Description

  • Immunoglobulin E (IgE)-mediated food allergy is a specific and reproducible immune response occurring after exposure to allergenic food that results in adverse health effects.
  • Presentation is acute, with a rapid onset, and may present as:
    • Anaphylaxis
    • Food-dependent exercise-induced anaphylaxis
    • Acute urticaria
    • Acute angioedema
    • Pollen-food syndrome: IgE cross-reactivity with heat-labile fruit/nuts in patients with pollen allergy
    • Food sensitivity: IgE antibodies to food without symptoms

Risk Factors

  • Family history of food allergy
  • Presence of atopic conditions
  • Environmental risk factors  
    • Delayed introduction of food (allergens) in infants  
    • Altered immune response (altered microbiome or vitamin D deficiency)
    • Latex allergy (due to cross-reactivity)

Causes

  • Foods
    • Most common 
      • Cow’s milk
      • Egg
      • Peanut
      • Finned fish (tuna, salmon, cod)
      • Crustacean shellfish (crab, lobster)
      • Wheat
      • Soy
      • Tree nuts (almond, cashew, hazelnut, pecan, pistachio, walnut)
    • Less common
      • Fruits (apple, kiwi, peach, etc)
      • Mammalian meats (red-meat allergy)
      • Seeds
  • Exercise, in patients with food-related exercise-induced anaphylaxis
    • Exercise induces anaphylaxis after ingestion of allergen (commonly wheat, celery, shellfish)
    • Without exercise, no reaction occurs    

Pathogenesis

  • Two phases of allergic reaction
    • Immediate (within 2 hours)
      • IgE interacts with food antigen, binds/cross-links to mast cells and basophils
      • Activated cells release inflammatory mediators (histamine, prostaglandins, leukotrienes, tryptase, cytokines, platelet-activating factors)
      • Vasoactive mediators are released into circulation (leads to vascular collapse/shock)
    • Late-phase (after several hours)
      • Results in influx of basophils and eosinophils
      • Involves granulocyte-macrophage colony-stimulating factors
      • Delayed-type reactions may occur 24 to 48 hours after ingestion

History and Physical

Clinical Presentation
  • Systems/symptoms involved may include:
    • Cutaneous: erythema, pruritis, urticaria, eczematous rash
    • Ocular: pruritis, conjunctival erythema, periorbital edema
    • Lower respiratory: cough, chest tightness, wheezing, intercostal retractions, accessory muscle use
    • Upper respiratory: nasal congestion, sneezing, hoarseness
    • Gastrointestinal: nausea, reflux, diarrhea, vomiting
    • Oral: pruritis, angioedema of lips/tongue
    • Cardiovascular: tachycardia, hypotension, dizziness, fainting
    • Neurologic: sense of impending doom
History of Present Illness
  • Ask about food consumed (preparation and amount ingested)
  • Age of and rapidity of symptom onset/reproducibility with repeat exposure
  • Ask about:
    • Exercise proximate to suspected ingestion
    • Occupational exposure to foods
    • Recent intimate behavior such as kissing
    • History of tick bites
  • In infants/young children, ask about feeding history (breastfed or formula) and food avoidance/refusal
Past Medical History
  • Ask about prior or family history of:
    • Asthma
    • Gastroesophageal reflux
    • Allergic conjunctivitis
    • Chronic gastrointestinal symptoms
    • Poor growth

Diagnosis

  • Suspect in patients with allergic symptoms and/or signs of anaphylaxis within minutes or hours of ingesting suspected food allergen
  • Proceed with testing only in patients with convincing clinical history (high sensitivity but low-to-moderate specificity of testing)
  • Approach to testing for diagnosis
    • Food-specific IgE skin prick and/or serum IgE testing
    • Oral food challenge in patients with unclear history or negative/borderline IgE testing 
    • Blind food challenge if diagnosis is unclear after oral food challenge 
    • Elimination diet in patients with unclear reactivity to suspected allergen 
  • Consider uncommon IgE-mediated food allergy conditions
    • Exercise-induced anaphylaxis (symptoms occurring only after allergen ingestion proximate to exercise)
    • Oral allergy syndrome (oropharyngeal symptoms after ingestion of raw foods cross-reactive with pollen antigens)
    • Contact urticaria (immediate urticarial rash at contact site)

Differential Diagnosis

  • Food sensitivity: IgE antibodies present without symptoms or history of allergen ingestion
  • Nonimmunoglobulin E (IgE)/mixed IgE-mediated food-related allergic disorders (celiac disease, food protein-induced enterocolitis syndrome, eosinophilic esophagitis)
  • Irritant effects and reactions due to:
    • Medications
    • Insect stings
    • Alcohol
    • EscherichiaShigella, or Salmonella species toxins
  • Food intolerance
  • Gastrointestinal reflux disease
  • Anorexia nervosa, bulimia nervosa, Munchausen syndrome by proxy

