diagnosis and dietary management of food allergy and intolerance

Diagnosis and Diagnosis and Dietary Management of Dietary Management of

Food Allergy and Food Allergy and IntoleranceIntolerance

Clinical PracticeClinical Practice

2

Major Allergenic FoodsMajor Allergenic Foods::Annex IIIa EU Directive on Labeling of Annex IIIa EU Directive on Labeling of

Foods Foods Which Must be DeclaredWhich Must be Declared Cereals containing glutenCereals containing gluten

CrustaceansCrustaceans EggsEggs FishFish PeanutsPeanuts SoybeansSoybeans Milk (including lactose)Milk (including lactose) NutsNuts CeleryCelery MustardMustard Sesame seedsSesame seeds Sulphur dioxide and sulphites at Sulphur dioxide and sulphites at

concentrations of more than 10mg/kg or 10 concentrations of more than 10mg/kg or 10 mg/litremg/litre

3

Priority Food Allergens In Priority Food Allergens In CanadaCanada

PeanutsPeanuts Tree nuts (almonds, Brazil nuts, cashews, Tree nuts (almonds, Brazil nuts, cashews,

hazelnuts (filberts), macadamia nuts, pecans, hazelnuts (filberts), macadamia nuts, pecans, pinenuts, pistachios, walnuts)pinenuts, pistachios, walnuts)

Sesame seedsSesame seeds MilkMilk EggsEggs Fish Fish Shellfish (e.g. clams, mussels, oysters, scallops Shellfish (e.g. clams, mussels, oysters, scallops

and crustaceans (e.g. crab, crayfish, lobster, and crustaceans (e.g. crab, crayfish, lobster, shrimp) )shrimp) )

SoySoy WheatWheat SulphitesSulphitesThese Priority Allergens account for more than These Priority Allergens account for more than

95% of severe adverse reactions related to 95% of severe adverse reactions related to food allergensfood allergens

4

U.S. Food and Drug AdministrationU.S. Food and Drug AdministrationFood Allergen Labeling and Consumer Food Allergen Labeling and Consumer

Protection ActProtection Act January 2006January 2006

MilkMilk EggEgg Fish (e.g., bass, flounder, or cod)Fish (e.g., bass, flounder, or cod) Crustacean shellfish (e.g., crab, lobster, or Crustacean shellfish (e.g., crab, lobster, or

shrimp)shrimp) Tree nuts (e.g., almonds, pecans, or walnuts)Tree nuts (e.g., almonds, pecans, or walnuts) WheatWheat PeanutsPeanuts SoybeansSoybeans

““These 8 major allergens account for 90 percent of food These 8 major allergens account for 90 percent of food allergiesallergies““

5

Additional Factors Involved in Additional Factors Involved in Symptoms of Food SensitivitySymptoms of Food Sensitivity

1.1. Increased permeability of the GI Increased permeability of the GI tracttract Inflammation:Inflammation:

InfectionInfection AllergyAllergy Autoimmune processesAutoimmune processes Other pathologyOther pathology

Immaturity (in infants)Immaturity (in infants) Alcohol ingestionAlcohol ingestion

2.2. Physical exertionPhysical exertion

6

Additional Factors Involved in Additional Factors Involved in Symptoms of Food SensitivitySymptoms of Food Sensitivity

3.3. StressStress

4.4. Level of inflammatory mediators Level of inflammatory mediators released in response to several released in response to several different foods concomitantlydifferent foods concomitantly

5.5. Level of inflammatory mediators Level of inflammatory mediators released in response to other released in response to other allergy (e.g. inhalant)allergy (e.g. inhalant)

Diagnosis of Diagnosis of Food AllergyFood Allergy

Detecting the Culprit Foods Detecting the Culprit Foods and Food Componentsand Food Components

8

Tests for Food Allergies:Tests for Food Allergies: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 Failure to recognize and treat genuine

diseasedisease Inappropriate and unbalanced dietsInappropriate and unbalanced diets MalnutritionMalnutrition

