Component testing or CRD aims, as the names suggest, to identify and quantitate IgE directed against specific (generally protein) components of each allergen as compared with traditional ssIgE or SPT which assess the presence of IgE to bind to the whole allergen protein sequence and therefore rely on crude allergen extracts. CRD can be performed through the detection of a specific single component of particular interest, such as omega-5-gliadin in wheat dependant exercise induced anaphylaxis (WDEIA), in small panels such as Ara h 1, 2, 3, 8, and 9 in peanut allergy, or increasingly as a microarray, where a large number of recombinant and/or purified components are assayed simultaneously (examples include ISAC microarray).

Oral food challenge is the gold standard in the diagnosis of food allergy and is also an important tool in safely demonstrating resolution of a known or proven food allergy. With the increasing prevalence of food allergy and testing for IgE sensitisation, and increasing data about decision points at which OFC may be offered for differing food sensitisations, a common uniform national and international standard for OFC is desirable. There have been several important moves towards standardisation of the OFC in recent years, which are helpful not only for clinical trials reporting and harmonising data across study sites and between trials, but also for improving clinical practice. Standardisation of challenge protocols for particular foods, outlining exact food type and vehicle, dosage schedule and protein content of a complete challenge, will further improve our ability to diagnose and manage children with food allergy.

The 2012 PRACTALL "Standardizing double-blind, placebo-controlled oral food challenges" report [10] is a consensus document produced by the AAAAI and EAACI and is an important step in the standardisation of all OFC. The report includes recommended minimum levels of safety, equipment and personnel, time to observe before discharge following a negative challenge, recommendation of semi-logarithmic dosage scheduling regimes and perhaps most importantly agreed objective criteria for determining a positive challenge reaction. A useful (although not validated) scoring criteria for IgE mediated acute allergic reactions on challenge is presented.

There is no international cross-regional consensus document for standardisation of OFC except the WAO DRACMA report [11], which is specific to cow's milk allergy, but does outline recommendations for best practice OFC to cow's milk in a variety of settings.

In our region, efforts to standardise food challenge protocols across countries such as Australia is occurring. The Australian Society for Allergy and Clinical Immunology (ASCIA) have now agreed challenge protocols for the most common food allergens, egg, baked egg, milk, wheat, peanut, soy and tree nuts (example of challenge protocol, Supplementary data 1) [12].

Food allergy is the commonest cause of anaphylaxis in children and can be fatal. Despite the increasing prevalence of food allergy and the incidence of food-induced anaphylaxis [13], the rate of fatal food anaphylaxis remains thankfully low [14, 15]. Nonetheless, allergic individuals and their families often perceive the risk of death to be much greater, resulting in a significant impact on their quality of life. This is partly because affected individuals (or their parents) interpret risk in a more emotion-led context while health professionals often take a rational, objective approach to risk [16].

Measures which may reduce risk of accidental exposure to known food allergens and food anaphylaxis include the provision of clear dietary avoidance instructions, easy-to-follow management plans and education in the use of adrenaline auto-injector devices [17]. A recent study found that provision of adrenaline auto-injector devices increases the impact of the food allergy on quality-of-life measures, although there is an assumption that provision of these medications is an important in reducing the risks of a fatal anaphylactic reaction [18]. Unfortunately there are currently no reliable indicators to accurately predict which food-allergic individuals are more at highest risk of fatal anaphylaxis. Case series fatal food anaphylaxis often quote asthma as a risk factor [14, 19] however the prevalence of asthma is so common that the predictive value for the individual patient is very poor.

There is a tendency to view food-allergic individuals who react to very small levels of allergen (i.e. who have a low eliciting dose or threshold of reactivity) as being more at risk of anaphylaxis. However, a large prospective series of peanut-allergic individuals undergoing DBPCFC did not demonstrate this to be the case [20].

Until recently, most allergy guidelines recommended strict avoidance of all forms and amounts of allergen for the diet of allergic children. This was partly on the basis of safety and also on the belief that that accidental allergen exposure may delay the onset of tolerance [21]. It is now widely held that this is unlikely to be the case, with a series of publication demonstrating that most children allergic to egg and milk can tolerate extensively heated egg and milk in serving size quantities. This is likely to be related to changes in the ability of the allergen to bind specific IgE through heat denaturation of susceptible conformational epitopes. It may also relate to the interaction between the matrix components (such as wheat) and the egg proteins in baked cakes and goods [22].

There are two potential positive effects related the incorporation of extensively heat treated egg and milk in diets of egg and milk allergic children. The first is the lessening on dietary restrictions resulting in improved quality of life. The second is the potential for altering the natural history of the disease, and accelerating acquisition of tolerance to egg and/or milk.