Testing

Skin Prick Testing
  • Preferred method
  • Compares response to a food protein to positive control (histamine) and negative control (saline) on pricked skin
  • Test results
    • Positive response
      • Wheal and flare response within 10 to 30 minutes
      • Mean wheal diameter ≥3 mm compared to negative control
    • Negative response
      • Helps rule out suspected allergen; may not ensure clinical tolerance
      • Consider further testing with oral food challenge
  • Contraindicated in patients with extensive skin disease, dermatographism, or ongoing antihistamine therapy
  • Consider prick-prick method with fresh food/slurry made of suspected food and sterile saline for allergy to vegetables/fruits
Blood Tests
  • Serum-specific IgE testing
    • For patients with negative skin prick test (with high clinical suspicion) or unable to undergo skin prick  
    • Higher titer of allergen-specific IgE in serum may indicate allergy 
    • Serum IgE levels may predict allergy but not reaction severity
  • Other blood tests
    • Alpha-gal oligosaccharide-specific IgE testing for history of delayed systemic reaction to mammalian meat or unexplained anaphylaxis, especially with history of tick bites (alpha-gal sensitization reported to result following Lone Star tick bites) 
    • Component-resolved diagnostics
      • Proteins derived from individual protein components of suspected food rather than whole allergen
      • Not routinely recommended (unclear utility and availability) 
Oral Food Challenge
  • Consider in patients with high suspicion of food allergy but negative/borderline skin prick or serum IgE results 
  • Do not perform if history of anaphylaxis or uncontrolled asthma
  • Delay or defer in patients with conditions affecting test interpretations (uncontrolled atopic dermatitis or urticaria)
  • Open/unmasked challenge
    • Suspected allergen fed to patient in its natural form
    • Negative results indicate oral tolerance
  • Blinded challenge
    • For patients with subjective symptoms (such as pruritus without rash)
    • Mix trigger food with another food or place in capsule
    • If food tolerance demonstrated, give unblinded full serving to ensure tolerance

Elimination Diets and Other Testing

  • Elimination diets
    • May be used as adjunctive diagnostic test
    • Elimination of ≥1 suspected allergens in patients with unclear history of reactivity
    • Should observe reduction in symptoms 
    • Reintroduce noncausal food to avoid nutritional deficits
  • Routine atopy patch testing not recommended, may be helpful in pediatric eosinophilic esophagitis (EoE)

Management

  • Management includes allergen avoidance and treatment of allergic symptoms
  • Perform emergency management if:
    • Mild/nonprogressing symptoms: antihistamines (diphenhydramine 1-2 mg/kg up to 50 mg)
    • Systemic/progressive or life-threatening symptoms
      • Epinephrine 1 mg/mL solution: for children 0.01 mg/kg (maximum 0.3 mg in prepubertal child, 0.5 mg in adolescent intramuscularly every 5-15 minutes [maximum dose, 0.5 mg]) as needed
      • Diphenhydramine 1 to 2 mg/kg (up to 50 mg)
      • Consider systemic steroids for late-phase reaction
  • Anaphylactic symptoms, provide airway and fluid support and  
    • Epinephrine intramuscularly every 5 to 15 minutes as needed
    • Histamine receptor H1 antagonist (consider histamine receptor H2 antagonist)
    • Albuterol 2.5 to 5 mg nebulized every 15 minutes or continually for bronchospasm/wheezing
    • Systemic corticosteroids
  • After acute allergic reaction
    • Observe patient ≥4 hours
    • Prednisone 1 to 2 mg/kg/d (up to 60 mg/d) orally
    • Antihistamine: histamine receptor H1 antagonist
    • Follow-up with specialist (if not previously diagnosed)
    • Follow-up with testing every 1 to 2 years
  • Sublingual immunotherapy (SLIT) and oral immunotherapy efficacy/safety research ongoing; not recommended for clinical use for food allergy treatment

Follow-Up

  • Follow-up with additional testing is recommended to determine whether allergy has been outgrown
  • Regular testing/follow-up every 12 to 18 months in first 5 years of life, then every 2 to 3 years
  • Improved skin prick test results or lower serum IgE levels may indicate improving food tolerance

Complications

  • Life-threatening and/or fatal reactions are rare (seen mostly with peanuts or tree nuts)
  • Asthma exacerbations
  • Risk for anaphylaxis with vaccines incorporating egg protein (recommendations vary based on concentration of egg protein and patient history of reactions)

Prognosis

  • Allergies to:
    • Milk, egg, soy, and wheat generally resolve in childhood
    • Peanut, tree nut, fish, and shellfish often persist into adulthood
  • Rate of allergy resolution varies based on:
    • Age of onset
    • Presence of atopic disease
    • Serum IgE level
    • Reaction severity

Prevention

  • Limited evidence on effectiveness for strategies for prevention
  • Infant diet
    • Encourage exclusive breastfeeding in first 4 to 6 months of life
    • Potentially allergenic foods may be introduced at 4 to 6 months of life
    • In infants with family history of atopy not being exclusively breastfed, consider feeding partially or extensively hydrolyzed infant formula to prevent cow’s milk allergy
    • Consider introduction of peanut-containing food at 4 to 6 months in infants with or without eczema and/or egg allergy to reduce risk of peanut allergy
    • Allergen avoidance during pregnancy or lactation not recommended due to lack of demonstrable efficacy in atopic disease prevention

Screening

  • In children with history of severe atopic disease and/or pertinent family history, consider serum food-specific IgE testing before introduction of potentially allergenic food

Kendra Church MS, PA-C, is a physician assistant at Dana-Farber Cancer Institute/Brigham & Women’s Hospital, and is also a senior clinical editor for DynaMed, an evidence-based, point-of-care database. 

Sources

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