II. Epidemiology

  1. Incidence of Food Allergy
    1. Adults: 2-3%
    2. Children: 4-5% (up to 8%)
      1. Up to 15% of parents believe their children have Food Allergy, but most cases are unproven
  2. Prevalence of most common specific food allergens
    1. Milk Allergy: 0.9% (up to 6% in studies based on parent or self-report)
    2. Egg Allergy: 0.3% (up to 1% in studies based on parent or self-report)
    3. Seafood allergy: Up to 2.8% of adults (based on parent or self-report)
    4. Peanut allergy: 0.6 to 2% (based on parent or self-report)
    5. Tree nut allergy: 0.4% (based on parent or self-report)
  3. Precautions
    1. Food allergies are often over-estimated (mislabeled food intolerances)

III. Risk Factors

  1. Latex Allergy (Odds Ratio 7.9)
  2. Asthma (Odds Ratio 3.2)
  3. Urticaria (Odds Ratio 2.9)
  4. Insect venom allergy (Odds Ratio 2.5)
  5. Allergic Rhinitis (Odds Ratio 2.3)
  6. Atopic Dermatitis (Odds Ratio 1.9)
  7. Family History of atopic disease (Atopic Dermatitis, Asthma, Allergic Rhinitis)
  8. Tick Bite (lone star tick) predisposes to Alpha-Gal Reaction
    1. Sensitization to galactose-alpha-1,3-galactose (alpha-gal), found in both ticks and red meat
    2. Results in severe, sudden, Allergic Reaction (Urticaria, Anaphylaxis) to beef, lamb, pork

IV. History

  1. History from parent, Caregiver or patient (consider food diary)
  2. Risk Factors (see above)
  3. Food eaten
    1. Preparation of food (e.g. raw, processed)
    2. Amount of food
    3. Symptoms after taking the food
    4. Timing of intake to reaction
    5. Number of prior reactions or frequency of reaction

V. Causes: Common Food Allergies

  1. Children
    1. Cow's Milk Allergy
    2. Egg Whites
    3. Wheat
    4. Soy
    5. Peanuts
  2. Adults
    1. Crustaceans (e.g. shrimp, lobster)
    2. Tree nuts
    3. Peanuts
    4. Fish

VI. Causes: Food Allergies associated with Anaphylaxis

  1. Nuts (allergy often seen in Atopic Patients)
    1. Peanuts (legume)
      1. Most common cause of food-related Anaphylaxis
    2. Tree nuts
      1. Pistachios
      2. Walnuts
      3. Cashews
      4. Almonds (and marzipan)
      5. Hazelnuts or filberts
      6. Macadamian Nuts
      7. Pecans
      8. Brazil nuts
      9. Pine nuts
  2. Fish
  3. Shellfish
    1. Crab
    2. Crayfish
    3. Prawns or shrimp
    4. Lobster
  4. Seeds
    1. Sesame seeds
    2. Sunflower seeds
    3. Caraway seeds

VII. Causes: Cross-reactivity with contact or air-borne allergens

  1. See Oral Allergy Syndrome
  2. Latex Allergy
    1. Banana
    2. Kiwi
    3. Avocado
  3. Birch pollen allergy
    1. Carrot
    2. Celery
    3. Hazelnuts
    4. Parsnips
    5. Potatoes
    6. Fresh fruit (apples, cherries, nectarines, peaches, pears)
  4. Grass pollen
    1. Kiwi
    2. Tomato
  5. Ragweed pollen
    1. Bananas
    2. Melons (canteloupe, honeydew, watermelon)

VIII. Pathophysiology

  1. Initial reaction (Sensitization)
    1. IgE antibodies produced to food
  2. Subsequent Reaction
    1. IgE fixed to Mast Cells in Skin, GI, Respiratory
    2. Reacts to allergen
    3. Releases
      1. Histamine
      2. Chemotactics attract Eosinophils
      3. Prostaglandins and Leukotrienes are released

IX. Types: Clinical Presentations of Food Allergies

  1. General
    1. IgE mediated Allergic Reaction (Urticaria, Anaphylaxis) are rapid onset (within minutes of exposure)
    2. Non-Ige mediated reactions are delayed hours to days
  2. Emergent presentations
    1. Food-induced Anaphylaxis
    2. Laryngeal Angioedema
  3. Skin reactions
    1. Acute Urticaria (IgE mediated)
    2. Allergic Contact Dermatitis (cell-mediated)
    3. Angioedema (IgE mediated)
    4. Contact Urticaria (IgE and non-Ige mediated)
  4. Gastrointestinal food allergies
    1. Dietary Protein-induced Proctocolitis (non-IgE mediated to milk in infants)
    2. Eosinophilic Esophagitis (IgE and non-IgE mediated)
    3. Food Protein-induced enterocolitis (non-IgE mediated)
    4. Immediate GI Hypersensitivity (IgE mediated)
    5. Oral Allergy Syndrome (cross-reactivity among foods; prevented by cooking offending food)

