Tree nut Desensitisation
Nut allergy effects around 1-2% of UK children and can cause severe allergic reactions, although fatal reactions are thankfully extremely rare. Whilst some food allergies, such as wheat, milk and egg are often outgrown in early childhood, others such as tree nuts are only outgrown in around 10% of cases, and if they are, usually by the age of 4. For most children, tree nut allergy is lifelong and can have a significant impact on quality of life. Until recently, the standard treatment has been careful avoidance but over a 2-year period, over 25% of food allergic patients will have an accidental reaction and this rises to 75% over a 5-year period with around 1-2% of patients per year needing adrenaline. This approach is starting to change and there has now been a 30-year history of medical research into desensitisation to food
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What is Oral Desensitisation?
Oral Desensitisation (OD), also known as Oral Tolerance Induction (OTI or OIT) or Food Desensitisation, is a treatment that involves giving very small, but gradually increasing, amounts of the food that the child is allergic to. The intention of OIT is to increase the tolerance to the allergenic food so that larger amounts of the food can be consumed without causing any symptoms and, as a result, accidental exposures to small amounts of allergen should not cause reactions. This treatment has been most studied most extensively for milk, egg and peanut and in early 2020, Palforzia, a peanut containing capsule, become the first licenced food immunotherapy treatment in the US, later receiving a UK market authorisation from the MHRA in October 2021 and was approved by NICE in Feb 2022 for children aged 4-17. The Food Allergy Immunotherapy Centre is the largest provider of Palforzia in Europe.
It is important to recognise that this type of treatment leads to a state of desensitisation (a temporary state, where greater amounts of an allergen can be tolerated without symptoms) and not necessarily true ‘tolerance’ (a permanent state where any amount of an allergen can be consumed without any risk of reaction). In practice, this means that the treatment is not a cure but doses of allergen must be continued regularly in the long term for the treatment effect to remain. If it isn’t, the risk of reaction returns. Whilst desensitisation can markedly increase the threshold at which reactions may occur, exposure to larger quantities may still cause a reaction and hence is usually advisable to continue to carry emergency medication, even after successful desensitisation.
How effective is oral desensitisation?
There are numerous studies from around the world as well as systematic reviews (where the results of lots of studies are combined) that demonstrate that OIT works well for peanut, milk and egg as well as other allergens such as sesame, wheat and tree nuts. The studies to use different treatment regimens, but report a high degree of success, if able to reach and maintain the target dose. Importantly, the studies also show an improvement in quality of life and in many US and European centres, OIT has become well established as a treatment although there remain numerous different protocols in use and no agreed consensus as to which is ‘best’.
The largest studies of peanut OIT included almost 500 peanut allergic children aged 4 – 17 years of which 67% were able to eat up to 600mg of peanut protein (2-3 peanuts) without troublesome symptoms. However, nearly all of the patients had some level of side effects and in a small number of cases, around 4%, this included significant anaphylaxis. In a large review of different peanut studies, whilst confirming a high degree of effectiveness of the treatment, concerns were raised about the frequency of severe allergic reactions (Link to the paper on our website). Peanut OIT has not been well established for adult patients and we do not commence patients older than 17 years on the treatment.
In a 2022 Swedish/Israeli study, Forty-four of 50 OIT-treated cashew allergic patients (88%) compared to 0% in controls tolerated a dose of 4000 mg cashew protein at the end of the study. An additional three patients were desensitized to 1200 mg cashew protein, and three patients stopped treatment. Three patients (6%) were treated with injectable Epinephrine for home reactions. None of these reactions was severe and this compares well with similar studies relating to peanut immunotherapy. Importantly, following cashew desensitization, all pistachio (n = 35) and four of eight walnut co-allergic patients were cross-desensitized to the respective ‘related’ nut (cashew is closely related to pistachio and walnut to pecan). All (n = 44) patients consuming a low cashew dose for ≥6 months following desensitization passed a full-dose cashew food challenge showing the potency of the effect.
In a similar study by the same group, 49 (89%) of 55 patients in the oral immunotherapy group were desensitised to walnut compared with none of 18 patients in the control group. Following walnut desensitisation, all patients who were co-allergic to pecan (n=46) were also desensitised to pecan. Additionally, 18 (60%) of 30 patients who were co-allergic to hazelnut or cashew, and 14 (93%) of 15 patients who were co-allergic to hazelnut alone, were either fully desensitised or responded to treatment. 47 (85%) of 55 patients had an adverse reaction (mostly mild) during up-dosing in the clinic; eight patients required intramuscular epinephrine in response to a dose at home but none of these reactions were severe. Of 45 patients who had follow-up data for the maintenance phase, all maintained walnut desensitisation and one patient required epinephrine during this period.
