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Diagnostic evaluation of IgE-mediated food allergy

Diagnostic evaluation of IgE-mediated food allergy
Author:
Wesley Burks, MD
Section Editor:
Scott H Sicherer, MD, FAAAAI
Deputy Editor:
Elizabeth TePas, MD, MS
Literature review current through: Nov 2022. | This topic last updated: May 13, 2021.

INTRODUCTION — The evaluation of a patient with possible immunoglobulin E (IgE) mediated food allergy is a clinical exercise that includes some combination of the following diagnostic tools, although not all of these elements are necessary in every patient [1-6]:

History and physical examination

Prick/puncture skin testing

In vitro testing

Food challenges

This topic reviews skin and in vitro testing for IgE-mediated food allergy. Other parts of the evaluation, including the history and physical examination and oral food challenges, are discussed in detail separately. Diagnostic tools under development are also reviewed elsewhere. (See "History and physical examination in the patient with possible food allergy" and "Clinical manifestations of food allergy: An overview" and "Future diagnostic tools for food allergy".)

This topic does not discuss general gastrointestinal tests that are used in the evaluation of non-IgE-mediated food allergy and eosinophilic gastrointestinal disorders, such as endoscopy, colonoscopy, and gastrointestinal biopsy. These procedures and other tests are presented in reviews of the individual disorders. (See "Food protein-induced allergic proctocolitis of infancy" and "Food protein-induced enterocolitis syndrome (FPIES)" and "Diagnosis of celiac disease in children" and "Diagnosis of celiac disease in adults" and "Clinical manifestations and diagnosis of eosinophilic esophagitis (EoE)" and "Eosinophilic gastrointestinal diseases".)

HISTORY AND PHYSICAL EXAM — Every evaluation begins with a detailed history and physical examination. The clinical history is critical in the diagnosis of food allergy since it is used to determine subsequent testing and interpretation of results. The history and physical examination and the various manifestations of food allergy are reviewed in detail separately. (See "History and physical examination in the patient with possible food allergy" and "Clinical manifestations of food allergy: An overview".)

ROLE OF ALLERGY TESTS IN DIAGNOSIS — Allergy testing, in the form of skin testing or in vitro tests, must always be selected and interpreted in the context of the patient's specific clinical history because a "positive" test (ie, sensitization, or formation of IgE to a specific substance) does not always indicate clinical allergy [3,7,8]. The details of the history are used to generate an estimate of the patient's pretest probability of having allergic disease. The pretest probability is essential for effective use of available testing modalities. Testing is not required for diagnosis in a patient with a clear IgE-mediated reaction such as anaphylaxis (table 1 and figure 1) to a single food, but a baseline value is helpful for monitoring over time. Testing should be avoided in most patients without a history consistent with an IgE-mediated reaction, unless it is felt that a negative test will encourage reintroduction of the food into the diet (algorithm 1). If a patient is tolerating a food without immediate symptoms, the food should not be eliminated from the diet solely because of a "positive" IgE test. Determining whether a reaction is consistent with an IgE-mediated allergy is reviewed in greater detail separately. (See "Clinical manifestations of food allergy: An overview" and "History and physical examination in the patient with possible food allergy" and "Food allergy in children: Prevalence, natural history, and monitoring for resolution".)

The sensitivity and specificity of tests for individual foods (and other allergens) have been defined in children for several of the most common foods. However, these values have not been determined or validated for the majority of foods or in adults. These values are reviewed in the topics on specific food allergies.

The way in which the pretest probability impacts the interpretation of allergy tests is illustrated by the following clinical vignettes [9]. Consider three different two-year-old children presenting for evaluation of egg allergy:

Patient 1 has experienced two severe allergic reactions following the isolated ingestion of scrambled egg, requiring and responding to treatment with epinephrine on both occasions. (See "Food-induced anaphylaxis".)

Patient 2 has severe atopic dermatitis and eats egg regularly. He has never experienced an apparent acute reaction to egg. However, his mother is aware that food allergy can exacerbate this condition and has therefore requested an allergy evaluation. (See "Role of allergy in atopic dermatitis (eczema)".)

Patient 3 has no history of allergic problems, but her parents think she misbehaves more after eating egg.

The pediatrician evaluating these children performs in vitro testing to egg in all three children. In each child, a moderately positive (egg white IgE: 3 kUA/L; ImmunoCAP) result is obtained. However, the interpretation of the result would be different in each case.

