Diagnosis and Diagnosis and Dietary Management of Food Dietary Management of Food

Allergies and IntolerancesAllergies and Intolerances

Clinical ApplicationsClinical Applications

Tests for Adverse ReactionsTests for Adverse Reactions to Foods to Foods

Rationale and LimitationsRationale and Limitations

3

Standard Allergy TestsStandard Allergy Tests Skin testsSkin tests

Scratch or prickScratch or prick Allergen extract applied to skin surfaceAllergen extract applied to skin surface of arm or backof arm or back Skin is scarified (scratched) or pricked with lancetSkin is scarified (scratched) or pricked with lancet Allergen encounters mast cells below skin surfaceAllergen encounters mast cells below skin surface

If allergen-specific IgE is present, allergen plus If allergen-specific IgE is present, allergen plus antibody causes release of mediators (mast cell antibody causes release of mediators (mast cell degranulation), especially histaminedegranulation), especially histamine

Histamine causes reddening and swelling: “wheal and Histamine causes reddening and swelling: “wheal and flare” reaction of the skin testflare” reaction of the skin test

Size of reaction measured (usually 1+ to 4+)Size of reaction measured (usually 1+ to 4+)

4

Standard Allergy TestsStandard Allergy Tests Skin tests continuedSkin tests continued

Intradermal testsIntradermal tests Allergen extract is injected into Allergen extract is injected into dermis Rationale: release of histamine produces wheal Rationale: release of histamine produces wheal

and flareand flareNote: many countries do not approve this type of testing because Note: many countries do not approve this type of testing because

of increased risk of anaphylaxis as allergen introduced of increased risk of anaphylaxis as allergen introduced directly into blood streamdirectly into blood stream Controls for all skin tests:Controls for all skin tests:

Negative: medium in which allergen is Negative: medium in which allergen is suspended (usually saline)suspended (usually saline)

Positive: measured amount of histaminePositive: measured amount of histamine

5

Wheal and Flare ReactionWheal and Flare Reaction

Skin prick testsSkin prick tests

6

Value of Skin Tests in PracticeValue of Skin Tests in Practice

Positive predictive accuracy of skin tests Positive predictive accuracy of skin tests rarely exceeds 50%rarely exceeds 50% Many practitioners rate them lowerMany practitioners rate them lower

Negative skin tests do not rule out the Negative skin tests do not rule out the possibility of non-IgE-mediated reactionspossibility of non-IgE-mediated reactions

Do not rule out non-immune-mediated food Do not rule out non-immune-mediated food intolerancesintolerances

7

Value of SkinValue of Skin Tests in PracticeTests in Practice

Tests for highly allergenic foods thought to Tests for highly allergenic foods thought to have close to 100% have close to 100% negativenegative predictive predictive accuracy for diagnosis of IgE-mediated accuracy for diagnosis of IgE-mediated reactionsreactions

Such foods include:Such foods include: Egg Egg Milk Milk Fish Fish Wheat Wheat Tree nuts Tree nuts Peanut Peanut

8

Reasons for False Positive Skin TestsReasons for False Positive Skin Tests

Degranulation of skin mast cells by stimuli Degranulation of skin mast cells by stimuli that do not degranulate mast cells in the that do not degranulate mast cells in the digestive tractdigestive tract

Differences in the form in which the food is Differences in the form in which the food is applied to the skin compared to that which applied to the skin compared to that which encounters immune cells in the digestive tractencounters immune cells in the digestive tract

Raw form in extract may be degraded during Raw form in extract may be degraded during cookingcooking

Digestion by gastric acid and digestive Digestion by gastric acid and digestive enzymes can degrade antigensenzymes can degrade antigens

Allergen extract contains histamineAllergen extract contains histamine

9

False Negative Skin TestsFalse Negative Skin Tests

Children younger than 2-3 years are more likely to Children younger than 2-3 years are more likely to have a negative skin test and positive food challenge have a negative skin test and positive food challenge than adultsthan adults

Adverse reaction is not mediated by IgEAdverse reaction is not mediated by IgE Commercial allergen may contain no material that the Commercial allergen may contain no material that the

immune system can recognizeimmune system can recognize Processing of food leads to degradation of allergen Processing of food leads to degradation of allergen

(e.g. crushing produces phenols and catabolic (e.g. crushing produces phenols and catabolic enzymes)enzymes)

10

Other Skin TestsOther Skin Tests Prick-to-PrickPrick-to-Prick Sterile needle is inserted into raw food, and the Sterile needle is inserted into raw food, and the

patient’s skin is pricked with the same needlepatient’s skin is pricked with the same needle Used for suspected contact allergyUsed for suspected contact allergy

e.g. oral allergy syndromee.g. oral allergy syndrome Especially where allergen is easilyEspecially where allergen is easily denatured by heat and aciddenatured by heat and acid Crushing plant tissue during preparation of Crushing plant tissue during preparation of

allergen extracts releases phenols that rapidly allergen extracts releases phenols that rapidly cause break-down of proteincause break-down of protein

