Food Allergy

Adverse food reactions are untoward responses following the ingestion of a food and can be divided into food allergies (immunologically mediated) and all other reactions (nonimmunologic). Adverse food reactions are common, but nonimmunologic reactions to food are more common than true immunologically mediated food allergies.

Nonimmunologic reactions may include gastrointestinal disorders (e.g., lactase deficiency), toxic reactions (including scombroid poisoning), intolerance (e.g., tyramine-containing foods), psychological reactions (food phobias or aversions), or accidental contamination, and these are not covered in this guide.

Food allergies can be divided into immunoglobulin E (IgE)-mediated or non-IgE-mediated processes.

IgE-Mediated Food Allergies

Presentation

IgE-mediated food allergy occurs within minutes to 2 hours after food ingestion. A notable exception is allergy to mammalian meat (beef, pork, lamb), which can be immediate or can be due to an allergy caused by galactose-alpha-1,3-galactose (alpha-gal), with symptoms evolving up to 6 hours after ingestion.

• Symptoms can include:

  • cutaneous reactions: urticaria, angioedema, flushing

  • gastrointestinal manifestations: nausea, vomiting, diarrhea, abdominal pain

  • oral symptoms: tongue, lip, or perioral edema and pruritus

  • respiratory symptoms: bronchoconstriction and wheezing

  • cardiovascular symptoms: hypotension, tachycardia

• The most commonly implicated foods include cow’s milk, eggs, peanuts, soy, tree nuts, fish, shellfish, and wheat.

Diagnosis

A thorough history is essential and should include temporal association, reproducibility, and clinical symptoms, as described in the following table:

(Source: Food Allergy. N Engl J Med 2008.)

Testing

Confirmation and assessment of food-specific IgE-mediated food allergy can be performed by skin-prick testing (SPT) or in vitro tests.

• Negative predictive value is >90%, but positive predictive value of food SPT is <50%. Therefore, testing is best used to evaluate a patient with a suggestive clinical history. The high sensitivity makes testing highly effective in ruling out allergy, but the low specificity and false-positive tests makes it a poor screening.

• In vitro tests are very sensitive and have a high false-positive rate. Thus, lab testing should only be performed to evaluate specific foods with clinical suspicion guiding the testing.

• Specific IgE testing can also be helpful when skin-testing results are equivocal, to evaluate patients who cannot be skin tested, and to trend sensitization over time, especially in children who are likely to outgrow food allergies and become candidates for oral food challenge.

• Food allergy guidelines do not recommend broadly testing a whole “panel” of foods.

• Specific immunoglobulin G (IgG) testing for foods is not a clinically relevant tool for diagnosing food allergies and should not be ordered.

• Oral food challenges can be performed for the diagnosis of food allergies and can help evaluate the development of tolerance.

  • Oral food challenges should only be performed in a clinic with trained staff who are knowledgeable and comfortable with the treatment of anaphylaxis and where medications and supplies for emergency resuscitation are immediately available (most often in an allergy-immunology clinic).

Treatment

Treatment for IgE-mediated food reactions includes avoidance of the food allergens and prompt treatment of reactions caused by accidental ingestion. Treatment of acute reactions depends on the severity of symptoms and progression.

• Anaphylaxis requires prompt treatment with epinephrine (see How to give an EpiPen and the section on Anaphylaxis in this rotation guide).

  • Emergency medical services should be called, and the patient should be transported to the nearest hospital.

  • Even after initial treatment, symptoms of anaphylaxis may recur several hours after initial reaction (biphasic or late-phase reactions).

• Risk factors for fatal food-induced anaphylaxis include:

  • presence of asthma

  • failure to use epinephrine autoinjectors promptly

  • history of severe reactions in the past

  • known food allergies

  • denial of symptoms

  • adolescence

(Source: Food Allergy. N Engl J Med 2017.)

Although many people outgrow allergies with time (e.g., cow’s milk and hen’s egg allergies during childhood/adolescence), allergy to certain foods (e.g., peanuts, tree nuts, and seafood) often persists through adulthood.