9

Consequences of Consequences of Mismanagement of Adverse Mismanagement of Adverse

Reactions to FoodsReactions to Foods Malnutrition; weight loss, due to extensive Malnutrition; weight loss, due to extensive

elimination dietselimination diets Especially critical in young children where Especially critical in young children where

nutritional deficiency at a crucial stage in nutritional deficiency at a crucial stage in development can cause permanent damagedevelopment can cause permanent damage

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

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

Disruption of lifestyle, social and family Disruption of lifestyle, social and family relationshipsrelationships

10

Risks associated with Risks associated with skin testsskin tests

High number of false positive and false High number of false positive and false negative testsnegative tests

Many allergists claim only 30% accuracy in Many allergists claim only 30% accuracy in identification of food components responsible identification of food components responsible for adverse reactionsfor adverse reactions

Danger of sensitisation to allergens through Danger of sensitisation to allergens through the skin:the skin: Initial exposure via the digestive tract most Initial exposure via the digestive tract most

likely to lead to tolerancelikely to lead to tolerance Initial exposure via the skin more likely to Initial exposure via the skin more likely to

lead to sensitization and initiation of allergylead to sensitization and initiation of allergy

Elimination and Challenge Protocols

12

Identification of Identification of Allergenic FoodsAllergenic Foods

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

teststests Long-term adherence to a restricted Long-term adherence to a restricted

diet diet should notshould not be advocated without be advocated without clear identification of the culprit food clear identification of the culprit food componentscomponents

13

Food Intolerance: Clinical Food Intolerance: Clinical DiagnosisDiagnosis

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

14

Elimination and Elimination and ChallengeChallenge

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 All foods, beverages, medications, and supplements ingestedsupplements ingested

Composition of compound dishes and Composition of compound dishes and drinks, including additives in manufactured drinks, including additives in manufactured foodsfoods

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

15

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 Was sleep disturbed during the night, and

if so, was it due to specific symptoms?if so, was it due to specific symptoms?

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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

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Selective Elimination Selective Elimination DietsDiets

Certain conditions tend to be associated with Certain conditions tend to be associated with specific food componentsspecific food components

Suspect food components are those that are Suspect food components are those that are probable triggers or mediators of symptomsprobable triggers or mediators of symptoms

Examples:Examples: Eczema: Eczema: Highly allergenic foodsHighly allergenic foods Migraine: Migraine: Biogenic aminesBiogenic amines Urticaria/angioedema: Urticaria/angioedema: HistamineHistamine Chronic diarrhea:Chronic diarrhea: DisaccharidesDisaccharides Asthma: Asthma: Cyclo-oxygenase inhibitors Cyclo-oxygenase inhibitors SulphitesSulphites Latex allergy:Latex allergy: Foods with structurally Foods with structurally similar similar

antigens to latexantigens to latex Oral allergy syndrome: Oral allergy syndrome: Foods with structurally Foods with structurally

similar antigens to pollenssimilar antigens to pollens

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Basic Hypoallergenic (“few Basic Hypoallergenic (“few foods”) Elimination Dietfoods”) Elimination Diet

Only listed foods are allowedOnly listed foods are allowed Nutritionally incompleteNutritionally incomplete Followed for maximum 10 daysFollowed for maximum 10 days

GRAINS:GRAINS: White riceWhite riceTapiocaTapioca

FRUITS:FRUITS: Pears; pear juicePears; pear juiceCranberries; cranberry juiceCranberries; cranberry juice

VEGETABLES:VEGETABLES: Squash (all varieties)Squash (all varieties)CarrotsCarrotsParsnipsParsnipsLettuceLettuce

MEAT:MEAT: LambLambWild gameWild gameTurkeyTurkey

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Basic Hypoallergenic (Basic Hypoallergenic (““few foodsfew foods”)”)Elimination Diet Elimination Diet (continued(continued ) )