Prick-to prick test transfers “native” allergenPrick-to prick test transfers “native” allergen

11

Other Skin TestsOther Skin Tests

Patch Test for Contact AllergiesPatch Test for Contact Allergies Involves Type IV (delayed) hypersensitivity reaction, Involves Type IV (delayed) hypersensitivity reaction,

requiring cell-to-cell contactrequiring cell-to-cell contact Examples:Examples:

Poison ivy rashPoison ivy rash Nickel contact dermatitisNickel contact dermatitis Preservatives, dyes and perfumes in cosmeticsPreservatives, dyes and perfumes in cosmetics

Allergen is placed on the skin, or applied as an Allergen is placed on the skin, or applied as an impregnated patch, which is kept in place by adhesive impregnated patch, which is kept in place by adhesive bandage for up to 72 hoursbandage for up to 72 hours

Local reddening, swelling, irritation, indicates positive Local reddening, swelling, irritation, indicates positive responseresponse

12

Other Skin TestsOther Skin Tests

DIMSOFT (dimethylsulphoxide test) for delayed DIMSOFT (dimethylsulphoxide test) for delayed reaction to foodreaction to food Food extract is suspended in 90% Food extract is suspended in 90%

dimethylsulfoxidedimethylsulfoxide Aids in skin penetration of allergenAids in skin penetration of allergen Patch held in place 48-72 hoursPatch held in place 48-72 hours Especially useful in skin and gastrointestinal Especially useful in skin and gastrointestinal

reactions which may not have immediate onset reactions which may not have immediate onset symptomssymptoms

Especially useful for milk and cereal grainsEspecially useful for milk and cereal grains

13

Risks associated with skin testsRisks associated with skin tests

High number of false positive and false negative tests High number of false positive and false negative tests creates risk of diagnostic inaccuracycreates risk of diagnostic inaccuracy

All tests must be considered together with:All tests must be considered together with: Clear medical history Clear medical history Exclusion of non-allergic causesExclusion of non-allergic causes Confirmation by elimination and challenge of suspect Confirmation by elimination and challenge of suspect

foodsfoods Danger of sensitisation to allergens through the skin:Danger of sensitisation to allergens through the skin:

Initial exposure via the digestive tract most likely Initial exposure via the digestive tract most likely to lead to toleranceto lead to tolerance

Initial exposure via the skin more likely to lead to Initial exposure via the skin more likely to lead to sensitization and initiation of allergy especially if sensitization and initiation of allergy especially if inflammation exists (e.g. eczema)inflammation exists (e.g. eczema)

14

Standard Allergy TestsStandard Allergy TestsBlood TestsBlood Tests

RAST: radioallergosorbent test (e.g. ImmunoCap-RAST; RAST: radioallergosorbent test (e.g. ImmunoCap-RAST; Phadebas-RAST)Phadebas-RAST)

FAST; Fluorescence allergosorbent testFAST; Fluorescence allergosorbent test ELISA: enzyme-linked immunosorbent assayELISA: enzyme-linked immunosorbent assay

Designed to detect and measure levels of allergen-specific Designed to detect and measure levels of allergen-specific antibodiesantibodies

Used for detection of levels of allergen-specific IgEUsed for detection of levels of allergen-specific IgE May measure total IgE - thought to be indicative of “atopic May measure total IgE - thought to be indicative of “atopic

potential”potential” Some practitioners measure IgGSome practitioners measure IgG (especially IgG4(especially IgG4) ) by ELISAby ELISA

15

Value of Blood Tests in PracticeValue of Blood Tests in Practice

Blood tests have about the same sensitivity as skin Blood tests have about the same sensitivity as skin tests for identification of IgE-mediated sensitisation tests for identification of IgE-mediated sensitisation to food allergensto food allergens

Anti-food antibodies (especially IgG) are frequently Anti-food antibodies (especially IgG) are frequently detectable in all humans, usually without any detectable in all humans, usually without any evidence of adverse effectevidence of adverse effect

IgG production likely to be the first stage of IgG production likely to be the first stage of development of oral tolerance to a fooddevelopment of oral tolerance to a food

Studies suggest that IgG4 indicates protection or Studies suggest that IgG4 indicates protection or recovery from IgE-mediated food allergyrecovery from IgE-mediated food allergy

16

Value of Blood Tests in PracticeValue of Blood Tests in Practice

There is often poor correlation between high There is often poor correlation between high level of anti-food IgE and symptoms when the level of anti-food IgE and symptoms when the food is eatenfood is eaten