Patient 1 has a very high pretest probability of egg allergy, so a moderately positive test is sufficient to validate the clinical suspicion (see "Glossary of common biostatistical and epidemiological terms", section on 'Measures of diagnostic test performance'). Further testing and referral to an allergy specialist is not necessary but is an option if assistance with management is desired. If the in vitro test had been negative, the pediatrician would be correct to question the result and refer the child to an allergy specialist for further evaluation.

Patient 2 has a moderate pretest probability since up to 40 percent of children with moderate-to-severe atopic dermatitis have underlying food allergy, and egg is a common cause of childhood food allergy [10-12]. In this patient, the positive result is suggestive of true allergy, although further evaluation is needed to demonstrate that egg allergy is contributing to skin inflammation prior to removal of egg from the diet. This evaluation may require a period of dietary elimination and readministration, perhaps as a medically supervised oral food challenge. For a child with a history of atopic dermatitis who had been ingesting egg in the diet without acute symptoms and, based on a positive test, had it removed, it is important to promptly assess the possibility of reintroducing it back into the diet. Prolonged dietary exclusion in this circumstance could result in acute or anaphylactic reactions upon reintroduction [13]. (See "Role of allergy in atopic dermatitis (eczema)", section on 'Food elimination diets'.)

Patient 3 has an extremely low pretest probability, and the test result is not sufficiently positive to impact the clinician's initial impression. Egg should not be removed from the child's diet. This case also illustrates one of the disadvantages of performing testing in patients whose histories are not consistent with allergic disease, as irrelevant results may confuse the situation.

REFERRAL — In vitro testing by a generalist is appropriate when the pretest probability of food allergy is moderate to high. Patients with positive results may be referred to an allergy specialist for further education of the patient/caregivers, particularly if the patient has multiple food allergies, and ongoing monitoring for resolution in pediatric patients. Referral for educational purposes may also be useful when the clinician feels that the pretest probability is low but the patient/caregiver(s) suspect food allergy and are avoiding the particular food(s). Finally, referral is indicated for additional testing and management in the patient with moderate-to-high pretest probability of food allergy and negative in vitro testing. (See 'Role of allergy tests in diagnosis' above.)

APPROACH TO TESTING — An overview of the approach to testing in the patient with a history that is consistent with or suggestive of an IgE-mediated food allergy is reviewed in the algorithm (algorithm 2). Testing is generally avoided in patients who lack a history suggestive of IgE-mediated allergy, unless it is felt that a negative test will encourage reintroduction of food into the diet, since a "positive" test in these patients is nearly always a false positive.

Determining whether the history is consistent with an IgE-mediated reaction is based upon several factors including the signs and symptoms of the reaction, timing in relation to food ingestion, and the suspected food. IgE-mediated food allergy presents with some combination of skin, gastrointestinal, upper and lower respiratory tract, and cardiovascular signs and symptoms (table 2). A patient may present with only one or two of these symptoms (eg, urticaria) or virtually all of them (eg, anaphylaxis). IgE-mediated reactions typically occur rapidly after ingestion of the culprit food (ie, within seconds to minutes), but reactions up to two hours and beyond can also occur. IgE-mediated food allergy occurs most often in association with certain foods, although any food has the potential to cause allergy. The history and physical examination and the various manifestations of food allergy are reviewed in detail separately. (See "History and physical examination in the patient with possible food allergy" and "Clinical manifestations of food allergy: An overview".)

The choice of testing depends upon a several factors including availability of testing, patient/caregiver and clinician preferences, and technical limitations and accuracy of the tests [14]. Options include skin prick testing (SPT) with food extracts or fresh foods, immunoassays to whole foods, and component immunoassays to specific food proteins. The specific tests are reviewed below. (See 'Skin testing' below and 'In vitro testing' below.)

Interpretation depends upon both the actual test results and the pretest probability of food allergy, as is described in the scenarios above (see 'Role of allergy tests in diagnosis' above). Both an SPT wheal <3 mm and a food-specific IgE (sIgE) <0.35 kUA/L have a high specificity and negative predictive value (NPV) but poor sensitivity and positive predictive value (PPV). Sensitivity can be improved by using higher cutoffs, which vary depending upon the specific food. Suggested cutoffs are discussed in the topics on specific foods. Test results between these two ranges are more ambiguous. Oral food challenges can help determine if a food allergy is present when test results are not definitive. (See "Oral food challenges for diagnosis and management of food allergies".)

