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Food Allergies

Last Literature Review: March 2026 Last Update:

Educational Videos From ARUP Laboratories

Role of Component-Resolved Testing in Food Allergies: From Peanuts to Red Meat Allergies
1 hr 21 min
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Food allergies and the symptoms they manifest, including hives, rash, difficulty breathing, gastrointestinal disruption, and in severe cases, anaphylaxis, are a result of hypersensitivity, or an exaggerated inflammatory response, to foods. The inflammatory response is mediated by the production of immunoglobulin E (IgE) antibodies in response to exposure to the food antigen (allergen).  At mucosal and skin barrier surfaces, factors such as tissue injury, psychological or physical stress, infections, and environmental pollutants can impair barrier integrity, allowing allergens to penetrate deeper into the tissue. Laboratory testing for the diagnosis of food allergies (e.g., peanut, milk, egg, tree nut [such as cashew, walnut, almond, and pecan], wheat, soy, fish, and shellfish allergies) is key to their identification.

A thorough clinical history is the cornerstone of food allergy diagnosis and plays a crucial role in guiding the selection and interpretation of subsequent testing.  Key questions to consider include the types of suspected culprit foods, the timing of symptoms after food consumption, the severity of symptoms, and the possibility of cofactors (e.g., exercise and nonsteroidal anti-inflammatory drugs [NSAIDs]). The diagnosis of food allergies allows for intervention through treatment, such as an elimination diet or immunotherapy. Laboratory testing, including the skin prick test (SPT), IgE serologic testing using immunoassays, component-resolved diagnostic (CRD) testing, and the basophil activation test (BAT), are used for the identification and diagnosis of food allergies; in some cases, an oral food challenge (OFC) may be appropriate. Unguided testing can lead to misinterpreted positive test results, which can result in misdiagnosis and unnecessary food restrictions. 

Quick Answers for Clinicians

When should the basophil activation test be considered in the diagnostic workup for food allergies?

When there is a discrepancy between a patient’s clinical history and the results of primary diagnostic tests, such as the skin prick test (SPT) or serum-specific immunoglobulin E (IgE) testing, or when initial testing is otherwise inconclusive, a basophil activation test (BAT) should be considered when available. ,   

The BAT mimics in vivo conditions by assessing the cellular response to allergen(s) in a controlled laboratory setting.  The BAT can help identify patients who may be candidates for immunotherapy and may reduce the need for a costly and potentially dangerous oral food challenge (OFC), which requires a carefully controlled setting with medical oversight because of the risk for potentially life-threatening anaphylaxis. Patients with negative or equivocal BAT results should still undergo an OFC when there remains a strong clinical suspicion of allergy. 

How is the positive predictive value utilized for test result assessment in the diagnostic workup for food allergies?

Cutoffs correlating with set positive predictive value (PPV) ranges have been suggested to distinguish reaction wheal sizes on the skin prick test (SPT) and allergen-specific immunoglobulin E (IgE) concentrations in serum that suggest a food allergy diagnosis; however, it is important to realize the interpretation of results can be variable from patient to patient. 

Can immunoglobulin G testing be useful in the diagnostic workup for food allergies?

Testing of immunoglobulin G (IgG) levels in the diagnostic workup for food allergies is controversial. Although IgG testing for food allergies (including IgG4) is commercially available, evidence does not support its clinical use.  Results of IgG testing may be misinterpreted, leading to inadequate nutritional intake for patients. The American Academy of Allergy, Asthma, and Immunology recommends against IgG testing for food sensitivities and intolerances as well as for diagnosing food allergies. 

What are the unique considerations and complexities in the diagnostic workup for food allergies in children and infants?

In infants and young children, limited or absent exposure to potential food allergens can complicate the interpretation of common diagnostic tests, such as the skin prick test (SPT) and specific immunoglobulin E (IgE) testing. As a result, positive sensitization results may be difficult to correlate with clinical reactivity in the absence of a clear exposure history. Although an oral food challenge (OFC) remains the reference standard for diagnosis, it may be associated with logistical challenges and the risk of allergic reactions. In this setting, the basophil activation test (BAT) may have value earlier in the diagnostic pathway, particularly when exposure history is absent or unclear and SPT and specific IgE findings are inconclusive. The BAT may help refine risk assessment and support clinical decision-making before proceeding to an OFC. 

