Improvement of Diagnostic mEthods for ALlergy assessment. Cashew allergy in children as a showcase (IDEAL study)

There is an urgent need for improvement of the diagnostic tools for food
allergy. Current tests jeopardize proper diagnosis due to poor sensitivity and
false-positive and false-negative results. The current standard is the double
blind, placebo controlled food challenge test. This test is expensive. time
consuming and includes the risk of allergic reactions. In addition this test is
time consuming and can therefore only be performed in approx. 10% of patients.
This means that in 90% of patients incomplete diagnostics are performed. This
group is gets dietary advice, while it is uncertain whether they really need
this. Mediator Release Assays (MRA) are promising tests for superior results in
comparison to the current diagnostic tests, because of a superior relationship
with the in-vivo situation. MRAs will result in a more relevant diagnosis, more
convenient test protocols for patients and a significant reduction of costs of
food challenges. The prevalence of allergy to cashew in children is increasing
considerably. The prevalence is unknown and to date no studies addressing the
best diagnostic tools have been performed. This study will provide knowledge
about the severity and prevalence of this type of allergy and it is expected
thatthe new test method will make the food challenge test redundant.
Because the food challenge test is only performed in 10% of regular patients,
this test is seen as a study related test in this study and not as being part
of regular diagnostics.

Protocol amendment Feb-14:
Some children already reacted positively during the first (=lowest
concentration cashew nut) or second step of the provocation test. This applies
to approx. 15 patients in Erasmus MC and approx. 5 patients in UMCG . The extra
tests will not be performed in the Reinier de Graaf Gasthuis.
It is relevant for the children to assess the actual no effect level. This has
also scientific relevance.
The parents of these children and the children themselves (if 12 years or
above) will be contacted to ask for their consent to conduct 2 extra
provocation tests: 1 with and 1 without cashew nut. De starting concentration
will be considerably lower than during the previous provocation test.

Protocol amendment Jan-15::
90% cross reactivity in the skin test has been found between cashew and
pistache. So far 75% of the provocations with cashew have been positive, so it
is important to know whether these children can use pistache or not. For this
reason the PI would like to add an extra double blind provocation (plus 1
blood draw) with pistache to the study.
There is also cross reactivity with mango (35%). An open provocation with mango
is also added to the study.
De studie wordt bij patiënten uit Rotterdam en Delft uitgevoerd. Alle testen
gebeuren in Rotterdam.

To improve diagnostic tools for food/cashew nut allergies with the use of
Mediator Release Assays.
Genetic component of cashewnut allergy.

Therapeutic non-drug intervention study.
Therapeutic, because the patient directly benefits for the improved diagnostic
actions. The diagnosis is more solid and therefore the dietary counseling can
be better targeted.
Conventional diagnostics
Plus for study purposes:
Double blind randomized food challenge test
6 skin prick tests
Blood draw 12 ml for Mediator Release Assays and 7 ml (alternative: saliva
test) for genetic research.
Questionnaires.
200 patients.
Duration approx.2 months per patient.

Double blind food challenge test, skin prick tests, blood draw, questionnaires.

Risk: allergic reaction to food challenge and skin prick test.
Burden: study duration approx. 8 weeks.
Skin prick tests.
Blood draw (19 ml extra for the study).
Questionnaire quality of life (parents and children of 8 years and above)
during visit 1 and after approx. 6 months.
Food challenges (double blind, randomized), time interval 2 weeks.
Amendment Jan-15: 1 extra double-blind set of 2 provocation tests (pistache)
and 1 open-label provocation test with mango, plus approx. 5 ml blood.