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Food Allergy

Food Allergy. Leo Galland M.D. 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.

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Food Allergy

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

  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) Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 (p<0.005) • Carbon oxidation (debrisoquine): normal • Theory: altered metabolism of food chemicals toxic/immunogenic metabolites by novel pathways Foundation for Integrated Medicine

  6. Foundation for Integrated Medicine

  7. Atopic Eczema Allergic Rhinitis, Asthma Anaphylaxis, Angioedema, Urticaria Oral Allergy Syndrome (Ortolani) Aphthous Ulceration Alveolitis, Hemosiderosis Infantile Colic Vomiting, Diarrhea, Abdominal Pain Irritable BowelSyndrome 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) FOOD ALLERGY/INTOLERANCE: WELL-DOCUMENTED MANIFESTATIONS Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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%) Foundation for Integrated Medicine

  13. 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

  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 Foundation for Integrated Medicine

  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 p=0.001, Severity p=0.002 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 hen’s eggs • Total remission for 7 years, avoids eggs Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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) Foundation for Integrated Medicine

  24. 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

  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%) Foundation for Integrated Medicine

  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) Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 (p<0.005) • Carbon oxidation (debrisoquine): normal • Theory: altered metabolism of food chemicals toxic/immunogenic metabolites by novel pathways Foundation for Integrated Medicine

  29. Foundation for Integrated Medicine

  30. Atopic Eczema Allergic Rhinitis, Asthma Anaphylaxis, Angioedema, Urticaria Oral Allergy Syndrome (Ortolani) Aphthous Ulceration Alveolitis, Hemosiderosis Infantile Colic Vomiting, Diarrhea, Abdominal Pain Irritable BowelSyndrome 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) FOOD ALLERGY/INTOLERANCE: WELL-DOCUMENTED MANIFESTATIONS Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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%) Foundation for Integrated Medicine

  36. 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

  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 Foundation for Integrated Medicine

  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 p=0.001, Severity p=0.002 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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 hen’s eggs • Total remission for 7 years, avoids eggs Foundation for Integrated Medicine

  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 Foundation for Integrated Medicine

  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) Foundation for Integrated Medicine

  47. 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

  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 Foundation for Integrated Medicine

  49. 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

  50. Foundation for Integrated Medicine

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