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Food%20Allergy

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Title: Food%20Allergy


1
Food Allergy
  • Leo Galland M.D.
  • Foundation for Integrated Medicine

2
HOW PREVALENT IS FOOD ALLERGY/INTOLERANCE?
  • 33 of 1000 teachers (56 response rate) reported
    avoidance specific foods because of unpleasant
    physiological reactions.
  • A poll of 5000 US physicians on prevalence of
    food allergy (14 response rate) 0-80 (mean 10)

3
Immunologic Mechanisms of Food Intolerance
  • Type I (IgE mediated, TH2 promoted)
  • Type II (IgG and complement mediated, cytotoxic,
    TH1 promoted)
  • Type III (IgG immune complex mediated, TH1
    promoted)
  • Type IV (cell-mediated, TH1 promoted)

4
Non-immunologic Mechanisms of Food Intolerance
  • Digestive (e.g., lactase deficiency)
  • Pharmacologic (e.g., caffeine, ethanol)
  • Biochemical (histamine, tyramine, salicylates,
    sulphites, MSG)
  • Non-specific mast cell degranulation
  • Lectin-mediated glycoprotein agglutination

5
Poor Sulphoxidation and Food Allergy (Scadding
1988)
  • 74 adults with non-IgE food allergy diagnosed by
    elimination and challenge
  • 78 slow carbocisteine sulfoxidizers vs 33 of
    controls (plt0.005)
  • Carbon oxidation (debrisoquine) normal
  • Theory altered metabolism of food chemicals
    toxic/immunogenic metabolites by novel pathways

6
(No Transcript)
7
FOOD ALLERGY/INTOLERANCE WELL-DOCUMENTED
MANIFESTATIONS
  • Atopic Eczema
  • Allergic Rhinitis, Asthma
  • Anaphylaxis, Angioedema, Urticaria
  • Oral Allergy Syndrome (Ortolani)
  • Aphthous Ulceration
  • Alveolitis, Hemosiderosis
  • Infantile Colic
  • Vomiting, Diarrhea, Abdominal Pain
  • Irritable Bowel Syndrome
  • Hematochyzia, Colitis
  • Pediatric Enteropathies
  • Celiac Disease
  • Protein-losing Enteropathy
  • Failure to thrive
  • Crohns Disease (exacerbation)
  • Migraine headches
  • Migraine-associated Epilepsy
  • ADHD
  • Nephrotic Syndrome
  • Allergic Arthritis
  • Rheumatoid Arthritis (exacerbation)

8
FOOD ALLERGY IN PEDIATRIC ATOPIC ECZEMA
  • 25-60 are food reactive
  • Increased gut permeability
  • at baseline
  • after food challenges
  • blocked by cromolyn
  • Histamine release
  • Circulating immune complexes
  • Multi-system reactivity in 2/3
  • 49 gastrointestinal
  • 23 rhinitic
  • 17 asthmatic
  • Poor correlation between food responses and prick
    tests, RAST milk, egg, citrus, additives, nuts,
    fish, wheat, tomatoes, lamb, chicken, soy

9
FOOD ALLERGY IN PERENNIAL RHINITIS(Ortolani et
al)
  • 210 patients over 1 year
  • 3-week oligoantigenic diet
  • 52 improved (24.8)
  • 28 IgE mediated (13.3), based upon
    correlation with RAST, skin testing
  • 24 no correlation

10
FOOD ALLERGY IN RECURRENT APHTHOUS STOMATITIS
  • Cytotoxic lymphocytes/antibodies
  • Histamine release to foods (23/60)
  • 30 correlation of HR and ulcers
  • Gluten, milk, food additives

11
FOOD ALLERGY IN HYPERKINETIC SYNDROME(Egger et
al, Lancet 1985)
  • 76 children seen on referral
  • (60 boys, 16 girls)
  • age 2-15 (mean 7.3)
  • 37 from dysfunctional families
  • 4 weeks oligoantigenic diet
  • 2 meats, 2 starch sources, 2 fruits,
  • 1 vegetable, calcium, multivitamin

12
RESPONSE TO OLIGOANTIGENIC DIET IN HYPERKINETIC
SYNDROME
  • Pre-diet Diet
  • Total number 76
    76 Hyperactivity
  • Normal 0 21
  • Mild 6 28
  • Moderate 31 19
  • Severe 39
    8
  • Conners score 24 12
  • Antisocial acts 32 13
  • Headache 48 9
  • Seizures 14 1
  • Abdominal pain 54
    8
  • Limb pain 33 6
  • Eczema, rash 29
    9
  • Aphthous ulcers 15
    5
  • Atopic (prick test) 30
    (39)

