Food Allergy

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Food Allergy

• Againdra K. Bewtra M.B.B.S., M.D.

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Food Allergy Outline

• Definitions
• Pathophysiology
• Signs and Symptoms
• Food Allergy - Induced Diseases
• Prevalence and Natural History
• Diagnosis and Management
• Prevention

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Introduction/Terms

• Adverse food reaction any aberrant reaction to
  food
• toxic vs. nontoxic
• Food intolerance any adverse reaction due to
  physiologic or nonimmunologic mechanism
• Food allergy any adverse reaction due to an
  immunologic mechanism

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Definitions Adverse Reactions to Food
A. Nonimmunologic
Toxic / Pharmacologic
Non-Toxic / Intolerance

• Bacterial food poisoning
• Heavy metal poisoning
• Scromboid fish poisoning
• Caffeine
• Alcohol
• Histamine

• Lactase deficiency
• Galactosemia
• Pancreatic insufficiency
• Gallbladder / liver disease
• Hiatal hernia
• Gustatory rhinitis
• Anorexia nervosa

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Definitions Adverse Reactions to Food
B. Immunologic Spectrum
IgE-Mediated
Non-IgE Mediated

• Oral Allergy Syndrome
• Anaphylaxis
• Urticaria
• Allergic Rhinitis
• Acute Bronchospasm

• Eosinophilic esophagitis
• Eosinophilic gastritis
• Eosinophilic gastroenteritis
• Atopic dermatitis
• Asthma

• Protein-Induced Enterocolitis
• Protein-Induced Enteropathy
• Eosinophilic proctitis
• Dermatitis herpetiformis
• Food-induced Pulmonary Hemosiderosis

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Prevalence

• More common in atopic patients
• One fourth of atopic adults report adverse
  reaction to food. (Allergy 197833189-196) Will
  alter dietary habits
• True prevalence unknown
• Public perception (20-25)gt true prevalence
• 28 mothers perceive kids to have food allergies
• 8 of these children were DBPCFC positive
  (pediatrics 198779683-196)
• 1/3 of those with suggestive history have IgE
  mediated food allergy
• 1-2 of adults
• 8 of children lt3 years, (worse if atopic)

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Pathophysiology Allergens

• Any food can cause allergic sx
• Protein (not fat / carbohydrate)
• 10-70 kD water soluble glycoproteins
• Stable to treatment with heat, acid and proteases
• Few foods cause most of food allergy
• Adults peanuts, shellfish, tree nuts, fish -gt85
• Children eggs, peanut, milk, soy, tree nuts,
  fish, shellfish, wheat -gt90
• Early introduction of foods stimulates excess IgE
• Dyes/flavorings can also elicit allergy symptoms
  but rare
• Tartrazine (FDC yellow dye No.5), found in
  orange, green or yellow food
• Flavorings nitrites, nitrates, MSG, sulfites
• Single food allergygt multiple food allergy
• Characterization of epitopes underway
• Linear vs conformational epitopes
• B-cell vs T-cell epitopes

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Food Allergy Prevalence in Specific Disorders
Disorder
Food Allergy Prevalence
Anaphylaxis
35-55
Oral allergy syndrome
25-75 in pollen allergic
37 in children (rare in adults)
Atopic dermatitis
20 in acute (rare in chronic)
Urticaria
5-6 in asthmatic or food allergic children
Asthma
Chronic rhinitis
Rare
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Pathogenesis of Food Allergy

• Gut barriers Physical
• defensive barrier against pathogens tolerate
  food protein
• gastric acid, proteolytic enzymes, mucus,
  peristalsis
• digest protein to make it less antigenic by
  reduce size, alter the structure
• Gut barrier Immunologic - Dominant response is
  tolerance
• GALT Peyers patches, appendix, IELC
  (Intraepithelial lymphocytic cells), LC, plasma
  cells, mast cells - lamina propria, mesenteric
  LN
• Food ingestion?Ab release (?sIgA) (?IgG, IgM,
  IgE)
• sIgA binds protein, forms complexes decreased
  absorption
• 2 macromolecules are absorbed-to these oral
  tolerance devel.

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Pathogenesis of Food Allergy

• Dominant response of GALT is suppression/tolerance
  
• Oral tolerance induction occurs by IELC and GALT
• IEC Soluble Ag(food) presented primarily by IELC
  leading to immune suppression
• Central APC for immunosuppression in the gut
• Have MHC-II and present Ag to CD8 by (CD1d)
• GALT Pathogens selectively presented to M cells
  in the (GALT)
• bacteria, viruses, parasites
• sampled by M cells (Peyers patches) ? IgA

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Barrier immaturity in the Infant

• Low basal acid output
• Immature intestinal proteolytic activity
• Immature microvilli-gt Ag transport into IEC
• Newborns lack sIgA and IgM in exocrine secretion
• Early introduction of numerous food Ag stimulates
  excess IgE

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Pathogenesis of Food Allergy

