Making a diagnosis of an allergy, whether it is to food, medication or anything else is a process that starts with a detailed clinical history. This is then followed by appropriate investigations which may be skin prick testing or blood testing. In most cases, a combination of the two will clarify whether a particular allergen is a problem or not but in some cases there is not quite enough information to confirm a diagnosis. A common example might be a small child with eczema who would be at high risk of allergies but has never eaten a food such as peanut before. When the allergy test is done, a very high level might be enough to confirm allergy but when it is only slightly raised, that leaves us wondering whether the child really is allergic or not. Other scenarios, for example, relate to medication allergy, when somebody has had a reaction following a range of different medications having been taken. Unfortunately the value of blood and skin prick tests with medication allergy is rather limited so in these types of cases, where the diagnosis is not clear, the next step is to do an oral provocation test. This is the gold standard test for diagnosing or ruling out an allergy.
What is an oral provocation test?
An oral provocation test is where a patient is deliberately exposed to a suspect food or medication in order to establish whether they are allergic or not. Usually this requires a degree of medical supervision so it will be done either in an Outpatient Clinic or in a dedicated Day Case Unit. In most cases, we would start with a small amount of the allergen and if there was no reaction after 20-30 minutes, a larger dose is given. After four or five increasing exposures, one of two things is likely to have happened. Either there would have been a reaction in which case this would be treated promptly and the diagnosis of allergy can be confirmed. Alternatively, there may have been no reaction despite a number of exposures, and if after a period of time this remains the case, then the patient can be confirmed to NOT be allergic.
Types of provocation tests
The two most common provocation tests are oral food provocation tests (“challenges”) and oral drug (medication) challenges. Both of these have very similar principles and are done under medical supervision. They involve small but increasing amounts of the suspected allergen being given with regular close observation. The provocation test is stopped if there is any sign of an allergic reaction which is then promptly treated and the allergy is confirmed.
Food provocation tests
These usually take two forms based on the level of perceived likelihood of there being an allergic reaction. In cases where an allergic reaction is considered to be unlikely or expected to be mild, then the provocation test is done in the form of a ‘supervised feed’. A supervised feed involves the patient being asked simply to eat a normal size portion of the food and is then watched for 1-2 hours for any sign of an allergic reaction. This would commonly be done, for example, if a patient is allergic to one nut such as peanut but testing to other nuts is very low. There is still a small chance of reacting so to be absolutely sure a supervised feed enables us to confirm that other nuts are safe to include in the diet. Where the risk is considered a little higher, then an incremental oral food challenge is carried out. Again, this is done under medical supervision but instead of simply eating a portion of the food, first a very small amount is given and then increasing amounts in 4-5 divided doses with about half an hour in between each one. This method ensures that a reaction will be spotted as soon as more than the amount that the patient is sensitive to is consumed and is thought to reduce the risk of more severe reactions happening. If the top dose of food, usually equivalent to a normal portion, appears to be tolerated without any reaction, then there is a further period of observation of 1-2 hours before the provocation test is concluded and if no reaction has happened, it can be confirmed that the patient is NOT allergic.
Drug (medicine) provocation tests
These are carried out in order to clarify whether a patient is allergic to a specific medication. Where the risk is considered very low, an initial dose of 10% of the usual dose may be given and then if there has been no reaction over a period of around 30 minutes, the remainder of the full dose is given, again followed by a period of observation up to 1-2 hours. Where there is a greater suspicion that the medication will cause a reaction, a larger number of smaller incremental doses may be given with around a 30-minute gap in between each dose to look closely for any sign of reaction. After the final dose has been given, there is a further 1-2 hour period of observation before the provocation test has concluded. Again, if a reaction happens at any point then the allergy can be confirmed whereas if it does not, allergy can be ruled out and the medication safely used in the future.
What allergies does a provocation test identify?
Provocation tests tend to be most useful for food allergy testing and medication allergy testing, using the methods described in the sections above. It is possible to do provocation tests for aeroallergens such as dust mites and pollens but this is much less commonly required. These can be done by a variety of methods including nasal provocation tests where allergens such as dust mite is squirted up the nose with careful observation and testing to see if this changes to nasal symptoms and nasal peak flow measurement or conjunctival challenges where a small amount of allergen is introduced into the eye. These tests can be rather unpleasant and hence are seldom done and almost never in the case of children.
How do food allergy provocation tests work?
Food and drug allergies are very reproducible in as much as if a large enough dose is given, then if the patient is allergic then there will always be some sort of reaction. This reaction is typically mild but still its presence will confirm the diagnosis. Unfortunately, having a mild reaction on a provocation challenge does not mean subsequent reactions will also be mild as these may occur when the patient is not in a state of good health or a larger amount of allergen may be accidentally consumed which may cause more significant reactions. Allergen provocation tests are therefore not useful at assessing the severity of allergy only at assessing whether there is an allergy or not.
Are allergy provocation tests safe?
Allergic reactions are unpredictable and can be more severe than expected. As a result, provocation challenges are only done if they have to be, because the allergy tests and clinical history do not give clear answers. However, there are a number of ways that provocation tests can ensure safety. The first is that they are only done in a medically supervised environment with staff experienced at identifying and promptly treating allergic reactions. They will have all the appropriate monitoring equipment and most importantly, injectable adrenaline for prompt treatment of severe reactions. By only conducting a provocation challenge when the patient is in good health, also markedly reduces risk. Furthermore, by using incremental doses, with a period of observation in between, ensures that any reaction happens to the smallest amount that the patient is sensitive to.
Food provocation test and medication challenges are done routinely as part of specialist allergy practice around the world and are considered to be a safe test as long as they are done by experienced people in the correct setting where allergic reactions can be recognised quickly and treated appropriately. This usually involves simple antihistamines and observation, but it is critical that there is immediate access to adrenaline injections in the unlikely event that these are required and that they can be administered by staff who are experienced in managing severe allergic reactions. That said, the overwhelming majority of provocation tests require minimal medical intervention even when there is a reaction.
Are provocation tests accurate?
Provocation tests are the most reliable of all allergy tests and are considered to be the gold standard. However, they are resource intensive and of course put the patient at a degree of risk and hence where possible we try to avoid doing these using a careful allergy history and allergy testing, which in most cases is enough to reach a firm diagnosis. Provocation tests are only done when these are not sufficient. On rare occasions, for example, if a patient is unable to eat the food required to do the provocation challenge or a reaction occurs which is not clearly allergic in nature, there may be a need to repeat the provocation challenge, but this is very unusual and in almost all cases a clear result is forthcoming.
Professor Adam Fox
Date reviewed: March 2022
Adam Fox is a Professor of Paediatric Allergy with over 20 years experience in both the NHS and private sector. Professor Fox is Commercial Medical Director at Guy’s & St Thomas’ Hospitals NHS Foundation Trust and Professor of Paediatric Allergy at King’s College London and the founding Director of the KCL Allergy Academy, a postgraduate educational programme, which was a finalist at the BMJ Awards in 2018.
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