Wheat allergy

Talking here about type 1 IgE mediated wheat allergy. Not coeliac disease, which is an autoimmune process triggered by gluten.

Only 10% persists to adulthood, equivalent to milk/egg.  Max IgE over 20 has median resolution age of 7, rises to 16 if max over 50. Unusually, IgE often remains positive even when tolerance has developed! But trend still useful for individual patient.

Wheat allergens – most commonly LMW glutenin, alpha and gamma gliadins, NOT omega. Technically gluten is found only in wheat, and is a complex of gliadin and other proteins, similar prolamins in other cereals have different names eg zein (rye), avenin (oat), hordein (barley)! 

Level of omega 5 antibodies correlates with clinical severity of exercise induced anaphylaxis! Not specific though – Omega 5 antibodies are present in 80% with anaphylaxis to wheat (non-exercise induced) and 20-30% of wheat allergic with eczema. Useful for predicting anaphylaxis??

Note that those with grass pollen allergy often have non clinically significant IgE to wheat.

[Nutrients 2017 – doi: 10.3390/nu9010035]

Lots of different names for wheat versions/products – Bulgar wheat, couscous, durum wheat, freekeh, einkorn, emmer, farola, kamut, malted wheat, semolina, spelt, triticale, wheat bran, wheat germ.

Presence of wheat starch in gluten free products (can be useful for producer) means the low level permitted for coeliac disease may still cause reactions if sufficient amount eaten, so avoid wheat based gluten free products if type 1 allergy.

But glutens present in non-wheat grains are not usually a problem for type 1 wheat allergy, so excessively restrictive to follow gluten free labels on things not made with wheat, eg oats!

Testing often suggests cross reactivity between different cereals but when you actually challenge, majority only react to one, and non wheat allergies pretty rare. Oat, rye, barley, maize allergy uncommon.

And strange how aeroallergy (to the pollen) so rarely translates to food allergy and vice versa. 

[J ALLERGY CLIN IMMUNOL 1995;96:341-51]

So I would say no need to avoid or test unless symptomatic.

Cross contamination (as in coeliac) a big issue – crumbly! Toasters, butter, surfaces etc.

Hydrolysed vegetable protein sometimes comes from wheat, has to be declared as allergen but little evidence that it is still allergenic.

There are reports of allergy to deamidated wheat (“wheat protein isolate”), where tolerant to normal wheat. Found in cosmetics too.

Reintroduction

Typical ladders suggest starting with 1/2 teaspoon of Weetabix, toast, biscuit or pasta, doubling every 3 days if non type 1, more slowly if type 1.

Immunotherapy

There has been some work in the field of wheat immunotherapy.

2018 US multicentre RCT with “high protein vital wheat gluten flour” (n=46, median age 8.7 years) – initial escalation dosing first day from 0.1mg irradiated wheat powder (0.07mg protein; much more than wheat flour, which is only 7-16% protein) up to 12mg (8.5mg protein), escalation every 2 weeks to 1445 mg wheat protein (about half a slice?). Vial/capsule initially. Placebo subjects crossed-over to a high-dose-OIT, maximum 2748 mg wheat protein daily dose. Both regimes induced desensitization to 4443mg in the majority after 1 year of therapy – 52.2% (low dose OIT), 57.1% (high dose OIT). At 2 years, only 13% had sustained unresponsiveness (stopped wheat OIT for 8 –10 weeks). Adverse reactions were “comparable” with oral immunotherapy to other foods; 24% of the subjects discontinued the trial, predominantly due to gastrointestinal symptoms.

2020 Thai 3 step protocol found threshold dose of 20 mg of wheat protein. Starting dose of 1mg of wheat flour (0.1 mg of wheat protein) and increment every 30 minutes – starting OIT dose was then dose below threshold. Carrying medium used was cow or soy milk. Systemic reactions seen on 13 occasions in 26 patients; adrenaline used 6 times.

2021 Review here, and almost identical one here. Only one RCT!? Some studies used rush introduction, others clinic or even home updosing. Vital wheat probably more concentrated than regular wheat – so easier to hide in things? Orzo pasta as more practical than flour!? 1 grain=5.2mg protein. But perhaps more measurement error/variation. Cooking time as factor?

Varying maintenance doses, from 53mg up to 5200mg (200g cooked noodles)!

Higher Omega 5 gliadin IgE less likely to achieve end point but otherwise no stratification appears possible.

It seems likely that sustained unresponsiveness is difficult to achieve.  

Even in the highest dose trial, no patients required adrenaline during up-dosing and only one patient required it during home dosing.  There is a concern about eosinophilic oesophagitis, as with other forms of food immunotherapy.   

Exercise as a co-factor perhaps even more important for wheat – one small study showed that 10 minutes of running 30 minutes after wheat ingestion triggered a reaction in 67% of patients who had successfully achieved maintenance dose, and still an issue in half 5 years later. No obvious clinical predictors. Need an exercise provocation test before liberalizing exercise restrictions?

No obvious benefit from co-administering antihistamines and/or montelukast.