• Genetic predisposition to lack of oral tolerance
• Food-specific IgE bind to Fc?RI on mast
  cells/basophils and Fc?RII on macrophages,
  monocytes, lymphocytes, eosinophils and platelets
• Release of mediators which produce vasodilation,
  smooth muscle contraction, mucus secretion.
• Non-IgE possibly Type III, Type IV

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Pathophysiology Immune Mechanisms

• Protein digestion
• Antigen processing
• Some Ag enters blood

IgE-Mediated
IgE-receptor
APC
Mast cell
Non-IgE Mediated
Histamine

• TNF-?
• IL-5

T cell
B cell
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Signs and Symptoms
IgE Non-IgE Acute
Chronic Skin Urticaria Angioedema Atopic
dermatitis Respiratory Throat
tightness Rhinitis Asthma Gut Vomit Diar
rhea Pain Anaphylaxis
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Clinical Disorders-Signs and Symptoms

• IgE vs. non-IgE
• GI, cutaneous, respiratory
• IgE
• GI vomit, diarrhea, pain
• Resp throat tightness, rhinitis, asthma
• Skin urticaria, angioedema, atopic dermatitis
• Other GI Findings gastric hypotonia, retention
  of meal, pylorospasm, peristaltic changes
• Non-IgE
• GI vomiting, diarrhea, pain
• Resp asthma
• Skin atopic dermatitis

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Oral Allergy Syndrome

• ? Contact urticaria
• Rapid onset, IgE-mediated, rarely progressive
• Oral pruritis, tingling, AE of lips, tongue,
  palate, throat
• Usually fresh fruits and vegetables
• Heat labile cooked forms no reaction
• Cause cross reactive proteins in pollen/food
  (fruit or vegetables)

Pollen
Foods
Birch Apple, apricot, carrot, cherry, kiwi,
plum Ragweed Banana, cucumber, melon,
watermelon Grass Cherry, peach, potato, tomato
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Fatal Food Anaphylaxis

• Frequency 150 deaths / year
• Risk
• Underlying asthma Delayed epinephrine
• Symptom denial Previous severe reaction
• History known allergic food
• Key foods peanut / nuts / shellfish
• Biphasic reaction
• Lack of cutaneous symptoms

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Anaphylaxis / Anaphylaxis Syndromes

• Food-induced anaphylaxis (IgE mediated)
• Rapid-onset
• Multi-organ system involvement
• Potentially fatal
• Any food, highest risk peanut, nut, seafood
• Symptoms cutaneous, respiratory, hypotension,
  vascular collapse, dysrythmias
• Pts usually have the following in common
• Asthma, accidental ingestion of the food
  allergen, previous allergic reaction to the same
  food, immediate symptoms
• Food-associated, exercise-induced (usually within
  2-4 hours after ingestion of food)
• Associated with a particular food
• Associated with eating any food

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Prevalence of Clinical Cross Reactivity Among
Food Families
Prevalence of Allergy to gt 1 Food in
Family
Food Allergy
Fish
30 -100
Tree Nut
15 - 40
Grain
25
Legume
5
Any
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Cross Reactivity of Foods
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Disorders Not Proven to be Related to Food Allergy

• Migraines
• Behavioral / Developmental disorders
• Arthritis
• Seizures
• Inflammatory bowel disease

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Natural History

• Dependent on food immuno-pathogenesis
• 85 CM, egg, wheat, soy allergy remit by 3 yrs
  
• Declining/low levels of specific-IgE predictive
• IgE binding to conformational epitopes predictive
• Allergy to peanut, nuts, seafood typically
  persist
• Non-IgE-mediated GI allergy
• Infant forms resolve 1-3 years
• Toddler / adult forms more persistent

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Diagnosis History / Physical

• History symptoms, timing, reproducibility
• Acute reactions vs chronic disease
• Diet details / symptom diary
• Specific causal food(s)
• Hidden ingredient(s)
• Physical examination evaluate disease severity
• Identify general mechanism
• Allergy vs intolerance
• IgE versus non-IgE mediated

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Signs and Symptoms of Food Allergy
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Diagnosis Laboratory Evaluation

• Suspect IgE-mediated
• Prick skin tests (fresh extract if oral allergy)
• RAST
• Suspect non-IgE-mediated
• Consider biopsy of gut, skin
• Suspect non-allergic, consider
• Breath hydrogen
• Sweat test
• Endoscopy
• Adjunctive tests
• Endoscopy,/biopsy, stool analysis (heme,
  leukocytes, eosinophils)
• Elimination diet ? proof of reactivity
• Oral food challenge DBPCFC
• Gold standard

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Interpretation of Laboratory Tests

• Positive prick test or RAST
• Indicates presence of IgE antibody NOT clinical
  reactivity (50 false positive)
• Negative prick test or RAST
• Essentially excludes IgE antibody (gt95)
• ID skin test with food
• Risk of systemic reaction not predictive
• Contraindicated
• Unproven/experimental tests (useless)
• Provocation/neutralization, cytotoxic tests,
  applied kinesiology, hair analysis, IgG4

