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Oral food challenges for diagnosis and management of food allergies

Oral food challenges for diagnosis and management of food allergies
Author:
Scott H Sicherer, MD, FAAAAI
Section Editor:
Robert A Wood, MD
Deputy Editor:
Elizabeth TePas, MD, MS
Literature review current through: Feb 2022. | This topic last updated: Oct 06, 2021.

INTRODUCTION — The diagnosis of a food allergy requires consideration of the details of an individual's history, knowledge about the epidemiology of different food allergies, and specific test results. When these elements do not clearly confirm or refute an allergy, the clinician, typically an allergy specialist or sometimes a gastroenterologist, may perform a clinician-supervised oral food challenge (OFC) [1-6]. OFCs may also be used to determine if a food allergy has resolved. In addition, they can be undertaken to define other adverse reactions to foods, such as intolerance.

OFCs generally consist of a gradual feeding of the test food under close observation. The test usually results in a definitive conclusion about whether the food was tolerated.

An OFC is preceded by a period of dietary elimination, performed either therapeutically (because the food was already suspected or known to have caused a reaction) or for diagnostic reasons (to determine if elimination of the suspect food resulted in amelioration of symptoms).

This topic review will present the role of diagnostic elimination diets, the selection of patients for OFCs, different types of OFCs, and a general approach to performing an OFC. Other related food allergy topics are covered separately. (See "Diagnostic evaluation of IgE-mediated food allergy" and "Management of food allergy: Avoidance" and "History and physical examination in the patient with possible food allergy" and "Food allergy in children: Prevalence, natural history, and monitoring for resolution".)

ELIMINATION DIETS — Elimination diets are undertaken prior to an OFC. Elimination diets are used diagnostically to determine if symptoms, usually chronic in nature, resolve after the suspected food(s) is removed from the diet. Elimination diets are discussed in greater detail in another topic review, and avoidance of a food allergen once the allergy is diagnosed is presented separately. (See "Diagnostic evaluation of IgE-mediated food allergy" and "Management of food allergy: Avoidance".)

There are three types of elimination diets:

Elimination of one or several foods suspected to be causing symptoms

Elimination of all but a defined group of "allowed" foods (oligoantigenic diet)

An elemental diet consisting of a hydrolyzed formula or an amino acid-based formula

The type of elimination diet chosen depends upon the clinical history and the results of specific immunoglobulin E (IgE) tests.

Acute IgE-mediated reactions — A patient may be instructed to avoid several potential causal foods if a reaction suggesting an IgE-mediated disorder (eg, urticaria) occurred suddenly after a meal but a single causal food allergen could not be identified by testing or history. It is improbable that more than one food in a given meal would cause a reaction.

Chronic illness — Elimination of multiple foods may be indicated for patients with certain chronic inflammatory diseases. For example, atopic dermatitis and eosinophilic gastrointestinal diseases are associated with food allergy that is usually non-IgE mediated or mixed IgE and non-IgE mediated [1,2,4]. History, testing, and epidemiologic considerations may yield an extensive list of suspect foods. Thus, elimination of multiple foods is typically needed to determine if the disorder is food responsive.

A provisional diagnosis of food allergy is given if symptoms resolve, as documented by history, symptom diaries, and/or physical examination. However, OFCs are still needed to confirm the causal foods. Elimination diets can sometimes result in acute allergic reactions to foods that were previously in the diet when these foods are reintroduced. (See 'Risk of reaction' below.)

INDICATIONS FOR OFC — The OFC serves two roles in managing food allergies: to confirm diagnosis of a specific food allergy and to determine if an identified allergy persists or has resolved.

Initial diagnosis — There are several settings in which clinician-supervised OFCs may be needed for diagnosis of food-allergic disease [1,4,6]:

To allow expansion of the diet when several foods are under consideration as a cause of symptoms, based upon history, positive specific IgE tests, and resolution of symptoms after elimination of all the suspected foods.

To evaluate foods that were removed from the diet or not introduced into the diet based primarily upon positive allergy tests [7].

When a food is highly suspected to have caused a significant acute allergic reaction, but specific IgE testing is negative.

When a food is highly suspected as an allergen, but elimination has not resulted in symptom resolution.

If tests for specific IgE are not relevant (eg, food protein-induced enterocolitis syndrome) [8] or only partly relevant (eg, atopic dermatitis or eosinophilic esophagitis) to the illness. (See "Food protein-induced allergic proctocolitis of infancy" and "Atopic dermatitis (eczema): Pathogenesis, clinical manifestations, and diagnosis" and "Clinical manifestations and diagnosis of eosinophilic esophagitis".)

