Transcript Lecture-4-Diagnosis-and-Dietary-Management-of-Food

Diagnosis and
Dietary Management of Food
Allergy and Intolerance
Clinical Practice
Major Allergenic Foods:
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Annex IIIa EU Directive on Labeling of Foods
Which Must be Declared
Cereals containing gluten
Crustaceans
Eggs
Fish
Peanuts
Soybeans
Milk (including lactose)
Nuts
Celery
Mustard
Sesame seeds
Sulphur dioxide and sulphites at concentrations of more
than 10mg/kg or 10 mg/litre
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Priority Food Allergens In Canada
Peanuts
 Tree nuts (almonds, Brazil nuts, cashews, hazelnuts
(filberts), macadamia nuts, pecans, pinenuts, pistachios,
walnuts)
 Sesame seeds
 Milk
 Eggs
 Fish
 Shellfish (e.g. clams, mussels, oysters, scallops and
crustaceans (e.g. crab, crayfish, lobster, shrimp) )
 Soy
 Wheat
 Sulphites
These Priority Allergens account for more than 95% of
severe adverse reactions related to food allergens
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U.S. Food and Drug Administration
Food Allergen Labeling and Consumer Protection Act January
2006
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Milk
Egg
Fish (e.g., bass, flounder, or cod)
Crustacean shellfish (e.g., crab, lobster, or shrimp)
Tree nuts (e.g., almonds, pecans, or walnuts)
Wheat
Peanuts
Soybeans
“These 8 major allergens account for 90 percent of food allergies“
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Additional Factors Involved in
Symptoms of Food Sensitivity
1. Increased permeability of the GI tract
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Inflammation:
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Infection
Allergy
Autoimmune processes
Other pathology
Immaturity (in infants)
Alcohol ingestion
2. Physical exertion
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Additional Factors Involved in Symptoms of
Food Sensitivity
3. Stress
4. Level of inflammatory mediators
released in response to several different
foods concomitantly
5. Level of inflammatory mediators
released in response to other allergy (e.g.
inhalant)
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Diagnosis of Food
Allergy
Detecting the Culprit Foods and Food
Components
Tests for Food Allergies:
Drawbacks of Unreliable Tests
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Diagnostic inaccuracy
Therapeutic failure
False diagnosis of allergy
Creation of fictitious disease entities
Failure to recognize and treat genuine disease
Inappropriate and unbalanced diets
Malnutrition
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Consequences of Mismanagement of
Adverse Reactions to Foods
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Malnutrition; weight loss, due to extensive elimination
diets
Especially critical in young children where nutritional
deficiency at a crucial stage in development can cause
permanent damage
Food phobia due to fear that “the wrong food” will
cause permanent damage, and in extreme cases, death
Frustration and anger with the “medical system” that is
perceived as failing them
Disruption of lifestyle, social and family relationships
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Risks associated with skin tests
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High number of false positive and false negative tests
Many allergists claim only 30% accuracy in
identification of food components responsible for
adverse reactions
Danger of sensitisation to allergens through the skin:
 Initial exposure via the digestive tract most likely to
lead to tolerance
 Initial exposure via the skin more likely to lead to
sensitization and initiation of allergy
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Elimination and Challenge Protocols
Identification of Allergenic Foods
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Removal of the suspect foods from the
diet, followed by reintroduction is the
only way to:
 Identify the culprit food components
 Confirm the accuracy of any allergy
tests
Long-term adherence to a restricted diet
should not be advocated without clear
identification of the culprit food
components
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Food Intolerance: Clinical Diagnosis
Elimination Diet: Avoid Suspect Food
Increase Restrictions
Symptoms Disappear
Symptoms Persist
Reintroduce Foods Sequentially or Double-blind
Symptoms Provoked
Diagnosis Confirmed
No Symptoms
Diagnosis Not Confirmed
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Elimination and Challenge
Stage 1: Exposure Diary
 Record each day, for a minimum of 5-7 days:
All foods, beverages, medications, and supplements
ingested
 Composition of compound dishes and drinks,
including additives in manufactured foods
 Approximate quantities of each
 The time of consumption
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Exposure Diary (continued)
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All symptoms graded on severity:
 1 (mild);
 3 (moderate)
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Time of onset
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How long they last
 2 (mild-moderate)
 4 (severe)
Record status on waking in the morning.