How does the timing of symptom onset in red meat allergy affect clinical suspicion and testing?

Red meat allergy, also known as alpha-gal syndrome (AGS), is increasingly recognized as a cause of food-related anaphylaxis in the United States. In the Eastern and Southeastern regions of the country, seropositivity for immunoglobulin E (IgE) to alpha-gal is estimated to exceed 30%.  Unlike typical food allergies, AGS differs in that the onset of symptoms is delayed, occurring 2-6 hours after consuming the allergen.

Indications for Testing

Indications for a diagnostic workup for food allergies include:

  • Suggestive clinical history of food allergy
    • Immunologic response (allergic reaction) within minutes to 2 hours following consumption of specific foods; symptoms may include hives, breathing restriction, swelling, digestive upset, anaphylaxis, cardiovascular findings 
    • In young children, occurrence of symptoms on two or more occasions of consumption of a specific food(s) 
  • Delayed allergic reaction (in 3 to 6 hours) following consumption of red meat in patients who may have been exposed to the lone star tick 

Testing may also be performed to determine if tolerance to an identified food allergen has developed over time.

Laboratory Testing

Sensitization Testing

The initial test typically performed in cases of suspected food allergy is the SPT using allergen extracts or fresh food. The SPT detects the presence of allergen-specific IgE bound to cutaneous mast cells. In this test, allergen extracts are applied to the skin, and after a designated time interval, the diameters of the wheal and flare are measured. This test enables the detection of sensitization with high confidence and provides an easy, quick method of assessment at a low cost.  Importantly, the individual undergoing testing should have skin clear of dermal reactions, and any anti-allergy medication(s) should be discontinued before testing. The size of the SPT wheal diameter on the skin surface can be correlated with the likelihood of allergy to the particular allergen being investigated.  Wheal diameter measurement cutoffs have been suggested for diagnosis that are believed to correlate with positive predictive values (PPVs) of 95-100%, although cutoffs may vary when comparing individuals with populations represented in available studies. 

The testing technique, operator characteristics and proficiency, and equipment and reagents used can cause variability of SPT results.  Patients themselves may differ in reactivity depending on multiple factors, such as the location of the testing, exercise before the test, body temperature, and time of day.  The SPT has high sensitivity and a high negative predictive value, making it effective in ruling out allergies when the test is negative. However, its specificity is lower, and its PPV for clinical food allergy diagnosis is also reduced. 

In vitro tests that measure specific IgE (also referred to as sIgE) to allergen extracts can also be used to assess the possibility of a reaction to certain foods. Serum allergen-specific IgE detection indicates patient sensitization, but it alone does not confirm allergy diagnoses in most cases. It is a sensitization test and not an allergy test. Subjects can be sensitized (i.e., have detectable allergen-specific IgE) while being tolerant to the suspected food or allergen. Factors influencing the allergenic functions of allergen-specific IgE include antibody avidity, affinity, the ratio to total IgE, the distribution of effector cells in various tissues, and even intracellular signaling. ,  The PPV can be used to determine the likelihood of a clinical reaction based on the specific IgE concentrations in serum following exposure to specific food allergens.  Higher specific IgE concentrations suggest a greater likelihood of a reaction.  Allergen-specific IgE testing may utilize singleplex allergen tests or multiallergen panels. Determining the clinical relevance of specific IgE test results requires interpretation by a healthcare professional, taking clinical history into account. Combining serology and SPT results can allow clinicians to confidently establish a food allergy diagnosis.

The identification of specific components of food-based allergens that exhibit high specificity, including certain peptides and epitopes, has made targeted testing possible for specific IgE to those components known to be associated with a high risk for severe reactions.  Examples include Ara h 2 in peanuts, Ana o 3 in cashews, and Cor a 14 in hazelnuts. This type of CRD testing involves the use of recombinant or purified proteins instead of allergen extracts for detecting allergen-specific IgE. By employing higher protein concentrations than those found in extracts, the analytic sensitivity and specificity of the immunoassay are significantly improved.

CRD testing presents notable advantages compared with testing for whole allergen extracts and SPTs, such as better standardization and risk stratification. ,  Detecting specific IgE to major allergenic proteins through CRD testing can aid in confirming allergy diagnoses, identifying high-risk patients, and distinguishing between genuine sensitization and cross-reactivity to other foods or pollen. 