Assessing resolution — In children with known food allergies, OFCs are commonly performed to determine the safety of adding foods back into the diet when it is suspected that the allergy has resolved. Variables to consider when trying to determine if a food allergy has resolved include specific IgE tests, age of the individual, time since the last reaction, and the outcomes after recent accidental exposures, if any. (See "Diagnostic evaluation of IgE-mediated food allergy" and "Food allergy in children: Prevalence, natural history, and monitoring for resolution".)

INAPPROPRIATE APPLICATIONS — There is generally no clinical reason to perform a diagnostic OFC if there has been recent, severe anaphylaxis to an isolated ingestion with a positive test for specific IgE antibody to the causal food. In addition, an OFC may not be relevant when the food or food family being eliminated is not important to the allergic individual's diet and can be simply avoided (eg, a rarely ingested fruit).

OFCs may not accurately reflect reactions outside of the challenge setting, because OFCs use a gradual administration of the tested food and the challenge is discontinued if symptoms occur [9]. Thus, OFCs should not be undertaken solely to document severity.

DECIDING TO PROCEED TO AN OFC — Medical and patient factors must be considered when determining if it is appropriate to undertake an OFC (table 1). Patient preferences and concerns are important to consider and should be discussed with the patient/caregiver(s). OFCs should only be performed when the food is expected to become part of the diet since recurrence of food allergy after a negative challenge, although uncommon, is associated with continued avoidance or infrequent ingestion of the challenge food [10,11]. Based upon a study of young children with hen's egg (hereafter in this topic referred to as "egg"), cow's milk (hereafter in this topic referred to as "milk"), or peanut allergy, OFCs resulting in reactions were not associated with increases in food-specific IgE or skin test responses, so this concern should not deter performing the diagnostic procedure [12].

Risk of reaction — The medical history, skin test results, and in vitro test results may be used to estimate the risk of current allergy. Data are conflicting as to whether increasing concentrations of food-specific antibodies and size of reactions on skin testing correlate with the severity of a reaction during a challenge, possibly because of additional factors affecting severity including dose ingested and comorbid conditions such as asthma [6,13-16]. (See "Diagnostic evaluation of IgE-mediated food allergy" and "Management of food allergy: Avoidance" and "History and physical examination in the patient with possible food allergy" and "Food allergy in children: Prevalence, natural history, and monitoring for resolution".)

As an example, a patient with an egg allergy had a reaction a few months ago after an accidental exposure. The in vitro test for food-specific IgE to egg is now negative. However, the prior probability that this patient is still allergic to egg is high, given the relatively recent reaction. A clinician may decide to proceed with the challenge if the skin test to egg is negative as this indicates a lower likelihood of reacting during the challenge. Conversely, a challenge may be deferred if the patient has a large positive reaction on skin testing [6].

OFCs performed after a period of elimination have resulted in acute and severe reactions, even though the food was previously associated only with chronic symptoms [17-19]. This occurs most commonly when there is a positive specific IgE test for the food. This risk must be considered prior to trial diagnostic elimination diets and during OFCs. As an example, in a retrospective chart review of patients presenting to a tertiary care allergy clinic with a concern for food-triggered atopic dermatitis, 19 percent with food-triggered atopic dermatitis and no prior acute allergic reactions to the eliminated food experienced immediate reactions on reexposure. Of these reactions, 30 percent were anaphylaxis [18].

Patient/caregiver preference — Agreement upon the correct time to undertake a food challenge requires shared decision making by the clinician and the patient/caregiver(s). Some clinicians typically offer food challenges for young children when risks of having a reaction to the challenge are approximately 50 percent [20,21]. Others suggest challenges when the risk is higher, on the grounds that avoidance, especially of staple foods, is a significant burden [22]. In contrast, some patients/caregivers may prefer to wait until there is a greater chance of tolerating the food (a negative challenge).

As an example, the caregivers of a two-year-old child with a 90 percent risk of peanut allergy may not consider an OFC worthwhile because the food is easily avoided and the chance of tolerating it may improve with time [23]. Conversely, it may be useful to perform on OFC in a teenager with the same 90 percent risk to determine with certainty whether the patient needs to continue avoidance since teenagers are more prone to risk taking and may otherwise try the food on their own.

Caregivers may decline an offered OFC based upon incorrect assumptions. As examples, they may not understand the benefit of adding that particular food to the diet, may assume a reaction is likely or fear a reaction, or may plan to attempt home introduction, which could result in reactions [24,25]. These are best addressed in anticipatory guidance.

Nutritional importance of the food — Food challenges may be indicated to allow expansion of the diet, despite poor odds of tolerance, in a child whose nutritional status is negatively impacted because of the avoidance of multiple foods [26].

Impact of a reaction (positive challenge result) — A child with fear of eating because of past severe reactions may warrant psychological treatment prior to OFC to reduce the risk that a reaction during OFC would increase food avoidance behaviors. Some studies suggest that an OFC, whether showing tolerance or allergy, may result in improved quality of life and may even decrease, rather than increase, anxiety [27,28].