MEAT MEAT Lentils Lentils SUBSTITUTES:SUBSTITUTES: Split peasSplit peas

Garbanzo beans (chick peas)Garbanzo beans (chick peas)

FLAVOURINGS:FLAVOURINGS: Sea saltSea salt

BEVERAGES:BEVERAGES: Distilled water in glass containersDistilled water in glass containers

OILSOILS Canola oil Canola oil oror olive oil olive oilSafflower oilSafflower oil

OTHEROTHER Agar-agarAgar-agar (Make jelly dessert with pears and (Make jelly dessert with pears and

pear juice)pear juice)

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Expected Results of Expected Results of Elimination DietElimination Diet

Symptoms often worsen on days Symptoms often worsen on days 2-4 of elimination2-4 of elimination

By day 5-7 symptomatic By day 5-7 symptomatic improvement is experiencedimprovement is experienced

Symptoms disappear after 10-Symptoms disappear after 10-14 days of exclusion14 days of exclusion

21

ChallengeChallenge

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

in gelatin capsulesin gelatin capsules Identical gelatin capsules contain a placebo Identical gelatin capsules contain a placebo

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

knows the identity of the contents of the knows the identity of the contents of the capsulescapsules

Positive test is when the food triggers Positive test is when the food triggers symptoms and the placebo does notsymptoms and the placebo does not

22

ChallengeChallenge (continued) (continued)

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

food to elicit a positive reactionfood to elicit a positive reaction May be other factors involved in May be other factors involved in

eliciting symptoms, e.g. taste eliciting symptoms, e.g. taste and smelland smell

23

Challenge Challenge (continued)(continued)

Single-blind food challenge (SBFC)Single-blind food challenge (SBFC)Supervisor knows the identity of Supervisor knows the identity of the food; patient does notthe food; patient does not

Food is disguised in a strong-Food is disguised in a strong-tasting “inert” food tolerated by tasting “inert” food tolerated by the patient:the patient:

lentil souplentil soup apple sauceapple sauce tomato sauce tomato sauce

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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 Starting with a small quantity and increasing

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

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

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

25

Open Food ChallengeOpen Food Challenge The basic elimination diet, or therapeutic The basic elimination diet, or therapeutic

diet continues during this phasediet continues during this phase

If an adverse reaction to the test food If an adverse reaction to the test food occurs at any time during the test occurs at any time during the test STOP. Do not continue to eat the test STOP. Do not continue to eat the test foodfood

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

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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 Wait four hours, monitoring for adverse reactionreaction

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

eaten in the morningeaten in the morning

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

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

eaten in the afternooneaten in the afternoon

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Incremental Dose Incremental Dose ChallengeChallenge (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 Continue to eat basic elimination

dietdiet Monitor for any adverse reactions Monitor for any adverse reactions

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

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

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

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Sequential Incremental Dose Sequential Incremental Dose ChallengeChallenge

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

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

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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 Test 4: Lactose in addition to casein and

whey 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 Test 8: Complex milk products (e.g. ice

cream)cream)

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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

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Sequence of Testing:Sequence of Testing:RyeRye

RyeRye: Test as for wheat:: Test as for wheat: Test 1Test 1. Rye Flakes (cooked). Rye Flakes (cooked)

Test 2.Test 2. Rye Cracker (Ryvita Rye Cracker (Ryvita™™ (wheat- (wheat-free) or Wasafree) or Wasa™ ™ (light)(light)

Test 3Test 3. Rye Bread (100% rye flour, . Rye Bread (100% rye flour, wheat-free)wheat-free)

33

Sequence of Testing:Sequence of Testing:CornCorn

Test 1:Test 1: pure grainpure grain corn-on-the-cobcorn-on-the-cob frozen corn niblets:frozen corn niblets:

Test 2:Test 2: corn oilcorn oil added to tolerated foodadded to tolerated food

Test 3Test 3: : corn syrupcorn syrup added to tolerated foodadded to tolerated food

