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Diagnosis and Dietary Management of Food Allergies and Intolerances


Diagnosis and Dietary Management of Food Allergies and Intolerances Clinical Applications J.M.Joneja, Ph.D. 2013 * J.M.Joneja, Ph.D. 2013 * J.M.Joneja, Ph.D. 2013 * J ... – PowerPoint PPT presentation

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Title: Diagnosis and Dietary Management of Food Allergies and Intolerances

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
  • 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)

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

Wheal and Flare Reaction
  • Skin prick tests

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

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

Reasons for False Positive Skin Tests
  • Degranulation of skin mast cells by stimuli that
    do not degranulate mast cells in the digestive
  • 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
  • Digestion by gastric acid and digestive enzymes
    can degrade antigens
  • Allergen extract contains histamine

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)

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

Other Skin Tests
  • Patch Test for Contact Allergies
  • Involves Type IV (delayed) hypersensitivity
    reaction, requiring cell-to-cell contact
  • Examples
  • 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

Other Skin Tests
  • DIMSOFT (dimethylsulphoxide test) for delayed
    reaction to food
  • Food extract is suspended in 90
  • 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
  • Especially useful for milk and cereal grains

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
  • Clear medical history
  • Exclusion of non-allergic causes
  • Confirmation by elimination and challenge of
    suspect foods
  • Danger of sensitisation to allergens through the
  • 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)

Standard Allergy TestsBlood Tests
  • 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
  • May measure total IgE - thought to be indicative
    of atopic potential
  • Some practitioners measure IgG
  • (especially IgG4) by ELISA

Value of Blood Tests in Practice
  • 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

Value of Blood Tests in Practice
  • 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

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
  • A negative skin test does not rule out sulphite
  • 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

Unorthodox Tests
  • Many people turn to unorthodox tests when
    avoidance of foods positive by conventional test
    methods have been unsuccessful in managing their
  • Tests include
  • Vega test (electro-dermal)
  • Biokinesiology (muscle strength)
  • Analysis of hair, urine, saliva
  • Radionics
  • ALCAT (lymphocyte cytotoxicity)

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
  • Meter to measure energy level
  • Technician holding probe held at acupuncture
    point on patients other hand
  • Disturbance in energy flow to meter indicates

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 patients
    other arm in resisting downward pressure
  • Weakening of resistance indicates a positive
    (allergic) reaction

Drawbacks of Unreliable Tests
  • Diagnostic inaccuracy
  • Therapeutic failure
  • False diagnosis of allergy
  • Creation of fictitious disease entities
  • Failure to recognize and treat genuine disease
  • Inappropriate and unbalanced diets

Consequences of Mismanagement of Adverse
Reactions to Foods
  • 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


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

Food Intolerance Clinical Diagnosis
Elimination Diet Avoid Suspect Food
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

Exposure Diary (continued)
  • All symptoms graded on severity
  • ? 1 (mild) ? 2
  • ? 3 (moderate) ? 4 (severe)
  • Time of onset
  • How long they last
  • Record status on waking in the morning.
  • Was sleep disturbed during the night, and if so,
    was it due to specific symptoms?

Elimination Diet
  • Based on
  • 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
  • Duration Usually four weeks

Selective Elimination Diets
  • 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 Highly allergenic foods
  • Migraine Biogenic amines
  • Urticaria/angioedema Histamine
  • Chronic diarrhea Carbohydrates Disaccharides
  • Asthma Cyclo-oxygenase inhibitors
  • Latex allergy Foods with structurally
    similar antigens to latex
  • Oral allergy syndrome Foods with structurally
    similar antigens to pollens

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
  • Limited time 10-14 days for an adult
  • 7 days maximum for a child
  • If all else fails use elemental formulae
  • May use extensively hydrolysed formula for a
    young child

Expected Results of Elimination Diet
  • 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

  • Double-blind Placebo-controlled Food Challenge
  • 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

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

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

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

Open Food Challenge
  • Each food or food component is introduced
  • 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

Incremental Dose Challenge
  • Day 1 Consume test food between meals
  • 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
  • If no symptoms
  • Evening Eat double the quantity of test food
    eaten in the afternoon

