The Oral Food Challenge; What It Is and How to Prepare for It

Image by Bethany Hicks on Pexels

And now for the details, which include:

What is an oral food challenge?

An oral food challenge (OFC) is a procedure during which someone who has a suspected food allergy eats small doses of their suspected trigger food in increasing amounts over the course of a few hours or days while under medical supervision.

The OFC generally carried out with one goal in mind: to obtain a ‘yes or no’ answer as to a whether a certain food has to be eliminated from a person’s diet.

Food challenges are rarely ever carried out in clinical practice settings. In the vast majority of cases, allergists make their diagnosis of food allergy based on a patient’s history of reactions and the results of their skin prick tests and/or blood tests. This diagnosis relies on a clinical history that agrees with the results of the lab tests; however, while skin and blood tests can show a possible sensitisation to a certain food, they do not prove an allergy.

Skin and blood tests are not altogether reliable; they can produce false positive and false negative results. And several factors—such as the specific food involved, whether it’s cooked or not, the age of the person taking the test, their specific clinical situation, the type of extract used to perform the tests—prevent a certain diagnosis.

A positive skin or blood test result to a food simply means that your body’s immune system recognises certain allergens in that food, it does not mean that you will actually have an allergic reaction to it. For example, when British researchers gave food challenges to 79 children diagnosed as sensitised to peanuts on the basis of their skin or blood test results, 66 of them had no reaction. The authors of the study concluded that ‘The majority of children considered peanut-sensitised on the basis of standard tests do not have peanut allergy.’

In fact, the correlation between results from skin-prick tests and/or blood tests and food challenges has been put at between 30% and 40%.

This has not stopped researchers trying to pinpoint weal sizes in skin tests and IgE levels in blood tests that can be taken as a good indication that someone is allergic (or not) to something—so-called cut-offs—and this is what a doctor will use to make a provisional diagnosis of their patient’s allergic status.

However, a clinical history which includes clear examples of someone consistently having reactions after eating a certain food is necessary in order to make this diagnosis. Unfortunately, a person’s clinical history is not always clear; symptoms can be subjective and it can be hard to pin down which food is causing the problems, especially in cases of allergies to multiple foods or delayed forms of food allergy. That’s where the food challenge comes in.

3 types of challenge

There are 3 ways to carry out a food challenge.

The open challenge

In the open challenge, there is no placebo (i.e. food item that does not contain the suspected trigger food), the food is in its natural form and both the doctor and the patient (and, potentially, their caregivers) know what is being eaten.

The open challenge is the most common type of challenge because it’s the least complicated to plan and carry out and the least expensive in terms of costs and time. It’s intended to reproduce the natural exposure to the food in both quantity and method of preparation and, as a typical patient visiting an allergy clinic, it’s the one you’re most likely to be offered.

It involves the gradually feeding of an age-appropriate amount of food, followed by an observation period of around 1 to 2 hours. There is no standard dosing schedule for this type of test; sometimes a person is fed a typical serving portion in one go, sometimes (if a patient is considered more likely to react) that portion is broken up into several smaller ones that are served with pauses for observation time in between. The allergist will follow a procedure that they think best fits your circumstances.

According to official European and American guidelines, an open food challenge is recommended when:

• a person is not expected to show symptoms—either because their skin and/or blood tests have produced a negative result or suggest very low levels of IgE antibodies, or because they have eaten the food in the past without symptoms even though their lab test results were positive
• a person is expected to show clear-cut, objective symptoms that corroborate their clinical history and their test results

It’s not recommended when a person is expected to experience subjective symptoms—such as stomach pain or headaches—that cannot be observed.

The main drawback of an open challenge is that some people who are aware that they are eating the potentially problematic food can become anxious. This puts them at risk of failing the challenge due to so-called ‘psychogenic factors’—physical symptoms brought on by stress or a strongly-held belief that the food will cause a reaction which leads to a self-fulfilling prophesy. For this reason, this type of challenge is more reliable when carried out with young children under the age of 3 (as long as their parents remain calm).

Older children and adults with a potential IgE-mediated food allergy sometimes undergo an open challenge before a double-blind placebo-controlled food challenge, in the (hope and) expectation of an unequivocally negative result which would render the blinded challenge unnecessary. An open challenge is considered a reasonable first choice in these cases because less than a third of suspected foods tend to produce a positive result, and most of the positive challenges will produce objective and clear-cut symptoms.

The results are considered definitive if the challenge produces either no symptoms, supporting a diagnosis of no allergy, or objective symptoms which back up the person’s medical history, preferably corroborated by lab tests that support a diagnosis of food allergy.

The production of subjective symptoms, like an itching mouth or a feeling of nausea, or very mild symptoms, or even symptoms that do not match the kind of reaction that is expected, is inconclusive. In these cases, a firm diagnosis of food allergy requires a blinded challenge.

The double blind challenge

Double-blind challenges have been used since 1976.

During a double-blind placebo-controlled food challenge (DBPCFC), a person is given increasing doses of a suspected food allergen and a placebo—which are presented in a way that makes them both look and taste exactly the same—often on different days. The term ‘double-blind’ is used because the test food(s) and placebo are prepared and coded by a third party and are administered in random order, so that neither the doctor nor the patient know whether the suspected food or the placebo is being eaten. This minimises the risk of psychologically induced reactions on the patient’s part and bias on the doctor’s part. For this reason, the DBPCFC is considered the ‘gold standard’ for the diagnosis of IgE-mediated food allergy.

The DBPCFC is the method recommended when:

• a positive, IgE-mediated reaction is expected—that is, a person has a positive history of immediate reactions and the skin and/or blood tests show moderate to high levels of IgE antibodies to a food
• a case of delayed, atypical, or chronic allergy—e.g. eczema or eosinophilic oesophagitis (EoE)—is suspected
• symptoms are subjective—such as stomach pain, feelings of nausea, headaches, chronic fatigue or joint complaints— or potentially psychological
• the person will be taking part in a study, for example to establish the prevalence of a food allergy in the population, to determine the effectiveness of a treatment or to define threshold doses for research or food manufacturing purposes

However, it’s a time-consuming, resource-intensive and expensive procedure, it requires a lot of care when processing the (‘active’) doses containing the trigger food and making and masking the placebo doses, and it runs the risk of inducing systemic and potentially serious allergic reactions. Therefore, it’s mostly used for research purposes and open challenges are recommended as the routine challenge in allergy clinical practices, only to be followed by a DBPCFC when the result of the open challenge is ambiguous.

The single blind challenge

During a single blind challenge, only the doctor knows when the potentially troublesome food is being eaten. This challenge can be carried out with or without a placebo.

If no placebo is used, the person taking the test is told that their trigger food may or may not be served during the challenge. If a person has to undergo a challenge to multiple foods on different days, they won’t be told which foods they have eaten until all the testing is over.

The problem with a single-blinded test is that the person taking the test may be influenced by the observers—the allergist and caregivers—if those people show worry (if the potential trigger food is given) or relief (when a non-trigger food is given). If this is expected to be a problem, a placebo will be needed.