34

Sequence of Testing:Sequence of Testing:Alcoholic beveragesAlcoholic beverages

Test 1Test 1. Distilled alcohol (t. Distilled alcohol (tequila; vodka; gin; equila; vodka; gin; white rum)white rum)

enhanced antigen uptakeenhanced antigen uptake Test 2. Test 2. White wine White wine

biogenic amines, especially histaminebiogenic amines, especially histamine Test 3Test 3. Red wine . Red wine

biogenic amines, especially tyraminebiogenic amines, especially tyramine Test 4. Test 4. Beer, ale, lagerBeer, ale, lager

fermented grainsfermented grains Test 5.Test 5. Cider Cider

fermented apple, pear, peach, etc.fermented apple, pear, peach, etc.

35

Sequence of Testing:Sequence of Testing:ChocolateChocolate

Test 1Test 1 : Unsweetened (“bitter”) baker’s : Unsweetened (“bitter”) baker’s chocolatechocolate

Melt and add honey (if tolerated) as Melt and add honey (if tolerated) as a sweetenera sweetener

Solidify on a flat surface (e.g. baking Solidify on a flat surface (e.g. baking sheet)sheet)

Break into squaresBreak into squares Test: 1, 2, 4 squaresTest: 1, 2, 4 squares

Test 2Test 2: Purchased chocolates: Purchased chocolates

Maintenance DietMaintenance Diet

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Final DietFinal Diet

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

Must be nutritionally complete, providing Must be nutritionally complete, providing nutrients from non-allergenic sourcesnutrients from non-allergenic sources

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 There is no indication of any benefit from There is no indication of any benefit from

a rotation diet in the management of a rotation diet in the management of food food allergyallergy

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Important Nutrients in Important Nutrients in Common AllergensCommon Allergens

Equivalent nutrients must be provided Equivalent nutrients must be provided from alternative sources when the from alternative sources when the following foods are eliminated from the following foods are eliminated from the diet:diet:

Milk and Milk ProductsMilk and Milk Products::

CalciumCalcium Riboflavin Riboflavin Smaller amounts:Smaller amounts:PhosphorusPhosphorus PotassiumPotassium Vitamin A* Vitamin A* Vitamin D*Vitamin D* Vitamin E Vitamin EVitamin B12 Vitamin B12 Pantothenic acid Pantothenic acid

*Usually added as fortification to the food product *Usually added as fortification to the food product

39


EggEgg::

Vitamin B12Vitamin B12 Folacin Folacin Smaller Smaller amounts:amounts:

Vitamin DVitamin D RiboflavinRiboflavinVitamin AVitamin A

Pantothenic acidPantothenic acid SeleniumSelenium Vitamin EVitamin E

BiotinBiotin IronIron Vitamin B6Vitamin B6

ZincZinc

40


WheatWheat::Thiamin*Thiamin* Smaller amounts:Smaller amounts:

Riboflavin*Riboflavin* MagnesiumMagnesium

Niacin*Niacin* FolacinFolacin

Iron*Iron* PhosphorousPhosphorous

SeleniumSelenium MolybdenumMolybdenum

Chromium Chromium

RiceRice::Thiamin* Thiamin* Niacin*Niacin*

Riboflavin* Riboflavin* Iron*Iron*

41


PeanutPeanut::NiacinNiacin Magnesium Magnesium Smaller amounts Smaller amounts

Pantothenic acid Pantothenic acid Manganese Manganese FolacinFolacin

Vitamin EVitamin E Chromium Chromium BiotinBiotin

Vitamin B6Vitamin B6

CopperCopper

PhosphorousPhosphorous

PotassiumPotassium

SoybeanSoybean::Thiamin Thiamin Folacin Folacin PhosphorousPhosphorous

Riboflavin Riboflavin Calcium Calcium MagnesiumMagnesium

Vitamin B6Vitamin B6 IronIron ZincZinc

42


Fish and ShellfishFish and Shellfish::

NiacinNiacin PhosphorousPhosphorous

Vitamin B6Vitamin B6 Calcium (in shellfish and fish bones)Calcium (in shellfish and fish bones)

