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
- Most common
- 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
- Immediate (within 2 hours)
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
- Escherichia, Shigella, 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
- Positive response
- 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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- Abrams EM, Sicherer SH. Diagnosis and management of food allergy. CMAJ. 2016;188(15):1087-1093. doi:10.1503/cmaj.160124
- Sampson HA, Aceves S, Bock SA, et al. Food allergy: a practice parameter update-2014. J Allergy Clin Immunol. 2014;134(5):1016-25.e43. doi:10.1016/j.jaci.2014.05.013
- Boyce JA, Assa’ad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol. 2010;126(6 Suppl):S1-58. doi:10.1016/j.jaci.2010.10.007
- Sackeyfio A, Senthinathan A, Kandaswamy P, et al. Diagnosis and assessment of food allergy in children and young people: summary of NICE guidance. BMJ. 2011;342:d747. doi:10.1136/bmj.d747
- National Institute for Health and Care Excellence (NICE). Food allergy in under 19s: assessment and diagnosis. February 23, 2011. Accessed June 8, 2021. https://www.nice.org.uk/guidance/cg116