A different approach has been to investigate the effectiveness of OIT in younger children, from 9 months of age, with a similar approach of giving small but increasing amounts of allergen. A US study published in 2016 using peanut showed this to be safe and effective in 37 children up to 3 years of age, with 91% of those who were able to keep to the programme able to tolerate peanut, even after 4 weeks of stopping their regular dose, with a lower number of side effects. A much larger Canadian study, published in 2019, showed that this treatment was safe and effective when carried out in 270 pre-schoolers. 90% of the children achieved a 300mg maintenance dose (approx. 1 peanut) with 10% of patients dropping out (either due to repeated allergic reactions, refusal to eat the dose or parental anxiety). In summary, desensitisation appears to be safer and more effective in younger children. Importantly, as discussed below, the long-term exposure to a regular 300mg daily dose confers a marked increase in the amount of peanut required to cause a reaction, with most children able to tolerate up to 16 peanuts and nearly all able to tolerate 4 peanuts, markedly reducing the risk of accidental reactions.
There is less published data relating to the success of OIT to sesame, wheat and tree nuts and this will be discussed with you at your assessment appointment but desensitisation to younger children, across all allergens appears to be safer and more effective and also raises the possibility of increasing the possibility of natural tolerance (outgrowing) occurring.
We ask all patients prior to undergoing desensitisation to complete the ‘Am I suitable form’ which is accessible via our website. Our team will also organise an assessment to discuss your suitability for treatment if this has not already been organised. Generally, desensitisation in younger patients is not only safer but is more effective. The likelihood of outgrowing it is also much higher in younger patients.
How safe is oral desensitisation?
Due to the possibility of severe allergic reactions to foods, there has been a lot of concern about the safety of this treatment. It is likely that most, if not all, children will experience some mild allergic reactions during treatment. Typical reactions are rashes, lip/face swelling, wheeze and abdominal discomfort. Severe reactions, requiring adrenaline are reported in a small number of patients in the published studies but with this treatment now widespread in the US, it is very reassuring that there have been no reported fatal or near fatal reactions reported.
While there are a number of clear ways to reduce the risk of severe reactions, many lessons have been learned from the severe reactions that have occurred. In medically supervised environments, severe reactions appear more likely when the dose is increased when treatment is immediately available. The risk of reacting must also be considered in the context of the risk of severe reactions that may happen if the child were not desensitised and had an accidental exposure. All updosing appointments under our care, are conducted under medical supervision and are carried out in a safe environment. Patients are also risk assessed prior to beginning any form of desensitisation.
Food-induced gut problems such as eosinophilic oesophagitis (EOE – inflammation of the oesophagus) are also concerns associated with OIT. A systematic review reported EoE in up to 2.7% of patients undergoing OIT for food allergy (although the review is based on incomplete datasets, because most trials of OIT have not reported the presence or absence of EoE as a longer-term adverse event) although as EoE is known to disproportionately affect children with allergies anyway, there is no evidence as yet of a causative link. In the Canadian study of pre-school children being desensitised to peanut, 3 patients developed symptoms suggestive of EoE, of which 1 had further tests which ruled it out.
Currently, international guidelines on the management of food allergy (published in 2017) have stated that OIT is now well enough understood in terms of safety or effectiveness to be offered as a treatment as long as this is under specialist supervision and this is increasingly becoming a standard treatment option in North America and Europe.
Are there any people who are unsuitable for food allergy immunotherapy?
Patients have typically been excluded from studies if they have experienced a recent life-threatening allergic reaction, poorly controlled asthma, suspicion of eosinophilic gastrointestinal disease, or other factors that would hinder their ability to cooperate with the treatment e.g. a high level of anxiety. However, a history of severe reactions can be a compelling reason to want to do the treatment and this needs to be discussed in detail with the risks and benefits carefully considered together.
What does the process of oral desensitisation involve?
Firstly, patients are required to undergo an assessment for suitability. Detailed history and examination is part of the initial assessment visit, focusing on the specific food allergy. You may require skin prick and blood testing, especially if these have not been done for more than 6-12 months. All patients must have a detailed asthma assessment and where appropriate, if your child is over 4 years of age, lung function tests are performed. All children who undergo desensitisation must have extremely well controlled asthma or eczema, otherwise they will not be suitable for treatment.