Many people with clinical signs of food allergy Many people with clinical signs of food allergy show no elevation in IgEshow no elevation in IgE

Reasons for failure of blood tests to indicate Reasons for failure of blood tests to indicate foods responsible for symptoms are the same as foods responsible for symptoms are the same as those for skin teststhose for skin tests

17

Tests for Intolerance of Food AdditivesTests for Intolerance of Food Additives

There are no reliable skin or blood tests to detect food There are no reliable skin or blood tests to detect food additive intoleranceadditive intolerance

Skin prick tests for Skin prick tests for sulphitessulphites are sometimes positive are sometimes positive

A negative skin test does not rule out sulphite sensitivityA negative skin test does not rule out sulphite sensitivity

History and oral challenge provocation of symptoms are History and oral challenge provocation of symptoms are the only methods for the diagnosis of additive the only methods for the diagnosis of additive sensitivity at presentsensitivity at present

CautionCaution: Challenge may occasionally induce : Challenge may occasionally induce anaphylaxis in sulphite-sensitive asthmaticsanaphylaxis in sulphite-sensitive asthmatics

18

Unorthodox TestsUnorthodox Tests

Many people turn to unorthodox tests when avoidance Many people turn to unorthodox tests when avoidance of foods positive by conventional test methods have of foods positive by conventional test methods have been unsuccessful in managing their symptomsbeen unsuccessful in managing their symptoms

Tests include:Tests include: Vega test (electro-dermal)Vega test (electro-dermal) Biokinesiology (muscle strength)Biokinesiology (muscle strength) Analysis of hair, urine, salivaAnalysis of hair, urine, saliva RadionicsRadionics ALCAT (lymphocyte cytotoxicity)ALCAT (lymphocyte cytotoxicity)

19

Controversial TestsControversial Tests

Electro-Dermal (Vega) TestElectro-Dermal (Vega) Test Measures change in electrical potential on skinMeasures change in electrical potential on skin Circuit linkingCircuit linking

Patient holding a metal rod Patient holding a metal rod Vial containing food, or other material being testedVial containing food, or other material being tested Meter to measure energy levelMeter to measure energy level Technician holding probe held at acupuncture point on Technician holding probe held at acupuncture point on

patient’s other handpatient’s other hand Disturbance in energy flow to meter indicates Disturbance in energy flow to meter indicates

reactivityreactivity

20

Controversial TestsControversial Tests

BiokinesiologyBiokinesiologyAssumption: muscles become weak when influenced Assumption: muscles become weak when influenced by the allergen to which the patient reactsby the allergen to which the patient reacts Patient holds a vial containing the suspect allergen Patient holds a vial containing the suspect allergen

(food)(food) Practitioner tests the strength of the patient’s other Practitioner tests the strength of the patient’s other

arm in resisting downward pressurearm in resisting downward pressure Weakening of resistance indicates a positive Weakening of resistance indicates a positive

(allergic) reaction(allergic) reaction

21

Drawbacks of Unreliable TestsDrawbacks of Unreliable Tests

Diagnostic inaccuracyDiagnostic inaccuracy Therapeutic failureTherapeutic failure False diagnosis of allergyFalse diagnosis of allergy Creation of fictitious disease entitiesCreation of fictitious disease entities Failure to recognize and treat genuine diseaseFailure to recognize and treat genuine disease Inappropriate and unbalanced dietsInappropriate and unbalanced diets

22

Consequences of Mismanagement of Consequences of Mismanagement of Adverse Reactions to FoodsAdverse Reactions to Foods

Malnutrition; weight loss, due to extensive elimination Malnutrition; weight loss, due to extensive elimination dietsdiets

Especially critical in young children where nutritional Especially critical in young children where nutritional deficiency at a crucial stage in development can cause deficiency at a crucial stage in development can cause permanent damagepermanent damage

Food phobia due to fear that “the wrong food” will cause Food phobia due to fear that “the wrong food” will cause permanent damage, and in extreme cases, deathpermanent damage, and in extreme cases, death

Frustration and anger with the “medical system” that is Frustration and anger with the “medical system” that is perceived as failing themperceived as failing them

Disruption of lifestyle, social and family relationshipsDisruption of lifestyle, social and family relationships

Elimination and Challenge Protocols

24

Identification of Allergenic FoodsIdentification of Allergenic Foods

Removal of the suspect foods from the diet, Removal of the suspect foods from the diet, followed by reintroduction is the only way followed by reintroduction is the only way to:to: Identify the culprit food componentsIdentify the culprit food components Confirm the accuracy of any allergy testsConfirm the accuracy of any allergy tests