TYPES OF FOOD CHALLENGES — There are three general types of OFCs: open, single-blind, and double-blind challenges [1-4,29].

Open OFC — An open OFC involves gradually feeding the tested food in its natural state (eg, peanut butter) to patients who know that they are eating the food being tested. This method is potentially prone to patient and observer bias because of expectations of a reaction, but it is easy to perform since no special preparation is needed. There is little concern about bias if the patient tolerates the ingestion of the food. However, bias must be considered when symptoms develop, especially if they are subjective.

Open challenges are a good option for screening when several foods are under consideration or there is minimal concern about observer or patient bias. The test can be repeated with blinding and controls if there is a reaction to an open challenge and there is concern that the reaction may have been anxiety related rather than physiologic. Open feeding is also used to follow a double-blind, placebo-controlled OFC (DBPCFC) to ensure a meal-sized portion of the food is tolerated in its natural state. (See 'Single-blind OFC' below and 'Double-blind, placebo-controlled OFC' below.)

Single-blind OFC — Single-blind challenges require that the food be masked in taste by adding it to another food. This procedure helps to alleviate some patient bias. However, the single-blind OFC does not remove observer bias.

The single-blind challenge may be performed with a placebo arm, or the operator may decide to use initial placebo doses to observe for subjective symptoms prior to proceeding with the challenge.

Double-blind, placebo-controlled OFC — The DBPCFC is considered the gold standard for diagnosing food allergy and is preferred for research purposes [29]. The tested food is hidden in another food. Bias is reduced because there are at least two feedings and neither patient nor operator knows which challenges contain the food being tested.

The procedure for DBPCFC is more labor intensive than the open- or single-blind challenge, but it can still be carried out in an office setting if the required materials and personnel are available. The aid of a third party is needed to prepare the challenges. A coin flip can be used by the third party to randomize the order of administration. It is sometimes difficult to provide a meal-sized portion of a food in its natural state because the food is masked.

The false-negative rate for DBPCFCs is 0.7 percent, and the false-positive rate is 2.8 to 3.2 percent, based primarily upon studies in children with atopic dermatitis [30-34]. Worsening eczema was the most frequent clinical reaction in one series, and reactions to placebo were more common in children ≤1.5 years of age compared with older children (4 versus 1.5 percent) [32].

The placebo arm and active arm may be performed in a single day in patients with a history of IgE-mediated reactions. There should be several hours between challenges. The practice of interspersing placebo and active food proteins during a single challenge (ie, random ordering of sequential doses of placebo and suspected allergen) should be discouraged because it may be difficult to differentiate whether a reaction following a placebo dose was due to the placebo or other factor or was a delayed reaction to the suspected allergen.

As noted above, an open feeding of a meal-sized portion of the tested food prepared in its usual manner is often performed as a follow-up to any negative DBPCFC [31]. A DBPCFC may need to be repeated using larger doses or different methods of food preparation if such an open feeding induces a reaction. Although DBPCFCs typically include only two separate challenges (a single placebo and only one active feeding component), increasing the number of challenges to both placebo and active allergen helps to diminish the possibility of a reaction due to chance rather than true allergy; however, this approach is very labor intensive [35].

PERFORMANCE OF AN OFC — In all challenges, the food is given in gradually increasing amounts. Consensus has not been reached on a uniform international protocol for performing OFCs, although suggestions for standardization have been published [4,6,8,29,36]. The protocol for OFC (eg, dosing, time between doses) may need to be varied to match clinical issues (eg, the history of the reaction pattern).

Patient preparation — Informed consent should be obtained from the patient or guardian and documented prior to beginning the challenge.

Patients should avoid the suspected food(s) for at least two weeks before the OFC for suspected IgE-mediated allergy and several weeks longer for non-IgE-mediated reactions. Patients should not eat or drink for at least two hours prior to challenge.

Antihistamines, beta-agonists, beta-adrenergic blockers (including eye drops), and other medications that may either alter symptoms of a reaction or interfere with its treatment should be discontinued for at least five half-lives (specific to each medication) prior to challenge. Patients should be instructed to bring their autoinjectable epinephrine to their appointment so that it is available to them on the trip home after the test in the event of a delayed reaction.

Patients are advised to cancel the OFC if they are experiencing acute allergic symptoms or are otherwise ill at the time of their appointment. Patients with asthma should be symptom free and be stable on current therapy with no recent exacerbations. Spirometry may be performed to ensure a good baseline. Infrequently, hospitalization may be necessary to treat severe or acute allergic disease and establish a stable baseline prior to challenges.

