Download Food Allergy

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
for Integrated Medicine
24 noFoundation
correlation
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
76
0
6
31
39
24
32
48
14
54
33
29
Foundation for Integrated
15 Medicine
30 (39%)
Diet
76
21
28
19
8
12
13
9
1
8
6
9
5
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
Soy
Milk
Chocolate
Grapes
Wheat
Oranges
Cheese
Eggs
Peanuts
Corn
Fish
Oats
Melon
Tomato
Foundation for Integrated Medicine
79
73
64
59
50
49
45
40
39
32
29
23
23
21
20
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
27/40 provoked by DBPC food trial
10/40 provoked by placebo also
Foundation for Integrated Medicine
3/40 provoked by neither
8
5
7
15
2
1
3
3
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 ricebased, 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
for Integrated Medicine
24 noFoundation
correlation
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
76
0
6
31
39
24
32
48
14
54
33
29
Foundation for Integrated
15 Medicine
30 (39%)
Diet
76
21
28
19
8
12
13
9
1
8
6
9
5
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
Soy
Milk
Chocolate
Grapes
Wheat
Oranges
Cheese
Eggs
Peanuts
Corn
Fish
Oats
Melon
Tomato
Foundation for Integrated Medicine
79
73
64
59
50
49
45
40
39
32
29
23
23
21
20
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
27/40 provoked by DBPC food trial
10/40 provoked by placebo also
Foundation for Integrated Medicine
3/40 provoked by neither
8
5
7
15
2
1
3
3
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 ricebased, 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)
Foundation for Integrated Medicine