SKIN TESTING

Overview — The prick/puncture (or epicutaneous) method of skin testing is commonly used in the evaluation of a suspected IgE-mediated food allergy. The test is still valid even if the patient is not eating the food. Allergy skin testing should only be performed by allergy specialists familiar with these tests and in settings equipped with the necessary medications, equipment, and staff to treat anaphylaxis. Intradermal skin testing should not be performed in the evaluation of food allergy, because it does not add to the diagnostic capability of the epicutaneous skin test and significantly increases the risk of triggering a systemic reaction. (See "Overview of skin testing for IgE-mediated allergic disease", section on 'Safety'.)

Prick/puncture skin tests — Skin prick testing (SPT) is best used to investigate the possibility of an IgE-mediated reaction to a specific food in a patient with a suggestive clinical history (ie, a high pretest probability) of allergy. It is also highly effective for excluding IgE-mediated allergy, particularly in a patient with a low pretest probability, because of its high sensitivity. Because of the low specificity of SPT, it should not be used to screen patients for allergy by testing with broad panels of food allergens without regard for clinical history, since this is likely to yield false-positive (clinically irrelevant) results.

Prick/puncture skin tests are highly reproducible and less costly to perform than in vitro testing. SPT causes minimal patient discomfort and yields results within 15 minutes. This type of testing can be safely performed in patients of any age. (See "Overview of skin testing for IgE-mediated allergic disease".)

Precautions and preparations — Allergy skin testing is considered a safe procedure [15]. However, it occasionally causes systemic reactions in very sensitive patients. Thus, it is recommended that this type of testing be performed by allergy specialists trained in the treatment of anaphylaxis and in a setting where full emergency equipment and medications are available. (See "Overview of skin testing for IgE-mediated allergic disease", section on 'Safety'.)

The following factors should be considered in the decision to perform skin testing:

SPT should be performed with caution in patients who, by history, are at high risk for a systemic reaction, such as patients with moderate or severe asthma who have experienced anaphylaxis previously. The decision to skin test such a patient should be made on an individual basis. SPT should be delayed or in vitro testing performed instead if such a patient has active allergy or asthma symptoms, particularly if their asthma is poorly controlled. (See "Overview of skin testing for IgE-mediated allergic disease", section on 'High risk for anaphylaxis'.)

Certain medications, such as antihistamines, can interfere with SPT and must be stopped beforehand. Preparations for SPT are discussed separately. (See "Overview of skin testing for IgE-mediated allergic disease", section on 'Medications that should be discontinued'.)

Generalized skin conditions, including dermographism and urticaria, uncommonly may preclude accurate SPT. In rare cases, atopic dermatitis is severe and widespread enough that there is not a clear area of skin sufficient for SPT. (See "Overview of skin testing for IgE-mediated allergic disease", section on 'Skin conditions'.)

SPT is not usually performed for several weeks after an episode of anaphylaxis, because it has been observed that anaphylaxis can render the skin temporarily nonreactive. The reasons for this refractory period have not been studied, although extensive depletion of surface IgE and/or granule contents within cutaneous mast cells are possible explanations. Full restoration of skin reactivity can take two to four weeks. (See "Overview of skin testing for IgE-mediated allergic disease", section on 'Recent anaphylaxis'.)

Testing in infants — The skin of infants may be less reactive, yielding more false-negative results, although this difference has not been formally studied. Nevertheless, positive results are commonly obtained in infants with a history consistent with food allergy. Unfortunately, very young children may also have more systemic reactions to SPT [16]. Thus, SPT can be performed even in infants and young children when indicated and with appropriate precautions.

Technique — To perform prick/puncture skin testing, a source of food allergen is applied to a testing device or directly to the skin. One of several commercially available devices (plastic probes, metal lancets, bifurcated needles) is used to prick through the allergen into the top layer of the skin. The patient is also tested with appropriate positive (histamine) and negative (saline) controls.

The food is pricked into the skin to introduce the allergen to cutaneous mast cells. If food-specific IgE (sIgE) antibody is present on the surface of the patient's mast cells, then the cells degranulate, releasing histamine and other mediators that cause localized cutaneous swelling (ie, a wheal). Vasodilation (ie, a flare) also develops as a result of an axonal reflex. General issues regarding the technique of SPT (for foods as well as other allergens) are reviewed elsewhere. (See "Overview of skin testing for IgE-mediated allergic disease".)

