1 Food&Drug Allergy .May 2006-

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ADVERSE REACTIONS TOFOODS

Pediatric Allergy-Immunology Division



Prevalence

Children 6-8%

Adults 1-2%



A term referring to any reaction

after ingestion of food

Definition



A- Non-immunologic Reaction

Toxic

Bacterial food poisoning

(salmonella, staphylococcus)

Scromboid fish poisoning(Histamine)

Pharmacologic

Caffeine in coffee

Alcohol

Tyramine in aged cheese

Metabolic/ Intolerance

Lactose deficiency-intolerance

Galactosemia

Pancreatic Insufficiency

Idiosynrotic

Food additives

Aspirin

NSAID

Phsycologic

Anorexia nervosa



B- Immunologic reactions

IgE mediated Non- IgE mediated

Oral allergy syndrome

Anaphylaxis

Urticaria

Eosinophilic gastroenteritis

Food induced enterocolitis

Food induced colitis (proctitis)

Dietary protein enteropathy



Pathophysiology

Barrier Mechanisms: Prevent ag invading blood stream

A- Non-immunologic

Gastic and pancreatic enzymes

Intestinal peristaltism

Intestinal mucosa

Microvilli

Cell barrier

B- Immunologic

Secretary IgA

RES cells



ORAL TOLERANCE

State of immunologic unresponsiveness to food ag¶s

Newborn-age related immaturity of barrier mechanisms

Tolerizing mechanisms subsequently developes

Early feeding with major food ag¶s prevents tolerance

and sensitizes



Immune Mechanisms

A. IgE-mediated

Genetic lack of development of oral toleranceBreakdown of tolerance in the GI tract

B. Non IgE-mediated

Limited scientific evidenceType I, II, III, IV rxs



Major Food Allergens

Children

Cow¶s milk (whey proteins, casein)

Egg (ovalbumin)

Peanut

Soy-bean

Wheat

Fish

Tree-nut

Adults

Peanut

Tree-nutFish

Shellfish



A- IgE Mediated

Prick ( RAST(+) )

Symptoms develop in minutesOral Allergy Syndrome

Contact urticaria

Confined to oroparynx

Pruritis-angioedema (tongue, lip, palate, throat)

Rapidly resolves

Fresh fruit and vegetables

Clinical Manifestations



Anaphylaxis

Cutaneous, respiratory, GI, CV symptoms

May be fatal

Exercise induced anaphylaxis

Nuts and fish



Respiratory Symptoms

Nasal ± rhinorrea, pruritis, sneezing

Larygeal ± dysphonia, hoarsness, laryngeal edema,

upper airway obstruction

Bronchial-wheezing Skin

Acute urticria

Chronic urticaria

Atopic dermatitis

Milk, egg, fish, peanut, soya



(a)GI allergy nausea vomiting

abdominal pain

cramping

diarrhea

(b) Allergic eosinophilic gastroentheropathy nausea vomiting

abdominal pain

diarrhea

failure to thrive in infants

(c) Infantfil colic 10-15 % IgE mediated

proxysmal crying, abdominal distension, excessive gus, flexion

of legs in the first 2-4 wks of life

GI



Symptoms develop 2-4 hrs after food ingestion

Prick ( RAST (-) )

B- Non ± IgE mediated



GASTROINTESTINAL

Enterocolitis Colitis Enteropathy

Age onset Infant Infant/newborn Infant/Toddler

Symptoms Vomiting Vomiting Vomiting

Diarrhea Diarrhea Diarrhea

Rectal bleeding Rectal bleeding Poor weight gain

ill apprence

Characteristic Prot. Losing entheropathy

Malabsorbtion Malabsorption

Edema

Dehydration

Acidosis

Causes Milk Milk Milk

Soy Soy Soy

Protein formulas Human milk Wheat

Egg



Diagnosis: History/Physical

History:

-symptoms, timing: Acute rx versus chronich rx-Diet details / symptom diary: specific food(s), hidden

ingredient

Physical examination:

evaluate disease severityIdentify general mechanism



DIAGNOSISHx/Physical Exam

Identify general mechanism

IgE-mediated

Prick RAST (+) Non IgE-mediated

Prick RAST (-)

Consider biopsy

ELIMI NATION

Resolution No Resolution

Consider biopsy

Challenge

Elimination

Challenge

Reintroduce



Only proven treatment isELIMINATION

Treatment



Wheezing - F2

agonists

Sneezing

Urticaria

Angioedema

Pruritis

Anaphylaxis - adrenalin

antihistamines

Treat Symptoms



Only if ³High risk´ infant

Delayed introduction of solid foods Milk 12 months

Egg 24 months

Fish/peanut 36 months

Prophylaxis



Both parents with atopic disease

Siblings with food allergy

Who is high risk?