Was sleep disturbed during the night, and if so, was
it due to specific symptoms?
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Elimination Diet
Based on:
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Detailed medical history
Analysis of Exposure Diary
Any previous allergy tests
Foods suspected by the patient
Formulate diet to exclude all suspect allergens and
intolerance triggers
Provide excluded nutrients from alternative sources
Duration: Usually four weeks
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Selective Elimination Diets
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Certain conditions tend to be associated with specific
food components
Suspect food components are those that are
probable triggers or mediators of symptoms
Examples:
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Eczema:
Migraine:
Urticaria/angioedema:
Chronic diarrhea:
Asthma:
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Latex allergy:
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Oral allergy syndrome:
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Highly allergenic foods
Biogenic amines
Histamine
Disaccharides
Cyclo-oxygenase inhibitors
Sulphites
Foods with structurally
similar antigens to latex
Foods with structurally
similar antigens to pollens
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Basic Hypoallergenic (“few foods”)
Elimination Diet
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Only listed foods are allowed
Nutritionally incomplete
Followed for maximum 10 days
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GRAINS:
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FRUITS:
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VEGETABLES:
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MEAT:
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White rice
Tapioca
Pears; pear juice
Cranberries; cranberry juice
Squash (all varieties)
Carrots
Parsnips
Lettuce
Lamb
Wild game
Turkey
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Basic Hypoallergenic (“few foods”)
Elimination Diet (continued )
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MEAT
SUBSTITUTES:
Lentils
Split peas
Garbanzo beans (chick peas)
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FLAVOURINGS:
Sea salt
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BEVERAGES:
Distilled water in glass containers
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OILS
Canola oil or olive oil
Safflower oil
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OTHER
Agar-agar
(Make jelly dessert with pears and pear juice)
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Expected Results of Elimination Diet
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Symptoms often worsen on days 2-4 of
elimination
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By day 5-7 symptomatic improvement is
experienced
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Symptoms disappear after 10-14 days of
exclusion
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Challenge
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Double-blind Placebo-controlled Food Challenge
(DBPCFC)
 Lyophilized (freeze-dried) food is disguised in gelatin
capsules
 Identical gelatin capsules contain a placebo (glucose
powder)
 Neither the patient nor the supervisor knows the
identity of the contents of the capsules
 Positive test is when the food triggers symptoms and
the placebo does not
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Challenge (continued)
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Drawback of DBPCFC
 Expensive in time and personnel
 Capsule may not provide enough food to
elicit a positive reaction
 May be other factors involved in eliciting
symptoms, e.g. taste and smell
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Challenge (continued)
 Single-blind
food challenge (SBFC)
 Supervisor knows the identity of the
food; patient does not
 Food is disguised in a strong-tasting
“inert” food tolerated by the patient:
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lentil soup
apple sauce
tomato sauce
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Challenge Phase
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continued
Open food challenge
 Sequential Incremental Dose Challenge (SIDC)
 Each food component is introduced separately
 Starting with a small quantity and increasing the
amount according to a specific schedule
 This is usually employed when the symptoms are
mild, and the patient has eaten the food in the
past without a severe reaction
Any food suspected to cause a severe or anaphylactic reaction
should only be challenged in suitably equipped medical facility
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Open Food Challenge
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The basic elimination diet, or therapeutic diet continues
during this phase
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If an adverse reaction to the test food occurs at
any time during the test STOP. Do not continue to
eat the test food
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Wait 48 hours after all symptoms have subsided
before testing another food
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Incremental Dose Challenge
Day 1: Consume test food between meals
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Morning: Eat a small quantity of the test food