13
Summary of Eggers Results
  • Open trial 82 of children responded favorably
    to the oligoantigenic diet
  • DBPCT 28 participated, with rating of response
    by parents, a neurologist and a psychologist
  • DBPCT 51-74 of the food intolerances confirmed

14
FOODS PROVOKING HYPERACTIVITY IN DOUBLE-BLIND,
PLACEBO-CONTROL TRIAL
  • REACTIVE
  • Additives 79
  • Soy 73
  • Milk 64
  • Chocolate 59
  • Grapes 50
  • Wheat 49
  • Oranges 45
  • Cheese 40
  • Eggs 39
  • Peanuts 32
  • Corn 29
  • Fish 23
  • Oats 23
  • Melon 21
  • Tomato 20

15
Cognitive-Emotional Symptoms and Food Allergy
(King, 1981)
  • DBPCT 30 adults, 28 food extracts, sub-lingual,
    multiple measures, 2 judges
  • Symptoms associated with allergen exposure
    anxiety, depression, brain fog, irritability,
    detachment, euphoria pruritus, cold hands,
    myalgia, nasal congestion, tinnitus, fatigue,
    headache
  • Occurrence p0.001, Severity p0.002

16
FOOD ALLERGY IN PEDIATRIC MIGRAINE (Egger, 1983)
  • 88 children, oligoantigenic diet
  • 93 cleared by 2 weeks
  • 90 relapsed on open challenge
  • 40 of these, DBPC TRIAL
  • 26 confirmed (4 reacted to placebo, 8 reacted to
    neither)
  • Atopy 55, 46 hyper, 16 seizures
  • Milk, egg, chocolate, orange, wheat
  • benzoate, cheese, tomato, tartrazine, rye, fish,
  • pork, beef, corn, soy, tea

17
MIGRAINE-ASSOCIATED SYMPTOMS AND FOOD INTOLERANCE
  • 88 PATIENTS
  • Pre-diet Diet
  • Abdominal pain,
  • diarrhea 61 8
  • Hyperactivity 41 5
  • Limb pain 41 7
  • Rhinitis 34
    15
  • RAS 15 2
  • Vaginal discharge 11 1
  • Asthma 7 3
  • Eczema 6 3
  • 27/40 provoked by DBPC food trial
  • 10/40 provoked by placebo also
  • 3/40 provoked by neither

18
EVIDENCE FOR ALTERED IMMUNE ACTIVATION IN
RESPONSE TO FOODS IN MIGRAINE(Marteletti 1991,
Acta Neurologica)
  • Increased circulating immune complexes
  • Increased activated T cells and total T cells
  • Increased plasma IL-2 levels
  • Effective prophylaxis with oral sodium
    cromoglycate

19
Food Allergy in Idiopathic Nephrotic Syndrome
  • Basophile histamine release test
  • - 65 of 34 patients
  • - 5 of 19 controls
  • wheat, beef, milk, egg, pork
  • 26 patients with refractory nephrosis
  • - 6 remitted on oligoantigenic diet

20
TM, a 26 old woman with massive proteinuria,
anasarca
  • Prior aesthetician, applying artificial nails,
    developed asthma, multiple inhalant allergies,
    provoked by allergy immunotherapy
  • Severe anasarca emergency
    hospitalization, furosemide, steroids
  • Proteinuria 4 gm/day, serum albumen 1.3 gm/L,
    marked hyperlipidemia, normal biopsy
  • Required prednisone 20 mg/day maintenance

21
TM, a 26 old woman with massive proteinuria,
anasarca
  • Initial evaluation Cushingoid, 3 proteinuria
  • Method modified fast, supported by a rice-based,
    oligoantigenic food supplement, tapering down
    prednisone and daily examination of urine protein
    by dipstick
  • Result clearing of proteinuria in 7 days, return
    of proteinuria within 24 hours of ingesting hens
    eggs
  • Total remission for 7 years, avoids eggs

22
Food Intolerance and Rheumatoid Arthritis
  • 5-46 of patients in various studies have
    exacerbation of symptoms provoked by specific
    foods, mostly wheat, milk, tomatoes, various
    additives, some confirmed with DBPC trials
  • An 18-year open study of foods provoking pain in
    100 patients found that certain spices and food
    additives were commonest agents