Natural History

Dependent on food and immunopathogenesis

IgE-mediated GI allergy

85% CM, egg, wheat, soy allergy remit by 3

yrs

Levels of specific IgE not predictive

Allergy to peanut, nut, seafood persist

Non IgE-mediated GI allergy

Infant forms resolve 1-3 yrs



Summary

History and Physical exam important

IgE & non-IgE mediated conditions exist

Diagnosis by elimination and challenge

Elimination/education/emergency treatment

Periodic rechallenge to monitor tolerance

S pecific IgE does not indicate tolerance



Any rx after administration of drug

ADVERSE REACTIONS TO DRUGS



A- Predictable (non-susceptible patients)

(1)Overdosage

Toxic pharmacologic efect

e.g. - Respiratory depression with sedatives

- Grand mal seizure with aminophyline

Classification of Adverse Drug Reactions



(2) Side effect ± undesirable but unavoidable effect

e.g Somnolence with antihistamines

Tachycardia with adrenalin



(4) Drug interactions

Alteration of drug metabolism by another drug

e.g Phenobarbital increases metabolism of teophylline



(1) Intolerance

- Toxic pharmacologic effect by normal dose

- Defect in the metabolism of drug

e.g convulsion with normal dose of aminophyline

B- Un-predictable (susceptible patients)



(2) IdiosyncrasyA bnormal response different than pharmacologic effect

- related to any enzyme deficiency

e.g coombs (+) hemolytic anemia in subjects with

GGPD deficiency with use of primaquine



(3) Allergy or Type I HS - ANAFLAKTK - Immune mechanism

- Exposure-latent period-re exposure ± rx (not on 1st exp)

- Symptoms different than pharmacologic effect

- May start with small doses

- Subsides when drug discontiuned

- Reccurs wen drug readministered

- e.g penicillin, sulphonamide



(4) Pseudoallergic rxs - ANAFLAKTOD- non - immune mechanism

- 1st exposure

- high dose

e.g anaphylactoid ± RCM, vancomisin

defect in arachidonic acid pathway-aspirin, NSAID



HAPTENIZATION

Drugs ³low molecular weight´ ³non immunogenic´

Drug-Protein conjugates =>Hapten

³Hapten´ is immunogenic



Immunologic Classification of Drug rxs

Type I, II, III, IV immunologic reactions



(1)History

Most important diagnostic tool

Identify all drugs used

Time of symptoms to start

Route

Duration of tx

Clinical manifestations

Duration of subsiding following discontinuation

Approach to patient with history of drug allergy



(2) Don¶t give drugs with CROSS-REACTIVITY

e.g ±Penicilin and cephalosporine

-Give another drug

(3) If that drug INDICATED

Skin test (Prick , intradermal) (IgE mediated)

Incremental challenge test (anaphylactoid)



(4) - Desensitization p start treatment

(5) If Type II, III, IV, rx

Never give the drug

No method for desensitization



Most common cause

Allergic rx 0,75-8 %

Systemic anaphylaxis 0.01%

20-49 yrs of age

PENICILLIN ALLERGY



Immunopathologic Rx

Gell and Coombs classification

Type I, II, III, IV HS rx

Antigenic DeterminantsMajor determinant

- Benzyl penicilloyl

Minor determinant-Benzyl penicillin

-Benzyl penicilloate

- Benzyl penilloate



(1) History

(2) Hx of Type I HS rx ± AVOID

(3) Have to use ± skin test

(4) Test only relevant to current situation ± NOT FUTURE

(5) Non-IgE mediated rx ± NOT PREDICTED by test

Diagnosis & Approach



(1) AVOID

(2) AVOID dugs with CROSS-REACTIVITY (posses-beta lactams)

Cephalosporins (1-16 %CR)

Monobactam

Cephacarbam 50 %CR

Carbopenem

Management of Patient with (+) Skin Test



(3) Desensitization

IndicatedpWhen no suitable alternative AB for substitution

PO/ Parenteral (PO safer)

Start with extremely small dosep doubling 15 mtsp Full dosepTx

Only relevant for current tx



(4) Future courses of penicillin needed

Repeat skin test

Repeat desensitization

1 Food&Drug Allergy .May 2006-

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