1. Consultant in Allergy, Asthma & Immunology
THE PHYSICIAN’S PERSPECTIVE ON FOOD ALLERGY NUTRITION EXCHANGE June 2, 2011
Antony Ham Pong MBBS
Consultant in Allergy, Asthma & Immunology
Clinical lecturer, Pediatrics, Univ of Ottawa;
Consultant, Chest Clinic, CHEO
Co-Chair, Infection/Immunology/Allergy Block, U of Ottawa School of Medicine

2. OBJECTIVES Define allergic and atopic disorders
The Allergic March & the Allergy Epidemic
What is a food allergy?
How to diagnose food allergies

3. ATOPY & ALLERGY
ATOPY is the genetic predisposition to produce IgE on allergen exposure, resulting from an imbalance between TH1 and TH2 helper lymphocytes
Specific IgE produced attaches to the surface of mast cells
Subsequent allergen exposure causes mast cell inflammatory mediator release
ALLERGY is the clinical hypersensitivity which occurs as a manifestation of atopy

4. Allergy testing detects specific IgE to an allergen
Allergy testing detects specific IgE to an allergen. Circulating IgE is measured by serum assays (eg RAST or Unicap)

5. Allergy skin tests detect specific IgE bound to mast cells
Allergy skin tests detect specific IgE bound to mast cells. The allergy skin test does not detect the IgE directly but measures the effect of the mediators released in the skin when the mast cell degranulates in response to allergen exposure during the allergy test

6. Early phase reaction occurs in minutes due to release of pre-formed mediators ( vasoactive amines and proteases eg histamine, tryptase, chymase and heparin; and TNFa) and newly generated mediators eg platelet activating factor, eosinophil chemotactic factor, leukotrienes, TNFa as well, prostaglandins & HETEs, IL 3,4,5 etc). The late phase reaction occurs 4-12 hours later due to recruitment of inflammatory cells to the area by which takes time for the cells to move to the area of inflammation (eosinophils. Neutrophils, TH2 cells)

8. urticaria

9. Childhood asthma : Blame your parents
Both parents asthmatic : % risk
One parent asthmatic : % risk
One parent & one sibling : % risk
No one with asthma : 5–10% risk

10. The Allergy Epidemic Atopic Eczema 10-20% Hay Fever 10-20%
Asthma %
Peanut allergy %

11. The Allergic March Atopic eczema onset age 0 - 2 yrs
Food allergy onset age yrs
Asthma onset age yrs
Allergic rhinitis onset age > 5 yrs

12. The Allergy Epidemic
The Hygiene Theory proposes that the major increase in allergies, which is seen only in well-developed countries, is due to excess cleanliness. Our immune system does not have enough work to do, therefore it begins to react to harmless things in our environment, causing allergies.
This may explain in part why 70% of allergic children have no family history of atopic disease

16. Microbial exposures associated with less allergy and asthma: Clinical studies
Older siblings / large family size
Early day care
Less antibiotic use
Lactobacillus ingestion
Infections
Respiratory tract: measles, tuberculosis, tuberculin positivity
Gastrointestinal : Hep A, H. pylori,
Being brought up on a farm
Animal exposure / Stables exposure
Drinking unpasteurized milk ( higher endotoxin levels)
Endotoxin levels higher
Keeping a dog/cat ( unless one is allergic to it!)
Home environment contaminated with endotoxin

17. Timing is everything
Genetics ,timing and degree of exposure to irritants, microbes and allergens will determine whether allergic sensitization or tolerance will develop