Incremental Dose Challenge (continued)
  • Day 2
  • 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

Incremental Dose Challenge (continued)
  • Day 3
  • If no adverse reactions experienced
  • 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

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

Sequence of TestingMilk 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
  • 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)

Sequence of TestingWheat
  • Test 1 Pure cereal grain
  • Test 2 Wheat Cracker without yeast
  • Test 3 White Bread
  • Test 4 Whole Wheat Bread

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
  • 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

Important Micronutrients in Common Allergenic Foods Important Micronutrients in Common Allergenic Foods Important Micronutrients in Common Allergenic Foods Important Micronutrients in Common Allergenic Foods Important Micronutrients in Common Allergenic Foods Important Micronutrients in Common Allergenic Foods Important Micronutrients in Common Allergenic Foods Important Micronutrients in Common Allergenic Foods Important Micronutrients in Common Allergenic Foods
Minerals Milk Egg Peanut Soy Fish Wheat Rice Corn
Vitamins Milk Egg Peanut Soy Fish Wheat Rice Corn
Folacin (folate folic acid)
B-1 (thiamin)
B-2 (riboflavin)
B-3 (niacin)
B-5 (pantothenic acid)
B-6 (pyridoxine)
B-12 (cobalamin)
E (alpha-tocopherol)
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

________________ Rautava et al 2005
Diet During Pregnancy and Lactation
  • There is no convincing evidence that women who
    avoid highly allergenic foods, or other foods
    during pregnancy and breast-feeding lower their
    childs 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

_______________ Kramer et al 2006
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 (n4089)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

_____________ 1Kull et al 2006
_______________ 2Calvani et al 2006
Introduction of Fish
  • 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
Recent Evidence for Early Introduction of Solids
  • Delaying initial exposure to cereal grains until
    after 6 months may increase the risk of wheat
  • Research suggests that high risk for celiac
    disease occurs if gluten-containing grains are
    introduced before 3 months or after 7 months2

______________ 2Norris et al 2005
_________________ 1Poole et al June 2006
Introduction of Peanuts
  • Study (n10,786) among primary school age Jewish
    children in UK and Israel
  • Prevalence of peanut allergy (PA)
  • In UK 1.85
  • In Israel 0.17
  • Median monthly consumption of peanut in infants
    aged 8 14 months
  • In UK 0
  • In Israel 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
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 ? Soy ? Peanut
  • ? Egg ? Wheat
  • 2 decrease in allergy to other foods

________________ Bishop et al 1990
  • Age at which milk was tolerated by milk-allergic
  • Diverse studies report different statistics
  • Allergy to some foods more often than others
    persists into adulthood
  • ? Peanut ? Tree nuts
  • ? Shellfish ? Fish

28 by 2 years 1 56 by 4 years 78 by 6 years 56 at 1 year 2 77 at 2 years 87 at 3 years 19 by 4 years 3 42 by 8 years 64 by 12 years 79 by 16 years
_____________________ 1Bishop et al 1990 2Host
and Halken 1990 3Skripak et al 2007
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
Desensitization to Cows Milk
  • 18 children with confirmed CMA gt4 years of age
    underwent SOTI
  • Starting dose 0.05 ml cows milk
  • Increased to 1 ml on first day
  • Increasing dosage weekly up to a daily dose of
    200-250 ml
  • Results 16/18 tolerated 200-250 ml milk
  • Length of process median 14 weeks (range 11-17
  • Tolerance has been maintained for gt1 year

_______________ Zapatero et al 2008
Oral Tolerance Induction to Milk, Egg, and Peanut
  • 36 of children with IgE-mediated allergy to
    cows milk and hens 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
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
  • 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
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
  • Food Allergy
  • Immune system response
  • Food Intolerance
  • Usually metabolic dysfunction
  • Diagnostic Laboratory Tests
  • Often ambiguous because different physiological
    mechanisms are involved in triggering symptoms

  • 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

  • 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

Invitation to Further Information
  • Website
  • www.allergynutrition.com
  • Janice Vickerstaff Joneja Ph.D
  • The Health Professionals
  • Guide to Food Allergies
  • and Intolerances
  • Academy of Nutrition and
  • Dietetics. Chicago 2013
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