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 treenuts are only outgrown in around 10% of cases, and if they are, usually by the age of 4. For most children, treenut 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.
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 peanut so that larger amounts of peanut can be consumed without causing any symptoms and, as a result, accidental exposures to small amounts of peanut should not cause reactions. This treatment has been most studied 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 approval by NICE in Feb 2022 for children age 4-17. It is important to recognise that this type of treatment treatment leads to a state of desensitisation (a temporary state, where greater amounts of peanut can be tolerated without symptoms) and not necessarily true ‘tolerance’ (a permanent state where any amount of peanut can be consumed without any risk of reaction). In practice, this means that the regular 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.
In our own practice, we have been offering OIT for milk and egg for some years and to peanut in younger children since 2020 and older children, using Palforzia, since it received a UK licence in October 2022. Our practice is now starting to offer OIT for children aged 5 and under for sesame, treenuts and wheat.
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 treenuts. Different studies use different approaches, in different children but report up to 100% effectiveness. 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 studies, whilst confirming the effectiveness of the treatment, concerns were raised about the frequency of severe allergic reactions. The treatment was not effective in adults.
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 nut. 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 much less published data relating to the success of OIT to sesame, wheat and treenuts 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.
How safe is oral desensitisation?
There has been a lot of concern around safety of this treatment, because of the known risk of severe allergic reactions that could happen to foods. Most, if not all children will have some allergic reactions during the treatment but these are usually mild. 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. In the Canadian peanut study of 270 pre-school children, 11 children required adrenaline for a more significant reaction (one patient required this on 2 occasions) which represents 0.029% (12 of 41,020) doses and experience amongst US and Canadian physicians suggests that desensitisation to other allergens has a broadly similar safety profile. However, there are a number of clear ways that the risk of severe reactions can be reduced and many lessons have been learned from the severe reactions that have occurred. Importantly, severe reactions appear to be more common when the dose is increased, which is done in a medically supervised environment, 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.
There is also a concern that OIT can result in the development of eosinophilic oesophagitis (EOE – an inflammatory condition of the oesophagus) and other food-induced gut related problems. 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.
What does oral desensitisation treatment actually involve?
The starting point is an assessment visit, to discuss the process and ensure that you fully understand it. The assessment will involve a detailed history and examination focussing on the specific food allergy and may require skin prick or blood tests if these have not been done for more than 6-12 months. It will also require a detailed asthma assessment and, where appropriate if your child is over 4 years of age, lung function testing as any child whose asthma or eczema is not extremely well controlled, would not be suitable for treatment. If it is felt your child is suitable for the treatment, you will be asked to sign a consent form to indicate that you have fully understood the risks involved. You will be prescribed an Epipen and trained in its use. If your child has never been exposed to the allergen (as the diagnosis is based just on allergy tests), it may be necessary to clarify if your child is able to tolerate, by consuming it under supervision (a process known as a food challenge). If they can eat a large quantity without a reaction, this suggests OIT would not be necessary.
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 treenut-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?
Potential risks of the desensitisation programme need to be weighed up with the benefits. It is likely that your child will experience some allergic symptoms during the programme. 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. Your child should continue with the amount, but if they do 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.
What is the long-term outlook?
Treenut desensitisation is not a cure – it induces a temporary state where the patient is less sensitive and if peanut is no longer consumed, the allergy will soon return to its previous state. As we do not know exactly how long children remain tolerant to an allergen if they stop taking the regular dose, we have to assume that children need to continue to eat allergen-containing food indefinitely at least 3 times a week to maintain their tolerance. If you child does not eat the allergen-containing food for more than 2-3 weeks or suffers from an asthma attack requiring oral steroids (prednisolone), then they will need to resume exposure under supervision at a lower dose again. However, as some children will outgrow their allergies, OIT can provide protection until this happens.
A recent 5 year follow up study of young children who undertook a similar desensitisation programme to peanut showed that 93% of the children were still consuming regular peanut, often in large quantities, and that only 7% reported any further symptoms of allergic reactions, all of which were minor. 90% of patients reported an improvement in lifestyle quality for themselves and their perception of that of their child (Herlihy et al, JACI 2020).
A follow-up study of children who had undergone the Canadian OIT protocol that we use, showed that about 78.6% of pre-schoolers on 300mg peanut oral immunotherapy maintenance for 1 year had a negative cumulative 4000-mg (approx. 16 peanuts) oral food challenge without symptoms, and 98.3% could tolerate greater than or equal to 1000 mg (approx. 4 peanuts), which importantly would be sufficient to protect against accidental exposures (Soller et al, JACI-In practice 2020).
What support can I expect for my child during the programme?
You and your child with be counselled throughout the programme and will be seen at regular intervals in a consultant-led clinic for ‘up-dosing’. If you have queries about your child’s OIT between their appointments, you can contact us on a special email address or call the Allergy London office during office hours and you will receive a response from one of the team within a day – before your next dose is due. If your child has a severe allergic reaction, you should follow your allergy management plan and come to the A&E, just as you would do if your child was not on the programme.
If you have any concerns about giving your child allergen-containing foods, you can withdraw from the programme at any time and we will revert to standard follow-up for children with food allergy.
What if it doesn’t work?
This treatment does not work for everybody and it is common that the dose has to be reduced or held for a while before it can be further increased. Even if only limited desensitisation is achieved, this can still protect from reactions due to accidental exposures.
Is oral desensitisation treatment the right thing for my child?
