Diagnosis of Food Allergy and Intolerance by E2rDP50A


									           Diagnosis and
   Dietary Management of Food
      Allergy and Intolerance

Clinical Practice
               Major Allergenic Foods:
        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
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   3
        U.S. Food and Drug Administration
Food Allergen Labeling and Consumer Protection Act January

    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“
                 Additional Factors Involved in
                 Symptoms of Food Sensitivity

1. Increased permeability of the GI tract
      Inflammation:
           Infection
           Allergy
           Autoimmune processes
           Other pathology
      Immaturity (in infants)
      Alcohol ingestion

2. Physical exertion
Additional Factors Involved in Symptoms of
             Food Sensitivity
3. Stress

4. Level of inflammatory mediators released
   in response to several different foods

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

Diagnosis of Food
Detecting the Culprit Foods and Food
          Tests for Food Allergies:
        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
   Malnutrition

     Consequences of Mismanagement of
        Adverse Reactions to Foods
   Malnutrition; weight loss, due to extensive elimination
   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
    Risks associated with skin tests

   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

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
   Long-term adherence to a restricted diet
    should not be advocated without clear
    identification of the culprit food
           Food Intolerance: Clinical Diagnosis
   Elimination Diet: Avoid Suspect Food

                                                 Increase Restrictions

   Symptoms Disappear                        Symptoms Persist

Reintroduce Foods Sequentially or Double-blind

 Symptoms Provoked                   No Symptoms

 Diagnosis Confirmed                     Diagnosis Not Confirmed

     Elimination and Challenge

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

        All foods, beverages, medications, and supplements
        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 (mild-moderate)
             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 sources
   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:        Disaccharides
       Asthma:                  Cyclo-oxygenase inhibitors
       Latex allergy:           Foods with structurally
                                 similar antigens to latex
       Oral allergy syndrome:   Foods with structurally
                                 similar antigens to pollens
Basic Hypoallergenic (“few foods”)
        Elimination Diet
   Only listed foods are allowed
   Nutritionally incomplete
   Followed for maximum 10 days

   GRAINS:               White rice
   FRUITS:               Pears; pear juice
                          Cranberries; cranberry juice
   VEGETABLES:           Squash (all varieties)
   MEAT:                 Lamb
                          Wild game
    Basic Hypoallergenic (“few foods”)
      Elimination Diet (continued )
   MEAT                 Lentils
    SUBSTITUTES:         Split peas
                         Garbanzo beans (chick peas)

   FLAVOURINGS:         Sea salt

   BEVERAGES:           Distilled water in glass containers

   OILS                 Canola oil or olive oil
                         Safflower oil

   OTHER                Agar-agar
                 (Make jelly dessert with pears and pear juice)

Expected Results of Elimination Diet

    Symptoms often worsen on days 2-4 of

    By day 5-7 symptomatic improvement is

    Symptoms disappear after 10-14 days of
   Double-blind Placebo-controlled Food Challenge
      Lyophilized (freeze-dried) food is disguised in gelatin
      Identical gelatin capsules contain a placebo (glucose
      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
     May be other factors involved in eliciting
      symptoms, e.g. taste and smell

         Challenge (continued)

 Single-blindfood 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
   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. Do not continue to eat
    the test food

   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 reaction
      If no symptoms:
   Evening: Eat double the quantity of test food eaten in
    the afternoon

      Incremental Dose Challenge

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
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 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
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 Testing:

Test 1: Pure cereal grain
Test 2: Wheat Cracker without yeast
Test 3: White Bread
Test 4: Whole Wheat Bread

             Sequence of Testing:
Rye: Test as for wheat:

   Test 1. Rye Flakes (cooked)

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

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

            Sequence of Testing:
   Test 1: pure grain
       corn-on-the-cob
       frozen corn niblets:
   Test 2: corn oil
     added to tolerated food
   Test 3: corn syrup
     added to tolerated food

                  Sequence of Testing:
                   Alcoholic beverages
   Test 1. Distilled alcohol (tequila; vodka; gin; white rum)
         enhanced antigen uptake
   Test 2. White wine
         biogenic amines, especially histamine
   Test 3. Red wine
         biogenic amines, especially tyramine
   Test 4. Beer, ale, lager
         fermented grains
   Test 5. Cider
         fermented apple, pear, peach, etc.
              Sequence of Testing:

   Test 1 : Unsweetened (“bitter”) baker’s chocolate
        Melt and add honey (if tolerated) as a
        Solidify on a flat surface (e.g. baking sheet)
        Break into squares
        Test: 1, 2, 4 squares