Wait four hours, monitoring for adverse reaction
If no symptoms:
Afternoon: Eat double the quantity of test food eaten in
the morning
Wait four hours, monitoring for adverse reaction
If no symptoms:
Evening: Eat double the quantity of test food eaten in
the afternoon
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Incremental Dose Challenge
(continued)
Day 2:
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Do not eat any of the test food
Continue to eat basic elimination diet
Monitor for any adverse reactions during the
night and day which may be due to a delayed
reaction to the test food
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Incremental Dose Challenge
(continued)
Day 3:
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If no adverse reactions experienced
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proceed to testing a new food, starting Day 1
If the results of Day 1 and/or Day 2 are unclear :
 Repeat Day 1, using the same food, the same test
protocol, but larger doses of the test food
Day 4:
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Monitor for delayed reactions as on Day 2
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Sequential Incremental Dose Challenge
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Continue testing in the same manner until all
excluded foods, beverages, and additives have
been tested
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For each food component, the first day is the
test day, and the second is a monitoring day for
delayed reactions
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Sequence of Testing
Milk and Milk Products
Test 1: Casein proteins
Test 2: Annatto, biogenic amines, plus casein
Test 3: Casein plus whey proteins
Test 4: Lactose in addition to casein and whey
proteins
Test 5: Modified milk components
Test 6: Whey proteins (lactose-free)
Test 7: Lactose (in whey)
Test 8: Complex milk products (e.g. ice cream)
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Sequence of Testing:
Wheat
Test 1: Pure cereal grain
Test 2: Wheat Cracker without yeast
Test 3: White Bread
Test 4: Whole Wheat Bread
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Sequence of Testing:
Rye
Rye: Test as for wheat:
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Test 1. Rye Flakes (cooked)
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Test 2. Rye Cracker (Ryvita™ (wheat-free) or
Wasa™ (light)
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Test 3. Rye Bread (100% rye flour, wheat-free)
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Sequence of Testing:
Corn
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Test 1: pure grain
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corn-on-the-cob
frozen corn niblets:
Test 2: corn oil
 added to tolerated food
Test 3: corn syrup
 added to tolerated food
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Sequence of Testing:
Alcoholic beverages
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Test 1. Distilled alcohol (tequila; vodka; gin; white rum)
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Test 2. White wine
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biogenic amines, especially tyramine
Test 4. Beer, ale, lager
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biogenic amines, especially histamine
Test 3. Red wine
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enhanced antigen uptake
fermented grains
Test 5. Cider
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fermented apple, pear, peach, etc.
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Sequence of Testing:
Chocolate
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Test 1 : Unsweetened (“bitter”) baker’s chocolate
 Melt and add honey (if tolerated) as a
sweetener
 Solidify on a flat surface (e.g. baking sheet)
 Break into squares
 Test: 1, 2, 4 squares
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Test 2: Purchased chocolates
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Maintenance Diet
Final Diet
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Must exclude all foods and additives to which a
positive reaction has been recorded
Must be nutritionally complete, providing
nutrients from non-allergenic sources
A rotation diet may be beneficial when the
condition is due to dose-dependent food intolerance
 There is no indication of any benefit from a
rotation diet in the management of food allergy
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Important Nutrients in Common
Allergens
Equivalent nutrients must be provided from
alternative sources when the following foods are
eliminated from the diet:
Milk and Milk Products:
Calcium
Phosphorus
Vitamin D*
Vitamin B12
Pantothenic acid
Riboflavin
Potassium
Smaller amounts:
Vitamin A*
Vitamin E
*Usually added as fortification to the food product
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Important Nutrients in Common
Allergens
Egg:
Vitamin B12
Vitamin D
Pantothenic acid
Biotin
Folacin
Riboflavin
Selenium
Iron
Smaller amounts:
Vitamin A
Vitamin E
Vitamin B6
Zinc
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Important Nutrients in Common
Allergens
Wheat:
Thiamin*
Riboflavin*
Niacin*
Iron*
Selenium
Chromium
Smaller amounts:
Magnesium
Folacin
Phosphorous
Molybdenum
Rice:
Thiamin*
Riboflavin*
Niacin*
Iron*
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Important Nutrients in Common
Allergens
Peanut:
Niacin
Pantothenic acid
Vitamin E
Magnesium
Manganese
Chromium
Smaller amounts
Folacin
Biotin
Vitamin B6
Copper
Phosphorous
Potassium
Soybean:
Thiamin
Riboflavin
Vitamin B6
Folacin
Phosphorous
Calcium Magnesium
Iron
Zinc
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Important Nutrients in Common
Allergens
Fish and Shellfish:
Niacin
Vitamin B6
Vitamin B12
Vitamin E
Smaller amounts:
Potassium
Magnesium
Phosphorous
Calcium (in shellfish and fish bones)
Selenium
Iron
Zinc
Vitamin A
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Current Areas of Research
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Promotion of Tolerance to Foods
Probiotics and Food Allergy
Recommendations for Introduction of
Solids to High Risk for Allergy Infants
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Most recent US consensus document
recommends for infant at risk for allergy:
Exclusive breast-feeding from birth to six
months
 Optimal age for introduction of solids is six
months
 Dairy products introduced at 12 months
 Eggs at 24 months
 Peanut, tree nuts, fish, seafood delayed until at
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least 36 months
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Fiocchi et al July 2006
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Pregnancy Diet and Fish Intake
2006 study
 Frequent maternal intake (2–3 times/wk or more)
of fish reduced the risk of food sensitizations by
over a third
 A similar trend (not significant) was found for
inhalant allergies
 In the whole study population, i.e. allergic group plus
non-allergic group: correlation between increased
consumption of fish and decreased prevalence of
SPT positivity for foods
 Reduced incidence of allergic sensitization thought
to be due to the omega-3 content of fish
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Calvani et al 2006
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Recent Evidence for Early Introduction of
Solids?
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“Delaying initial exposure to cereal grains until after 6
months may increase the risk of wheat allergy”1
Based on questionnaires and parental report of wheat allergy
Excluded children with celiac disease
16 children reported to have wheat allergy by parents
Four had wheat-specific IgE
These four were reported to have been first exposed to
wheat grains after 6 months of age
Previous studies:
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“The possibility of cereal allergy after the
introduction of cereal formula during the lactation
period should not be underestimated”2
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1Poole et al June 2006
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2Armentia et al 2002
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Introduction of Solid Foods in Relationship
to Celiac Disease
Concept of “window of opportunity”
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Research suggests that high risk for celiac disease
occurs if gluten-containing grains are introduced before
3 months or after 7 months
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Final conclusions:
 “Current infant feeding practices should not be
changed”
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Norris et al 2005
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Development of Tolerance
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25% of infants lost all food allergy symptoms after
1 year of age
Most infants will outgrow milk allergy by 3 years
of age, but may have become intolerant to other
foods in the meantime
Tolerance of specific foods :
After 1 year:
 26% decrease in allergy to:
Milk
 Egg
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Soy
Wheat
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Peanut
2% decrease in allergy to other foods
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Bishop et al 1990
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Prognosis
Age at which milk was tolerated by milk-allergic
children:
 28% by 2 years of age
 56% by 4 years of age
 78% by 6 years of age
 About 25% of allergic children develop
respiratory allergies
 Allergy to some foods more often than others
persists into adulthood:
 Peanut
 Tree nuts
 Shellfish
 Fish
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Progression of Peanut Allergy
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Peanut allergy, like many early food allergies, can be
outgrown
In 2001 pediatric allergists in the U.S. reported that
about 21.5 per cent of children will eventually outgrow
their peanut allergy1
Those with a mild peanut allergy, as determined by the
level of peanut-specific IgE in their blood, have a 50%
chance of outgrowing the allergy2
Only about 9% of patients are reported to outgrow
their allergy to tree nuts3
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1Skolnick et al 2001
2Fleischer et al 2003
3Fleischer et al 2005
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Maintaining Tolerance of Peanut
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When there is no longer any evidence of
symptoms developing after a child has
consumed peanuts, it is preferable for that
child to eat peanuts regularly, rather than avoid
them, in order to maintain tolerance to the
peanut
Children who outgrow peanut allergy are at
risk for recurrence, but the risk has been
shown to be significantly higher for those