Children may be more cooperative if they are supplied with videos, games, and other distractions.

Location — OFCs are almost always performed under direct medical supervision either in a clinic or hospital setting. Options for location include clinician offices, outpatient centers designed for procedures, inpatient hospital units, and monitored intensive care units. In unusual circumstances, foods may be gradually added back into the diet at home, possibly with telehealth supervision [37]. This may be undertaken when specific IgE tests are negative or trivially positive, symptoms are mild or chronic, and there is little concern for potential anaphylaxis. (See "Food allergy in children: Prevalence, natural history, and monitoring for resolution".)

Selection of an appropriate setting requires clinician judgment about risks and availability of advanced treatment of anaphylaxis. Oral challenges can elicit severe anaphylactic reactions in any setting [38]. The clinician must have appropriate training and be prepared with emergency medications and equipment to promptly treat such a reaction [1,15,39,40]. Assessment of risk may determine that an OFC is appropriate for a clinic or a hospital setting [41]. Intravenous access for rapid fluid resuscitation should be readily available for patients with food protein-induced enterocolitis syndrome (FPIES) undergoing a food challenge since they are at risk for hypotension with reexposure to the food [8]. (See "Food protein-induced allergic proctocolitis of infancy".)

Safety — The rate and severity of reactions to OFCs depends upon many factors, including the criteria used to decide whether to proceed with the challenge (eg, blood and/or skin test results, severity of prior reactions, time since the last reaction) and comorbidities such as asthma (see 'Risk of reaction' above). Fatal outcomes from OFCs are a risk, which should be minimized by the approaches described here and outlined in various reports and guidelines [1-5,42]. There have been two reported fatalities due to an OFC [43,44].

Several studies have examined the overall level of risk associated with food challenges:

In a review of 1273 food challenges performed in patients with pre-OFC risk of reactivity assessments of ≤50 percent, 34 percent of OFCs resulted in allergic reactions, and epinephrine was administered for 11 percent of the reactions [45]. In contrast, in a review of positive food challenges performed in children expected to react (performed for screening for interventional studies), epinephrine was used for 39 percent of 74 reactions [46].

A retrospective series reviewed 584 OFCs performed in children who were estimated to have a ≤50 percent risk of a reaction [20]. Forty-three percent of the challenges were positive. Thirty-nine percent of the reactions were mild, 33 percent moderate, and 28 percent severe. The type and incidence of the different reactions were cutaneous (78 percent), gastrointestinal (43 percent), oral (26 percent), lower respiratory (26 percent), and upper respiratory (25 percent). No children had cardiovascular symptoms. There was no difference among foods in the severity of positive challenges or the type of treatment required to reverse symptoms, despite presumptions about certain foods causing more severe reactions than others (eg, peanut compared with egg or milk). All reactions were reversed with antihistamines without epinephrine, beta agonists, and/or glucocorticoids. Patients were observed for a minimum of four hours after completion of the challenge, and none had a delayed reaction after discharge.

A study of 6377 open OFCs in five US centers performed in clinical (not research) settings found a reaction rate of 14 percent and an anaphylaxis rate of 2 percent [47].

Food preparation — In blinded challenges, the allergenic food is hidden in another food.

Opaque capsules have been used but are now in disfavor because they pose several potential problems. Some patients, especially young children, are unable to ingest enough capsules or even swallow them at all. In addition, capsules can bypass oral contact, which would normally provide the earliest symptoms/clues of a clinical response. Finally, slow degradation of capsules may result in overlapping doses (ie, administration of a subsequent dose before the previous dose was fully released). This can lead to unintended administration of a higher-than-needed dose to elicit symptoms and to more severe reactions.

Thus, allergenic foods may be mixed into masking foods. Equipment used for food preparation includes paper plates, cups, disposable utensils, mixing bowls, scale, mortar/pestle, blender, and a microwave. Suggestions for masking foods are shown in the table (table 2) [6,48,49]. The following points should also be considered:

It is often easier to mask liquid into liquid or to use powdered or dehydrated forms of foods that can be folded into solid vehicles.

If a gritty allergen is being hidden in a vehicle, then a similarly gritty food should be added as placebo to the carrier vehicle. For example, for a challenge with ground oats hidden in applesauce, cornmeal may be mixed into applesauce as a placebo.

It is preferable not to use fatty foods as vehicles, since they can delay gastric absorption [50].

Certain flavoring agents, such as mint, tuna, or garlic, can mask odors (such as the odor of peanut butter). However, it is important to select vehicles that are clearly tolerated by the patient.

Measuring small amounts (eg, fractions of a mg) may be difficult and inaccurate; mixing and diluting the food in a carrier vehicle is often a more practical approach.