X. Symptoms

XI. Differential Diagnosis: Postprandial collapse

  1. Airway Foreign Body
  2. Non-allergic Food Reaction
    1. Monosodium Glutamate
    2. Sulfite reaction
    3. Scombroid Fish Poisoning (vasoactive amines)

XII. Differential Diagnosis: Non-allergic Gastrointestinal Food Reactions

  1. Lactose Intolerance
  2. Irritable Bowel Syndrome
  3. Carcinoid Syndrome
  4. Giardiasis
  5. Celiac Sprue
    1. Celiac Sprue is an autoimmune Enteropathy (not a Food Allergy)
    2. Unlike food allergies, Celiac Sprue does not cause Anaphylaxis

XIII. Diagnosis

  1. See Allergy Screening
  2. Immediate Reacting IgE skin Test (preferred)
    1. See Skin Prick Test
    2. Epicutaneous stick with Fresh Food Extract
    3. High Test Sensitivity and Test Specificity
    4. Indicated in patients with high probability of Food Allergy based on detailed history
    5. Contraindications
      1. Do NOT perform for food suspected of Anaphylaxis
      2. Only perform in settings with providers prepared for Anaphylaxis
  3. In-Vitro test for allergen-specific IgE Antibodies (RAST, ELISA)
    1. See Allergen Specific IgE Antibody Measurement
    2. Less sensitive than skin test
    3. Safe alternative to skin test (e.g. Anaphylaxis suspected)
  4. Double Blind Open Food Challenge
    1. Performed under medical provider supervision
    2. Use for reintroduction of foods after 2-3 years
      1. For foods with less serious reactions (e.g. Hives to milk or eggs)
  5. Other methods
    1. Diet diaries
    2. Short-term Elimination Diets

XIV. Management: General

  1. Anaphylaxis Reaction History
    1. See Anaphylaxis
    2. Indefinitely avoid causative food
    3. Epinephrine Self-Injectors for home/school (Should have 2 pens available)
      1. Child over age 6
        1. Epinephrine (1:1000) 0.3 mg SQ (EpiPen)
      2. Child under age 6
        1. Epinephrine (1:2000) 0.15 mg SQ (Epi-Pen Jr)
  2. Reintroduction of Prior Food Allergies (not Anaphylaxis)
    1. Mix with other foods
      1. Eggs in baked products (instead of scrambled eggs)
      2. Milk in Cheese or yogurt (instead of glass of milk)
    2. Do not reintroduce foods with previous Anaphylaxis
      1. Do not re-introduce nuts, seeds or seafood if prior Allergic Reaction (especially if history of Anaphylaxis)
  3. Other measures
    1. Allergen Immunotherapy
    2. Omalizumab
      1. Prophylaxis of serious Food Allergy reactions from accidental exposure (egg, milk, peanuts, tree nuts)
      2. Indicated in high risk patients (e.g. Anaphylaxis to food allergan) OR dual indications (e.g. Asthma and Food Allergy)
      3. FDA approved indication in 2024
      4. (2024) Presc Lett 31(5): 28

XV. Management: Specific Food Issues

  1. Egg Allergy and Vaccinations
    1. Indicated Vaccines regardless of egg allergy severity (these Vaccines contain only minute egg amounts)
      1. Measles Mumps Rubella Vaccine (MMR Vaccine)
      2. Varicella Vaccine
    2. Influenza Vaccine
      1. See Influenza Vaccine
      2. May be given if egg Allergic Reaction was limited to Urticaria (especially if tolerates egg containing foods)
        1. Consider monitoring for 2 hours after Vaccination
        2. Skin Testing for Influenza Vaccine reaction is not recommended due to high False Positive Rate
      3. Some Influenza Vaccines have no risk of egg Protein exposure
        1. Quadrivalent recombinant Influenza Vaccine (RIV4, Flublok)
        2. Cell culture Based Quadrivalent Inactivated Influenza Vaccine (ccIIV4, Flucelvax)
    3. Contraindicated Vaccines (if hives, Angioedema, Anaphylaxis to egg)
      1. Rabies Vaccine
      2. Yellow Fever Vaccine
  2. Fish Allergy
    1. Avoid fresh and saltwater fish
    2. Most fish-allergic patients can tolerate canned tuna
  3. Nut allergy (often associated with Anaphylaxis)
    1. See Palforzia (Peanut Allergen Powder)
    2. Do not eat at buffets
    3. Avoid unlabeled candies and desserts
    4. Avoid ice cream parlors
  4. Crustacean allergy
    1. Avoid all crustaceans (shrimp, lobster, crab...)
  5. Milk allergy
    1. Avoid not only cow's milk, but also sheep and goat's milk
    2. Avoid butter or margarine containing milk
    3. Infants
      1. Differentiate from Infantile Colic
        1. Colic will resolve spontaneously after 3-4 months
        2. Milk substitution is unnecessary
      2. Substitute Casein Hydrolysate (Cow's Milk) Formula
        1. Nutramigen, Pregestimil, Alimentum
        2. Soy-based formula is not appropriate substitution