Vitamin B12Vitamin B12 SeleniumSelenium

Vitamin EVitamin E

Smaller amounts:Smaller amounts:

PotassiumPotassium IronIron Vitamin AVitamin A

MagnesiumMagnesium ZincZinc

Current Areas of Current Areas of ResearchResearch

1.1. Promotion of Tolerance to Promotion of Tolerance to FoodsFoods

2.2. Probiotics and Food Probiotics and Food AllergyAllergy

44

Recommendations for Recommendations for Introduction of Solids to High Introduction of Solids to High

Risk for Allergy InfantsRisk for Allergy Infants Most recent US consensus document Most recent US consensus document

recommends for infant at risk for recommends for infant at risk for allergy:allergy: Exclusive breast-feeding from birth to six Exclusive breast-feeding from birth to six

monthsmonths Optimal age for introduction of solids is Optimal age for introduction of solids is

six monthssix months Dairy products introduced at 12 monthsDairy products introduced at 12 months Eggs at 24 monthsEggs at 24 months Peanut, tree nuts, fish, seafood delayed Peanut, tree nuts, fish, seafood delayed

until at least 36 monthsuntil at least 36 months__________________Fiocchi et al July 2006

45

Pregnancy Diet and Fish Pregnancy Diet and Fish IntakeIntake

2006 study2006 study Frequent maternal intake (2–3 times/wk or Frequent maternal intake (2–3 times/wk or

more) of fish reduced the risk of food more) of fish reduced the risk of food sensitizations by over a thirdsensitizations by over a third

A similar trend (not significant) was found A similar trend (not significant) was found for inhalant allergiesfor inhalant allergies

In the In the whole study populationwhole study population, i.e. allergic , i.e. allergic group plus non-allergic group: correlation group plus non-allergic group: correlation between increased consumption of fish between increased consumption of fish and decreased prevalence of SPT positivity and decreased prevalence of SPT positivity for foodsfor foods

Reduced incidence of allergic sensitization Reduced incidence of allergic sensitization thought to be due to the omega-3 content thought to be due to the omega-3 content of fishof fish_______________

Calvani et al 2006

46

Recent Evidence for Early Recent Evidence for Early Introduction of Solids?Introduction of Solids?

““Delaying initial exposure to cereal grains until after Delaying initial exposure to cereal grains until after 6 months may increase the risk of wheat allergy”6 months may increase the risk of wheat allergy”11

Based on questionnaires and parental report of Based on questionnaires and parental report of wheat allergywheat allergy

Excluded children with celiac diseaseExcluded children with celiac disease 16 children reported to have wheat allergy by 16 children reported to have wheat allergy by

parentsparents Four had wheat-specific IgEFour had wheat-specific IgE These four were reported to have been first exposed These four were reported to have been first exposed

to wheat grains after 6 months of ageto wheat grains after 6 months of age

Previous studies:Previous studies: ““The possibility of cereal allergy after the The possibility of cereal allergy after the

introduction of cereal formula during the introduction of cereal formula during the lactation period should not be lactation period should not be underestimated”underestimated”2 2

_________________1Poole et al June 2006

________________2Armentia et al 2002

47

Introduction of Solid Foods in Introduction of Solid Foods in RelationshipRelationship

to Celiac Disease to Celiac Disease

Concept of “window of opportunity”Concept of “window of opportunity”

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

Final conclusions:Final conclusions: ““Current infant feeding practices Current infant feeding practices

should not be changed”should not be changed”_______________Norris et al 2005

48

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

49

PrognosisPrognosis

Age at which milk was tolerated by milk-Age at which milk was tolerated by milk-allergic children:allergic children: 28% by 2 years of age28% by 2 years of age 56% by 4 years of age56% by 4 years of age 78% by 6 years of age78% by 6 years of age

About 25% of allergic children develop About 25% of allergic children develop respiratory allergiesrespiratory allergies