Long-term adherence to a restricted diet Long-term adherence to a restricted diet should notshould not be advocated without clear be advocated without clear identification of the culprit food identification of the culprit food componentscomponents

25

Food Intolerance: Clinical DiagnosisFood Intolerance: Clinical Diagnosis

Symptoms Disappear

Elimination Diet: Avoid Suspect Food

Symptoms Persist

Increase Restrictions

Reintroduce Foods Sequentially or Double-blind

Symptoms Provoked No Symptoms

Diagnosis Confirmed Diagnosis Not Confirmed

26

Elimination and ChallengeElimination and Challenge

Stage 1Stage 1: : Exposure DiaryExposure Diary Record each day, for a minimum of 5-7 days:Record each day, for a minimum of 5-7 days:

All foods, beverages, medications, and supplements All foods, beverages, medications, and supplements ingestedingested

Composition of compound dishes and drinks, Composition of compound dishes and drinks, including additives in manufactured foodsincluding additives in manufactured foods

Approximate quantities of eachApproximate quantities of each The time of consumptionThe time of consumption

27

Exposure Diary (continued)Exposure Diary (continued)

All symptoms graded on severity:All symptoms graded on severity: 1 (mild); 1 (mild); 2 (mild-moderate) 2 (mild-moderate)

3 (moderate) 3 (moderate) 4 (severe) 4 (severe)

Time of onsetTime of onset

How long they lastHow long they last

Record status on waking in the morning.Record status on waking in the morning. Was sleep disturbed during the night, and if so, Was sleep disturbed during the night, and if so,

was it due to specific symptoms?was it due to specific symptoms?

28

Elimination DietElimination Diet

Based onBased on:: Detailed medical historyDetailed medical history Analysis of Analysis of Exposure DiaryExposure Diary Any previous allergy testsAny previous allergy tests Foods suspected by the patientFoods suspected by the patient

Formulate dietFormulate diet to exclude all suspect allergens to exclude all suspect allergens and intolerance triggersand intolerance triggers

ProvideProvide excluded nutrients from alternative excluded nutrients from alternative sourcessources

DurationDuration: Usually four weeks: Usually four weeks

29

Selective Elimination DietsSelective Elimination Diets

Certain conditions tend to be associated with specific food componentsCertain conditions tend to be associated with specific food components Suspect food components are those that are probable triggers or mediators Suspect food components are those that are probable triggers or mediators

of symptomsof symptoms ExamplesExamples::

Eczema: Eczema: Highly allergenic foodsHighly allergenic foods Migraine: Migraine: Biogenic aminesBiogenic amines Urticaria/angioedema: Urticaria/angioedema: HistamineHistamine Chronic diarrhea:Chronic diarrhea: Carbohydrates; DisaccharidesCarbohydrates; Disaccharides Asthma: Asthma: Cyclo-oxygenase inhibitors Cyclo-oxygenase inhibitors

SulphitesSulphites Latex allergy:Latex allergy: Foods with structurally Foods with structurally

similar antigens to latexsimilar antigens to latex Oral allergy syndrome: Oral allergy syndrome: Foods with structurally Foods with structurally

similar antigens to pollenssimilar antigens to pollens

30

Few Foods Elimination DietFew Foods Elimination Diet

When it is difficult to determine which foods When it is difficult to determine which foods are suspects a few foods elimination diet is are suspects a few foods elimination diet is followedfollowed Limited to a very small number of foods and Limited to a very small number of foods and

beveragesbeverages Limited time: 10-14 days for an adultLimited time: 10-14 days for an adult 7 days maximum for a child7 days maximum for a child

If all else fails use elemental formulae:If all else fails use elemental formulae: May use extensively hydrolysed formula for a May use extensively hydrolysed formula for a

young childyoung child

31

Expected Results of Elimination DietExpected Results of Elimination Diet

Symptoms often worsen on days 2-4 of Symptoms often worsen on days 2-4 of eliminationelimination

By day 5-7 symptomatic improvement is By day 5-7 symptomatic improvement is experiencedexperienced

Symptoms disappear after 10-14 days of Symptoms disappear after 10-14 days of exclusionexclusion

32

ChallengeChallenge

Double-blind Placebo-controlled Food Challenge Double-blind Placebo-controlled Food Challenge (DBPCFC)(DBPCFC) Lyophilized (freeze-dried) food is disguised in Lyophilized (freeze-dried) food is disguised in

gelatin capsulesgelatin capsules Identical gelatin capsules contain a placebo Identical gelatin capsules contain a placebo

(glucose powder)(glucose powder) Neither the patient nor the supervisor knows the Neither the patient nor the supervisor knows the

identity of the contents of the capsulesidentity of the contents of the capsules Positive test is when the food triggers symptoms Positive test is when the food triggers symptoms

and the placebo does notand the placebo does not

33

ChallengeChallenge (continued) (continued)