If your child has not been exposed to the allergen (as the diagnosis is based just on allergy tests), it might be necessary to clarify if your child is able to tolerate it, by consuming it under supervision, especially if the allergy tests do not give clear confirmation of allergy. This is also referred to as a food challenge. If they are found to tolerate a large quantity of the allergen without a reaction, this eliminates the need for OIT as it would not be necessary.
If the outcome of the assessment is that your child is suitable for desensitisation, a consent process is carried out where after being provided with detailed information about the treatment, you will eventually be asked to read a consent form and sign to indicate that you have understood the risks involved. Patients are prescribed Adrenaline Autoinjector devices and full training is provided on their use.
The treatment itself would involve your child eating a small, measured amount of allergen in the form of the relevant tree-nut flour. If this is tolerated, then you would give your child the same dose at home every day for 2 weeks before returning to try a higher dose. Each increase in dose is done under direct medical supervision, either by one of our nurse specialists or doctors. Once a top dose (which will vary depending on the allergen) has been reached, then this dose is continued daily, although this may be reduced to 3 times a week, to maintain the effect. There will be ongoing follow up throughout this period and depending on the course of the initial part of the process, the maintenance dose may be increased.
What are the potential benefits?
The aim is to allow your child to be more tolerant to the allergen so that they can eat tree nut-containing foods and will not react to the food after accidental exposure. It should also help to lift restrictions in diet and lifestyle such as eating out and going on group activities or avoiding ‘may contain’ foods. In our nut OIT programme we aim to have children regularly consuming the equivalent of 1-2 nuts thus offering ‘bite-proof protection’. If the process is well tolerated, this may be set at a higher level although this is usually not required as long-term exposure to this amount is associated with tolerance of much larger exposure (see below). It is estimated that having this level of tolerance to a nut, reduces the risk of accidental reactions due to contamination by around 99% (Baumert et al, 2018). However, this does not rule out the possibility of more severe reactions to larger doses and emergency medication will still be needed. It is important to note that desensitisation is a temporary state of being less sensitive, but the underlying allergy is still there and will return if the maintenance dose is not regularly continued.
What are the potential risks of oral desensitisation?
It is important to weigh the risks and benefits of desensitisation programmes. This can vary between individuals and is discussed in the initial assessment and consent process. During the programme, your child may experience some allergic symptoms. These symptoms are likely to be minor e.g. hives, lip swelling, vomiting, particularly in preschool children. More severe reactions (anaphylaxis) including wheeze and difficulty breathing may occur but are uncommon. An allergy management plan will be provided so you know what to do if your child suffers an allergic reaction. If your child is unwell with colds, coughs or vomiting bugs, they may be more prone to allergic symptoms and thus the dose will be reduced or missed on those days. If your child does get symptoms then the dose will be reduced before going back up again. You will be carefully briefed as to how to manage these situations and have daily direct access to our team to support any decisions on dosing. We ensure that we fully support all patients under our care for desensitisation and ask that should you experience any symptoms, that these are documented and reported to a member of our clinical team.
What if it doesn’t work?
Desensitisation does not work for everyone. It is common that the dose needs to be held or reduced for a period of time, prior to increasing this further. Even if the top dose is not achieved, lower doses can still protect patients from reactions due to accidental exposures.
What is the cost?
The cost of oral immunotherapy to a tree nut costs £4,800. Unfortunately, it is unlikely that insurance will cover the cost of the treatment. However, we can offer payment plans which allow you to spread the cost.
Interested in desensitisation to other food allergens such as sesame, treenuts, milk, egg or wheat?
We hope to soon be able to offer desensitisation to sesame and treenuts. If you would like to know more about these treatments when they are available please click below:
Here’s what our patients have to say…
Each member of the team that we dealt with, whether medical or support staff, were excellent.
The support has been excellent throughout.
We had a clear plan from early in the process and managed to follow through with only a couple of amendments (which we made).
We have been impressed and very grateful for the speed at which our queries have been responded to.
Parents of Isaac, age 9, Isle of Wight
Excellent. All of the team were very efficient and we found the chart with the dates and dosage for the updosing appointments particularly helpful.
The team were easy to reach, including direct contact with the consultants, even at the weekend and over holiday periods.
The overall experience was excellent.
Parents of Ernie, age 7, Nottingham