A single-blinded challenge that includes a placebo is typically made up of 2 sessions, one that includes the potential trigger food and one that includes the placebo. This often happens on the same day, with both sessions being separated by at least a couple of hours and the person taking the test being kept in the dark about which sequence the foods will be served in. If this is not logistically possible, one session in which placebo doses are interspersed with potential trigger food doses may be carried out instead.

The results are considered definitive if the challenge either produces no symptoms, supporting a diagnosis of no allergy, or produces objective symptoms in a patient who also has a supportive medical history and skin and/or blood test results.

In cases where a reaction has been provoked by someone who is suspected of having a psychological response to testing, a double-blind challenge to the foods they reacted to may be needed, just to make sure.

Blinded challenges that produce negative results should be followed by an open, unblinded feeding of a larger portion of the tested food either 2 hours after finishing the challenge or on another day, just to make sure the food really doesn’t cause problems. But they probably won’t be; it’s a question of time and resources.

Image by Ann H on Pexels

What are the benefits of an oral food challenge?

A food challenge is the only way to get definitive answers about your allergic status, including whether or not you have an allergy, how sensitive your allergy is and whether you’re allergic to cross-reacting foods. But it has other benefits, too.

A food challenge that provokes an allergic reaction is called a positive or failed challenge, and a food challenge that doesn’t is called a negative or passed challenge.

A positive/failed challenge tells you:

• that you are definitely allergic to that particular food
• what a reaction looks like, how long it lasts and how to treat it properly; note, however, that it cannot tell you how severe your reactions are likely to be in the future, firstly because a challenge is normally stopped at the first sign of objective symptoms, secondly because reaction severity can be different in the same person thanks to things called cofactors
• what your threshold—the amount of a food needed to provoke a reaction—is and whether or not you will need to avoid it completely to stay healthy

If you have a reaction during a challenge, it will essentially result in a live demonstration of what symptoms to look for, how to administer treatment, how to decide on which treatment is appropriate (e.g. whether or not an antihistamine is good enough or whether you should use your adrenaline autoinjector) and it will enable you to see first-hand the effect of the treatment which, in the case of adrenaline, tends to be reassuringly fast.

A reaction will also enable you to see what your threshold is, at least when you’re in general good health (cofactors like illness and medicine can lower your threshold), and the allergist should also be able to tell you whether or not this means that you can eat food products that carry a PAL warning because they ‘may contain’ your food trigger.

A negative/passed challenge tells you:

• that you do not have a recognised allergy to the food tested (and if you have an undiscovered intolerance, at least you can be fairly certain it won’t kill you)
• if you were allergic, that you (or your child) have developed tolerance for the food that you were once allergic to
• that you don’t need to worry about meal prep and social situations involving food
• that you can expand and improve your diet

One of a food challenge’s greatest benefits is its ability to eliminate unnecessary and possibly harmful dietary restrictions in people who are sensitised, but not allergic, to food.

This is what it did for 125 American children with eczema who were sensitised to a whole range of different foods and were on very restricted diets as a result of their skin and/or blood tests. After undergoing challenges, the children were able to reintroduce around 9 in 10 of the foods that they were avoiding into their diets, allowing them to eat more healthily. 

Similarly, when it comes to foods that can be prepared in various different ways, such as eggs that can be eaten friend, scrambled, boiled or baked, a challenge to raw eggs and to baked eggs will show whether a person can eat one form without experiencing symptoms and allow that form of the food to be introduced into their diet. And, in the case of, for example, baked egg being introduced into an allergic child’s diet, after completing the test, a parent will know exactly how much egg to cook, at what temperature and for how long, to make their child a symptom-free muffin.

Food challenges give you the knowledge that you need to make sure that your (child’s) diet is as safe and healthy as possible. They provide peace of mind and increase the quality of life of both people suffering from allergies and caregivers, even if the test is positive.

Image by Ann H on Pexels

When will you be offered a food challenge?

There are several reasons why you might be offered a food challenge.

Your clinical history suggests an allergy to a certain food but your skin and blood tests are negative or show very low levels of IgE, perhaps because:

• the extracts used for testing did not contain the specific allergens that you react to
• there are no extracts to test for the things that you seem to be allergic to, such as food additives, herbs or little-known food allergens
• you have chronic, late-onset reactions like eczema and gastrointestinal symptoms, which are not always IgE-mediated and will therefore not give positive skin or blood tests results

You have had systemic reactions to a suspected food trigger or you have a chronic disease and food is suspected to be the source of the problem, but the specific culprit food cannot be identified, perhaps because:

• the food is ‘hidden’ in a ready meal, a takeaway or restaurant meal, or it’s an ingredient in a special family recipe
• multiple foods have been identified as potential culprits
• the reactions are delayed and difficult to pin down

In such cases, testing may be done with the actual meal that you have eaten to try and verify the reaction so that the problem allergen can be pinpointed.

Skin and/or blood tests indicate that you are sensitised to a food or foods, but these sensitisations may not be ‘clinically relevant’—i.e. may not produce symptoms—because they are examples of asymptomatic secondary allergies (i.e. cross reactive allergies); for example, you are allergic to grass pollen and you test positive to wheat, but you won’t actually have symptoms after eating it.

You are avoiding certain staple food(s) because your skin and/or blood tests are positive, but you don’t know whether you are actually allergic to the food(s) because you’ve not had any definitive symptoms after eating it/them.

Undergoing a challenge in this type of situation is especially useful when a person needs to add more nutrients to their diet, for example, because they are a growing child or they are vegan and need more sources of protein.

Skin and/or blood tests indicate that you are sensitised to a food or foods, but you have not eaten that food before, perhaps because you’ve had serious reactions to another food in the past and have avoided related foods that may provoke cross-reactive allergic reactions. For example, you’re allergic to walnuts and therefore have been told to avoid other tree nuts and peanuts, or you’re allergic to a certain type of fish and have not eaten any other type of fish.

This kind of situation also applies to infants who are sensitised to a well-known allergenic food like milk or peanuts that they have never been fed because they are considered at ‘high risk’ of developing a food allergy as they have severe eczema or their parents and/or siblings have food allergies.

You have subjective (often controversial) complaints, such as chronic fatigue, migraines or joint complaints. In such cases, a placebo-controlled test can be arranged with repeated challenges and complicated statistical analysis to come to an objective conclusion.

To see whether whether cooking or other types of food processing might eliminate your symptoms—for example, many people with pollen food syndrome can tolerate cooked fruit and veg, and many people who are allergic to fish can eat canned tuna. Knowing whether or not this is the case allows people to expand their diets with more healthy foods.

To see whether an elimination diet has been responsible for an improvement in symptoms—for example, if you are suffering from a chronic condition like eosinophilic oesophagitis and you undertake an elimination diet that makes your symptoms disappear, a food challenge with the food(s) that you have eliminated from your diet will help to confirm whether or not the food(s) were responsible for your symptoms in the first place, and enable the doctor to establish an accurate diagnosis.