Drawback of DBPCFCDrawback of DBPCFC Expensive in time and personnelExpensive in time and personnel Capsule may not provide enough food to Capsule may not provide enough food to

elicit a positive reactionelicit a positive reaction Patient may be allergic to gelatin in Patient may be allergic to gelatin in

capsulecapsule May be other factors involved in eliciting May be other factors involved in eliciting

symptoms, e.g. taste and smellsymptoms, e.g. taste and smell

34

Challenge Challenge (continued)(continued)

Single-blind food challenge (SBFC)Single-blind food challenge (SBFC)Supervisor knows the identity of the Supervisor knows the identity of the

food; patient does notfood; patient does notFood is disguised in a strong-tasting Food is disguised in a strong-tasting

“inert” food tolerated by the patient:“inert” food tolerated by the patient: lentil souplentil soup apple sauceapple sauce tomato sauce tomato sauce

35

Challenge Phase Challenge Phase continuedcontinued

Open food challengeOpen food challenge Sequential Incremental Dose Challenge (SIDC)Sequential Incremental Dose Challenge (SIDC) Each food component is introduced separatelyEach food component is introduced separately Starting with a small quantity and increasing the Starting with a small quantity and increasing the

amount according to a specific scheduleamount according to a specific schedule This is usually employed when the symptoms are This is usually employed when the symptoms are

mild, and the patient has eaten the food in the mild, and the patient has eaten the food in the past without a severe reactionpast without a severe reaction

Any food suspected to cause a severe or anaphylactic Any food suspected to cause a severe or anaphylactic reaction should only be challenged in suitably reaction should only be challenged in suitably equipped medical facilityequipped medical facility

36

Open Food ChallengeOpen Food Challenge

Each food or food component is introduced Each food or food component is introduced individuallyindividually

The basic elimination diet, or therapeutic diet The basic elimination diet, or therapeutic diet continues during this phasecontinues during this phase

If an adverse reaction to the test food occurs at If an adverse reaction to the test food occurs at any time during the test STOP. any time during the test STOP.

Wait 48 hours after all symptoms have Wait 48 hours after all symptoms have subsided before testing another foodsubsided before testing another food

37

Incremental Dose ChallengeIncremental Dose Challenge

Day 1: Day 1: Consume test food between mealsConsume test food between meals

MorningMorning: Eat a small quantity of the test food: Eat a small quantity of the test food

Wait four hours, monitoring for adverse reactionWait four hours, monitoring for adverse reaction

If no symptoms:If no symptoms: AfternoonAfternoon: Eat double the quantity of test food eaten in : Eat double the quantity of test food eaten in

the morningthe morning

Wait four hours, monitoring for adverse reaction Wait four hours, monitoring for adverse reaction

If no symptoms:If no symptoms: EveningEvening: Eat double the quantity of test food eaten in : Eat double the quantity of test food eaten in

the afternoonthe afternoon

38

Incremental Dose ChallengeIncremental Dose Challenge (continued) (continued)

Day 2:Day 2:

Do not eat any of the test foodDo not eat any of the test food Continue to eat basic elimination dietContinue to eat basic elimination diet Monitor for any adverse reactions during the Monitor for any adverse reactions during the

night and day which may be due to a delayed night and day which may be due to a delayed reaction to the test foodreaction to the test food

39

Day 3:Day 3: If no adverse reactions experiencedIf no adverse reactions experienced

Proceed to testing a new food, starting Day 1Proceed to testing a new food, starting Day 1

If the results of Day 1 and/or Day 2 are unclear :If the results of Day 1 and/or Day 2 are unclear : Repeat Day 1, using the same food, the same test Repeat Day 1, using the same food, the same test

protocol, but larger doses of the test food protocol, but larger doses of the test food

Day 4:Day 4: Monitor for delayed reactions as on Day 2Monitor for delayed reactions as on Day 2

Incremental Dose Challenge(continued)

40

Sequential Incremental Dose ChallengeSequential Incremental Dose Challenge

Continue testing in the same manner until all Continue testing in the same manner until all excluded foods, beverages, and additives have excluded foods, beverages, and additives have been testedbeen tested

For each food component, the first day is the For each food component, the first day is the test day, and the second is a monitoring day test day, and the second is a monitoring day for delayed reactionsfor delayed reactions

41

Sequence of TestingSequence of TestingMilk and Milk ProductsMilk and Milk Products

