Download Lecture 4 Diagnosis and Dietary Management of Food Allergies and

Diagnosis and
Dietary Management of Food
Allergies and Intolerances
Clinical Applications
Tests for Adverse Reactions
to Foods
Rationale and Limitations
Standard Allergy Tests
Skin tests

Scratch or prick
Allergen extract applied to skin surface
of arm or back
 Skin is scarified (scratched) or pricked with lancet
 Allergen encounters mast cells below skin surface


If allergen-specific IgE is present, allergen plus
antibody causes release of mediators (mast cell
degranulation), especially histamine
Histamine causes reddening and swelling: “wheal and
flare” reaction of the skin test
 Size of reaction measured (usually 1+ to 4+)

3
Standard Allergy Tests
Skin tests continued

Intradermal tests
 Allergen extract is injected into dermis
 Rationale: release of histamine produces wheal
and flare
Note: many countries do not approve this type of testing because
of increased risk of anaphylaxis as allergen introduced
directly into blood stream

Controls for all skin tests:
 Negative: medium in which allergen is
suspended (usually saline)
 Positive: measured amount of histamine
4
Wheal and Flare Reaction
Skin prick tests
5
Value of Skin Tests in Practice

Positive predictive accuracy of skin tests
rarely exceeds 50%
 Many practitioners rate them lower

Negative skin tests do not rule out the
possibility of non-IgE-mediated reactions
Do not rule out non-immune-mediated food
intolerances

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Value of Skin Tests in Practice


Tests for highly allergenic foods thought to
have close to 100% negative predictive
accuracy for diagnosis of IgE-mediated
reactions
Such foods include:
 Egg
 Milk
 Fish
 Wheat
 Tree nuts
 Peanut
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Reasons for False Positive Skin Tests


Degranulation of skin mast cells by stimuli
that do not degranulate mast cells in the
digestive tract
Differences in the form in which the food is
applied to the skin compared to that which
encounters immune cells in the digestive tract
Raw form in extract may be degraded during
cooking
 Digestion by gastric acid and digestive
enzymes can degrade antigens


Allergen extract contains histamine
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False Negative Skin Tests




Children younger than 2-3 years are more likely to
have a negative skin test and positive food challenge
than adults
Adverse reaction is not mediated by IgE
Commercial allergen may contain no material that the
immune system can recognize
Processing of food leads to degradation of allergen
(e.g. crushing produces phenols and catabolic
enzymes)
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Other Skin Tests


Prick-to-Prick
Sterile needle is inserted into raw food, and the
patient’s skin is pricked with the same needle
 Used for suspected contact allergy
 e.g. oral allergy syndrome
 Especially where allergen is easily
denatured by heat and acid
 Crushing plant tissue during preparation of
allergen extracts releases phenols that rapidly
cause break-down of protein
 Prick-to prick test transfers “native” allergen
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Other Skin Tests

Patch Test for Contact Allergies


Involves Type IV (delayed) hypersensitivity reaction,
requiring cell-to-cell contact
Examples:




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Poison ivy rash
Nickel contact dermatitis
Preservatives, dyes and perfumes in cosmetics
Allergen is placed on the skin, or applied as an impregnated
patch, which is kept in place by adhesive bandage for up to
72 hours
Local reddening, swelling, irritation, indicates positive
response
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Other Skin Tests

DIMSOFT (dimethylsulphoxide test) for delayed
reaction to food
 Food extract is suspended in 90%
dimethylsulfoxide
 Aids in skin penetration of allergen
 Patch held in place 48-72 hours
 Especially useful in skin and gastrointestinal
reactions which may not have immediate onset
symptoms
 Especially useful for milk and cereal grains
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Risks associated with skin tests


High number of false positive and false negative tests
creates risk of diagnostic inaccuracy
All tests must be considered together with:

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Clear medical history
Exclusion of non-allergic causes
Confirmation by elimination and challenge of suspect foods
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 especially if
inflammation exists (e.g. eczema)
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Standard Allergy Tests
Blood Tests

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RAST: radioallergosorbent test (e.g. ImmunoCap-RAST;
Phadebas-RAST)
FAST; Fluorescence allergosorbent test
ELISA: enzyme-linked immunosorbent assay
Designed to detect and measure levels of allergen-specific
antibodies
Used for detection of levels of allergen-specific IgE
May measure total IgE - thought to be indicative of “atopic
potential”
Some practitioners measure IgG
(especially IgG4) by ELISA
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Value of Blood Tests in Practice

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Blood tests have about the same sensitivity as skin
tests for identification of IgE-mediated sensitisation
to food allergens
Anti-food antibodies (especially IgG) are frequently
detectable in all humans, usually without any
evidence of adverse effect
IgG production likely to be the first stage of
development of oral tolerance to a food
Studies suggest that IgG4 indicates protection or
recovery from IgE-mediated food allergy
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Value of Blood Tests in Practice