To determine the amount of a trigger food—the threshold dose—needed to provoke a reaction. These kinds of risk assessment challenges can be performed to confirm your sensitivity level, i.e. your risk of having a reaction to certain amounts of food and the potential severity of your symptoms—although, as challenges are often stopped as soon as symptoms are seen, a challenge cannot say anything about the symptoms that you might get if you ate more of your trigger food without realising it. Still, it should give you an idea about how strict you have to be with your diet and whether, for example, you have to avoid all food that ‘may contain’ your trigger allergen or whether you can ignore PAL warning labels and eat food with potential traces of your trigger food.

This kind of challenge can also be the first step in a course of oral immunotherapy or in a clinical trial to, for example, validate a new type of treatment or determine when to apply warning labels to processed foods.

To see whether you are still allergic to your trigger food—the allergy may have resolved, either because you have outgrown it or it has spontaneously resolved, or because you have successfully undertaken a course of immunotherapy.

In fact, one of the most common reasons to undergo a food challenge is to see whether a child has outgrown their allergy to a certain food. Food allergy is a dynamic process that changes over time. Young children are expected to outgrow allergies to certain foods like egg, milk, wheat and soy and a food challenge is needed to see whether the allergies have resolved or not.

Allergies to other foods like peanuts, tree nuts and shrimp, on the other hand, are more likely to be lifelong. But they are not lifelong for everyone. Even adults who develop allergies to these foods may develop tolerance to the foods again after a period of abstinence.

So, repeated food challenges can be carried out to check whether a person is still allergic or not, based on whether their lab test results indicate that their levels of specific IgE antibodies to their trigger foods have decreased over time. These food challenges can be as frequent as once every few months in young children who have allergies that they are expected to lose, or as infrequent as once every few years if they have food allergies that are not expected to resolve. For some types of food like shrimp, a food challenge may never be performed unless skin and/or blood tests produce a negative result.

Image by Zafer Erdoğan on Pexels

When will you not be offered a food challenge?

Food challenges can be risky. The importance of getting a conclusive diagnosis has to be weighed against the possibility of provoking a serious allergic reaction.

The potential risk of a reaction, which is based on a person’s clinical history and their skin and/or blood test results, is contrasted with the benefit of the importance of adding the food to their diet and decreasing their anxiety around meal times.

So, for example, someone who is allergic to peanuts is actually relatively unlikely to react to most tree nuts. However, if you’re unlikely to incorporate tree nuts into your diet, there’s no point carrying out a food challenge. But if your diet is significantly restricted because of multiple food allergies, the possibility of adding some tree nut proteins to your intake would be nutritionally beneficial and make a challenge worthwhile.

You will not be offered a food challenge if:

You have recently experienced an anaphylactic (or severe systemic) reaction to your trigger food, especially if this has occurred more than once.

You are considered highly likely to fail the challenge and have a bad allergic reaction, perhaps because

• your skin and/or blood tests have produced results exceeding the cut-off values for that food
• your component blood tests have shown that you react to specific food allergens known to provoke severe reactions

You have an ongoing health problem. You may be currently unwell or you may have a chronic condition that could pose a serious threat in the event of anaphylaxis, such as an underlying heart condition like unstable angina, a severe chronic lung disease like cystic fibrosis or mastocytosis. Not only could such a health problem put you at risk of suffering a more severe reaction, it could also confound the interpretation of the test results.

You have poorly-controlled symptoms of hay fever, eczema and/or asthma; these symptoms could also both worsen your reactions and make it more difficult to interpret the challenge results. Likewise, if you have hay fever and it’s (your trigger) pollen season, your challenge should be postponed because you run the risk of having more serious reactions.

You cannot stop taking certain medications which could either suppress (e.g. antihistamines, corticosteroids, certain antidepressants and sedatives, Omalizumab, an immunosuppressive drug often used during immunotherapy) or enhance (e.g. beta-blockers, ACE inhibitors, aspirin and other NSAIDs, proton pump inhibitors) your allergic reactions to food.

You are pregnant; a potential anaphylactic attack could harm you or your baby.

Additionally, infants who cannot tolerate solid foods and young children who do not want to try unfamiliar foods with new textures and flavours, including those that may be used to mask the suspect food during a blinded challenge (e.g. a chocolate pudding or a smoothie), are not suitable candidates for food challenges.

Image by Fez Brook on Pexels

What happens during a food challenge?

Oral food challenges should always be carried out in a safe environment with access to the right kind of allergy medication and medical equipment. The type, severity and timing of the expected symptoms will influence the selection of the location. In order to estimate those, the allergist will take into account:

• your history of reactions—if you have a history of severe reactions or of reacting to small amounts of food, more care will be taken
• the food(s) you are suspected of reacting to—if it’s peanuts, nuts, milk or wheat, extra precautions should be taken
• your age—the older you are, the bigger the chances of a more severe reaction
• any co-allergies (e.g. asthma, eczema) and underlying health issues
• whether you were on an elimination diet prior to the challenge, which could also influence the severity of your reactions

When the chances of a reaction are small and you are not feeling overly anxious about taking the challenge, it can be carried out in the allergist’s office. Challenges to reproduce delayed or mild symptoms like a skin rash can also be handled in the office.

If more severe reactions are expected, the challenge will be carried out in an allergy clinic or a hospital with immediate access to emergency treatment and under the close supervision of specialists with the knowledge and skills needed to recognise and respond to the signs and symptoms of allergic reactions.

Before the challenge begins, a nurse or doctor will check and record your vital signs—temperature, heart rate, respiratory rate and baseline blood pressure. People with asthma will also have lung function measurements (peak flow, spirometry) and pulse oximetry (a measurement of the amount of oxygen in the blood) taken.

During the challenge

When it comes to diagnosing an IgE-mediated allergy, administration of the food during the challenge is done in a graded fashion, starting with an initial dose that—based on your clinical history—is less than that thought to be needed to produce symptoms. This will enable your threshold dose and the risk of a reaction to be determined.

In general, quantities between 3 mg and 3 g of food protein have been shown to work for most common food allergens. People who are especially sensitive and react to less food protein will have their doses adjusted accordingly.

Challenges typically consist of between 3 and 6 doses that are either (kind of) doubled each time—for example 1, 2, 4, 8 and 16 g of boiled egg white or 1, 5, 10, 25, 50 and 100 ml of milk—or increased in semi-logarithmic increments, for example 3, 10, 30, 300, 1000, and 3000 mg (meaning that you will have taken a maximum of 4343 mg by the end of the test). The maximum dose should be equivalent to the average age-appropriate meal serving of the food in question.

Challenges carried out in research settings have to follow strict guidelines but, when it comes to an open challenge being carried out in a day-to-day clinical setting, the doses do not need to be measured with such a high degree of accuracy.

In cases where a negative outcome is expected and there are no safety concerns, you may be given a single dose.