Sources of food allergen include:

Commercially prepared food extracts (1:10 or 1:20 weight/volume in glycerin)

Fresh foods (wet foods can be applied directly; dry foods can be made into pastes or slurries)

When fresh foods are used, the lancet can also be used to prick the food and then prick the patient's cleaned skin ("prick-by-prick" method). This is commonly used for testing of fresh fruits as the proteins in fruits are prone to degradation during commercial processing [17]. (See "Clinical manifestations and diagnosis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Prick-by-prick skin testing with fresh foods'.)

Positive and negative results — An SPT eliciting a wheal at least 3 millimeters in diameter after the saline control wheal diameter is subtracted is technically considered positive. However, the specificity of the test is relatively low at this threshold (see 'Accuracy' below). The specificity can be increased by using a higher threshold. Numerous studies have shown that the 95 percent positive predictive value (PPV) for most foods is a wheal of at least 8 mm [18,19]. Anything <3 mm is considered negative [20].

Accuracy — SPT is highly sensitive but only moderately specific (see "Glossary of common biostatistical and epidemiological terms", section on 'Measures of diagnostic test performance'). The general sensitivity and specificity of SPT for the diagnosis of food allergy are often estimated to be greater than 90 and approximately 50 percent, respectively [9]. However, this figure incorporates important variables, including the quality of the extract used and the degree of positivity.

The quality of commercially available skin testing food reagents is generally good, but there is some variability. Extracts of milk, eggs, peanuts, tree nuts, soy, fish, and shellfish are usually reliable. In contrast, commercial extracts of fruits and vegetables are sometimes inadequate because the responsible allergen may be labile and altered during processing, making false-negative tests more likely.

Prick-by-prick testing with fresh foods, although less convenient, has a higher correlation to clinical reactivity than testing with commercial extracts for some foods, particularly fruits and vegetables. In a study of children with food allergies, for example, concordance between skin testing and challenge was 59 percent for commercial extracts and 92 percent for fresh food [21].

The larger the wheal, the greater the likelihood of clinical allergy [22]. Importantly, the size of the skin test does not correlate with the severity of a clinical allergic reaction. Large positive SPTs in children tested to cow's milk, egg, and peanut were shown in one study to have excellent specificity and PPVs for subsequent positive food challenge [23]. In this study, which tested 467 children with a median age of three years using commercial extracts, a peanut SPT >8 mm was "100 percent" diagnostic for a positive food challenge to peanut (the corresponding reaction for children less than two years of age was >4 mm). These findings were confirmed in a subsequent study of children up to 16 years old with peanut sensitivity in which a different manufacturer's extracts were used, suggesting the findings may be generalizable to children suspected of having peanut allergy [24]. Similar cutoff values have not yet been validated for the other common food allergens or in adults. In addition, these results may not be generalizable to all populations. Additional studies are needed.

In contrast, the sensitivity and negative predictive accuracy for SPT to foods, other than some fruits and vegetables, is uniformly high. A negative SPT confirms the absence of an IgE-mediated reaction with 90 to 95 percent accuracy [25]. Therefore, SPT is useful for excluding IgE-mediated food allergy. (See "Clinical manifestations and diagnosis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Objective testing for food allergy'.)

Intradermal skin tests — Intradermal skin testing should not be performed in the evaluation of food allergy, since it does not add to the diagnosis and carries a greater risk of inducing a systemic reaction than does SPT [26]. Fatalities have been reported with intradermal testing to foods [16,27]. (See "Overview of skin testing for IgE-mediated allergic disease", section on 'Intradermal testing and high-risk allergens'.)

Atopy patch tests — Atopy patch testing is a type of skin testing that has been studied for the diagnosis of delayed, non-IgE-mediated food allergy. It involves the topical application of a food-containing solution to the skin for 48 hours. However, there are no standardized reagents, application methods, or guidelines for interpretation, and this type of testing cannot be recommended outside of research settings. This method is discussed in greater detail separately. (See "Future diagnostic tools for food allergy", section on 'Atopy patch testing'.)

IN VITRO TESTING

Immunoassays — Immunoassays are in vitro assays used to identify food-specific IgE (sIgE) antibodies in the serum. As with skin testing, the test is still valid even if the patient is not eating the food. (See "Overview of in vitro allergy tests".)