23
GLUTEN INTOLERANCE IS PREVALENT AND PROTEAN
  • Gliadin antibodies were found in 30/53 patients
    with neurological disease of unknown cause (73
    had abnormal small bowel biopsies)
  • Hadjivassiliou et al, Lancet 347 369-371 (1996)
  • IgG and IgA gliadin antibodies occur in 2 of
    Italian school children
  • Catassi et al, Lancet 343 200-203 (1994)

24
Cows Milk Allergy and IDDM
  • Children with IDDM have IgG against a peptide
    fraction of bovine serum albumen that cross-react
    with a pancreatic beta-cell surface protein
  • Adults with recent-onset IDDM show excessive
    T-cell proliferation in response to beta-casein,
    compared to normal and auto-immune controls

25
HOW PREVALENT IS FOOD ALLERGY/INTOLERANCE?
  • 33 of 1000 teachers (56 response rate) reported
    avoidance specific foods because of unpleasant
    physiological reactions.
  • A poll of 5000 US physicians on prevalence of
    food allergy (14 response rate) 0-80 (mean 10)

26
Immunologic Mechanisms of Food Intolerance
  • Type I (IgE mediated, TH2 promoted)
  • Type II (IgG and complement mediated, cytotoxic,
    TH1 promoted)
  • Type III (IgG immune complex mediated, TH1
    promoted)
  • Type IV (cell-mediated, TH1 promoted)

27
Non-immunologic Mechanisms of Food Intolerance
  • Digestive (e.g., lactase deficiency)
  • Pharmacologic (e.g., caffeine, ethanol)
  • Biochemical (histamine, tyramine, salicylates,
    sulphites, MSG)
  • Non-specific mast cell degranulation
  • Lectin-mediated glycoprotein agglutination

28
Poor Sulphoxidation and Food Allergy (Scadding
1988)
  • 74 adults with non-IgE food allergy diagnosed by
    elimination and challenge
  • 78 slow carbocisteine sulfoxidizers vs 33 of
    controls (plt0.005)
  • Carbon oxidation (debrisoquine) normal
  • Theory altered metabolism of food chemicals
    toxic/immunogenic metabolites by novel pathways

29
(No Transcript)
30
FOOD ALLERGY/INTOLERANCE WELL-DOCUMENTED
MANIFESTATIONS
  • Atopic Eczema
  • Allergic Rhinitis, Asthma
  • Anaphylaxis, Angioedema, Urticaria
  • Oral Allergy Syndrome (Ortolani)
  • Aphthous Ulceration
  • Alveolitis, Hemosiderosis
  • Infantile Colic
  • Vomiting, Diarrhea, Abdominal Pain
  • Irritable Bowel Syndrome
  • Hematochyzia, Colitis
  • Pediatric Enteropathies
  • Celiac Disease
  • Protein-losing Enteropathy
  • Failure to thrive
  • Crohns Disease (exacerbation)
  • Migraine headches
  • Migraine-associated Epilepsy
  • ADHD
  • Nephrotic Syndrome
  • Allergic Arthritis
  • Rheumatoid Arthritis (exacerbation)

31
FOOD ALLERGY IN PEDIATRIC ATOPIC ECZEMA
  • 25-60 are food reactive
  • Increased gut permeability
  • at baseline
  • after food challenges
  • blocked by cromolyn
  • Histamine release
  • Circulating immune complexes
  • Multi-system reactivity in 2/3
  • 49 gastrointestinal
  • 23 rhinitic
  • 17 asthmatic
  • Poor correlation between food responses and prick
    tests, RAST milk, egg, citrus, additives, nuts,
    fish, wheat, tomatoes, lamb, chicken, soy

32
FOOD ALLERGY IN PERENNIAL RHINITIS(Ortolani et
al)
  • 210 patients over 1 year
  • 3-week oligoantigenic diet
  • 52 improved (24.8)
  • 28 IgE mediated (13.3), based upon
    correlation with RAST, skin testing
  • 24 no correlation

33
FOOD ALLERGY IN RECURRENT APHTHOUS STOMATITIS
  • Cytotoxic lymphocytes/antibodies
  • Histamine release to foods (23/60)
  • 30 correlation of HR and ulcers
  • Gluten, milk, food additives