Doses are typically given every 15 to 30 minutes. There is some debate as to whether these waiting times are long enough. For example, when researchers gave oral food challenges to 63 children with peanut allergy and waited up to 2 hours in between doses to give symptoms a proper chance to develop, they found that many reactions happened around 55 minutes after the peanut was eaten. Similarly, more recent research has shown that, while reactions to milk tend to happen around the 30 minutes mark, symptoms to egg tend to appear around 75 minutes after the egg is eaten.

Some experts now recommend waiting longer in between doses to make sure that enough time is given for symptoms to appear before someone is fed even more of their food trigger. Others say that shorter times do not make a significant difference to either the amount of food that produces symptoms or the type of symptoms experienced and that 30 minutes is good enough.

Ultimately, if your clinical history suggests that your symptoms normally take around 45 minutes to appear, then the dosing schedule during your challenge should take that into account.

Before each dose, someone should check your skin for rashes, your heart rate, blood pressure and oxygen saturation, and listen to the sounds of your lungs and stomach. You will also be asked if you feel any subjective symptoms.

If there are signs of an allergic reaction, the next dose will be postponed to give the allergist time to observe the progress of the symptoms and record them all—subjective or objective—and score them (for severity).

If subjective symptoms occur, the allergist may choose to wait a bit longer to see whether objective symptoms develop, or they may repeat the same dose again instead of a higher one.

Stopping the challenge

Food challenges are generally stopped as soon as a clear, objective reaction occurs or when the final, largest dose has been given.

In general, challenges are supposed to be continued until there are objective and/or (a) severe or (b) reproducible or (c) persisting symptoms.

Subjective symptoms are quite common during challenges and often manifest a few doses before the appearance of objective symptoms. They are also reported quite often during placebo challenges, and symptoms like nausea or difficulty breathing can be the result of anxiety rather than allergy. When symptoms are ambiguous, rather than stopping the challenge, the allergist may decide to delay the next dose to see if the symptoms progress.

There is no standard procedure when it comes to stopping challenges due to subjective symptoms. Sometimes the challenge is continued only after the symptoms have completely resolved. Sometimes the challenge is stopped if the symptoms last for at least 45 minutes or one hour. Sometimes the challenge is stopped if the symptoms occur on 3 consecutive doses.

A 2020 analysis of 592 positive challenges from four separate studies found that using only objective symptoms as criteria to stop a challenge reduced the chance of getting a false positive result and did not pose a significant risk of more serious reactions.

Still, physicians face a dilemma—if they stop a challenge too early, they risk producing a false positive result and subjecting a patient to unnecessary dietary restrictions. And they will not know whether a larger amount of food could provoke a more severe reaction. But if they choose to continue the challenge, they may be putting the patient in danger of suffering severe symptoms.

In such cases, the risks versus the benefits of continuing the challenge are considered. Your general health also factors into these considerations. For example, subjective symptoms in a person with poor lung function are more likely to bring a challenge to an end than the same symptoms in an otherwise healthy person.

Subjective symptoms affecting more than one organ (e.g. an itchy mouth and stomach pain) are also more likely to result in the challenge being stopped or continuing after a longer period of observation.

Observation periods

If no reaction has occurred, you will normally be observed for about 2 hours after the last dose and then sent home with instructions to watch for possible late-onset symptoms.

If a reaction of some kind has occurred, especially if it required medication, you could be observed for 2 to 4 hours. For example, if you got mild symptoms like a few hives that resolved quickly with or without treatment, you will probably be discharged 2 hours after the symptoms resolve, as long as the supervising doctor deems that the reaction is unlikely to get worse. If you get a couple more new hives or other mild symptoms, you may be sent home after 4 hours of observation.

If you have a history of biphasic reactions (a recurrence of anaphylaxis without re-exposure to an allergen after the first episode was treated and the symptoms went away), you may be observed for up to 6 hours even if you have no more symptoms, just to be safe. The occurrence of biphasic reactions during OFCs is rare; studies examining hundreds of challenges have put the percentage chance of them happening at between 2% to 4%.

In the case of delayed allergies like food protein induced enterocolitis syndrome (FPIES), you will probably be observed for 6 hours before you can go home.

Sometimes you may get a pack of ‘rescue medication’ (antihistamines, β-agonists and steroids) to take home with you in case of a reaction. Before taking any strong medication, you will probably have to call the doctor.

Serious reactions during the challenge may require an overnight stay in a hospital for treatment and observation.

A second day of testing

You may be invited back to a second day of testing for one of 2 reasons:

• you need to take placebo doses on a different day than the test food
• the results of your challenge testing were negative (no reaction) and need to be verified

Placebos

When a challenge is undertaken with a placebo, the active and placebo doses should preferably be given on separate days.

Same-day challenges are possible when investigating an IgE-mediated, immediate type of reaction—in theory, when objective symptoms are easy to provoke, only two challenges are needed with both the test food and a placebo, because studies have shown that these types of patients rarely react to a placebo. But a same-day challenge is not possible if the challenge is to detect a delayed reaction which could take several hours to appear.

Negative results

Sometimes, a food challenge will provoke no reactions, not because a person is not allergic but because the challenge has failed to pick this up. False negative results are, in fact, not that uncommon; experts think that this may happen in just over 50% of the cases in which a food allergy is suspected.

This can be because:

• the threshold for a reaction was not reached during the challenge—some types of food, like fish, often contain relatively high amounts of protein in one portion, and this dose may be higher than the amount given during the challenge. This possibility can be tested in another blind challenge using greater quantities of food (but it probably won’t be)
• the allergens in the food may have been destroyed during the preparation of the challenge by, for example, cooking or other types of food processing
• one of the medications that you were still taking during the test suppressed your reaction
• you experienced short-term clinical non-reactivity, aka ‘specific tolerance induction’ during the first challenge, which is a short-term period of oral tolerance that can be induced when increasing amounts of the offending food are administered

False negatives are particularly common when fish is being tested, but it happens with all kinds of food from cow’s milk to peanut. Open feedings following negative challenges carried out with children have been shown to provoke reactions in around 4% of cases.

It’s therefore recommended that a blinded challenge that ends in a negative result is followed by an open challenge the next day, just to make sure that the negative result is correct and you don’t suffer from an unexpected allergic reaction when you sit down to dinner at home.

The next day’s challenge normally consists of one dose which is either the total (cumulative) amount of all the doses eaten the day before, or the portion of the food that is normally consumed in one sitting.

The food

The food for an open challenge is given without subterfuge and is sometimes even by brought along by patients or parents.

If an infant, a young child or a picky eater is going to be tested, the parent is generally offered some challenge options beforehand to minimise the possibility of the food being refused: for example, soy can be tested either as soy ice cream, soy milk, tofu or edamame beans.

Blinded challenges are generally based on two meals that look and smell exactly the same—one contains the suspect food in a defined amount and the other does not. The suspect food is carefully engineered to be as anonymous as possible, so that its looks, taste, smell, structure and texture are thoroughly masked, which ‘can be a great challenge to the imagination and creativity of a dietitian.’

