Lipid transfer protein. One of the allergen families. Cross reactions therefore seen with fruit (stoned fruit but also raspberry), nuts, seeds (eg linseed/flaxseed), pulses, even cereals, tomatoes, vegetables (lettuce! Cabbage!). You may also see reactions only to composite foods eg pizza, curry, due to multiple allergens being present, but only producing reaction due to co-factors.

A less common cause of Pollen food syndrome than PR10 allergy. Thought of as a Mediterranean thing but increasing reports from Northern and Western Europe. Plane tree and mugwort have LTP but not thought to be the usual cause for sensitisation (except maybe in China). In N/W Europe, often birch sensitised too but not to be confused with PR10 type PFS!

Important to identify because heat stable (so not affected by heat, processing, digestion etc in the way PR10 allergens are) and potential for severe reactions.

So do component testing if atypical (eg unusually severe) reactions to fruit.

LTP allergy also seems to be more likely to cause reactions of varying severity, compared with primary food allergy, with co-factors perhaps more important. Eating multiple different plant foods at the same time seems to be the most likely cause of co-factor associated severe reactions. Of course, co-factors can co-exist too (alcohol and dancing, for example). So some would advise:

• Avoid exercise for 2 hours before (more in same cases) and 4 hours after eating
• Avoid NSAIDs for 2 hours before and 2 hours after
• Avoid alcohol with food or after
• Eat cautiously if not had for many months
• (sleep deprivation, cannabis, stress, fasting, anti-reflux medication…)

Diagnosis

Danger that with LTP allergy you show sensitisation to multiple foods, and then you end up on a restricted diet without knowing whether there is allergy or not.

Peach allergen Pru p 3 is a good surrogate for LTP allergy, even if peach hasn’t been a problem! If not available, you could test with SPT reagent for peach that is rich in pru p 3 (but might be false positive due to other components being present. London plane and mugwort allergy would also support.

Wheat is a bit tricky – the wheat LTP Tri a 14 is only 45% homologous with Pru p 3 so may get missed. Given the co-factor issue, probably good to do Tri a 19 (omega 5 gliadin, as in exercise induced anaphylaxis) as well.

Where hay fever and atypical reactions to nuts, do the LTPs Ara h 9 (peanut), Cor a 8 (hazelnut), Jug r 3 (walnut). You would do the other components to exclude primary food allergy which can co-exist with LTP sensitisation.

Food challenges have limited use in this situation – if positive, unclear whether LTP is the cause, and if negative, perhaps because of co-factor issue! Exercise challenge?? May just need a bigger dose!

Management

Individualize, to balance risk of reaction against dietary restriction.

Safest fruit/veg appear to be potato, carrot/root vegetables, beans, peas, melon, cashew and pistachio. Avoid pips and skin. Banana is hit and miss.

Good results with Pru p 3 sublingual and oral peach juice immunotherapy in Spain and Portugal.

Julie McCabe died in 2011 as a result of anaphylaxis to Para-Phenylenediamine (PPD) in hair dye. Black henna is known to contain PPD, so may sensitise.

Getting it right is important because otherwise people end up scared of foods, cut out different foods and risk nutritional/growth problems as well as aversion in the child. Having unproven food allergies also causes huge problems for schools and nurseries, and may lead to the public becoming sceptical of true allergy, with potentially disastrous consequences.

Getting it right can identify other potential allergies; it can help estimate risk of anaphylaxis; it can help with predicting whether the allergy is going to go away or not.

Allergy focused history

EATERS method –

• Exposure – did they actually eat it!? Or was there clear skin contact? Perhaps from surface contamination?
• Allergen (suspected) – one of the common ones? Although you can be allergic to pretty much anything, it is really rare to have an isolated rare food allergy.
• Timing – type 1 is immediate (within 15 minutes, rarely up to 1hr after) and then settles even without treatment within 24 hours. Rare to fluctuate.
• Environment – home (usually during weaning)? Outside home? Co-factors (infection, medicines, exercise, sleep deprivation) come in here.
• Reproducible – consistent reactions with exposure? May have had before with type 1 allergy but often on trying for the first time, and won’t have had recently. Milk/egg different, of course…
• Symptoms – type 1 vs non type 1. Some overlap of course.