Immunoassays are more costly than skin testing, and the results are not as immediately available. However, immunoassays for sIgE have several useful features. In vitro tests are:

Widely available

Unaffected by the presence of antihistamines or other medications

Useful in patients with severe anaphylaxis in whom skin testing may carry an unacceptable degree of risk

Useful in patients with dermatologic conditions that may preclude skin testing (see 'Precautions and preparations' above)

The test results are reported as food-specific IgE (sIgE) levels (in kUA/L). Although higher concentrations of sIgE correlate to an increased likelihood of a reaction upon ingestion [28-30], an individual patient with a significant food allergy can have a high, medium, low, or even negative in vitro test using these systems [31]. Importantly, as with skin testing, the sIgE level does not correlate well with the severity of a reaction. It is also true that a patient can have a positive sIgE for a food to which they are tolerant. Thus, the patient's clinical history is critical to both determining the tests to perform and confirming the diagnosis. The results of immunoassays are also reported using percentage, class, or numerical ranks that compare the amount of IgE present in the patient's serum to a standard curve, although these values are generally not helpful due to the great variability in thresholds used to improve sensitivity that vary depending upon the food, age of the patient, and history.

Several large studies have used the ImmunoCAP fluorescent enzyme immunoassay system, and so normative results from studies on selected patient groups are available for this specific product. It is important to understand that values obtained with other testing systems are not necessarily interchangeable [32]. Very high sensitivity and positive predictive accuracy in children can be achieved using the ImmunoCAP system. In a retrospective study of nearly 200 pediatric patients with food allergy, minimum levels of IgE to specific foods were identified that were associated with a 95 percent positive predictive value (PPV) for clinical food hypersensitivity [28]. Approximately 90 percent of these children had atopic dermatitis.

The validity of these values in a less selected population was then prospectively evaluated in a study in which the sera of 100 children and adolescents (mean age of 3.8 years, range 0.4 to 14 years) with possible food allergy was assessed for reactivity to egg, milk, peanuts, and fish [31]. The concentrations of specific IgE antibodies were compared with the clinical history and the results obtained by skin testing and/or double-blind, placebo-controlled food challenge (DBPCFC). Based upon the same minimum values obtained in the previous study, PPVs of 96, 100, 100, and 100 percent were obtained for clinical allergies to egg, milk, peanut, and fish, respectively.

Subsequent studies have generated somewhat different predictive values, most likely due to variations in the patient populations and/or testing protocols [30,33,34]. In addition, the predictive values vary with age, such that younger children and infants display symptoms at lower serum levels of sIgE compared with older children [34].

Based primarily upon studies performed in the United States in children with a history of food allergy and eczema older than two years of age, the 95 percent positive predictive levels for egg, milk, peanut, tree nuts, and fish are as follow [25]:

Egg, 7 kUA/L (2 kUA/L for children less than two years of age)

Milk, 15 kUA/L (5 kUA/L for children less than two years of age)

Peanut, 14 kUA/L

Tree nuts, approximately 15 kUA/L

Fish, 20 kUA/L

Thus, children over two years old with a convincing history of egg allergy have a greater than 95 percent likelihood of experiencing an allergic reaction to egg upon challenge if their egg-specific IgE exceeds 7 kUA/L. Therefore, challenge is unnecessary in such children. Equivalent predictive positive levels for soy and wheat have not yet been established. To reiterate, these data were developed in children, and there are no recommendations regarding their interpretation in adults with food allergy.

Some children with egg allergy may tolerate egg in baked goods but react on ingestion of lightly cooked egg. Similar findings are seen with milk allergy. The suggested approach for determining when to try to introduced baked egg or baked milk is reviewed in detail separately.(See "Egg allergy: Management", section on 'Monitoring for resolution and reintroduction' and "Egg allergy: Clinical features and diagnosis", section on 'Pathogenesis' and "Milk allergy: Management", section on 'Monitoring for resolution and reintroduction' and "Milk allergy: Clinical features and diagnosis", section on 'Pathogenesis'.)

Component testing — Foods are comprised of numerous proteins, and an individual with a food allergy may have immune responses of varying degrees to any of them. The potency of individual proteins in a food may relate to their lability. Proteins that are destroyed easily by heating or digestion are less likely to cause significant allergic reactions compared with heat or digestion-stable proteins. Ara h 2, for example, is a peanut seed storage protein that is stable. IgE responses to this protein are associated with allergic reactions compared with IgE responses to the peanut protein Ara h 8, which is a labile protein homologous to a protein in birch tree pollen. An individual with a strong immune response to Ara h 2 and no response to Ara h 8 will probably have peanut allergy compared with a person with no response to Ara h 2 and a modest response to Ara h 8, even though a positive test to whole peanut extract would be positive in both, possibly with the same result [35,36]. This testing is discussed in detail separately. (See "Component testing for pollen-related, plant-derived food allergies" and "Component testing for animal-derived food allergies".)