The goal is to come up with something that either presents the food in a form as close as possible to the one the person ate (when testing for a reaction to a suspect meal/snack) or that presents the food in its most allergenic form (when testing for a possible reaction to a food that has not been eaten before).

Recipes must be concocted while remembering that food processing influences the allergenicity of the food; this is especially important when it comes to testing for Pollen Food Syndrome (PFS), as most people with PFS react to allergens in raw fruit or vegetables which are destroyed when the plant food is heated.

When the idea is to allow the less allergenic form of food into a person’s diet for nutritional purposes, as is the case with milk- or egg-allergic who are often able to tolerate a well-cooked version of their trigger food, these patients will typically be offered some form of baked goods, boiled egg or well-cooked omelette.

Countless hours of labour in the lab have gone into making recipes for more easily disguisable items like milk to more pungent foods like fish, and the end results undergo all sorts of testing to make sure that the placebo and real (aka ‘verum’) samples are indistinguishable from each other. These recipes are then shared between allergists.

Meals often come in dessert form, like pudding or mousse, whether the suspect food is sweet or savoury. Food for infant challenges can also be disguised in formulas and baby food. Other common challenge ‘vehicles’ include fruit juice and smoothies, apple sauce, oatmeal, ice cream, custard, soup, mashed potato, potato pancakes and burgers.

Finally, in cases where a reaction to additives is suspected, the food will probably be masked in a gelatine capsule. The capsule introduces a lag phase into the procedure as it first has to dissolve in the stomach before a potential reaction can be observed.

Image by Nancy Zjaba on Pexels

Variations on the theme

Low-dose challenges

Sometimes challenges are carried out with low doses of the trigger food. If that challenge is passed, another one to medium-sized doses of the trigger food can be scheduled within the next few months and, if that one is passed, a final challenge aiming to reach the maximum dose (an age-appropriate portion of the food) can be scheduled a few months later.

There are several reasons for doing this. Decades ago, when someone received a diagnosis of food allergy, they were told to cut the food out of their diet completely. Since then, research has started to change the dogma that strict dietary avoidance is the best and only way to deal with food allergy. Rather, exposure to small amounts of a trigger food that don’t provoke reactions seems to help, rather than hinder, the resolution of food allergy in children. Which is also the principle behind the milk ladder and the egg ladder, which take advantage of the fact that many children (and adults) with milk or egg allergy tolerate extensively heated versions of their trigger food, a tolerance which can be built on to assist many children to outgrow their allergy.

In the case of a child who may still become tolerant to their food allergen, including some of it in their diet may even speed up the resolution of their allergy. At the very least, knowing that a child can tolerate some of their food trigger is a relief for their parents. It’s also a relief for the children who are able to socialise more easily. Not to mention the fact that they will benefit from a more nutritious diet if their trigger food is a staple food like milk, which will help their growth and development.

In the case of a food allergic person of any age with a persistent allergy, a low dose food challenge can be used to see whether or not they would be good candidates for immunotherapy. Research also suggests that being able to eat a bit of a trigger food can, in some cases, help to increase a person’s threshold to that food, without the need for immunotherapy.

Lastly, a great reason to include some of a trigger food in your diet is that avoiding itc ompletely may lead to worse reactions when you are accidentally exposed to it, something that has been shown in several studies involving people with milder forms of food allergy.

Nowadays, guidelines tend to advise keeping some amount of a food allergen in a person’s diet, if at all possible. So, while a person’s first challenge may be carried out with the aim of seeing whether or not they can tolerate a maximum dose of an allergen in order to determine whether they have an allergy in the first place, if they do, the objective for any further challenges should be to optimise the management of their food allergy.

A final advantage of low-dose challenges is that they are less likely to provoke severe symptoms than challenges using large doses of food allergen which, in the case of challenges involving infants or particularly hazardous food allergens like nuts, is particularly reassuring if you’re a parent.

Testing for alpha-gal syndrome (AGS)

Most cases of allergy to red meat (e.g. pork, beef, lamb) and mammalian-derived products (e.g. milk, gelatin)—also known as alpha-gal syndrome, because they involve a reaction to the carbohydrate galactose-alpha-1,3-galactose—are diagnosed based on a medical history of symptoms and positive skin and/or blood tests to red meat.

But alpha-gal syndrome is difficult to diagnose. The signs and symptoms can be very different in different people, as are the medical histories; some people may require the presence of cofactors like aspirin or exercise in order to react, and others may only respond to a certain type of red meat. Additionally, standard diagnostic tests are often insufficient.

In 2020, one of the leaders in this field published a review of the diagnoses of 2,500 patients with alpha-gal syndrome. In it, he reported that up to 1 in 5 (15–20%) of the reactions during AGS challenges required one or more doses of adrenaline and/or emergency medical transport. Which is why doctors try very hard to diagnose AGS without an oral food challenge, but sometimes it’s unavoidable.

You may be offered a challenge to red meat if:

• your medical history is ambiguous because you have had possible reactions to red meat and your lab tests suggest sensitisation, but you can also sometimes eat red meat/dairy without reacting
• you have a history of delayed reactions to red meat/dairy but your lab test results are negative
• you have been bitten by ticks and are sensitised to alpha-gal and have been told to avoid red meat based on those lab tests, but you have not actually reacted after eating red meat/dairy and your allergic status is unknown
• lab tests have shown moderately high levels of IgE antibodies to alpha-gal in your blood, but you seem to tolerate small amounts of red meat and dairy and you don’t think that you have ever been bitten by a tick
• you have been formally diagnosed with alpha-gal allergy in the past, but your lab test results show very low/no IgE antibodies to alpha-gal, suggesting that your allergy may have resolved

Because of the wide range of triggers and symptoms involved in alpha-gal syndrome, as well as the fact that it’s a relatively newly discovered disease, there is no standardised challenge procedure. But due to its exceptional characteristics—namely that it’s an IgE-mediated reaction with objective symptoms that typically appear between 3 and 6 hours after eating red meat, and those symptoms can be very severe—it requires a different protocol than oral challenges to other foods.

For a start, your doctor should clearly explain the risks involved so that they can get your informed consent, and food challenges for alpha-gal syndrome must be carried out in specialised allergy centres with the right equipment and personnel to deal with severe reactions.

In contrast to other types of food allergy, you will probably be asked to consume quite a lot of food in one go for your challenge, for example, 2 to 3 pork sausage patties (at around 70 g per patty).

People undergoing an AGS challenge typically need to be observed for 4 to 6 hours, depending on their history of reactivity. If you have a history of very delayed reactions to red meat, you may be asked to start your challenge (i.e. eat your burgers) at home so that you can spend a couple of hours there before going to the clinic or hospital for further monitoring.

About 1 in 10 of these types of challenges may produce a false negative result. People who don’t react but are still suspected of having AGS because, for example, they have a very suggestive medical history and their previous reactions could have involved cofactors, may be asked to undergo another challenge with a larger quantity of red meat.