Other issues are age (adolescents with hay fever more likely to develop secondary pollen food syndrome type allergies), alpha-gal allergy can be delayed up to 3 hours; raw vs cooked food sometimes makes a difference; usually you already have eczema and family history of atopy.

Testing

At the end of history taking, you should have be able to assess probability of type 1 allergy. If low, you may wish to proceed straight to challenge (unless reactions sound severe). Otherwise testing may help confirm or refute.

If negative/equivocal on initial skin prick or specific IgE testing, do another test! Skin prick if negative/equivocal IgE, and vice versa.

IgE Component testing may give added information, esp where potential pollen co-sensitisation – best evidence (mostly in US population, however) for Peanut, Hazelnut, Cashew (respectively Ara h 2, Cor a 14, Ana o 3 – other components may give extra information in some cases). Jug r 1 v specific (walnut) but not v sensitive.

Challenge

Challenge will be useful where results still equivocal – viz

• Results positive but never eaten or history inconsistent
• Results positive but possibly co-sensitivity without allergy
• Food in alternative form might be OK eg baked

Gold standard is double blind challenge, but who has time for that?

Mostly based on history – combination of characteristic features without other, more likely, explanation.

NICE has list of type 1 vs non type 1 allergy signs/symptoms – some overlap, eg vomiting, diarrhoea, itch.

EAACI guidance 2023 says where type 1 allergy suspected (signs/symptoms but also timing and consistency of reaction):

• Do skin prick testing and/or specific IgE testing as first line
• For peanut, hazelnut or cashew, if in doubt do component tests Ara h 2, Cor a 14, Ana o 3 respectively as well (if available) – otherwise do skin prick or IgE if not done already.
• Where peanut or sesame allergy still in doubt, do basophil activation test (BAT – if available)
• “Reassessment of food allergic children, at regular intervals, depending on age, food and patient’s history, is suggested for possible development of spontaneous tolerance”

Ara h 2 (cut off 0.44) has 82% sensitivity and 92% specificity cf 84 and 86% for SPT of 4mm. Cor a 14 (cut off 0.64%) has 73 and 95%, Ana o 3 (cut off 0.4) 96 and 94%.

Common hidden allergens (!): celery, mustard, cochineal, lupin, soy, fenugreek, other legumes such as pea/bean/lentil protein, insects/mealworm, pink peppercorns).

Proteins responsible for a minority of allergic reactions to peanut, hazelnut, sesame among others – hydrophobic, so tend not to be well represented in skin prick and IgE test solutions. May explain false negatives.

Specific IgE tests have been developed, but otherwise you just have to challenge.

Dutch study however didn’t find that specific testing for oleosins helped much.

First do no harm – parents tend to overestimate risk of anaphylaxis, whereas there are clear consequences to restricting the child’s ability to sit with other children at snack/meal times, or restricting the food choices of other children.

Probably better to increase allergy awareness (which varies widely) than rely on classroom or school-wide bans [Dave Stukus editorial]

George Raptis has shown how allergy training can improve allergy awareness, not just confidence in managing an allergic emergency.

Alliums, as are leeks, shallots and chives. Part of same bigger family as asparagus but probably not co-sensitivity.

The main issue with onion is the chemicals released from cut surfaces, which can trigger eye/nose reactions and potentially asthma. But there’s actually some evidence that onion has an anti-allergy action.

With garlic, there is a well recognised contact dermatitis relating to chopping it.

Otherwise, allergy is very rare. Potentially part of celery-spice-mugwort syndrome.

As with that syndrome, the problem for the allergic person is that not only is it not one of the 14 UK recognised allergens for food labelling and restaurants, but it can be included under “spices” if less than 2% of the overall product, without further detail.

Mixed up with “intolerance” and “sensitivity” – intolerance is a vague term for any kind of reaction, agnostic to cause (most commonly used for gastrointestinal symptoms); “sensitisation” has a specific meaning (see allergy diagnosis) so not to be confused. Allergy is where there is an immune mediated problem (based ideally on history and testing) – but sometimes hard to know the mechanism.