The following is an extract from a US Consensus report following a meeting of expert and patients advocates in 2019, published in the Journal of Allergy & Clinical Immunology (the journal of the American Academy of Allergy):
OIT is an emerging option for the treatment of food allergy, but it is not appropriate for all patients with a history of allergic reactions to food. European food allergy guidelines published in 2018 have recommended the use of OIT in ‘‘highly specialized clinical centers with expertise and facilities to safely deliver this therapy’’ for milk, egg, or peanut, whereas the older US practice guidelines recommend against its use and need to be updated, especially with the approval of Palforzia.4 Patients must have confirmed IgE-mediated food allergy to undergo OIT. This should be determined through a thorough history with supportive allergen-specific IgE blood and/or skin testing. If the history is unclear, an oral food challenge is needed for diagnosis. The summit participants recognize that food challenges are not without risks and potential harms and the need for alternative methods to confirm food allergy is pressing. OIT is not appropriate for the treatment of food intolerances, food sensitivity without confirmed allergy, or other non–IgE-mediated indications. In addition, OIT may not be appropriate for patients with a high likelihood of spontaneous food allergy resolution, such as some young children with cow’s milk or hen’s egg allergy for which FDA-approved OIT products are not currently available. Other allergic diseases, especially asthma, should be well controlled before OIT initiation and during OIT treatment.1 Because a history of eosinophilic esophagitis (EoE) may create additional risks and added complexity in interpreting symptoms during OIT, providing OIT to patients with EoE should be avoided until data support an alternative view.
OIT is most beneficial for fully informed, motivated patients and families who desire enhanced normalcy and a reduced influence of food allergy in their lives, and who are willing to accept the added potential harms and burdens of the treatment.
OIT is not right for everyone. If your child has suffered severe reactions, especially to very small exposures to the allergen or has poorly controlled asthma or other illnesses, then this treatment is not suitable. If you are unable to commit to very reliable daily dosing, then this would also not be suitable. If your child’s allergy tests are very high, then this increases the change of problematic side effects and reduces the chance that the treatment will be successful.
If your absolute priority in managing your child’s allergy is avoiding any reactions, then a policy of strict avoidance is probably best. If you are prepared to accept a regular daily treatment, with occasional mild allergic reactions and a small risk of more severe reactions then OIT is worth considering.
What is the cost of treenut oral desensitisation?
As a treatment for allergy, it is very unlikely this will be covered by your insurance, which normally only covers diagnosis of allergy. We are hoping that this will change over time. Most commonly, suitability for OIT will be addressed as part of your child’s routine appointment with Prof Fox, when a diagnosis is made. If you are not an existing patient and would like to be considered for OIT, then you will need to arrange an initial clinic visit to consider suitability. If you have had recent allergy testing, it’s helpful to provide this in advance. This initial clinic visit will be billed at standard rates as would any allergy testing or food challenges required. Please consider the information in this document carefully to limit the risk of you attending an assessment visit and finding you are not suitable for the treatment.
If your child is suitable for OIT and you wish to progress, a separate document will be provided related to overall cost of a package of care. This would typically include a total of eight visits, including an initial visit where full training, supported by written information, will be provided, alongside the first dose of allergen. The package includes any unanticipated, additional visits that may be required as well as any additional skin prick testing required. It does not cover the cost of any further blood tests, dietetic support or food challenges (although these are rarely needed) nor does it cover the cost of any follow up beyond the course of treatment. It should be anticipated that annual follow up (and possibly a food challenge to check the acquired level of tolerance) may be recommended beyond completion of the course of treatment.
What are the next steps?
If you have any specific questions, please email us on firstname.lastname@example.org or if you would like to book an assessment visit or progress treatment once suitability has been agreed, please contact us on 020 3758 9160 or by email. It is strongly recommended that before you attend an initial treatment visit, you review the attached consent form as you will be asked to sign this before treatment can begin.
The following key papers are recommended reading:
Begin P et al. CSACI guidelines for the ethical, evidence-based and patient-oriented clinical practice of oral immunotherapy in IgE-mediated food allergy. Allergy Asthma Clin Immunol. 2020 Mar 18;16:20.
Vickery BP et al. Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective. Journal of Allergy & Clinical Immunology 2017.
Soller et al. First Real-World Safety Analysis of Preschool Peanut Oral Immunotherapy. Journal of Allergy & Clinical Immunology 2019.
Chu et al. Oral Immunotherapy for peanut allergy (PACE): a systematic review and meta-analysis of efficacy and safety. Lancet 2019.
Herlihy et al. Five-year follow-up of early intervention peanut oral immunotherapy. Journal of Allergy & Clinical Immunology – In Practice 2020.
Soller et al. First Real-World Effectiveness Analysis of Preschool Peanut Oral Immunotherapy. Journal of Allergy & Clinical Immunology – In Practice 2020.
Elizur A, Appel MY, Nachshon L, Levy MB, Epstein-Rigbi N, Pontoppidan B, Lidholm J, Goldberg MR.Walnut oral immunotherapy for desensitisation of walnut and additional tree nut allergies (Nut CRACKER): a single-centre, prospective cohort study. Lancet Child Adolesc Health. 2019 May;3(5):312-321.
Elizur A, Appel MY, Nachshon L, Levy MB, Epstein-Rigbi N, Koren Y, Holmqvist M, Porsch H, Lidholm J, Goldberg MR. Cashew oral immunotherapy for desensitizing cashew-pistachio allergy (NUT CRACKER study). Allergy. 2022 Jun;77(6):1863-1872.
You can also see a blog by one of our patients: https://goingnutsweb.com/2021/07/21/were-doing-peanut-immunotherapy-and-its-working/
Date written: August 2022