Testing for non IgE-mediated disease

When it comes to non-IgE-mediated allergies which typically consist of delayed reactions and different types of symptoms to the ones commonly seen in IgE-mediated allergies, oral food challenges are carried out slightly differently; they are always preceded by an elimination diet, they are always open challenges, the feeding is generally faster and the observation period is longer. Here are 3 examples.

Eczema

After a 4 to 6 week period spent avoiding the suspected food(s), an open challenge is carried out, following the same feeding procedure as a standard IgE-mediated challenge. About half (45%) of the positive oral food challenges carried out in people with eczema are expected to result in both immediate and delayed reactions, so the person taking the test will be monitored for both types of symptom.

Any skin symptoms provoked by the challenge preferably need to be recorded and scored by a doctor and, as food-induced exacerbation of eczematous symptoms typically occurs around 24 hours after the trigger food is eaten and can even occur up to 48 hours later, you will probably be asked back the next day (or the day after) to undergo a skin examination. In cases where there is no reaction after the first challenge, but food is strongly suspected of causing the problem, you may be asked to repeat the challenge with the test food for another 1 or 2 days. It might be possible for you to score the symptoms yourself using a specially-tailored scoring system so that you don’t have to visit a doctor every day of the test.

Although an open food challenge is the recommended way to confirm a diagnosis of food-induced eczema, in practice, the elimination and reintroduction of a certain food based on a reliable history of reactions is often considered sufficient.

Eosinophilic oesophagitis (EoE)

Diagnosis of EoE typically starts with a 4 to 6 week elimination diet which often involves several foods.

If the elimination diet has succeeded in eliminating your symptoms, each food is reintroduced one by one into your diet and you are monitored for:

• recurrence of EoE symptoms such as stomach pain, difficulty swallowing, food impaction, reflux and vomiting
• recurrence of tissue damage, which involves endoscopies and biopsies to look for specific levels of eosinophils (a type of white blood cell) in the oesophageal tissue—15 or more eosinophils per high-powered field, to be precise

As EoE can be a mixed disease, meaning that it can involve both IgE-mediated and non-IgE-mediated immune responses to allergens, if you have tested positive for IgE to the eliminated foods, when each food is first re-introduced into your diet it will be done following the protocol for the standard IgE-mediated food challenge, to check for immediate symptoms of allergy. If this food challenge is negative, you can go home and continue eating the suspect food until your next colonoscopy/biopsy appointment.

Food protein induced enterocolitis syndrome (FPIES)

An FPIES challenge, always open/unblinded, also follows an elimination diet which, if successful, results in the symptoms resolving within 3 to 19 days. A formal diagnosis involves a challenge to the suspected food(s) and monitoring for specific diagnostic criteria:

• in the case of acute FPIES: vomiting within 4 hours of eating, with or without other minor criteria including extreme lethargy, pallor, diarrhoea, low blood pressure
• in the case of chronic FPIES: rapid symptom resolution after eliminating the trigger food(s) and the symptoms of acute FPIES after eating the food again

There is no standardised approach when it comes to carrying out a challenge for FPIES. Sometimes several doses of the suspect food are given over a period of time—the official recommendation is for 3 equal doses of between 0.06 to 0.6 g of food (at 0.3 grams of food protein per kilo of body weight) over half an hour—followed by an observation period of 4 to 6 hours. People who have had severe reactions in the past are given lower starting doses and/or longer periods of observation between doses.

Sometimes one dose, or one dose per day on 2 to 3 non-consecutive days, is given, which has been shown to be as effective.

If a small dose of food has been eaten and no reaction has been observed after 2 to 3 hours, some experts advocate trying a full age-appropriate serving of the food, followed by a 4 hour period of observation. If there’s still no reaction, you will probably be advised to slowly introduce the food in your diet over the following days.

FPIES can also be a mixed disease and involve an IgE-mediated immune responses, in which case it is called ‘atypical FPIES’ and the challenge procedure follows the same feeding procedure as a standard food challenge (more doses of smaller amounts of food), to check for immediate symptoms to the trigger food, followed by a longer period of observation to check for the delayed symptoms.

Food challenges for FPIES, especially atypical FPIES, should only be carried in a setting with trained personnel and the right kind of equipment needed to deal with severe symptoms because up to 15% of reactions can result in unstable blood pressure and hypotension, symptoms of severe anaphylaxis. That said, reactions during FPIES challenges rarely result in emergency department care or ICU admission.

Although an oral food challenge is the official recommendation for a diagnosis of FPIES, in practice, a history of symptoms consistent with FPIES which resolve when a suspect food is removed from the diet is often good enough for a doctor’s diagnosis. The challenge is then only necessary in cases where multiple trigger foods are suspected, or to check to see if the allergy has resolved.

A food challenge for FPIES can also be used to check whether it’s safe to introduce new high-risk foods into someone’s diet—e.g. a challenge with wheat for someone who has FPIES to rice.

Testing for cofactor-induced reactions

Allergic reactions can be triggered or worsened by certain things called ‘cofactors’, including physical exercise, medications like aspirin, alcohol, temperature or pollen.

People who are affected by cofactors are sensitised to the food responsible for the reaction but often have lower specific IgE levels to that food. However, the cofactors lower their thresholds to the foods in question and/or magnify their reactions. There is generally no reaction without the cofactor and no reaction without the food.

For example, if you have food-dependent, exercise-induced anaphylaxis (FDEIA), you can often eat the food that you are allergic to without reacting to it if you don’t exercise, and you can exercise without having a reaction as long as you don’t eat the food that you are allergic to. In rare cases, a reaction can be provoked by any kind of food; this is called nonspecific FDEIA, and it’s the filling of the stomach in combination with exercise that provokes a reaction.

All cofactors can count when you have this particular type of food allergy—although exercise is the most well known, people who suffer from FDEIA can also have a reaction to food when they have not exercised, but instead are ill and have taken aspirin, or have drunk too much, or have eaten too much of the culprit food.

There’s no standard way of testing for cofactor-induced reactions—the test is based on your personal medical history, so the amount of food will vary per person, as will the intensity and duration of exercise, and the requirement to add augmenting factors such as aspirin or alcohol—but it generally goes something like this:

1. First, no diagnosis of a cofactor-induced food allergy can be made until the allergist knows for sure that the cofactor is also necessary and that it’s not just the food causing the reaction. Therefore you will probably be asked to undergo a separate challenge to the food alone before you are challenged with food + cofactor.

2. For the food + ingested cofactor challenge, you may be given aspirin with or without it being called for by your medical history, and/or alcohol and/or antacids and/or food additives.

3. After half an hour or so, you will eat a relatively large amount of the suspect food (or foods, in different challenges) or, if there is no one suspect food, you will eat the meal that caused the reaction in your medical history. Then, if exercise is involved you will wait up to 90 minutes before the next step.

4. Finally, you will exercise between 15 and 60 minutes on a treadmill or other machine, or you will go jogging or do whatever best replicates the type of exercise you were doing before having the allergic reaction

5. You could be monitored for up to 4 hours after exercising, depending on your history (symptoms often develop within 30 minutes)

6. If there are no symptoms, the exercise challenge may be repeated a few times.

Due to all the different possible combination of factors, a challenge trying to determine the involvement of several cofactors can take up to 6 days.