Test 1: Casein proteinsTest 1: Casein proteinsTest 2: Annatto, biogenic amines, plus caseinTest 2: Annatto, biogenic amines, plus caseinTest 3: Casein plus whey proteinsTest 3: Casein plus whey proteinsTest 4: Lactose in addition to casein and whey Test 4: Lactose in addition to casein and whey

proteinsproteinsTest 5: Modified milk componentsTest 5: Modified milk componentsTest 6: Whey proteins (lactose-free)Test 6: Whey proteins (lactose-free)Test 7: Lactose (in whey)Test 7: Lactose (in whey)Test 8: Complex milk products (e.g. ice cream)Test 8: Complex milk products (e.g. ice cream)

42

Sequence of Testing:Sequence of Testing:WheatWheat

Test 1:Test 1: Pure cereal grain Pure cereal grain

Test 2:Test 2: Wheat Cracker without yeast Wheat Cracker without yeast

Test 3Test 3: White Bread: White Bread

Test 4Test 4: Whole Wheat Bread: Whole Wheat Bread

Maintenance DietMaintenance Diet

44

Final DietFinal Diet

Must exclude all foods and additives to which a Must exclude all foods and additives to which a positive reaction has been recordedpositive reaction has been recorded

Must be nutritionally complete, providing all Must be nutritionally complete, providing all macro and micro-nutrients from non-allergenic macro and micro-nutrients from non-allergenic sourcessources

There is no benefit from a rotation diet in There is no benefit from a rotation diet in the management of the management of food allergyfood allergy

A rotation diet may be beneficial when the A rotation diet may be beneficial when the condition is due to dose-dependent condition is due to dose-dependent food food intoleranceintolerance

45

Important Micronutrients in Common Allergenic Foods

Minerals Milk EggEgg PeanutPeanut Soy Fish WheatWheat RiceRice CornCorn

Calcium + + +

Phosphorus + + + + +

Iron + + + + + +

Zinc + + +

Magnesium + + +

Selenium + + +

Potassium + + +

Molybdenum +

Chromium + + +

Copper +

Manganese +

46

VitaminsMilk Egg Peanut Soy Fish Wheat Rice Corn

A + + +

Biotin + + +

Folacin (folate; folic acid) + + + +

B-1 (thiamin) + + + +

B-2 (riboflavin) + + + + + +

B-3 (niacin) + + + + +

B-5 (pantothenic acid) + + +

B-6 (pyridoxine) + + + +

B-12 (cobalamin) + + +

D + + +

E (alpha-tocopherol) + + + +

K + + +

Current Areas of ResearchCurrent Areas of Research

Promotion of Tolerance to FoodsPromotion of Tolerance to Foods

48

Prevention of Food Allergy in Clinical Prevention of Food Allergy in Clinical PracticePractice

Significant changeSignificant change in directives within the past 3 in directives within the past 3 years:years:

Previously: Previously: Avoidance of allergen to Avoidance of allergen to prevent prevent

sensitizationsensitization (allergen-specific IgE) (allergen-specific IgE) Current: Current:

Active stimulation of the immature Active stimulation of the immature immune system to immune system to induce toleranceinduce tolerance of the of the antigens in foodantigens in food

________________Rautava et al 2005

49

Diet During Pregnancy and Diet During Pregnancy and LactationLactation

There is no convincing evidence that women who There is no convincing evidence that women who avoid highly allergenic foods, or other foods during avoid highly allergenic foods, or other foods during pregnancy and breast-feeding lower their child’s risk pregnancy and breast-feeding lower their child’s risk of allergiesof allergies

Current directive: the atopic mother should strictly Current directive: the atopic mother should strictly avoid her own allergens and replace the foods with avoid her own allergens and replace the foods with nutritionally equivalent substitutesnutritionally equivalent substitutes

There are There are no indicationsno indications for mother to avoid other for mother to avoid other foods during pregnancyfoods during pregnancy

A nutritionally complete, well-balanced diet is A nutritionally complete, well-balanced diet is essentialessential

_______________Kramer et al 2006

50

Introduction of FishIntroduction of Fish

Historically, fish consumption during infancy was Historically, fish consumption during infancy was considered to be a risk factor for allergyconsidered to be a risk factor for allergy

Recent research indicates otherwise:Recent research indicates otherwise: Regular fish consumption during the first year of life Regular fish consumption during the first year of life

associated with a reduced risk for allergic disease by age 4 associated with a reduced risk for allergic disease by age 4 years (n=4089)years (n=4089)11

Babies of mothers who frequently consumed fish (2-3 Babies of mothers who frequently consumed fish (2-3 times per week or more) during pregnancy had one third times per week or more) during pregnancy had one third less food sensitivities than those whose mothers did not less food sensitivities than those whose mothers did not consume fish during pregnancyconsume fish during pregnancy22