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There is often poor correlation between high
level of anti-food IgE and symptoms when the
food is eaten
Many people with clinical signs of food allergy
show no elevation in IgE
Reasons for failure of blood tests to indicate
foods responsible for symptoms are the same as
those for skin tests
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Tests for Intolerance of Food Additives

There are no reliable skin or blood tests to detect food
additive intolerance

Skin prick tests for sulphites are sometimes positive

A negative skin test does not rule out sulphite
sensitivity

History and oral challenge provocation of symptoms
are the only methods for the diagnosis of additive
sensitivity at present

Caution: Challenge may occasionally induce
anaphylaxis in sulphite-sensitive asthmatics
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Unorthodox Tests

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Many people turn to unorthodox tests when
avoidance of foods positive by conventional test
methods have been unsuccessful in managing their
symptoms
Tests include:
 Vega test (electro-dermal)
 Biokinesiology (muscle strength)
 Analysis of hair, urine, saliva
 Radionics
 ALCAT (lymphocyte cytotoxicity)
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Controversial Tests

Electro-Dermal (Vega) Test
 Measures change in electrical potential on skin
 Circuit linking
Patient holding a metal rod
 Vial containing food, or other material being tested
 Meter to measure energy level
 Technician holding probe held at acupuncture point on
patient’s other hand

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Disturbance in energy flow to meter indicates
reactivity
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Controversial Tests

Biokinesiology
Assumption: muscles become weak when influenced
by the allergen to which the patient reacts
 Patient holds a vial containing the suspect allergen
(food)
 Practitioner tests the strength of the patient’s other
arm in resisting downward pressure
 Weakening of resistance indicates a positive
(allergic) reaction
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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
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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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Elimination and Challenge
Protocols
Identification of Allergenic Foods


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)

All symptoms graded on severity:
 1 (mild);
 3 (moderate)
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Time of onset

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:

Eczema:
Migraine:
Urticaria/angioedema:
Chronic diarrhea:
Asthma:

Latex allergy:

Oral allergy syndrome:

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Highly allergenic foods
Biogenic amines
Histamine
Carbohydrates; Disaccharides
Cyclo-oxygenase inhibitors
Sulphites
Foods with structurally
similar antigens to latex
Foods with structurally
similar antigens to pollens
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Few Foods Elimination Diet

When it is difficult to determine which foods
are suspects a few foods elimination diet is
followed
Limited to a very small number of foods and
beverages
 Limited time: 10-14 days for an adult
 7 days maximum for a child

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If all else fails use elemental formulae:

May use extensively hydrolysed formula for a
young child
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Expected Results of Elimination Diet

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Symptoms often worsen on days 2-4 of
elimination
By day 5-7 symptomatic improvement is
experienced
Symptoms disappear after 10-14 days of
exclusion
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Challenge

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)

Drawback of DBPCFC
 Expensive in time and personnel
 Capsule may not provide enough food to
elicit a positive reaction
 Patient may be allergic to gelatin in
capsule
 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:



lentil soup
apple sauce
tomato sauce
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Challenge Phase
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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Each food or food component is introduced
individually
The basic elimination diet, or therapeutic diet
continues during this phase
If an adverse reaction to the test food occurs at
any time during the test STOP.
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:

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:

Monitor for delayed reactions as on Day 2
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Sequential Incremental Dose Challenge

Continue testing in the same manner until all
excluded foods, beverages, and additives have
been tested

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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Maintenance Diet
Final Diet


Must exclude all foods and additives to which a
positive reaction has been recorded
Must be nutritionally complete, providing all
macro and micro-nutrients from non-allergenic
sources

There is no benefit from a rotation diet in
the management of food allergy

A rotation diet may be beneficial when the
condition is due to dose-dependent food
intolerance
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Important Micronutrients in Common Allergenic Foods
Minerals
Milk
Calcium
+
Phosphorus
+
Egg
Peanut
+
Soy
Fish
Wheat
+
+
+
+
+
+
Iron
+
+
+
Zinc
+
+
+
+
+
+
+
+
Magnesium
Selenium
Potassium
+
+
+
Molybdenum
Manganese
Corn
+
+
+
+
Chromium
Copper
Rice
+
+
+
+
+
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Milk
Egg
A
+
+
Biotin
+
+
Folacin (folate; folic acid)
+
+
Peanut
Soy
Fish
Wheat
Rice
Corn
Vitamins
B-1 (thiamin)
B-2 (riboflavin)
+
B-3 (niacin)
B-5 (pantothenic acid)
+
B-6 (pyridoxine)
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
B-12 (cobalamin)
+
+
+
D
+
+
+
E (alpha-tocopherol)
+
+
K
+
+
+
+
+
+
+
+
+
+
+
+
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Current Areas of Research
Promotion of Tolerance to Foods
Prevention of Food Allergy in Clinical
Practice
Significant change in directives within the past 3
years:
 Previously:
Avoidance of allergen to prevent
sensitization (allergen-specific IgE)
 Current:
Active stimulation of the immature
immune system to induce tolerance of the
antigens in food
________________
Rautava et al 2005
48
Diet During Pregnancy and
Lactation