Certain preparation methods (eg, canning, dehydration) may alter allergens [51]. For this reason, a negative challenge should always be followed by an open feeding of the food, prepared in the way it is normally ingested. (See 'Discontinuing a challenge' below.)

Dosing and timing — No single approach to dosing and timing is universally established for food challenges. Dose amounts and timing between doses should be adjusted to match the patient's history (eg, if days of ingestion are needed to elicit symptoms) or concerns about heightened sensitivity (eg, starting with minimal doses spaced out over longer periods of observation).

For example, a child with a history of atopic dermatitis flaring over days with milk ingestion who carries positive IgE tests to milk and has been avoiding this protein for a year may have an acute allergic reaction on the day of challenge or may experience a flare over days of ingestion. A graded OFC under clinician supervision on the first day would evaluate the risk of an acute reaction and, if tolerated, following the child's symptoms over the following days with milk added to the diet, would evaluate for delayed responses.

The general approach is to select a regimen that is unlikely to result in a severe acute reaction by cautiously and gradually increasing the amount ingested (with the target cumulative dose of a meal-sized portion), while also considering time constraints.

For patients with past food reactions that occurred immediately after ingestion, doses are generally administered at 15- to 30-minute intervals over approximately 90 to 120 minutes, followed by a larger, meal-sized portion of food a few hours later.

Different dosing regimens are suggested when performing OFC for FPIES. (See "Food protein-induced allergic proctocolitis of infancy".)

Total dose — One approach used for double-blind, placebo-controlled, OFCs (DBPCFCs) [1,52] is to administer a total of 8 to 10 grams of the dry food or 100 mL of wet/liquid food (double amount for meat/fish, eg, 20 grams). Dry forms of peanut (flour), milk, and egg are often used. The grams used may not match the protein content of ingested foods in their natural form. Powdered forms with a weight of 8 to 10 grams are approximately equivalent to 105 mL skim milk, 1.2 eggs, and 21 mL of peanut butter. Open OFCs often aim for a cumulative consumption of a serving size portion for age [6].

Starting dose — The starting dose should be low enough that it does not trigger a reaction in most patients. Estimation of a starting dose may differ based on estimation of the risk of reaction based on history and testing. Starting doses in the 1 to 3 mg range are generally safe and unlikely to elicit severe reactions [6].

According to one workgroup report, the challenge may begin with 0.1 to 1 percent of the total challenge food, which may represent 1 to 5 mg of the food protein and 8 to 10 mg of the whole food, depending on the type of food and its preparation [1]. The European Academy of Allergology and Clinical Immunology proposed starting doses as follows (shown as protein weight or liquid volume): peanut 0.1 mg, milk 0.1 mL, egg 1 mg, cod 5 mg, wheat 100 mg, soy 1 mg, shrimp 5 mg, hazelnut 0.1 mg [53]. Another consensus report suggested starting with 3 mg of food protein [29].

Starting doses of 100 mg or less are recommended in part based upon results from a series of 513 positive challenges to six common allergenic foods in children with atopic dermatitis [52]. In this series, starting doses ranged from 100 to 500 mg. Neither prick skin test size nor specific IgE antibody concentration was predictive of the dose required to trigger a reaction. Eleven percent of the reactions that occurred on first dose were severe. The following results were reported:

Approximately 50 percent of children reacted at the first dose for egg and milk; 25 percent for soy, wheat, and peanut; and 15 percent for fish.

Twenty-two percent of milk challenges and 8 percent of egg challenges were positive at a first dose of 250 mg.

Three percent of milk and egg challenges were positive at a first dose of 100 mg.

One could argue for starting doses that begin under the thresholds reported to induce reaction, especially in patients who have a history of reacting to trace amounts of a food [54]. However, threshold data are not available for most foods, and the thresholds that are published vary logarithmically. Reactions are usually not reported under 0.25 mg of protein for peanut (1 mg of peanut, an amount about the size of the head of a pin), 0.13 mg for egg (similar to the weight and volume of peanut butter), and 0.6 mg for milk (approximately 0.02 mL) [55,56]. These doses are difficult to measure accurately with typical office equipment. Single-dose, low-dose challenges may be used to confirm that a patient is not reactive to low doses [57].

Labial food challenge (LFC) or lip dose challenge (LDC), which involves placing the food on the lower lip for two minutes and observing for local or systemic reactions in the ensuing 30 minutes [58], has been suggested by some as a starting point before an OFC. However, we do not perform an LFC, due to concerns about diagnostic accuracy and validity of the test. An online survey of registered pediatric allergy clinics in the United Kingdom found that 80 percent of allergy specialists were still performing an LFC, although there was a wide variation in the performance and interpretation of this test [59]. In addition, one-third of respondents made the diagnosis of food allergy on the basis of subjective symptoms with the LFC without confirming the diagnosis with an OFC. In a separate prospective study of 198 children undergoing "low-risk" OFCs with an LFC as the first step, the LFC was estimated to have a sensitivity of only 32 percent, with the majority of patients with a negative test going on to develop symptoms with subsequent oral doses [59]. Two of the 12 children with a positive LFC passed the OFC.