_____________1Kull et al 2006

_______________2Calvani et al 2006

51

Introduction of FishIntroduction of Fish

Babies who were fed fish before nine months Babies who were fed fish before nine months of age were 24% less likely to develop eczema of age were 24% less likely to develop eczema by age 1 yearby age 1 year11

Children less likely to develop allergy to fish if Children less likely to develop allergy to fish if the mother consumes fish two or three times a the mother consumes fish two or three times a week during pregnancyweek during pregnancy22

Regular fish consumption during the first year Regular fish consumption during the first year of life was associated with a reduced risk for of life was associated with a reduced risk for allergic disease by age fourallergic disease by age four3 3

____________Alm et al 2009

_______________Calvani et al 2006

_____________Kull et al 2006

52

Recent Evidence for Early Recent Evidence for Early Introduction of SolidsIntroduction of Solids

Delaying initial exposure to cereal Delaying initial exposure to cereal grains until after 6 months may grains until after 6 months may increase the risk of wheat allergyincrease the risk of wheat allergy11

Research suggests that high risk for Research suggests that high risk for celiac disease occurs if gluten-celiac disease occurs if gluten-containing grains are introduced before containing grains are introduced before 3 months or after 7 months3 months or after 7 months22

_________________1Poole et al June 2006

______________2Norris et al 2005

53

Introduction of PeanutsIntroduction of PeanutsStudy (n=10,786) among primary school age Jewish Study (n=10,786) among primary school age Jewish

children in UK and Israelchildren in UK and Israel Prevalence of peanut allergy (PA):Prevalence of peanut allergy (PA):

In UK:In UK: 1.85%1.85% In Israel:In Israel: 0.17%0.17%

Median monthly consumption of peanut in infants Median monthly consumption of peanut in infants aged 8 – 14 months:aged 8 – 14 months: In UK:In UK: 00 In Israel:In Israel: 7.1 g7.1 g

Difference not due to atopy, genetic background, Difference not due to atopy, genetic background, social class, or peanut allergenicitysocial class, or peanut allergenicity

Israeli infants consume peanuts in high quantities Israeli infants consume peanuts in high quantities during the first year of lifeduring the first year of life

______________Du Toit et al 2008

54

Development of Development of ToleranceTolerance

25% of infants lost all food allergy 25% of infants lost all food allergy symptoms after 1 year of agesymptoms after 1 year of age

Most infants will outgrow milk allergy by Most infants will outgrow milk allergy by 3 years of age, but may have become 3 years of age, but may have become intolerant to other foods in the intolerant to other foods in the meantimemeantime

Tolerance of specific foods :Tolerance of specific foods :After 1 year:After 1 year: 26% decrease in allergy to:26% decrease in allergy to:

MilkMilk Soy Soy Peanut Peanut Egg Egg Wheat Wheat

2% decrease in allergy to other foods2% decrease in allergy to other foods________________Bishop et al 1990

55

PrognosisPrognosis Age at which milk was tolerated by milk-allergic Age at which milk was tolerated by milk-allergic

children:children: Diverse studies report different statisticsDiverse studies report different statistics

Allergy to some foods more often than others persists into Allergy to some foods more often than others persists into adulthood:adulthood:

PeanutPeanut Tree nuts Tree nuts ShellfishShellfish Fish Fish

28% by 2 years 28% by 2 years 11

56% by 4 years56% by 4 years

78% by 6 years78% by 6 years

56% at 1 year 56% at 1 year 22

77% at 2 years77% at 2 years

87% at 3 years87% at 3 years

19% by 4 years 19% by 4 years 33

42% by 8 years42% by 8 years

64% by 12 years64% by 12 years

79% by 16 years79% by 16 years

_______________________________________________________________________

1Bishop et al 1990 2Host and Halken 1990 3Skripak et al 2007

56

Induction of Oral ToleranceInduction of Oral Tolerance

Allergy to a specific food can be induced by Allergy to a specific food can be induced by oral administration of the offending food oral administration of the offending food (SOTI: specific oral tolerance induction)(SOTI: specific oral tolerance induction)

Starting with very low dosagesStarting with very low dosages Gradually increasing daily dosage up to the Gradually increasing daily dosage up to the

equivalent of the usual daily intakeequivalent of the usual daily intake Followed by daily maintenance doseFollowed by daily maintenance dose

__________________Niggemann et al 2006

57

Desensitization to Desensitization to Cow’s MilkCow’s Milk

18 children with confirmed CMA >4 years of age 18 children with confirmed CMA >4 years of age underwent SOTIunderwent SOTI

Starting dose 0.05 ml cow’s milkStarting dose 0.05 ml cow’s milk Increased to 1 ml on first dayIncreased to 1 ml on first day Increasing dosage weekly up to a daily dose of 200-Increasing dosage weekly up to a daily dose of 200-