34
FOOD ALLERGY IN HYPERKINETIC SYNDROME(Egger et
al, Lancet 1985)
  • 76 children seen on referral
  • (60 boys, 16 girls)
  • age 2-15 (mean 7.3)
  • 37 from dysfunctional families
  • 4 weeks oligoantigenic diet
  • 2 meats, 2 starch sources, 2 fruits,
  • 1 vegetable, calcium, multivitamin

35
RESPONSE TO OLIGOANTIGENIC DIET IN HYPERKINETIC
SYNDROME
  • Pre-diet Diet
  • Total number 76
    76 Hyperactivity
  • Normal 0 21
  • Mild 6 28
  • Moderate 31 19
  • Severe 39
    8
  • Conners score 24 12
  • Antisocial acts 32 13
  • Headache 48 9
  • Seizures 14 1
  • Abdominal pain 54
    8
  • Limb pain 33 6
  • Eczema, rash 29
    9
  • Aphthous ulcers 15
    5
  • Atopic (prick test) 30
    (39)

36
Summary of Eggers Results
  • Open trial 82 of children responded favorably
    to the oligoantigenic diet
  • DBPCT 28 participated, with rating of response
    by parents, a neurologist and a psychologist
  • DBPCT 51-74 of the food intolerances confirmed

37
FOODS PROVOKING HYPERACTIVITY IN DOUBLE-BLIND,
PLACEBO-CONTROL TRIAL
  • REACTIVE
  • Additives 79
  • Soy 73
  • Milk 64
  • Chocolate 59
  • Grapes 50
  • Wheat 49
  • Oranges 45
  • Cheese 40
  • Eggs 39
  • Peanuts 32
  • Corn 29
  • Fish 23
  • Oats 23
  • Melon 21
  • Tomato 20

38
Cognitive-Emotional Symptoms and Food Allergy
(King, 1981)
  • DBPCT 30 adults, 28 food extracts, sub-lingual,
    multiple measures, 2 judges
  • Symptoms associated with allergen exposure
    anxiety, depression, brain fog, irritability,
    detachment, euphoria pruritus, cold hands,
    myalgia, nasal congestion, tinnitus, fatigue,
    headache
  • Occurrence p0.001, Severity p0.002

39
FOOD ALLERGY IN PEDIATRIC MIGRAINE (Egger, 1983)
  • 88 children, oligoantigenic diet
  • 93 cleared by 2 weeks
  • 90 relapsed on open challenge
  • 40 of these, DBPC TRIAL
  • 26 confirmed (4 reacted to placebo, 8 reacted to
    neither)
  • Atopy 55, 46 hyper, 16 seizures
  • Milk, egg, chocolate, orange, wheat
  • benzoate, cheese, tomato, tartrazine, rye, fish,
  • pork, beef, corn, soy, tea

40
MIGRAINE-ASSOCIATED SYMPTOMS AND FOOD INTOLERANCE
  • 88 PATIENTS
  • Pre-diet Diet
  • Abdominal pain,
  • diarrhea 61 8
  • Hyperactivity 41 5
  • Limb pain 41 7
  • Rhinitis 34
    15
  • RAS 15 2
  • Vaginal discharge 11 1
  • Asthma 7 3
  • Eczema 6 3
  • 27/40 provoked by DBPC food trial
  • 10/40 provoked by placebo also
  • 3/40 provoked by neither

41
EVIDENCE FOR ALTERED IMMUNE ACTIVATION IN
RESPONSE TO FOODS IN MIGRAINE(Marteletti 1991,
Acta Neurologica)
  • Increased circulating immune complexes
  • Increased activated T cells and total T cells
  • Increased plasma IL-2 levels
  • Effective prophylaxis with oral sodium
    cromoglycate

42
Food Allergy in Idiopathic Nephrotic Syndrome
  • Basophile histamine release test
  • - 65 of 34 patients
  • - 5 of 19 controls
  • wheat, beef, milk, egg, pork
  • 26 patients with refractory nephrosis
  • - 6 remitted on oligoantigenic diet

43
TM, a 26 old woman with massive proteinuria,
anasarca
  • Prior aesthetician, applying artificial nails,
    developed asthma, multiple inhalant allergies,
    provoked by allergy immunotherapy
  • Severe anasarca emergency
    hospitalization, furosemide, steroids
  • Proteinuria 4 gm/day, serum albumen 1.3 gm/L,
    marked hyperlipidemia, normal biopsy
  • Required prednisone 20 mg/day maintenance