18. Adverse reactions to food can be sub-divided into…
What is food allergy?
Adverse reactions to food can be sub-divided into…
Non-toxic
Toxic
Food intolerance: non allergic (non-immune) reactions
Pharmacological reactions
Eg, sulphites
Food allergy
Toxins
Eg, salmonella, scrombroid fish
IgE-mediated
Non-IgE
Immediate onset
Conditions include:
oral allergy syndrome
anaphylaxis
Delayed onset
celiac disease
dietary protein enterocolitis
Adverse reactions to food can be sub-divided into non-toxic or toxic
The term food allergy is used when an adverse reaction is due to an immunologic mechanism.
The IgE-antibody is responsible for immediate allergic reactions occurring after eating foods
Allergic reactions involving immune cells (T-cells) tend to be delayed reactions, where symptoms first occur 4 to 28 hours after eating the food
Non-allergic (non-immune) adverse reactions are termed food intolerance
Pharmacological reactions to foods are due to chemicals naturally present in the foods
Toxic reactions to food can occur in up to 100% of the population provided a sufficient amount of the food is ingested; they are due to toxins (poisons), e.g., to histamine in scombroid fish or salmonella toxins in foods.
Oral Allergy Syndrome
A severe pollen allergic reaction dut to common proteins that are found both in pollens and in plants and fruits
A form of contact urticaria from ingesting a food (usually fresh fruit)
Symptoms confined to lips, mouth and throat including itching of the lips, tongue, roof of mouth and throat, with or without facial swelling
Most commonly affects patients who are allergic to pollens
Examples of causes of adverse reactions to foods
Pharmacologic:
Caffeine (jitteriness), tyramine in aged cheese (migraine), alcohol, histamine
Toxins:
Bacterial food poisoning
Intolerance (nonallergic hypersensitivity):
lactose intolerance, galactosemia, alcohol
Food allergy:
IgE mediated: urticaria, angioedema, acute rhinoconjunctivities, acute asthma, anaphylaxis, food-associated, exercise-induced anaphylaxis
Not IgE mediated: dermatitis herpetiformis, Celiac disease, Heiner syndrome, food protein induced enteritis, eosinophilic esophagitis
Masqueraders of food allergy Auriculotemporal syndrome (facial flush with salivation), gustatory rhinitis, scombroid fish poisoning
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Sicherer and Sampson JACI 2006:117(2);S470-S475; Motala, C. Food Allergy, available at
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Sicherer and Sampson JACI 2006; Food Allergy, available at

19. Features of IgE-mediated food induced allergic reactions
Onset within 30 mins, rarely up to 4 hrs
Duration < 4-6 hours
Reactions recur reliably with re-exposure
Threshold dose (usually small amount)
Anaphylaxis can occur with a small amount of a potent allergen or a larger amount of a ‘milder’ allergen

20. FLUSHING IN A BABY WITH COW’S MILK ALLERGY AFTER HIS FIRST BOTTLE OF MILK FORMULA

22. angioedema

23. Atopic eczema

24. ANAPHYLAXIS: OVERVIEW
Anaphylaxis is a severe, potentially fatal systemic allergic reaction that occurs suddenly (minutes to hours) after contact with an allergy-causing substance
Death can occur in minutes, usually due to closure of airways
Allergic reaction affects many body systems : rash & swelling, breathing difficulties, vomiting & diarrhoea, heart failure & low blood pressure  ANAPHYLACTIC SHOCK
The most severe manifestation of a food allergy

25. Common Allergenic Foods and their Labeling in Canada – A Review
(Zarkadas M., Scott F, Salminen J, Ham Pong AJ.
Can J Allergy Clin Immunol 1999, 4: )
ANAPHYLAXIS
Common Less common
Peanut Soy
Tree Nuts Wheat
Fish * Mustard
Shellfish: Crustaceans Shellfish: Mollusks
Cow’s Milk Sulfites
Egg
Sesame
The top 11 priority food allergens in North America, plus sulfites ( not a food allergen but used in foods and can provoke fatal asthma and anaphylaxis by unknown mechanisms). The original proposal did not include mustard, which was later added in 2011

26. Factors Affecting Food Allergy
Early Dietary Exposure & Food Allergy Prevalence
Peanut North America
Rice E. Asia esp. Japan
Fish Scandinavia
Sesame Israel
Chickpea India
Wheat America, Europe
Edible Bird’s Nest Singapore
(dried cave swallow saliva)

