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Foundation for Integrated Medicine
Food Allergy
Leo Galland M.D.
Foundation for Integrated Medicine
Foundation for Integrated Medicine
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%)
Foundation for Integrated Medicine
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)
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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 (p<0.005)
• Carbon oxidation (debrisoquine): normal• Theory: altered metabolism of food
chemicals toxic/immunogenic metabolites by novel pathways
Foundation for Integrated Medicine
Foundation for Integrated Medicine
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• Crohn’s Disease
(exacerbation)• Migraine headches• Migraine-associated Epilepsy• ADHD• Nephrotic Syndrome• Allergic Arthritis• Rheumatoid Arthritis
(exacerbation)
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
RESPONSE TO OLIGOANTIGENIC DIET IN HYPERKINETIC SYNDROME
Pre-diet DietTotal number 76 76
Hyperactivity: Normal 0 21 Mild 6 28 Moderate 31 19 Severe 39 8Conners’ score 24 12Antisocial acts 32 13Headache 48 9Seizures 14 1Abdominal pain 54 8Limb pain 33 6Eczema, rash 29 9Aphthous ulcers 15 5Atopic (prick test) 30 (39%)
Foundation for Integrated Medicine
Summary of Egger’s 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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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 p=0.001, Severity p=0.002
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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 hen’s eggs
• Total remission for 7 years, avoids eggs
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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)
Foundation for Integrated Medicine
Cow’s 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
Foundation for Integrated Medicine
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%)
Foundation for Integrated Medicine
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)
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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 (p<0.005)
• Carbon oxidation (debrisoquine): normal• Theory: altered metabolism of food
chemicals toxic/immunogenic metabolites by novel pathways
Foundation for Integrated Medicine
Foundation for Integrated Medicine
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• Crohn’s Disease
(exacerbation)• Migraine headches• Migraine-associated Epilepsy• ADHD• Nephrotic Syndrome• Allergic Arthritis• Rheumatoid Arthritis
(exacerbation)
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
RESPONSE TO OLIGOANTIGENIC DIET IN HYPERKINETIC SYNDROME
Pre-diet DietTotal number 76 76
Hyperactivity: Normal 0 21 Mild 6 28 Moderate 31 19 Severe 39 8Conners’ score 24 12Antisocial acts 32 13Headache 48 9Seizures 14 1Abdominal pain 54 8Limb pain 33 6Eczema, rash 29 9Aphthous ulcers 15 5Atopic (prick test) 30 (39%)
Foundation for Integrated Medicine
Summary of Egger’s 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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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 p=0.001, Severity p=0.002
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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 hen’s eggs
• Total remission for 7 years, avoids eggs
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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)
Foundation for Integrated Medicine
Cow’s 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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
D-XYLOSE ABSORPTION DECREASES AFTER FOOD ALLERGEN CONSUMPTION
• In children with cow’s 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)
Foundation for Integrated Medicine
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
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
Foundation for Integrated Medicine
Probiotics for Managing Food Allergy
• Infants with atopic eczema and cow’s 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
Foundation for Integrated Medicine
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%), RR=0,51
Kalliomaki et al, Lancet 357: 1076-79 (2001)