44
TM, a 26 old woman with massive proteinuria,
anasarca
  • Initial evaluation Cushingoid, 3 proteinuria
  • Method modified fast, supported by a rice-based,
    oligoantigenic food supplement, tapering down
    prednisone and daily examination of urine protein
    by dipstick
  • Result clearing of proteinuria in 7 days, return
    of proteinuria within 24 hours of ingesting hens
    eggs
  • Total remission for 7 years, avoids eggs

45
Food Intolerance and Rheumatoid Arthritis
  • 5-46 of patients in various studies have
    exacerbation of symptoms provoked by specific
    foods, mostly wheat, milk, tomatoes, various
    additives, some confirmed with DBPC trials
  • An 18-year open study of foods provoking pain in
    100 patients found that certain spices and food
    additives were commonest agents

46
GLUTEN INTOLERANCE IS PREVALENT AND PROTEAN
  • Gliadin antibodies were found in 30/53 patients
    with neurological disease of unknown cause (73
    had abnormal small bowel biopsies)
  • Hadjivassiliou et al, Lancet 347 369-371 (1996)
  • IgG and IgA gliadin antibodies occur in 2 of
    Italian school children
  • Catassi et al, Lancet 343 200-203 (1994)

47
Cows Milk Allergy and IDDM
  • Children with IDDM have IgG against a peptide
    fraction of bovine serum albumen that cross-react
    with a pancreatic beta-cell surface protein
  • Adults with recent-onset IDDM show excessive
    T-cell proliferation in response to beta-casein,
    compared to normal and auto-immune controls

48
DIAGNOSIS OF FOOD ALLERGY
  • History
  • atopic disease
  • multisystem complaints
  • fluctuations
  • provocations
  • - rough skin, red ears, geographic tongue
  • Skin tests, IgE (total/food specific)
  • Dietary elimination/challenge
  • symptom change
  • gut permeability change

49
D-XYLOSE ABSORPTION DECREASES AFTER FOOD ALLERGEN
CONSUMPTION
  • In children with cows milk protein enteropathy
    (diarrhea, pain), 1 hour blood d-xylose was
    significantly higher on a milk-free diet than 4
    days after starting a milk-containing diet
  • Morin et at, Lancet i 1102-1104 (1979)

50
(No Transcript)
51
Elimination Diets
  • Elemental
  • Oligoantigenic
  • Avoid commonest allergens milk, wheat, corn,
    soy, eggs, citrus, nuts, fish
  • Gluten and/or casein-free
  • Yeast and mold-free
  • Low-salicylate

52
Technique of Food Elimination
  • Obtain baseline measure of target symptoms or
    signs
  • Complete avoidance of all food/drink containing
    test components for 5-14 days
  • Instruct patients/parents in foods that can or
    should be eaten and in monitoring of symptoms

53
Food Challenge Techniques
  • If there is no change in target parameters,
    return to usual diet en bloc and observe for
    exacerbation
  • If improvement is observed, introduce foods
    singly, one every 1-2 days, 2-6 challenges for
    each food delayed reactions are common
  • If symptoms occur, hold challenges until clear
  • Avoid suspected symptom provokers
  • Re-challenge with these after completion

54
TREATMENT OF FOOD ALLERGY
  • Symptomatic pharmacotherapy
  • Dietary avoidance
  • Pre-prandial cromolyn 800-1600 mg/day
  • Intestinal repair
  • Probiotics
  • Hyposensitization by anergy induction
  • Counseling nutritional, psychological

55
Probiotics for Managing Food Allergy
  • Infants with atopic eczema and cows milk allergy
    fed hydrolyzed whey formula with or without
    Lactobacillus GG
  • -Clinical improvement associated with 95
    decline in fecal TNF-alpha in the Lactobacillus
    group, signifying reduced GI inflammation
  • Majamaa, Isolauri, J All Clin Immunol 1997

56
Probiotics for Prevention of Food Allergy in
Infants
  • DBPCT Lactobaciilus GG given to high risk
    mothers during last 2 weeks of pregnancy and for
    6 months after birth to their offspring
  • Atopic eczema at 2 years
  • Controls 31/68 (46)
  • Lactobacillus 15/64 (23), RR0,51
  • Kalliomaki et al, Lancet 357 1076-79 (2001)
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