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 (child but also the rest of the family) end up anxious and scared of foods, cut out different foods, spend out on expensive alternatives, and risk nutritional/growth problems as well as aversion in the child.

In young infants, avoiding foods unnecessarily makes it more likely that you will become allergic in the future (“iatrogenic food allergy”). This is especially true with atopy and sensitisation – one series of 11 patients sensitized to cow milk found that all developed true cow milk allergy after a median time of avoidance of 2.3 years (with no significant improvement in their atopic dermatitis, which was the initial reason for avoidance). Pronuts study confirmed that multiple nut/sesame allergies was a factor of age – “secondary spread”. Similarly, in the Learning Early About Peanut (LEAP) study, it was precisely the infants sensitized to peanuts who were more likely to benefit from early introduction.

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? And dangerous!

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

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
• After that, if still doubt then for peanut, hazelnut or cashew, if in doubt do component tests Ara h 2, Cor a 14, Ana o 3 respectively (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 – nowhere in Scotland, as far as I know)
• “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, so equivalent. Cor a 14 (cut off 0.64) has 73 and 95%, so not great sensitivity. Ana o 3 (cut off 0.4) pretty good – 96 and 94%.

If random reactions, then consider hidden allergens: celery, mustard, cochineal, lupin, soy, fenugreek, other legumes such as pea/bean/lentil protein, insects/mealworm, pink peppercorns.

Panel tests

=multiple specific IgE tests done at the same time (the ultimate being the ALEX test, where 250 different antigens are tested simultaneously) – likely reduced sensitivity, compared with individual test, but more importantly, potential for false positives, with attendant harms (including iatrogenic food allergy, if that food then avoided unnecessarily).

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.