 95 100 100 95 73 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 symptoms



severe

inflammatory

Leukotriene inhibitors (Montelukast), cromolyn Na

Treatmen t Future approaches allergy:        

to

food

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 “outgrown”

Usually not “outgrown”

Cow’s milk Egg Soy

Peanut Tree nut 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 J Agri Food Chem peanut sack pack)2003;51:4273-7

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;106:346349

Prevention AAP recommendations for high risk infants & infants with cow milk allergy  Cow 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;106:346349

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;106:346349

Food Allergy Reactions

IgE mediated rxn

Non-IgE mediated rxn

Prick S.T. Laboratory studies &/or endoscopy, biopsy

+

-

-

Open feeding

Strong hx of anaphylaxis? +

Restrict food

-

CAP-FEIA > Dx value

< Dx value

Elimination diet

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

Ssx improved? +

Open challenge

-

Suspect other condition

Open challenge

For Non-IgE mediated rxn

For IgE mediated rxn

(+)

(-)

Restrict food

Continue feeding up to 5 days

(+)

Equivocal

Restrict food

(-)

Add to diet

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.