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

PeanutPeanut Tree nuts Tree nuts

ShellfishShellfish FishFish

50

Progression of Peanut AllergyProgression of Peanut Allergy Peanut allergy, like many early food Peanut allergy, like many early food

allergies, can be outgrownallergies, can be outgrown In 2001 pediatric allergists in the U.S. In 2001 pediatric allergists in the U.S.

reported that about 21.5 per cent of reported that about 21.5 per cent of children will eventually outgrow their children will eventually outgrow their peanut allergypeanut allergy11

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

Only about 9% of patients are reported to Only about 9% of patients are reported to outgrow their allergy to tree nutsoutgrow their allergy to tree nuts33__________________

1Skolnick et al 20012Fleischer et al 20033Fleischer et al 2005

51

Maintaining Tolerance of Maintaining Tolerance of PeanutPeanut

When there is no longer any evidence of When there is no longer any evidence of symptoms developing after a child has symptoms developing after a child has consumed peanuts, it is preferable for consumed peanuts, it is preferable for that child to that child to eat peanuts regularlyeat peanuts regularly, rather , rather than avoid them, in order to maintain than avoid them, in order to maintain tolerance to the peanuttolerance to the peanut

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

_________________Fleischer et al 2004

52

ProbioticsProbioticsMicroorganisms in the BowelMicroorganisms in the Bowel

The healthy large bowel sustains a The healthy large bowel sustains a resident microbiota of bacteria, fungi, and resident microbiota of bacteria, fungi, and other harmless microorganismsother harmless microorganisms

Beneficial effects include:Beneficial effects include: Synthesis of vitamins:Synthesis of vitamins:

Vitamin KVitamin K BiotinBiotin ThiaminThiamin Folic acidFolic acid Vitamin B12Vitamin B12

Interaction with immune cells to maintain a Interaction with immune cells to maintain a healthy epitheliumhealthy epithelium

Positive competition with invading pathogens Positive competition with invading pathogens to resist diseaseto resist disease

53

Bowel Microflora and AllergyBowel Microflora and Allergy

The type of gut colonization during the first The type of gut colonization during the first weeks of life may predispose an individual to weeks of life may predispose an individual to atopic diseaseatopic disease

Microflora of the bowel of a breastfed infant is Microflora of the bowel of a breastfed infant is different from that of a formula-fed babydifferent from that of a formula-fed baby

The gut microflora influences:The gut microflora influences: Resistance to infectionResistance to infection Immunological environment for subsequent Immunological environment for subsequent

challenges, including food allergenschallenges, including food allergens May influence predominance of Th1 or Th2 May influence predominance of Th1 or Th2

responseresponse_________________Kirjavainen et al 1999

54

Clinical Trials of ProbioticsClinical Trials of Probiotics Not all probiotics have been tested in Not all probiotics have been tested in

clinical studies with regard to allergy clinical studies with regard to allergy prevention or treatment prevention or treatment

L. bulgaricusL. bulgaricus seemed to have no effect seemed to have no effect on immune parameters, whereas it was on immune parameters, whereas it was associated with lower frequency of associated with lower frequency of allergiesallergies

L. acidophilusL. acidophilus consumption accelerated consumption accelerated recovery from food allergy symptomsrecovery from food allergy symptoms

These effects have also been observed in These effects have also been observed in infants with eczema and cow's milk infants with eczema and cow's milk allergy using infant formulas allergy using infant formulas supplemented with supplemented with L. rhamnosusL. rhamnosus. .