Diagnostic Testing

OFCs are often performed when the results of serologic testing and the SPT are inconclusive and do not enable a definitive diagnosis.  This testing can be performed as open-food testing, single-blind testing, or the preferred double-blind placebo-controlled food challenge (DBPCFC), which is the most specific diagnostic approach. Studies using the DBPCFC have demonstrated that only approximately one-third of suspected food allergens are confirmed to cause true allergic reactions. A negative OFC effectively rules out an allergy to the tested food.  However, OFCs have several limitations, including the risk of severe allergic reactions, necessitating close medical supervision during testing.  During an OFC, the suspected allergenic food (or placebo) is administered with a gradual increase in dosage while monitoring for clinical reactions.  If a persistent subjective or clear objective reaction is observed, the testing is typically discontinued; alternatively, in uncertain cases, the patient can be retested in a few days. The elimination diet is another useful diagnostic tool in certain circumstances, such as in the case of gastrointestinal symptoms and/or chronic skin findings, and is often used in the initial stages of workup. 

Third-line tests like the BAT are gaining popularity. These tests help clinicians and patients reduce their reliance on OFCs and avoid reactive challenges.  The BAT mimics in vivo conditions by assessing the degranulation of peripheral blood basophils after adding allergens (e.g., peanut extract) in a test tube. If a patient’s cells are sensitized to an allergen (i.e., specific IgE to the allergen is bound to surface FceR1), basophils will degranulate. This degranulation can be measured using flow cytometry.  Therefore, the BAT can be useful for diagnosing allergies and monitoring responses to treatments and allergen immunotherapy.

The advantages of the BAT include its reduced cost and time required to perform testing, as well as elimination of the need for medical supervision and the risk of anaphylaxis. The BAT has allowed clinicians to bypass or defer an OFC in certain circumstances because of its high sensitivity, specificity, and PPV.  In particular, the high sensitivity of the BAT enables confirmation of a food allergy diagnosis when SPT and specific IgE testing is suggestive or inconclusive, although the BAT cannot exclude a diagnosis when negative.

The BAT is particularly useful for supporting diagnostic testing in cases of suspected peanut and sesame allergies, based on studies.  With respect to peanut allergy, two meta-analyses have shown excellent diagnostic performance and consistency of the BAT using peanut extract. ,  Among patients with high Ara h 2-specific IgE levels (>7 kU/L), the BAT showed 100% concordance with OFC outcomes. The combined use of BAT and Ara h 2-specific IgE testing has been proposed as an alternative to OFCs and may help identify highly reactive patients, thereby reducing the need for potentially reactive OFCs. , 

An OFC is important to consider when a BAT result is negative or inconclusive.  Importantly, the BAT may not be readily available, and interpretation requires expert knowledge due to its complexity.  BAT results should be considered in combination with all risk factors and clinical characteristics when determining severity and other parameters of food allergies. 

Limitations of the BAT include the need for it to be validated for specific allergens individually in specified populations. ,  Performance of the BAT can be influenced by laboratory procedures, the reagent used, and sample characteristics, as well as protocols used and features of the studied population.  Specimen stability is also a significant issue in the BAT, as basophils quickly lose reactivity and viability, and this factor needs to be considered in specimen submission and transport to a laboratory, as well as processing. 

Monitoring

As tolerance to allergenic foods often develops over time, periodic follow-up testing (i.e., annually) using in vitro and in vivo approaches is advised, possibly including OFCs.  The BAT can offer a useful testing approach to monitor for resolution of food allergies, whether naturally or in response to immunotherapy, and to determine if and/or when a follow-up OFC might be needed to confirm foods can be safely reintroduced into the patient’s diet.  The BAT can be useful to assess the clinical success of allergy immunotherapies by measuring basophil reactivity to the allergenic foods after treatment. 

ARUP Laboratory Tests

Refer to the ARUP Laboratory Test Directory for additional testing options for food allergies.

References

  1. ACAAI - Food allergy

    American College of Allergy, Asthma, and Immunology; American Academy of Allergy, Asthma, and Immunology. Food allergy. Guideline Central. Updated May 2026; accessed Aug 2026.