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CAP-RAST FEIA
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Diagnosis Elimination Diets and Food Challenges

• Elimination diets (1 to 6 weeks)
• Eliminate suspected food(s), or
• Prescribe limited eat only diet, or
• Elemental diet
• Oral challenge testing (MD supervised, ER meds
  available)
• Open
• Single-blind
• Double-blind, placebo-controlled (DBPCFC)

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Diagnostic Approach IgE-Mediated Allergy

• Test for specific-IgE antibody
• Negative reintroduce food
• Positive start elimination diet
• Elimination diet
• No resolution reintroduce food
• Resolution
• Open / single-blind challenges to screen
• DBPCFC for equivocal open challenges

Unless convincing history warrants supervised
challenge
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Diagnostic Approach Non-IgE-Mediated Disease

• Includes disease with unknown mechanisms
• Food additive allergy
• Elimination diets (may need elemental diet)
• Oral Challenges
• Timing/dose/approach individualized for disorder
• Enterocolitis syndrome can elicit shock
• Enteropathy / eosinophilic gastroenteritis may
  need prolonged feedings to develop symptoms
• DBPCFCs preferred
• May require ancillary testing
  (endoscopy / biopsy)

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Diagnostic Approach to Evaluating Food Allergy
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Treatment

• Strict avoidance
• Difficult
• Of 32 peanut allergic patients studied by bock et
  al. Only 8 were successful at peanut avoidance
  for 5 years.
• Impossible
• Peanut allergens on airplanes.

• Medicine
• Epi-pen carried at all times
• Instructed use in office
• Use and go to E.R.
• Observe 4 hours
• Risk of fatality increases with delay in
  epinephrine administration
• 1/3 of pts with fatal or near fatal anaphylaxis
  had biphasic reaction

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Treatment Dietary Elimination

• Hidden ingredients (peanut in sauces or egg
  rolls)
• Labeling issues (spices, changes, errors)
• Cross contamination (shared equipment)
• Code words (Natural flavor may be CM)
• Seeking assistance
• Registered dietitian (www.eatright.org)
• Food Allergy Network (www.foodallergy.org
  800-929-4040)

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Example Milk Elimination

• Artificial butter flavor, butter, butter fat,
  buttermilk, casein, caseinates (sodium, calcium,
  etc.), cheese, cream, cottage cheese, curds,
  custard, HalfHalf, hydrolysates (casein, milk,
  whey), lactalbumin, lactose, milk (derivatives,
  protein, solids, malted, condensed, evaporated,
  dry, whole, low-fat, non-fat, skim), nougat,
  pudding, rennet casein, sour cream, sour cream
  solids, sour milk solids, whey (delactosed,
  demineralized, protein concentrate), yogurt. MAY
  contain milk brown sugar flavoring, natural
  flavoring, chocolate, caramel flavoring, high
  protein flour, margarine, Simplesse.

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Treatment Emergency Medications

• Epinephrine drug of choice for reactions
• Self-administered epinephrine readily available
• Train patients indications/technique
• Antihistamines secondary therapy
• Emergency plan in writing
• Schools, spouses, caregivers, mature sibs /
  friends
• Emergency identification bracelet

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Treatment Follow-Up

• Re-evaluate for tolerance periodically
• Interval and decision to re-challenge
• Type of food allergy
• Severity of previous symptoms
• Allergen
• Ancillary testing
• Skin prick test/RAST may remain positive
• Reduced concentration food specific-IgE
  encouraging

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Allergy Prevention
Pollutants, Tobacco smoke
Food allergens early
Infections
?
Genes Gender
Inflammation
Sensitization
Primary
Damage
Secondary
Tertiary
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Other Treatments

• Possibly effective
• Immunotherapy
• Treatment of peanut allergy with rush I.T.
  Oppenheimer JJ et al. JACI 199290256-262
• Oral allergen gene immunization
• Mice
• Roy et al
• Horner et al reported decreased anaphylaxis with
  DNA vaccine

• Generally found not effective
• H1 and H2 antihistamines
• Oral Cromolyn sodium
• Ketotofin
• Antiprostaglandins

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Future Immunomodulatory Therapies

• Recombinant anti-IgE antibody
• Gene (naked DNA) immunization
• Mutated B-cell epitopes
• Minimal T-cell epitopes
• Immune-modulating adjuvants (ISS)
• Probiotics

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Reasons for Allergy Referral

• Identification of causative food
• Institution of elimination diet
• Education on food avoidance
• Development of action plan
• Prevention of other allergies

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Guidelines for Food Allergy
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Conclusion

• 2 of the population have food allergy
• Children milk, eggs, peanuts, soy, wheat
• Adults peanuts, shellfish, nuts, fish
• History and physical
• IgE and non-IgE mediated conditions exist
• Dx by elimination and challenge
• Tx avoidance, education, preparation for
  emergencies
• Periodic re-challenge to monitor tolerance

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