Other in vitro tests — Other in vitro tests for IgE-mediated allergy that are not commercially available but are performed at some research centers include the basophil activation test (BAT), mast cell activation test (MAT), and sIgE to allergen epitopes. These tests are discussed in detail separately. (See "Future diagnostic tools for food allergy", section on 'IgE-mediated food allergy'.)

FOOD CHALLENGES — Oral food challenges are structured protocols in which the patient ingests a suspect food under clinician supervision. Food challenges should only be performed by allergy specialists familiar with food-allergic reactions and in settings equipped with the necessary medications, equipment, and staff to treat anaphylaxis. Food challenges are covered in detail separately. (See "Oral food challenges for diagnosis and management of food allergies".)

UNVALIDATED METHODS — Patients may present after having food allergy tests performed that have not been validated [3,5,26,37]. These can include food-specific immunoglobulin G (IgG) and IgG4 tests, which typically yield multiple positive results and may represent a normal immune response to food [38]. Other types of testing for food allergy that are not supported by scientifically valid concepts include sublingual or intradermal provocation tests, tests of lymphocyte activation, kinesiology, cytotoxic tests, and electrodermal testing [3]. Unproven and disproven methods are discussed in detail separately. (See "Unproven and disproven tests for food allergy".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Food allergy".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Food allergy (The Basics)")

Beyond the Basics topic (see "Patient education: Food allergy symptoms and diagnosis (Beyond the Basics)")

SUMMARY

The first step in the evaluation of food allergy is the history and physical exam. This is typically followed by skin testing, in vitro testing, and/or food challenges. (See 'Introduction' above.)

The history is critical in the diagnosis of food allergy and is the first step in discerning the type of food allergy present (immunoglobulin E [IgE] mediated or not), whether there is an alternative explanation for the patient's symptoms (eg, viral rash, food intolerance, etc) that should not be evaluated with allergy tests, and the suspected causative food. This essential component of food allergy diagnosis is discussed separately. (See 'History and physical exam' above and "History and physical examination in the patient with possible food allergy".)

Skin testing for food-specific immunoglobulin E (sIgE) is used only in the diagnosis of IgE-mediated food allergies. Skin testing is more sensitive than in vitro testing in some cases. It should be performed by an allergy specialist because of both the risk of anaphylaxis and the skill required for proper interpretation. Skin testing is contraindicated or unreliable in certain subsets of patients. (See 'Skin testing' above and "Overview of skin testing for IgE-mediated allergic disease", section on 'Contraindications'.)

A positive skin test to a particular food only indicates the possibility that the patient has true allergy to that food because of lower specificity of the test, which varies from 50 to 95 percent depending upon the food in question and the size of the skin test reaction. Further tests or challenges may be needed to confirm that the patient is truly reactive to the food upon ingestion, depending upon the patient's pretest probability of having allergy. In contrast and importantly, a negative skin test result has a high sensitivity and indicates the absence of an IgE-mediated allergy upon subsequent challenge with a 90 to 95 percent predictive accuracy. Further testing or challenge is sometimes indicated. (See 'Role of allergy tests in diagnosis' above and 'Skin testing' above.)

IgE immunoassays are in vitro assays used to identify sIgE in the serum. These tests are widely available and are unaffected by the presence of medications. Their sensitivity varies among different foods. In at least one system, immunoassays have demonstrated very high specificity and positive predictive accuracy in children for several of the major food allergens at particular thresholds. Values have been established for egg, milk, peanut, tree nuts, and fish that correspond to a positive predictive accuracy of 95 percent for a reaction on challenge, such that a child with a test result higher than these values, in combination with a suspicion of an allergy to the food, does not require challenge for definitive diagnosis. (See 'In vitro testing' above and "Overview of in vitro allergy tests".)

Supervised food challenges are sometimes required for the definitive diagnosis of food allergy. Foods are selected for testing based upon the history and the results of skin and/or in vitro testing. Food challenges should only be performed by allergy specialists familiar with food-allergic reactions and equipped with the necessary medications, equipment, and personnel to treat anaphylaxis and shock. (See 'Food challenges' above and "Oral food challenges for diagnosis and management of food allergies".)

There are a variety of unvalidated forms of testing for food allergy that are available but have no role in the diagnosis of food allergy. (See 'Unvalidated methods' above.)

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Topic 2396 Version 30.0

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