Dose escalation — The total amount of food to be administered is given in escalating portions. The dosing increments and frequencies may be adjusted based upon assessment of risk. A reaction occurring after a dose may represent symptoms due to just that dose or to the cumulative effect of previous doses given [13].

As an example, for a milk challenge with the target dose of 100 mL (1 mL = 1 percent of the total dose), the doses could be: 1, 4, 10, 20, 20, 20, and 25 percent [1]. However, a variety of other challenge regimens have been used, including lower starting doses, variations in the dosing increments (for example, in mg protein: 1 mg, 3 mg, 10 mg, 100 mg, 300 mg, 600 mg, 1000 mg, 3000 mg, etc), and different time intervals [1,29,36]. A workgroup report suggested a four-dose regimen (1/12, 1/6, 1/4, and 1/2 of the total serving) or a six-dose regimen (1, 4, 10, 20, 20, and 30 percent) for open OFCs [6].

Monitoring — Patients should be examined carefully prior to an OFC to determine their baseline and to confirm that they do not have any current significant allergic signs/symptoms or an illness that would interfere with assessment and/or treatment of a reaction during the challenge. Vital signs and signs and symptoms are assessed and recorded at baseline, prior to each dose, and at set intervals after the final dose. Assessments are made for symptoms affecting the skin, cardiovascular system, and gastrointestinal and respiratory tracts (table 3). Scoring systems are useful in the research setting [29,60] but are not generally implemented in clinical practice [1].

Children may become suddenly quiet or assume a fetal position prior to exhibiting more objective symptoms. Early indications of a reaction can include subtle signs, such as moving the tongue in the mouth to rub an itchy palate or ear pulling as an indication of pruritus. Oropharyngeal pruritus or pain often precedes objective symptoms [61,62]. Children with atopic dermatitis may display an eczematous flare.

Discontinuing a challenge — Challenges are terminated when a reaction becomes apparent (eg, new objective symptoms or an increase in objective symptoms over baseline). Expert judgment is needed about whether or not to discontinue a challenge if symptoms are not clear. Generally, a challenge is discontinued if subjective symptoms are repetitive or prolonged.

Following a negative OFC in which the allergen was administered in a form not normally eaten (eg, peanut flour or powdered egg), an open challenge with a meal-sized portion of the food in the state in which it is normally ingested (eg, peanut butter or boiled egg) is recommended. This is done to ensure that the processing of the allergenic food for challenge did not alter the allergen and to confirm the negative result.

Medical treatment for a reaction — Medications are given as needed to treat allergic or anaphylactic reactions. Generally, antihistamines are given at the earliest sign of a reaction. Epinephrine and other treatments are given if there is progression of symptoms or any potentially life-threatening symptoms. (See "Anaphylaxis: Emergency treatment".)

Acute abdominal pain is a frequent manifestation of IgE-mediated food reactions and can be prolonged and difficult to manage. Beta-2 receptor agonists relax visceral smooth muscle and have been used to treat other causes of visceral pain. In a retrospective case-control study of 26 patients with peanut allergy who had a positive DBPCFC and were treated with salbutamol (albuterol) 8 to 10 inhalations of 100 micrograms metered dose inhaler (MDI) via a valved holding chamber in rapid sequence and 21 historical controls, time to onset of improvement and time to complete resolution were significantly lower in treated than control patients (median 12.5 versus 65 minutes and 32.5 versus 90 minutes, respectively) [63]. These results suggest that high-dose albuterol hastens resolution of abdominal pain due to IgE-mediated allergy. However, the study approach carries significant potential biases (observer and patient biases, placebo effect), and these findings need confirmation in a clinical trial before it is used in routine clinical practice.

Severe allergic reactions are an uncommon outcome of OFCs in children when typical criteria are used in deciding to proceed with a challenge. Biphasic reactions are uncommon [45,64]. (See 'Indications for OFC' above and 'Deciding to proceed to an OFC' above and "Food allergy in children: Prevalence, natural history, and monitoring for resolution", section on 'Monitoring for resolution'.)

Full medical therapy (eg, epinephrine, antihistamines, intravenous fluids, oxygen, vasopressors, and histamine receptor type 2 [H2] blockers), materials for resuscitation (ie, intubation), and personnel who can manage anaphylaxis should be immediately available. Doses for all rescue medications should be calculated in advance of challenges.

