Transcript Food Allergy - What is 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
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
Total number Hyperactivity: Normal Mild Moderate Severe Conners’ score Antisocial acts Headache Seizures Abdominal pain Limb pain Eczema, rash Aphthous ulcers Atopic (prick test) Pre-diet Diet 76 76 0 6 31 21 28 19 39 8 24 12 32 13 48 14 29 9 1 54 8 33 6 9 5 30 (39%)
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
Additives Soy Milk Chocolate Grapes Wheat Oranges Cheese Eggs Peanuts Corn Fish Oats Melon Tomato % REACTIVE Foundation for Integrated Medicine 39 32 29 23 23 21 20 79 73 64 59 50 49 45 40
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 Hyperactivity Limb pain Rhinitis RAS Vaginal discharge Asthma Eczema 61 41 41 34 15 11 7 6 8 5 7 15 2 1 3 3 27/40 provoked by DBPC food trial 10/40 provoked by placebo also Foundation for Integrated Medicine 3/40 provoked by neither
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
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
Total number Hyperactivity: Normal Mild Moderate Severe Conners’ score Antisocial acts Headache Seizures Abdominal pain Limb pain Eczema, rash Aphthous ulcers Atopic (prick test) Pre-diet Diet 76 76 0 6 31 21 28 19 39 8 24 12 32 13 48 14 29 9 1 54 8 33 6 9 5 30 (39%)
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
Additives Soy Milk Chocolate Grapes Wheat Oranges Cheese Eggs Peanuts Corn Fish Oats Melon Tomato % REACTIVE Foundation for Integrated Medicine 39 32 29 23 23 21 20 79 73 64 59 50 49 45 40
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 Hyperactivity Limb pain Rhinitis RAS Vaginal discharge Asthma Eczema 61 41 41 34 15 11 7 6 8 5 7 15 2 1 3 3 27/40 provoked by DBPC food trial 10/40 provoked by placebo also Foundation for Integrated Medicine 3/40 provoked by neither
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 exacerbation
en bloc
and observe for • 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)
Foundation for Integrated Medicine