BACKGROUND
IgE-mediated tree nut allergy in children is common, often serious, and usually lifelong [1]. Australia has the highest reported prevalence of tree nut allergy [2-4]. Accidental ingestion is common, and nuts are the most common trigger of fatal anaphylaxis in <20 year olds [5-7]. Tree nut allergy resolution is very low, at around 10%, [8] hence once established in young children, tree nut allergy is usually life-long and avoidance remains the mainstay of management.
Systematic review and meta-analyses have shown that early peanut and egg introduction reduces the risk of a child developing peanut or egg allergy compared with delaying until after 12 months of age [9]. This has resulted in a paradigm shift in clinical practice, from advice to delay the introduction of peanut and egg, to actively encouraging introduction before 12 months of age. Accordingly, infant feeding guidelines in Europe, Canada, the US and Australia have been revised to recommend the introduction of peanut and egg (and in some countries other common allergens) in the first year of life [10-12].
There are, however, no specific prevention strategies for tree nut allergy. There is emerging evidence from the HealthNuts cohort, which observed a protective effect of early cashew introduction with no participants (0%: 95% CI, 0%-2.6%) who were introduced to cashew before 12 months developing cashew allergy by 6 years of age [13], compared to 3.6% (95% CI 2.9-4.4%) cashew allergy in infants who did not consume cashew in the first year. Infants with peanut allergy are at higher risk of developing tree nut allergies, with up to 40% of children with peanut allergy developing one or more tree nut allergies by age 6 [2, 14]. Of concern, the EarlyNuts study found that parents of infants at high risk of tree nut allergy (peanut allergic and/or eczema) were more likely to delay tree nut introduction compared to infants without peanut allergy and/or eczema in the first year of life [15].
Initial recommendations in the US suggested infants with peanut allergy should be screened for tree nut allergies with tests of allergen specific IgE sensitisation (skin prick test or serum IgE) and an individual OFC performed for all sensitised tree nuts to determine allergy status [16]. This approach may minimize parental anxiety and assist with home introduction of the negative tree nuts but the concern is the poor positive predictive value of IgE testing may mean a risk of over diagnosis of tree nut allergy. Given long wait times and limited access to hospital based OFCs, this approach may result in delayed introduction of the sensitised tree nuts, potentially amplifying the risk of developing additional nut allergies [17]. Given this, there is a move towards recommendations against pre-emptive tree nut screening for those with peanut allergy [10, 11].
The current practice in Australia is to advise infants with a diagnosed food allergy to introduce all other food allergens one by one (including tree nuts) via a cautious home introduction protocol without prior allergy testing (screening). Whilst the risk of anaphylaxis in infants via a cautious graded approach is considered low [17], there remains the risk of IgE mediated reactions. Another concern is that it can be labour intensive and time-consuming to introduce each of the 8 individual tree nuts (almond, brazil nut, cashew, hazelnut, macadamia, pecan, pistachio and walnut) in a meal or ground form safe for infants.
We hypothesise a supervised multi-nut OFC (compared to home based individual tree nut introduction) will reduce tree nut allergy prevalence at 18 months of age in infants with peanut allergy, facilitate earlier and ongoing ingestion of tree nuts, improve parental anxiety and quality of life and reduce the healthcare costs associated with the management of multiple nut allergies.
METHODS AND ANALYSIS