XVI. Associated Conditions

  1. Oral Allergy Syndrome
  2. Food dependent Exercise induced Anaphylaxis (rare)
    1. Wheat is most common associated food trigger
    2. Anaphylaxis occurs only if specific food trigger ingested before Exercise
    3. Space Exercise at least 6 hours after trigger food is ingested
  3. Food-induced Urticaria
    1. Food allergies account for 30% of acute cases but rarely cause Chronic Urticaria
  4. Atopic Dermatitis
    1. Improves when eggs, milk and peanuts are removed from diet

XVII. Associated Conditions: Conditions NOT associated with Food Allergy

  1. Abnormal Child Behavior
    1. Myths:
      1. Hyperactivity, Insomnia, Anxiety (Shannon,1922)
      2. "Allergic Attention Fatigue Syndrome" (Rowe, 1950)
    2. Reality
      1. No proven relationships
  2. Attention-Deficit Disorder (ADD)
    1. Myth: Attention Deficit Disorder related to dietary additives
      1. Dietary Salicylates
      2. Artificial food colors and flavors
        1. Feingold, 1975
    2. Reality
      1. Only 2% ADD Children would benefit from diet change
    3. Reference
      1. Lipton (1983) J Am Diet Assoc 83:132-4 [PubMed]
  3. Sugar "Allergy"
    1. Myth: Refined sugars aggravate behavioral problems
      1. Suggested to provoke hyperactivity, aggressive, inappropriate behavior
    2. Reality
      1. Sugar does not increase activity
        1. Milich (1986) Clin Psychol Rev 6:493-513 [PubMed]
        2. Mahan (1988) Ann Allergy 61:453-8 [PubMed]
      2. Sucrose has "calming effect" when c/w Aspartame
        1. Kruesi (1986) Annu Rev Nutr 6:113-30 [PubMed]
        2. Bachorowski (1990) Pediatrics 86:244-53 [PubMed]

XVIII. Prognosis

  1. Transient Food Allergies
    1. Most food allergies last only a few years
    2. Milk, eggs, wheat or soy allergies usually resolve
      1. Egg allergy: 70% resolve by age 5 years
      2. Milk allergy: 85% resolve by age 5 years
  2. Lifelong Food allergies
    1. Foods associated with systemic Anaphylaxis
    2. Nuts, fish, seed allergies persist
      1. However, peanut allergy resolves in up to 20% of children in first 5 years

XIX. Prevention

  1. Recommended strategies to prevent Food Allergy
    1. Avoid cow's milk supplementation in the first few days of life
      1. Reduces risk of cow's milk, egg and wheat allergies in the first 3 years of life in children with atopy
      2. Urashima (2019) Pediatr Allergy Immunol 32(5): 843-58 [PubMed]
    2. Solid food introduction by 6 months of age
      1. Potentially allergenic foods may be introduced at this time
      2. Early (age 4 to 6 months) sequential exposure to allergenic foods reduces risk of future Food Allergy
        1. Includes peanut containing food
        2. Skjerven (2022) Lancet 399(10344): 2398-411 [PubMed]
  2. Strategies to avoid (not effective or unsupported)
    1. Soy infant formula substitution for cow's milk infant formula is not recommended
    2. Maternal dietary restrictions during pregnancy and Lactation are not recommended
    3. Exclusive Breast Feeding until 4-6 months of age does NOT appear to reduce Food Allergy risk
      1. However, does reduce Asthma and Eczema risk

XX. Resources

  1. Food Allergy and Anaphylaxis Network
    1. http://www.foodallergy.org

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