250 ml250 ml Results: 16/18 tolerated 200-250 ml milkResults: 16/18 tolerated 200-250 ml milk Length of process median 14 weeks (range 11-17 Length of process median 14 weeks (range 11-17

weeks)weeks) Tolerance has been maintained for >1 yearTolerance has been maintained for >1 year_______________Zapatero et al 2008

58

Oral Tolerance Induction to Oral Tolerance Induction to Milk, Egg, and PeanutMilk, Egg, and Peanut

36% of children with IgE-mediated allergy to 36% of children with IgE-mediated allergy to cow’s cow’s milkmilk and and hen’s egghen’s egg developed permanent tolerance of developed permanent tolerance of the foods after a median 21 months specific oral the foods after a median 21 months specific oral tolerance induction (SOTI)tolerance induction (SOTI)11

4 peanut-allergic children underwent SOTI:4 peanut-allergic children underwent SOTI: Daily doses of Daily doses of peanut flourpeanut flour starting at 5 mg peanut protein starting at 5 mg peanut protein 2-weekly dosage increase up to 800 mg protein2-weekly dosage increase up to 800 mg protein All subjects tolerated at least 10 whole peanuts (2.38 g All subjects tolerated at least 10 whole peanuts (2.38 g

protein) on post-intervention challengeprotein) on post-intervention challenge22

______________1Staden et al 2007

____________22Clark et al 2009

59

Progression of Peanut AllergyProgression of Peanut Allergy

Peanut allergy, like many early food allergies, can be Peanut allergy, like many early food allergies, can be outgrownoutgrown

In 2001 pediatric allergists in the U.S. reported that In 2001 pediatric allergists in the U.S. reported that about 21.5 per cent of children will eventually about 21.5 per cent of children will eventually outgrow their peanut allergyoutgrow their peanut allergy11

Those with a mild peanut allergy, as determined by Those with a mild peanut allergy, as determined by the level of peanut-specific IgE in their blood, have a the level of peanut-specific IgE in their blood, have a 50% chance of outgrowing the allergy50% chance of outgrowing the allergy22

Only about 9% of patients are reported to outgrow Only about 9% of patients are reported to outgrow their allergy to tree nutstheir allergy to tree nuts33

__________________1Skolnick et al 20012Fleischer et al 20033Fleischer et al 2005

60

Maintaining Tolerance of PeanutMaintaining Tolerance of Peanut When there is no longer any evidence of When there is no longer any evidence of

symptoms developing after a child has consumed symptoms developing after a child has consumed peanuts, it is preferable for that child to peanuts, it is preferable for that child to eat eat peanuts regularlypeanuts regularly, rather than avoid them, in , rather than avoid them, in order to maintain tolerance to the peanutorder to maintain tolerance to the peanut

Children who outgrow peanut allergy are at risk Children who outgrow peanut allergy are at risk for recurrence, but the risk has been shown to be for recurrence, but the risk has been shown to be significantly higher for those who significantly higher for those who continue to continue to avoid peanutsavoid peanuts after resolution of their symptoms after resolution of their symptoms

_________________Fleischer et al 2004

61

SummarySummaryFood AllergyFood Allergy::

Immune system responseImmune system response

Food Intolerance:Food Intolerance: Usually metabolic dysfunctionUsually metabolic dysfunction

Diagnostic Laboratory TestsDiagnostic Laboratory Tests:: Often ambiguous because different physiological Often ambiguous because different physiological

mechanisms are involved in triggering symptomsmechanisms are involved in triggering symptoms

62

SummarySummary

Reliable testsReliable tests for the detection of for the detection of adverse reactions to foods:adverse reactions to foods:

Elimination and ChallengeElimination and Challenge

Final dietFinal diet

Must provide complete nutrition while Must provide complete nutrition while avoiding all of the foods and food avoiding all of the foods and food components that elicit symptoms on components that elicit symptoms on challengechallenge

63

SummarySummary

Recognition of development of toleranceRecognition of development of tolerance Periodic test and challenge after usually Periodic test and challenge after usually

several years of avoidance of allergenic several years of avoidance of allergenic foodfood

Maintenance of tolerance by regular Maintenance of tolerance by regular consumption of allergenic foodconsumption of allergenic food

Invitation to Further Invitation to Further InformationInformation

Website:Website:

www.allergynutrition.com

Janice Vickerstaff Joneja Ph.DJanice Vickerstaff Joneja Ph.D

The Health Professional’sThe Health Professional’s

Guide to Food AllergiesGuide to Food Allergies

and Intolerancesand IntolerancesAcademy of Nutrition andAcademy of Nutrition and

Dietetics. Chicago 2013Dietetics. Chicago 201364