Observation following challenge — After a negative OFC, we typically observe a patient for one to two hours. It is possible to have later-onset symptoms, and we extend this period if the history suggests delayed reactions (especially for suspected delayed reactions to mammalian meats (see "Allergy to meats")) that may warrant up to six hours of observation [65] or if prior reactions were severe. We inform the patient not to eat more of the test food that day and to report and treat any symptoms. The food is added to the diet the next day if no delayed symptoms are reported.

Following a positive challenge, we observe patients for a minimum of one to two hours past resolution of mild symptoms that required minimal treatment and at least four hours for more significant reactions. Biphasic anaphylaxis appears to be rare following OFCs. (See "Biphasic and protracted anaphylaxis", section on 'Biphasic anaphylaxis'.)

Post-challenge counseling — Patients who tolerate a challenge require counseling about how to introduce or reintroduce the food [6]. Typically, the food is started in the diet in normal portions the day after the challenge. Some patients and caregivers may continue to be fearful about eating the food, or not prefer it, despite a negative challenge [66-68], and this can result in continued avoidance [69,70]. Patients and caregivers should be counseled that delayed reactions or reactions to a normal serving size of the food eaten all at once can occur, usually within a few days of the challenge, but they should also be reassured that these reactions are rare. As noted above regarding peanut, avoidance or infrequent exposure may result in resensitization to the allergen. It is therefore important to encourage normal incorporation of the food into the diet. Patients should be asked at subsequent visits about regular ingestion of the former allergen. A repeat challenge may be required in patients who have continued to avoid the food.

Patients who have had a negative OFC to one allergen may have remaining food allergies. These patients must be cautioned specifically about cross-contamination by foods that are commonly associated with the food that they are now able to ingest.

Some patients may wish to continue carrying epinephrine even when there are no remaining food allergies. Patients may be advised to continue to have epinephrine available until it is clear that the food is tolerated as a routine part of the diet [11].

Patients who have reacted during the OFC can be partly consoled to know that their hard work at avoidance was necessary. Though reactions may vary and strict avoidance is typically advised, knowledge about the dose causing symptoms may provide helpful information to patients and caregivers [27,71]. Review of food avoidance measures is also helpful. The nutritional impact of food avoidance should be reevaluated.

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 e-mail 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

Oral food challenges (OFCs) are a means to determine definitively if an allergy or other adverse reaction is related to a food and to determine if an identified food allergy has resolved. These challenges are typically undertaken by allergy specialists and occasionally by gastroenterologists. (See 'Introduction' above and 'Indications for OFC' above.)

Elimination diets are undertaken prior to introducing a food during an OFC. (See 'Elimination diets' above.)

OFCs may be performed as open feedings, single-blind, or double-blind, placebo-controlled studies. The potential for bias will determine the type of OFC to be performed. (See 'Types of food challenges' above.)

OFCs are generally performed by gradually feeding the test food under supervision, with personnel and emergency treatments available in the event of anaphylaxis. (See 'Performance of an OFC' above.)

Dosing amount and regimen, location of challenge (eg, in a clinic, hospital, or monitored unit), and preparation of the patient with intravenous access is determined by assessment of various risk factors. (See 'Performance of an OFC' above.)

A successful OFC requires ingestion of a meal-sized portion of the tested food prepared in its usual state. It is uncommon for subsequent reactions to occur if the feeding was tolerated. (See 'Performance of an OFC' above.)

REFERENCES

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Topic 2399 Version 26.0

References

1 : Work Group report: oral food challenge testing.

2 : Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel.

3 : Food allergy: a practice parameter update-2014.

4 : EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy.

5 : Conducting an Oral Food Challenge to Peanut in an Infant.

6 : Conducting an Oral Food Challenge: An Update to the 2009 Adverse Reactions to Foods Committee Work Group Report.

7 : Oral food challenges in children with a diagnosis of food allergy.

8 : International consensus guidelines for the diagnosis and management of food protein-induced enterocolitis syndrome: Executive summary-Workgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma&Immunology.

9 : Does severity of low-dose, double-blind, placebo-controlled food challenges reflect severity of allergic reactions to peanut in the community?

10 : Recurrent peanut allergy.

11 : Peanut allergy: recurrence and its management.

12 : Impact of Allergic Reactions on Food-Specific IgE Concentrations and Skin Test Results.

13 : Modified oral food challenge used with sensitization biomarkers provides more real-life clinical thresholds for peanut allergy.

14 : Outcome of oral food challenges in children in relation to symptom-eliciting allergen dose and allergen-specific IgE.

15 : Food Challenge and Community-Reported Reaction Profiles in Food-Allergic Children Aged 1 and 4 Years: A Population-Based Study.

16 : Improving Diagnostic Accuracy in Food Allergy.

17 : Acute allergic reactions in children with AEDS after prolonged cow's milk elimination diets.