27. How much is too much? MILK – fatality from 2.5ml ( ½ tsp)
EGG – anaphylaxis from 10mg (1/3,000 oz)
FISH - anaphylaxis from 1 gm (1/30 0z)
SHRIMP – anaphylaxis from 1 gm (1/4 shrimp)

28. Threshold Doses: How much peanut is too much?
Dose of peanut causing a subjective reaction eg itchy mouth = 10 ug or 1/50,000 peanut
Objective reaction in challenge studies = to 2mg ( 1/2,000 to 1/250 peanut )
Usual starting dose in challenge studies = 100mg peanut flour ( 1/5 peanut )

29. Can the smell or touch of peanut cause anaphylaxis?
Possibility that high level peanut dust can provoke anaphylaxis in airplanes ( Sicherer 1999)
Smell of peanut butter does not cause allergic reactions– reactions to this are most likely due to intense dislike of the smell ( the smell is due to volatile organic molecules and not allergenic proteins), or inadvertent ingestion
Anaphylaxis has been induced inhalation of steam carrying food particles eg shrimp, fish, milk

30. FOOD ALLERGY : ROUTE OF EXPOSURE
Ingestion – directly or indirectly (eg maternal dietary proteins via breast mlk)
Inhalation eg boiling foods (eg shrimp, milk), food dust (eg peanut, egg, wheat, psyllium), ?milk contaminated lactose in asthma dry powder inhalers
Musosal contact : eye (eg shrimp), rectal (eg milk enema)
Skin : abraded skin eg milk containing ointment or lactobacillus capsules; egg lecithin containing creams
Parenteral : drug & intralipid formulations

31. Diagnosis of Food Allergy
Positive Allergy Skin Prick Test (SPT) or blood test (CAP IgE)
Indicates presence of IgE antibody NOT clinical reactivity
Must be interpreted in the context of clinical history
Negative SPT and CAP IgE
Essentially excludes IgE antibody (>95%)
(OPTIONAL)
It is true that negative skin tests exclude food allergy at > 95%. Negative CAP IgE does not reach 95%. When we look at different probability curve, at 0.35 kUA/L the probability of reacting is often around 20%.
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Sampson et al. JACI 2003 31

32. Allergy Skin tests
Prick/puncture – most common technique, introduces allergen into the very superficial skin (epicutaneous layer) usually flexor surface of forearm, sometimes on back; is more specific but not as sensitive as intradermal
Intradermal – introduces a larger quantity of allergen into a deeper layer of skin of upper forearm; more sensitive but less specific than prick
Scratch – old technique, not used now as too variable
A test which is more specific means that if positive, the test is more likely to indicate clinical disease is less false positives; unfortunately this is also often associated with more false negatives. A test which is more sensitive indicates that it is more likely to detect the greatest number of people with a disease, but is often associated with more false positives ie it may indicate some people have the disease when they do not. Testing on the back is not used as much now as it is more painful, scarier for the patient who cannot see it, and is probably too sensitive

33. Different devices to do prick allergy tests
Different devices to do prick allergy tests. They all introduce the allergen solution in the skin, then wait mins for a localized allergic reacvtion ( a hive)

34. Positive allergy skin test results in a child
Positive allergy skin test results in a child. Cant tell whether he’s happy or sad; but prick testing is only a minor discomfort – the real discomfort is when there is a positive test and you cannot itch it for 15 minutes

35. ALLERGY PRICK SKIN TEST “SIZE DOES MATTER”
Peanut PST > 6mm : ½ will be allergic
Peanut PST > 8mm : Most likely allergic
Cow’s Milk PST > 8mm : “ “
Egg PST > 7mm : “ “

36. Probability Curve for Peanut
Note that at a Unicap level of 14 kU/L of peanut specific IgE, a patient has a 95% probability of reacting to ingestion of peanut. Note that if the Uniicap is under 0.35 kU/L, in a patient with a previous history of peanut allergy, there is still a 15 – 27% chance of reacting to peanut on ingestion.