Prevention

In the past, infants at high risk for food allergy and pregnant and lactating mothers were advised to exclude allergenic foods in their diets. However, a randomized, controlled trial published in 2015 found that early introduction of peanuts in children at high risk for allergy (patients with egg allergy or moderate-to-severe eczema) significantly reduced the risk of developing peanut allergy.

Guidelines sponsored by the American Academy of Allergy, Asthma, and Immunology; American College of Allergy, Asthma, and Immunology; and the Canadian Society for Allergy and Clinical Immunology now recommend early introduction of peanuts and egg in infants at age 4 to 6 months to prevent development of food allergy. Other foods known to be allergenic should be introduced around this time as well. Based on these guidelines, screening with food allergy testing before introduction for high-risk infants is no longer required, although testing may be preferred by some families.

The following figure outlines risk factors for development of food allergy in infants. Although eczema is considered the highest risk factor for developing IgE-mediated food allergy, children without risk factors can still develop food allergy.

(Source: A Consensus Approach to the Primary Prevention of Food Allergy Through Nutrition: Guidance from the American Academy of Allergy, Asthma, and Immunology; American College of Allergy, Asthma, and Immunology; and the Canadian Society for Allergy and Clinical Immunology. J Allergy Clin Immunol Pract 2021).

(Source: Food Allergy. N Engl J Med 2008.)

Management

The following table outlines the current recommendations for management of food allergy.

(Source: Food Allergy. N Engl J Med 2017.)

Several different forms of immunotherapy are being investigated to promote desensitization or tolerance to foods through daily low-dose administration.

(Source: Food Allergy. N Engl J Med 2017.)

In January 2020, the FDA approved the first drug for treatment of peanut allergy in children aged 4-17. Palforzia (peanut [Arachis hypogaea] allergen powder-dnfp) introduces peanut in small increasing doses to induce desensitization in peanut-allergic patients. Treatment with oral immunotherapy carries the risk of anaphylaxis and should be considered in the setting of shared decision-making with the patient and family.

Oral Allergy Syndrome (Pollen-Food Allergy Syndrome)

Oral allergy syndrome is suspected when a patient with pollen allergy reports oropharyngeal erythema, oropharyngeal edema, or pruritus following exposure to classical culprit foods including fruits, vegetables, and nuts. The reaction is due to contact urticaria to cross-reactant, pollen-related proteins in these foods when ingested in uncooked preparations. Reactions are generally isolated to the oropharynx, although systemic manifestations have been reported. Any systemic symptoms should prompt allergy testing to exclude a potentially life-threatening IgE-mediated food allergy. Patients with oral allergy syndrome can generally prevent symptoms by cooking, baking, or even gently microwaving culprit foods to denature the proteins sufficiently to prevent cross-reaction.

Non-IgE-Mediated Food Allergies

Non-IgE-mediated food allergies present as subacute or chronic gastrointestinal-tract or cutaneous symptoms. Non-IgE-mediated food allergy disorders include food protein-induced enterocolitis syndrome (FPIES), food protein-induced enteropathy, food protein-induced proctitis and proctocolitis, and food-induced pulmonary hemosiderosis. Celiac disease is not classically considered a food allergy, but it is caused by a non-IgE-mediated immune reaction to gluten, a food protein.

FPIES is a non-IgE-mediated food hypersensitivity characterized by profuse, repetitive vomiting leading to dehydration and lethargy, with chronic symptoms leading to weight loss and failure to thrive. The most common triggers include cow’s milk or soy protein or rice, but numerous other potential causes exist. Food protein-induced proctocolitis (which was previously known as allergic or eosinophilic proctocolitis) is a cause of rectal bleeding in usually otherwise healthy infants, with inflammation of the distal colon. The most common triggers are cow’s milk and soy protein, and it is not thought to be an IgE-mediated process. In most cases, it resolves by late infancy.

Mixed IgE- and Non-IgE-Mediated Reactions

Some food allergy disorders have both IgE- and non-IgE-mediated components (e.g., atopic dermatitis, eosinophilic esophagitis, and eosinophilic gastroenteritis). Food allergies may exacerbate atopic dermatitis, especially in young children with severe allergy. Eosinophilic gastrointestinal disorders are characterized by postprandial gastrointestinal dysfunction and eosinophilic infiltration of the intestinal tract on biopsy.