Up to 70% of egg allergic children [23, 24] and milk allergic children [25] will tolerate extensively heated egg or milk in their diet at OFC, whilst still being allergic to the naïve protein. Higher ssIgE to ovomucoid appears to be associated with a higher likelihood to being unable to tolerate extensively heated egg in muffin or cake on OFC [8, 26]. Ovomucoid SPT wheal size of > 11 mm has been shown to be associated with more severe generalised allergic reaction on baked muffin OFC [9]. SPT size to egg over time was not shown to be different in children strictly avoiding egg compared with those with regular baked egg ingestion [27] in a recent Australian retrospective study. Although the British Society of Allergy and Clinical Immunology support a home baked egg challenge protocol for selected egg allergic children without a prior history of asthma [28], most other authors and experts recommend that these challenges still take place in a supervised setting, in view of the potential for anaphylaxis [9, 29].

Recently an association between the regular ingestion of clinically tolerated heat-treated egg [30] and milk [25] and a reduction in time to whole milk/egg tolerance has been described in two prospective studies on children consuming regular heated egg or milk following demonstration of tolerance at OFC. Whether this is due to regular ingestion of the heated allergen hastening resolution of the allergy is unknown, as it is possible that children who tolerate extensively heated egg/milk may outgrow their allergy more rapidly irrespective of exposure. Interestingly, these children demonstrate immunological changes consistent with the induction of tolerance, implying the former may be more likely [14, 20]. However as these studies were not randomised controlled trials, no conclusive recommendation can be made at this time to support this as a management strategy purely for the reason of accelerated tolerance.

Finally, although dietary incorporation of extensively-head modified allergens are likely to become standard practice over the next few years for children with egg and cow milk allergy, there have been a few concerning reports of the development of eosinophilic oesophagitis (EoE) following SOTI to egg [31] and milk [32]. It is possible that EoE could also be precipitated by incorporation of extensively heat-treated egg and milk. Therefore careful follow-up of such patients is advised, with particular attention to any emerging symptoms suggestive of EoE.

Much like traditional subcutaneous and sublingual immunotherapy (SLIT) for aeroallergen allergy, immunotherapy for food allergy is based upon administration of gradually increases doses of allergen, most commonly via the oral route, with up-dosing and maintenances phases. Clinical trials to date have tended to be small, with egg, milk and peanut as the most frequently examined allergens. Most published studies have demonstrated a positive effect, although this may be due to a degree of reporting bias associated with negative studies. Primary outcomes have primarily assessed desensitization rather than sustained long term tolerance, and only a few more recent studies have conducted long term follow up [33, 34]. Those studies with follow up have generally shown disappointingly low rates of sustained tolerance, with the vast majority achieving only a temporary state of desensitisation which is rapidly lost without regular ongoing exposure to the allergen [33-35]. The current state of SOTI for food allergens has been comprehensively recently reviewed by several leading food allergy experts [36, 37]. A recent meta-analysis concluded that SOTI cannot currently be recommended for routine clinical practice and that larger, better designed RCTs are required [38].

The potential to improve efficacy and safety and to decrease side effects in SOTI has prompted trials involving combination adjuvant and oral immunotherapy protocols.

The finding that patients undergoing birch SLIT were noted to have improvement in their oral allergy symptoms [46] led to the possibility that SLIT might be an effective route for the treatment of other food allergies, where the primary sensitising agents is not an aeroallergen. Small clinical trials utilising food-based SLIT have now shown some efficacy by increasing threshold eliciting doses for allergic reactions to hazelnut [47], peanut [48] and kiwi fruit [49]. Most recently, the trans-epithelial route has been reported in a trial of milk allergic children [50], however no change was noted in the subsequent eliciting dose between control and intervention groups.

Currently under investigation are Chinese herbal preparations, which have been examined at the Mount Sinai centre in New York and collaborating institutions for some years. There is encouraging animal data where the herbal mixture FAHF-2 was demonstrated to completely block experimentally induced peanut anaphylaxis in sensitised mice [51]. Phase 2 human studies are now underway [52].

Allergen-specific T-cell epitopes are targets for a novel potential therapy in food allergy which seeks to induce immunomodulation and oral tolerance by administration of short T-cell epitope peptides, which can target allergen specific T cells without binding IgE. Animal models have demonstrated efficacy [53, 54], and desensitisation has been trialled in human subjects with insect and cat allergy but not, as yet, in food allergy. Promisingly, candidate T cell epitopes for peanut have been identified and research is ongoing [55].