18 : Natural History of Food-Triggered Atopic Dermatitis and Development of Immediate Reactions in Children.

19 : Development of anaphylactic cow's milk allergy following cow's milk elimination for eosinophilic esophagitis in a teenager.

20 : Risk of oral food challenges.

21 : The relationship of allergen-specific IgE levels and oral food challenge outcome.

22 : The predictive value of specific immunoglobulin E levels in serum for the outcome of oral food challenges.

23 : The natural history of peanut allergy.

24 : Factors resulting in deferral of diagnostic oral food challenges.

25 : Caregiver perceptions of when to offer an oral food challenge for children with food allergy.

26 : Impact of elimination diets on nutrition and growth in children with multiple food allergies.

27 : Oral food challenge and food allergy quality of life in caregivers of children with food allergy.

28 : The impact of oral food challenges for food allergy on quality of life: A systematic review.

29 : Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma&Immunology-European Academy of Allergy and Clinical Immunology PRACTALL consensus report.

30 : False-negative food challenges in children with suspected food allergy.

31 : Use of food-challenge tests in children.

32 : Positive reactions to placebo in children undergoing double-blind, placebo-controlled food challenge.

33 : Accurate oral food challenge requires a cumulative dose on a subsequent day.

34 : Prevalence of adverse reactions following a passed oral food challenge and factors affecting successful re-introduction of foods. A retrospective study of a cohort of 199 children.

35 : Statistical issues in clinical trials that involve the double-blind, placebo-controlled food challenge.

36 : Food challenges.

37 : Novel Approaches to Food Allergy Management During COVID-19 Inspire Long-Term Change.

38 : Severe anaphylaxis requiring intensive care during oral food challenge-It is not always peanuts.

39 : What safety measures need to be taken in oral food challenges in children?

40 : Risk Factors for Severe Reactions during Double-Blind Placebo-Controlled Food Challenges.

41 : Implementation of a Standardized Clinical Assessment and Management Plan (SCAMP) for Food Challenges.

42 : Diagnosis and Rationale for Action Against Cow's Milk Allergy (DRACMA): a summary report.

43 : Diagnosis and Rationale for Action Against Cow's Milk Allergy (DRACMA): a summary report.

44 : Food-related anaphylaxis fatalities: Analysis of the Allergy Vigilance Network®database.

45 : Epinephrine treatment is infrequent and biphasic reactions are rare in food-induced reactions during oral food challenges in children.

46 : Epinephrine use in positive oral food challenges performed as a screening test for food allergy therapy trials.

47 : Multicenter prevalence of anaphylaxis in clinic-based oral food challenges.

48 : Development and validation of challenge materials for double-blind, placebo-controlled food challenges in children.

49 : Double-blind placebo-controlled challenges for peanut allergy the efficiency of blinding procedures and the allergenic activity of peanut availability in the recipes.

50 : Presentation of allergen in different food preparations affects the nature of the allergic reaction--a case series.

51 : Seafood allergy in children: a descriptive study.

52 : Dose-response in double-blind, placebo-controlled oral food challenges in children with atopic dermatitis.

53 : Standardization of food challenges in patients with immediate reactions to foods--position paper from the European Academy of Allergology and Clinical Immunology.

54 : A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much?

55 : Factors affecting the determination of threshold doses for allergenic foods: how much is too much?

56 : How much is too much? Threshold dose distributions for 5 food allergens.

57 : Peanut Allergen Threshold Study (PATS): Novel single-dose oral food challenge study to validate eliciting doses in children with peanut allergy.

58 : Labial food challenge in children with food allergy.

59 : Lip Dose Challenges in Food Allergy: Current Practice and Diagnostic Utility in the United Kingdom.

60 : A new framework for the documentation and interpretation of oral food challenges in population-based and clinical research.

61 : Oropharyngeal symptoms predict objective symptoms in double-blind, placebo-controlled food challenges to cow's milk.

62 : Clinical reactivity to hazelnut in children: association with sensitization to birch pollen or nuts?

63 : Potential Efficacy of High-Dose Inhaled Salbutamol for the Treatment of Abdominal Pain During Oral Food Challenge.

64 : Biphasic reactions in children undergoing oral food challenges.

65 : Diagnostic and experimental food challenges in patients with nonimmediate reactions to food.

66 : Changes in diet and life of children with food allergies after a negative food challenge.

67 : Rate of food introduction after a negative oral food challenge in the pediatric population.

68 : Brief ganglioside treatment produces delayed enhancement of functional recovery after medial septal lesions.

69 : Continuing food-avoidance diets after negative food challenges.

70 : Failure of introduction of food allergens after negative oral food challenge tests in children.

71 : Determination of no-observed-adverse-effect levels and eliciting doses in a representative group of peanut-sensitized children.