   Test 2: Purchased chocolates

Maintenance Diet
                    Final Diet
   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

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

Milk and Milk Products:
   Calcium                  Riboflavin         Smaller amounts:
   Phosphorus               Potassium          Vitamin A*
   Vitamin D*                                  Vitamin E
   Vitamin B12
   Pantothenic acid

*Usually added as fortification to the food product

     Important Nutrients in Common

Vitamin B12        Folacin      Smaller amounts:
Vitamin D          Riboflavin   Vitamin A
Pantothenic acid   Selenium     Vitamin E
Biotin             Iron         Vitamin B6

    Important Nutrients in Common

  Thiamin*                Smaller amounts:
  Riboflavin*             Magnesium
  Niacin*                 Folacin
  Iron*                   Phosphorous
  Selenium                Molybdenum

  Thiamin*      Niacin*
  Riboflavin*   Iron*

      Important Nutrients in Common
Niacin             Magnesium              Smaller amounts
Pantothenic acid   Manganese              Folacin
Vitamin E          Chromium               Biotin
                                          Vitamin B6
Thiamin            Folacin         Phosphorous
Riboflavin         Calcium Magnesium
Vitamin B6         Iron            Zinc
       Important Nutrients in Common
Fish and Shellfish:

   Niacin          Phosphorous
   Vitamin B6      Calcium (in shellfish and fish bones)
   Vitamin B12     Selenium
   Vitamin E

Smaller amounts:
  Potassium        Iron              Vitamin A
  Magnesium        Zinc

Current Areas of Research

1.   Promotion of Tolerance to Foods
2.   Probiotics and Food Allergy
          Recommendations for Introduction of
          Solids to High Risk for Allergy Infants
        Most recent US consensus document
         recommends for infant at risk for allergy:
          Exclusive breast-feeding from birth to six
         Optimal age for introduction of solids is six
         Dairy products introduced at 12 months

         Eggs at 24 months

         Peanut, tree nuts, fish, seafood delayed until at
           least 36
__________________ months
Fiocchi et al July 2006                                       44
          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
   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
Calvani et al 2006                                            45
    Recent Evidence for Early Introduction of
   “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:
   “The possibility of cereal allergy after the
    introduction of cereal formula during the lactation
    period should not be underestimated”2
_________________                             ________________
1Poole et al June 2006                        2Armentia et al 2002
     Introduction of Solid Foods in Relationship
                  to Celiac Disease

 Concept of “window of opportunity”

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

    Final conclusions:
       “Current infant feeding practices should not be

Norris et al 2005                                           47
             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                                   48

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
           Progression of Peanut Allergy
   Peanut allergy, like many early food allergies, can be
   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                                         50
      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
   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
                  Microorganisms in the Bowel
   The healthy large bowel sustains a resident microbiota
    of bacteria, fungi, and other harmless microorganisms
   Beneficial effects include:
       Synthesis of vitamins:
            Vitamin K
            Biotin
            Thiamin
            Folic acid
            Vitamin B12
       Interaction with immune cells to maintain a healthy
       Positive competition with invading pathogens to resist

          Bowel Microflora and Allergy
   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
Kirjavainen et al 1999                                       53
          Clinical Trials of Probiotics
   Not all probiotics have been tested in clinical
    studies with regard to allergy prevention or
   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.

    Trials on Probiotics and Eczema Prevention

     Pregnant women took capsules containing Lactobacillus
      rhamnosus GG (LGG) during the last two to four weeks of
     The newborn infants were given the same microorganism
      from birth to six months
     Breast-feeding mothers continued to take the capsules during
     The babies were given the bacteria mixed with water by spoon
     Subjects taking the probiotic had a reduced risk of
      developing atopic dermatitis (eczema) compared to
      controls up to 4 years of age
     Other studies found no reduced incidence of eczema in babies
      treated with probiotics
    Kalliomaki et al 2003                                        55
      Probiotics and Lactose Intolerance

   Lactobacilli, bifidobacteria and Streptococcus
    thermophilus, assist in reducing the symptoms of
    lactose intolerance
   Produce the enzyme beta-galactosidase (lactase) in
   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.

        Microflora and Lactose Intolerance
   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
         Status of Probiotics as Therapy
   Great care must be taken in transferring data from
    laboratory and experimental animal studies into human
   Applies also to the use of known probiotics, some of
    which are already present in human nutrition, such as
   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

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 food
       Elimination and Challenge
Restrict elimination phase before challenge to a
    maximum of:
   •   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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