who continue to avoid peanuts after resolution of
their symptoms
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Fleischer et al 2004
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Probiotics
Microorganisms in the Bowel
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The healthy large bowel sustains a resident microbiota
of bacteria, fungi, and other harmless microorganisms
Beneficial effects include:
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Synthesis of vitamins:
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Vitamin K
Biotin
Thiamin
Folic acid
Vitamin B12
Interaction with immune cells to maintain a healthy
epithelium
Positive competition with invading pathogens to resist disease
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Bowel Microflora and Allergy
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The type of gut colonization during the first weeks of
life may predispose an individual to atopic disease
Microflora of the bowel of a breastfed infant is
different from that of a formula-fed baby
The gut microflora influences:
 Resistance to infection
 Immunological environment for subsequent
challenges, including food allergens
 May influence predominance of Th1 or Th2
response
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Kirjavainen et al 1999
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Clinical Trials of Probiotics
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Not all probiotics have been tested in clinical
studies with regard to allergy prevention or
treatment
L. bulgaricus seemed to have no effect on
immune parameters, whereas it was associated
with lower frequency of allergies
L. acidophilus consumption accelerated recovery
from food allergy symptoms
These effects have also been observed in infants
with eczema and cow's milk allergy using infant
formulas supplemented with L. rhamnosus.
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Trials on Probiotics and Eczema Prevention
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Pregnant women took capsules containing Lactobacillus
rhamnosus GG (LGG) during the last two to four weeks of
pregnancy
The newborn infants were given the same microorganism
from birth to six months
Breast-feeding mothers continued to take the capsules during
lactation
The babies were given the bacteria mixed with water by spoon
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Subjects taking the probiotic had a reduced risk of
developing atopic dermatitis (eczema) compared to
controls up to 4 years of age
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Other studies found no reduced incidence of eczema in babies
treated with probiotics
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Kalliomaki et al 2003
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Probiotics and Lactose Intolerance
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Lactobacilli, bifidobacteria and Streptococcus
thermophilus, assist in reducing the symptoms of
lactose intolerance
Produce the enzyme beta-galactosidase (lactase) in
yogurt
Microbial lactase breaks down lactose
The fermented milk itself delays gastrointestinal transit,
thus allowing a longer period of time in which both the
human and microbial lactase enzyme can act on the
milk lactose.
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Microflora and Lactose Intolerance
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Lactose tolerance in people who are deficient in lactase
may be improved by continued ingestion of small
quantities of milk
Does not improve or affect the production of lactase in
the brush border cells of the small intestine
Continued presence of lactose in the colon contributes
to the establishment and multiplication of bacteria
capable of synthesizing the beta-galactosidase enzyme
over time
Resident micro-organisms will break down the
undigested lactose in the colon
Reduces the osmotic imbalance within the colon that is
the cause of much of the distress of lactose intolerance
_________________
de Vrese et al 2001
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Status of Probiotics as Therapy
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Great care must be taken in transferring data from
laboratory and experimental animal studies into human
use
Applies also to the use of known probiotics, some of
which are already present in human nutrition, such as
yoghurt
Not all strains of bacteria in use as probiotics are
completely harmless
Their immune-modifying effects and possible
antiallergic and anti-cancer actions require large clinical
studies
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Summary
Food Allergy:
 Immune system response
Food Intolerance:
 Usually metabolic dysfunction
Diagnostic Laboratory Tests:
 Often ambiguous because different physiological
mechanisms are involved in triggering symptoms
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Summary
Reliable tests for the detection of adverse food
reactions:
Elimination and Challenge
Restrict elimination phase before challenge to a
maximum of:
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four weeks for selective elimination diets
two weeks for a few foods elimination diet
Final diet
Must provide complete nutrition
while avoiding all of the foods and food
components that elicit symptoms on challenge
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