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There is no convincing evidence that women who
avoid highly allergenic foods, or other foods during
pregnancy and breast-feeding lower their child’s risk
of allergies
Current directive: the atopic mother should strictly
avoid her own allergens and replace the foods with
nutritionally equivalent substitutes
There are no indications for mother to avoid other
foods during pregnancy
A nutritionally complete, well-balanced diet is
essential
_______________
Kramer et al 2006
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Introduction of Fish


Historically, fish consumption during infancy was
considered to be a risk factor for allergy
Recent research indicates otherwise:


Regular fish consumption during the first year of life
associated with a reduced risk for allergic disease by age 4
years (n=4089)1
Babies of mothers who frequently consumed fish (2-3
times per week or more) during pregnancy had one third
less food sensitivities than those whose mothers did not
consume fish during pregnancy2
_____________
1Kull et al 2006
_______________
2Calvani et al 2006
50
Introduction of Fish

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
Babies who were fed fish before nine months
of age were 24% less likely to develop eczema
by age 1 year1
Children less likely to develop allergy to fish if
the mother consumes fish two or three times a
week during pregnancy2
Regular fish consumption during the first year
of life was associated with a reduced risk for
allergic disease by age four3
____________
Alm et al 2009
_______________
Calvani et al 2006
_____________
Kull et al 2006
51
Recent Evidence for Early
Introduction of Solids
Delaying initial exposure to cereal
grains until after 6 months may
increase the risk of wheat allergy1
 Research suggests that high risk for
celiac disease occurs if glutencontaining grains are introduced before
3 months or after 7 months2

_________________
1Poole et al June 2006
______________
2Norris et al 2005
52
Introduction of Peanuts
Study (n=10,786) among primary school age Jewish
children in UK and Israel
 Prevalence of peanut allergy (PA):

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1.85%
0.17%
Median monthly consumption of peanut in infants
aged 8 – 14 months:


In UK:
In Israel:
In UK:
In Israel:
0
7.1 g
Difference not due to atopy, genetic background,
social class, or peanut allergenicity
Israeli infants consume peanuts in high quantities
during the first year of life
______________
Du Toit et al 2008
53
Development of Tolerance



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




Soy
Wheat

Peanut
2% decrease in allergy to other foods
________________
Bishop et al 1990
54
Prognosis


Age at which milk was tolerated by milk-allergic
children:
Diverse studies report different statistics
28% by 2 years
56% by 4 years
78% by 6 years

1
56% at 1 year
77% at 2 years
87% at 3 years
2
19% by 4 years
42% by 8 years
64% by 12 years
79% by 16 years
3
Allergy to some foods more often than others persists into
adulthood:
 Peanut
 Tree nuts
 Shellfish
 Fish
_______________________________________________________________________
1Bishop
et al 1990
2Host
and Halken 1990
3Skripak
et al 2007
55
Induction of Oral Tolerance




Allergy to a specific food can be induced by
oral administration of the offending food
(SOTI: specific oral tolerance induction)
Starting with very low dosages
Gradually increasing daily dosage up to the
equivalent of the usual daily intake
Followed by daily maintenance dose
__________________
Niggemann et al 2006
56
Desensitization to
Cow’s Milk







18 children with confirmed CMA >4 years of age
underwent SOTI
Starting dose 0.05 ml cow’s milk
Increased to 1 ml on first day
Increasing dosage weekly up to a daily dose of 200250 ml
Results: 16/18 tolerated 200-250 ml milk
Length of process median 14 weeks (range 11-17
weeks)
Tolerance has been maintained for >1 year
_______________
Zapatero et al 2008
57
Oral Tolerance Induction to
Milk, Egg, and Peanut


36% of children with IgE-mediated allergy to cow’s
milk and hen’s egg developed permanent tolerance of
the foods after a median 21 months specific oral
tolerance induction (SOTI)1
4 peanut-allergic children underwent SOTI:



Daily doses of peanut flour starting at 5 mg peanut protein
2-weekly dosage increase up to 800 mg protein
All subjects tolerated at least 10 whole peanuts (2.38 g
protein) on post-intervention challenge2
______________
1Staden et al 2007
____________
2Clark et al 2009
58
Progression of Peanut Allergy




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
__________________
1Skolnick et al 2001
2Fleischer et al 2003
3Fleischer et al 2005
59
Maintaining Tolerance of Peanut


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
_________________
Fleischer et al 2004
60
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
61
Summary
Reliable tests for the detection of
adverse reactions to foods:
 Elimination and Challenge
Final diet
Must provide complete nutrition while
avoiding all of the foods and food
components that elicit symptoms on
challenge
62
Summary


Recognition of development of tolerance
 Periodic test and challenge after usually
several years of avoidance of allergenic
food
Maintenance of tolerance by regular
consumption of allergenic food
63
Invitation to Further
Information
Website:
www.allergynutrition.com
Janice Vickerstaff Joneja Ph.D
The Health Professional’s
Guide to Food Allergies
and Intolerances
Academy of Nutrition and
Dietetics. Chicago 2013
64