55

Trials on Probiotics and Eczema Trials on Probiotics and Eczema PreventionPrevention

Pregnant women took capsules containing Pregnant women took capsules containing Lactobacillus rhamnosusLactobacillus rhamnosus GG GG (LGG) during the (LGG) during the last two to four weeks of pregnancylast two to four weeks of pregnancy

The newborn infants were given the same The newborn infants were given the same microorganism from birth to six monthsmicroorganism from birth to six months

Breast-feeding mothers continued to take the Breast-feeding mothers continued to take the capsules during lactationcapsules during lactation

The babies were given the bacteria mixed with The babies were given the bacteria mixed with water by spoonwater by spoon

Subjects taking the probiotic had a Subjects taking the probiotic had a reduced risk of developing atopic reduced risk of developing atopic dermatitis (eczema) compared to dermatitis (eczema) compared to controls up to 4 years of age controls up to 4 years of age

Other studies found no reduced incidence of Other studies found no reduced incidence of eczema in babies treated with probioticseczema in babies treated with probiotics

__________________________________Kalliomaki et al 2003Kalliomaki et al 2003

56

Probiotics and Lactose Probiotics and Lactose IntoleranceIntolerance

Lactobacilli, bifidobacteria and Lactobacilli, bifidobacteria and Streptococcus thermophilusStreptococcus thermophilus, assist in , assist in reducing the symptoms of lactose intolerancereducing the symptoms of lactose intolerance

Produce the enzyme beta-galactosidase Produce the enzyme beta-galactosidase (lactase) in yogurt(lactase) in yogurt

Microbial lactase breaks down lactoseMicrobial lactase breaks down lactose The fermented milk itself delays The fermented milk itself delays

gastrointestinal transit, thus allowing a gastrointestinal transit, thus allowing a longer period of time in which both the longer period of time in which both the human and microbial lactase enzyme can act human and microbial lactase enzyme can act on the milk lactose. on the milk lactose.

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Microflora and Lactose IntoleranceMicroflora and Lactose Intolerance Lactose tolerance in people who are deficient Lactose tolerance in people who are deficient

in lactase may be improved by continued in lactase may be improved by continued ingestion of small quantities of milkingestion of small quantities of milk

Does not improve or affect the production of Does not improve or affect the production of lactase in the brush border cells of the small lactase in the brush border cells of the small intestineintestine

Continued presence of lactose in the colon Continued presence of lactose in the colon contributes to the establishment and contributes to the establishment and multiplication of bacteria capable of multiplication of bacteria capable of synthesizing the beta-galactosidase enzyme synthesizing the beta-galactosidase enzyme over timeover time

Resident micro-organisms will break down Resident micro-organisms will break down the undigested lactose in the colonthe undigested lactose in the colon

Reduces the osmotic imbalance within the Reduces the osmotic imbalance within the colon that is the cause of much of the colon that is the cause of much of the distress of lactose intolerance distress of lactose intolerance __________________________________

de Vrese et al 2001de Vrese et al 2001

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Status of Probiotics as TherapyStatus of Probiotics as Therapy

Great care must be taken in transferring Great care must be taken in transferring data from laboratory and experimental data from laboratory and experimental animal studies into human useanimal studies into human use

Applies also to the use of known Applies also to the use of known probiotics, some of which are already probiotics, some of which are already present in human nutrition, such as present in human nutrition, such as yoghurtyoghurt

Not all strains of bacteria in use as Not all strains of bacteria in use as probiotics are completely harmlessprobiotics are completely harmless

Their immune-modifying effects and Their immune-modifying effects and possible antiallergic and anti-cancer possible antiallergic and anti-cancer actions require large clinical studiesactions require large clinical studies

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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 Often ambiguous because different

physiological mechanisms are involved in physiological mechanisms are involved in triggering symptomstriggering symptoms

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SummarySummary

Reliable testsReliable tests for the detection of for the detection of adverse food reactions:adverse food reactions:

Elimination and ChallengeElimination and ChallengeRestrict Restrict elimination phase before elimination phase before

challenge to a maximum of:challenge to a maximum of:• four weeks four weeks for selective elimination dietsfor selective elimination diets• two weekstwo weeks for a few foods elimination diet for a few foods elimination diet

Final dietFinal dietMust provide complete nutritionMust provide complete nutrition while avoiding all of the foods and foodwhile avoiding all of the foods and food components that elicit symptoms on components that elicit symptoms on

challengechallenge

diagnosis and dietary management of food allergy and intolerance

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