The diagnosis of cofactor-induced reactions is tricky, because a reaction can’t always be reproduced. The diversity in the level of exercise needed to cause a reaction is very wide, ranging from something you could barely consider exercise like ironing to more vigorous exercise like dancing or football. Cofactors like medicine and alcohol also vary, and other things like temperature and even hormones can have an effect.

Exercise-based OFCs are therefore often negative—according to one review of 234 cases, only about two thirds of the challenges were successful—which means that a negative challenge does not exclude the diagnosis.

Because these types of challenges can result in life-threatening reactions, they are only carried out when strictly necessary and planned very carefully.

Lip challenges

Lip challenges—aka labial challenges (LFC)—generally involve rubbing a small amount of the suspect food on the inner lower lip and leaving it there for a few seconds. They are often used in the UK for testing young children, sometimes as an alternative to a food challenge, often as the first step.

A 2017 study examined the data of hundreds of children who underwent food allergy testing on the Isle of White (UK) at different stages of their childhood. In all, 108 labial challenges were followed by an open food challenge, enabling the accuracy of the labial challenge to be assessed. The researchers concluded that ‘a positive LFC was highly indicative of a positive oral food challenge, but a negative LFC does not rule out a positive oral food challenge.’

Another British study carried out 2 years later mentioned that the many variations in how lip challenges were performed and interpreted by health practitioners made it impossible to properly assess their validity. Still, the study examined 198 children who had had lip challenges and conclusive oral challenges and determined that the lip challenges had poor sensitivity and produced many false negative results.

So… when in doubt, the oral challenge is still the best solution for most people.

Assessments of lung function without eating the trigger food

Sometimes food allergies produce respiratory symptoms which require monitoring with spirometry. This can happen alongside an oral food challenge, or it can be instead of, depending on the history of symptoms.

Spirometry— derived from the Latin words spirare (to breathe) and meter (to measure)—is a test used to assess a person’s lung function.

During a spirometry test:

• You sit in a chair and the doctor or nurse places a clip on your nose to keep your nostrils closed
• You are asked to inhale deeply, hold your breath for a few seconds and then exhale as quickly as you can while blowing into a device—the spirometer—that measures the amount of air you breathe out in 1 second as well as the total volume of air you exhale
• You’ll be asked to repeat this procedure at least 3 times to ensure that the results are consistent

In one case, a 7-year-old girl who started wheezing whenever she visited her parents bakery and whenever they returned home after baking sesame bread was asked to handle some sesame seeds for 15 minutes before being given a spirometry test which showed a decrease in her lung function.

In another case series, children who developed asthma when exposed to cooking vapours were put in a small room for 20 minutes while the offending food was cooked and their symptoms and lung function were monitored as they took in the aromas of the cooking food.

Image by Ellie Burgin on Pexels

When is a food challenge considered positive?

Deciding when to accept symptoms as definitive is not as straightforward as you might think.

A challenge is generally considered positive if objective symptoms occur.

But if, for example, that subjective symptom is vomiting, it may be of psychological origin. So vomiting just once is usually not enough to consider the challenge positive. Repeated vomiting, however, especially if it’s severe, is more likely to be considered a positive response.

Mild objective symptoms are also not necessarily enough to consider a challenge result positive—e.g. one or two patches of hives around the mouth could be due to contact with the food, which may be tolerated when eaten. But patches of hives elsewhere on the body (i.e. not in contact with the food) could be considered a clear and objective positive reaction.

Essentially, the sooner the symptoms appear and the more organ systems are involved, the easier it is to assess a challenge as positive.

When it comes to late-onset reactions like FPIES, a challenge is considered positive if the symptoms normally associated with the condition—profuse vomiting, lethargy, pallor, limpness, and/or diarrhoea—occur anywhere between 1 to 6 hours after the food is eaten. For conditions like eczema, the time window for a positive challenge can take up to 2 days.

Subjective symptoms are trickier to assess. They include:

• Generalised itchy skin
• Itchy nose and/or eyes
• Scratchy throat
• A feeling of throat tightness
• Shortness of breath (without objective signs)
• Stomach ache
• Nausea
• Feeling weak, dizzy, generally unwell

Making an assessment based purely on subjective symptoms is not easy, because they could be caused by aversion—a simple dislike of the food—or the nocebo effect—which is when someone person anticipates an allergic reaction, and this causes symptoms—or simply by excitement.

Or they could be a sign of an allergic reaction.

Children who are too young to verbalise their discomfort have to be monitored for other signs that could be clues the onset of a reaction—such as refusing food, putting a hand in their mouth, rubbing their tongue, picking their ears or scratching their neck—or a change in their general demeanour, such as stopping play, becoming quiet and withdrawn or staying in mother’s arms; basically, a child who is happily running up and down a corridor is unlikely to be diagnosed as allergic, even if they have one or two hives.

In older children, complaints of tickling or tightness in the throat, nausea, stomach ache or general malaise can be seen as the prelude to a more severe reaction.

Ultimately, having repetitive subjective symptoms (at least 3 times to the trigger food but not placebos) or multiple subjective symptoms in several organ systems—e.g. shortness of breath, stomach ache and dizziness—is generally considered a positive reaction.

Image by Dmytro Koplyk on Unsplash

What are the risks involved in a food challenge?

The symptoms reproduced in food challenges can be categorised as:

• Skin complaints, including severe itching caused by eczema (atopic dermatitis), hives (urticaria), facial swelling (angio-oedema) and superficial red patches (erythematous rashes)
• Gastrointestinal complaints, including stomach pain and cramps, nausea, vomiting, diarrhoea, bloating and gas
• Respiratory complaints, including sneezing, a runny nose, throat swelling, coughing and wheezing
• Cardiovascular complaints, including rapid heartbeat (tachycardia), irregular heartbeat (arrhythmia) and low blood pressure (hypotension)

Most of the reactions provoked by food challenges tend to fall into the category of skin or gastrointestinal complaints and to be mild, because:

• people with a history of severe reactions tend to be excluded from challenges
• the feeding is normally done gradually with small amounts of food
• the test is generally stopped at the first sign of symptoms

The risk and severity of reactions often depends on whether the challenge is being performed to rule out a food allergy or to confirm it.

Most people who undergo a challenge to rule out allergy are at a low risk of reaction, because they tend to have negative or small skin/blood test responses (small skin weals, low blood IgE levels) or a lack of (recent) reactions to the trigger food.

A review of 6,377 open food challenges (85% in children) carried out between January 2008 and December 2013 in 5 clinics across America revealed that only 14% resulted in a reaction and just 2% in anaphylaxis—bear in mind that the official medical definition of anaphylaxis (2) is the involvement of 2 or more organ systems, for example, hives and stomach pain, it does not necessarily mean that a person is lying on the floor, passed out. Antihistamines were used to treat 76% of the reactions and adrenaline was used in 14% of the cases.