37. Food Challenge Reasons to challenge:
Confirm reactivity
Confirm non-reactivity
Follow for tolerance
Oral challenge testing (MD supervised, ER meds available)
Open
Single-blind
Double-blind, placebo-controlled (DBPCFC)
Sensitivity, Specificity, PPV, NPV ~ 100%
Limitations:
Risk to patient
Dose
Duration of challenge
Success of blinding
(OPTIONAL)
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Saleh Al-Muhsen et al CMAJ 2003 37

38. Food allergy IgE non-IgE.
Food types
11 priority allergens
Milk,soy,wheat
Symptoms
Skin, respiratory, GI, systemic
GI, Failure to thrive, Eczema, anemia, hypo-
albuminemia
Time to onset of symptoms
Acute: minutes to 4 hours
Subacute to chronic: days to weeks
Duration
4-6 hours
Days to weeks
FTT – failure to thrive; hypoalbuminemia – low serum albumin, which in food allergy is due to loss of albumin by leakage into the gut due to increased gut permeability from the allergic reaction to foods in the gut.

39. Food allergy IgE non-IgE
Threshold dose
Single dose, small amounts eg grams
Cumulative doses, usually large exposures
Atopic family
Yes
Variable
Antihistamine Rx
Usually responds
No response
Lab
Blood eosinophils, elevated IgE
Stool mucus, WBC
Biopsy-flattened villi, eosinophilia
Allergy tests/
Specific IgE
Often positive with good clinical correlation
Variable-clinical correlation often not as dramatic .
Know the differences between these two reactions and also what food intolerance is.

40. FOOD ALLERGY PROGNOSIS
Onset before age 3 years esp cow’s milk (age 2-3), egg(age 5-7), soy & wheat (age 2-3) : usu outgrown
Onset after age 3 years : usu lifelong
Peanut allergy : up to 20% reported to be outgrown ( probably optimistic)
Usually lifelong : Peanut, tree nuts, fish, shellfish, seeds

41. end

42. ACTIONS OF HISTAMINE Peripheral vasodilation
Increased vascular permeability
Altered cardiac conduction
Bronchial/intestinal smooth muscle contraction
Nerve stimulation-Cutaneous pruritus/pain
Increased glandular mucus secretions
Pruritus- itch

43. Food Allergy: not just nuts
Young Children
Adult
Milk
2.5%1
0.3% 1
Egg
1.3% 1
0.2% 1
Peanut
0.8% 1
1.62% 2
0.6% 1
Tree nuts
0.5% 1
Fish
0.1% 1
0.4% 1
Shellfish
2.0% 1
(OPTIONAL SLIDE)
The estimated prevalence of peanut allergy is 1.62 as per results of a Canadian follow-up study conducted in Montreal
Peanut
Peanut has been a leading cause of severe, life-threatening, and even fatal allergic reactions
Peanut allergy requires stringent avoidance and management plans as it is one of the most common food allergies in children, adolescents, and adults
Milk & egg
Many young children outgrow an allergy to milk and egg within the first decade of life, some will continue to remain at risk of anaphylaxis
About 2.5% of newborn infants have hypersensitivity reactions to cow milk. About 80% outgrow the allergy by their fifth birthday
Fish and shellfish
Can be severe and life threatening; therefore, strict avoidance must be practiced
Reference:
CSACI Guidelines for anaphylaxis in schools and other child care settings. Available at
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H Sampson Food Allergy Update JACI 2004
Ben-Shosham et al, JACI 2009 43

44. Signs and Symptoms: IgE vs Non-IgE
IgE Non-IgE
Skin
Urticaria
Angioedema
Atopic dermatitis
Respiratory
Throat tightness
Rhinitis
Asthma
Gut
Vomit
Diarrhea
Pain
Anaphylaxis
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Sicherer and Sampson JACI 2006; Sampson JACI 2003