2 basic types of food allergy, you can have both at the same time – type 1 (IgE mediated), and non-type 1 (non-IgE mediated – possibly type 4 hypersensitivity).

Most commonly (in Scotland – but varies across UK, especially with different ethnic groups), and varies widely across the world):

• Milk
• Egg
• Peanut
• Tree nuts
• Legumes/Pulses
• Sesame
• Wheat
• Crustaceans/molluscs
• Various fruits

Birch pollen sensitization in Northern Europe changes the kinds of allergies you get – cross sensitivity with fruit and nuts (pollen food syndrome) – whereas in the rest of Western Europe you get more fruit and seed allergies based on LPS.

Allergy has increased over recent decades – “hygiene hypothesis” has now been developed further to address entire “exposome“. Eczema increases the risk of food allergies 6-fold, via genetic and environmental factors (esp filaggrin mutations, and IL-4 receptor alpha chain polymorphisms).

Hospital admissions for food allergy in the UK have increased 3 fold over the last 30 years, with the biggest increase in children [BMJ 2021; 372: n251]. In big English study of primary care records, estimated incidence of probable food allergy doubled between 2008 and 2018; prevalence highest in children under 5 years (4·0%). Rate in children aged 5–9 years 2·4%, 15-19 years 1·7%. In those with previous food anaphylaxis, only 64∙0% of children and young people had at least one prescription for adrenaline autoinjector, and only 50.3% had them on repeat. Adrenaline autoinjectors prescription was less common in those resident in more deprived areas. 93.3% of first health care encounters for children regarding allergy were in primary care, with 2.2% in emergency departments. Only 7.4% of children had been seen for allergy in a hospital clinic. 92.2% of children had only ever been seen for food allergy in primary care (and looking at those prescribed AAIs, 93.5% only ever seen in primary care!).[Lancet Public Health 2024, Paul Turner]

If you ask people about their children’s allergies, up to 28% of infants will report allergies! Lifetime and point prevalence of self-reported food allergy 20% and 13%, respectively – point prevalence of sensitization as assessed by sIgE stands at 17%, skin prick test 6%, and food challenge positivity 1%. Based on clinical history or positive food challenge, food allergies have increased from 2.6% in 2000–2012 to 3.5% in 2012–2021. Point prevalence for under 16s for self reported but physician diagnosed food allergy is 3.75%. Patterns vary across European regions but not in a consistent way. [Spolidoro and Venter 2022]

Having a child with a food allergy has a significant effect on the quality of life for the whole family. One study suggested that having a peanut allergic child had a worse effect on a family than having a child with diabetes, even though with diabetes you also have restrictions on eating and the potential for serious adverse events. A similar study found the same comparing food allergic families with families where a child had a rheumatological diagnosis. The main domains affected were social. Patient/parent feedback pretty consistent across the world however (although most studies done in Europe and English speaking countries), and across time:

• Parents lived in fear after the first reaction, often perceiving it as traumatic, and often feeling guilt too
• They tried to live an ordinary family life and had to learn how to be one-step ahead and understand early signs.
• The family’s social life was also influenced.
• Parents asked for support and information from health professionals
• More knowledge and skills increased parents’ confidence (and by implication quality of life – Knibb 2015)

Mothers tend to report greater impact on the child’s quality of life and experience more anxiety and stress than fathers. Mothers tend to shelter the child, whereas fathers more often express a desire to expand their child’s life, and these differences are often greater where parents are separated.

The concern for the child’s safety affected eating outside the home, with birthday parties and visits to peers’ homes particularly threatening. School and nursery are a major source of concern and often led to more parental work, preparing safe lunches.

Parents often felt they had to teach themselves about allergies, due to the lack of early information provided by health care, and then ended up having to teach family, friends and educational institutions too.

Adolescence is a particularly stressful time, as parents recognize the need for the child to become more independent, at the same time that the adolescent can see the parents as excessively controlling (at least with respect to peanut allergy). Supportive friends particularly important for adolescents.

[Larsen Moen, J Ped Nursing 2019]