A review of 701 open food challenges performed in one American clinic between August 2008 and May 2010 in patients aged between 8 months and 21.8 years reported that 18.8% resulted in a reaction. Most (56.8%) of those reactions involved skin complaints and the vast majority (87.9%) were treated with antihistamines. 9.1% of the reactions required adrenaline. All of the patients who underwent open food challenges in this clinic were deemed to have a less than 50% chance of having a reaction.

A previous study of challenges carried out in a higher risk population (people with IgE cut-offs that suggested a good chance of having a reaction) found a reaction rate of 43%. This study included data from 584 challenges involving ‘high risk’ foods—i.e. milk, egg, peanut, soy, and/or wheat. 78% of the reactions involved skin complaints, 51%, respiratory complaints and 43%, gastrointestinal complaints. There were no cardiovascular symptoms. 28% were classified as severe reactions, but no-one required emergency treatment.

This data is corroborated by results an Italian study which looked at 544 OFCs carried out between January 2007 and December 2008 at 3 allergy centres in Italy and reported that 48.3% of the challenges were positive. Of those, 65.7% were defined as mild reactions, 31.9% were multi-organ reactions and 2.4% were classified as (more serious) anaphylaxis. No patients, however, had cardiovascular symptoms.

The difference between what to expect in low-risk versus high-risk challenges is best exemplified by a study in which patients were triaged into low- and high-risk groups. Challenges that were considered lower risk were carried out in the outpatient allergy clinic and higher risk challenges were carried out in a hospital. The failure rate of challenges in the allergy clinic was lower than those that took place in the hospital (13% vs 21%) and the reactions in the higher-risk category were, indeed, more serious, with more requiring the administration of adrenaline than in the lower-risk category (5% vs 1%). Even then, only 3 of the 1009 OFCs conducted were categorised as serious and no reactions involved the cardiovascular system. Having asthma was a significant predictor of reactions requiring treatment with adrenaline.

Reaction rates tend to be higher in confirmatory challenges because these challenges are generally intended to select patients for clinical trials and treatments.

A review of 1,445 challenges carried out between September 2010 and March 2016 in patients selected for oral immunotherapy treatments reported a reaction rate of 73%. However, even in these patients, who were strongly suspected of being allergic to food,  the most common adverse events were skin complaints (54%) followed by gastrointestinal complaints (33%). 27% did not react at all. People with a history of asthma were more likely to have a severe reaction than those without. But even when it came to the more serious types of reaction—respiratory and cardiovascular—74% were graded as mild, 15% as moderate, and only 11% as severe.

Another study specifically investigating the use of adrenaline during challenges performed to screen patients for food therapeutic trials found that just over a third of the participants were treated with adrenaline. Even then, just under two thirds of the reactions were categorised as mild, one third as moderate and 2.7% as severe.

All in all, the oral food challenge is considered a safe procedure when performed by experienced personnel. However, despite all the careful selection and planning, food challenges still come with a small risk of anaphylaxis and an incredibly minute chance of death. To date, in the 5 decades since oral food challenges have been carried out, there have been 2 reported deaths; one in 2017 in which a 3-year-old boy died after a baked milk challenge in America, and another in 2019 in which an 11-year-old boy died after a challenge to peanut in France.

Note: The results of your food challenge cannot be used to predict the severity of future reactions. Although a food challenge can give you some idea of your threshold and the severity of your allergy, research has shown that the severity of reaction you suffered during an oral food challenge may be different from reactions you experienced in day to day life.

This may be because, during a challenge, you eat gradually increasing amounts of food, and challenges are often stopped at the first sign of symptoms, which is not the same as sitting down in front of the TV and quickly gulping down a ready meal which, unbeknown to you, contains your food trigger. Additionally, food challenges are taken when a person feels well, and things like infection, temperature, exercise, alcohol and medications—so-called cofactors—can all lower thresholds and/or worsen reactions, and any of those could be involved in any of your future reactions.

Image by Breakingpic on Pexels

Image by Towfiqu barbhuiya on Pexels

After the food challenge

In very rare cases, you (or your child) may suffer some delayed reactions—such as itching, a rash, coughing or vomiting—when you get home. If this is the case, call the allergy clinic or hospital where you took the test. In the case of a serious allergic reaction, use your adrenaline auto-injector (if you have one) and call the emergency services.

If the food challenge did not cause any symptoms, you will probably be advised to avoid the challenge food for the remainder of the day (in case of a rare delayed reaction) and then to start eating it regularly.

The amount of food you that will be advised to eat and the way you should prepare it will depend on the total amount of food that you were able to eat during the challenge and how it was prepared—for example, you may have passed a challenge to a cooked version of a certain food (e.g. baked egg), but this does not mean that you can tolerate a less cooked version of that food (e.g. scrambled egg).

And if you have passed a food challenge to a highly cross-reactive food, you can eat as much of that particular food as you like as you like, but you will still have to avoid the other foods that it may cross-react with. For example, a peanut-allergic person who has passed a challenge with walnuts will still have to avoid food containing other nuts, includes nut mixes, chocolates or snacks that ‘may contain nuts’.

You should be scheduled for a follow-up visit one to two months after the challenge (or more quickly and frequently, if you need physician supervision), so that a doctor and dietician can check your food diary and discuss any adverse reactions and nutritional concerns.

If you had no reactions, you will be probably advised to keep increasing the amount of the food that you eat gradually until it reaches normal serving levels.

If the food challenge did cause symptoms, the type of symptoms you got and the amount of food that you were able to eat without having symptoms will dictate the advice you are given.

For example, someone who gets symptoms that are very mild or classified as ‘uncertain’, such as a localised skin rash, isolated cough or slight stomach ache, may be advised to try the food at home a few times to see if the symptoms appear again. One study reported that such symptoms provoked during open food challenges in 454 children were followed by the successful introduction of the test food at home in 80% of the cases. All of the other children, who were eventually classified as ‘intolerant’, only had mild reactions at home.

Sometimes people who can eat a small amount of their trigger food before experiencing symptoms are instructed to introduce small amounts of it—at 1-10% of their threshold level—or a processed version of the food which might be less allergenic, with the aim of inducing tolerance that way.

If your (child’s) reaction to the test food during the challenge were serious, you will be advised to avoid that food and (in a perfect world) you should also be given:

• instructions regarding food avoidance
• information about associated nutritional implications (especially when the allergy affects a growing child) and a possible referral to see a dietician
• an emergency management plan for allergic reactions
• emergency medications including an adrenaline auto-injector
• the contact details of the physician in charge of the test
• a recommendation to plan an appointment for a follow-up visit sometime in the next few months

Finally, it’s entirely normal to feel anxious about managing your food allergy following a reaction during a food challenge. You should feel free to talk to your doctor about your concerns—they may also be able to give you a referral to a mental health professional if you are experiencing significant distress.

That said, try not to worry, There’s a 99.9999999% chance that everything will be okay.

Image by Anna Tarazevich on Pexels