The epidemiology of food allergy in Europe: protocol for a systematic review

The umbrella term ‘food hypersensitivity’ can be used to describe any‘adverse reaction to food’ [1]. The term ‘food allergy’ refers to the sub-group offood-triggered reactions in which immunological mechanisms have been implicated,whether IgE-mediated, non-IgE-mediated, or involving a combination of IgE- andnon-IgE-mediated etiologies [2]. All other reactions to food that were in the past sometimes referred toas ‘food intolerance’ constitute non-allergic food hypersensitivityreactions and are out of the focus of this enquiry.

Allergic sensitisation to a specific food does not always lead to clinical reactions.Consequently, serological tests for food-specific IgE or the determination ofpositive skin prick test results are of themselves insufficient to establish thediagnosis of food allergy. Rather, there must also be evidence of the clinicalexpression of disease. IgE-mediated reactions can, for example, manifest asangioedema, urticaria, atopic eczema/dermatitis, oral allergy syndrome andanaphylaxis. Non-IgE-mediated immunological reactions result from activation ofother immunological pathways (e.g., T-cell mediated) and can manifest as atopiceczema/dermatitis, gastro-esophageal reflux disease, food protein-inducedenterocolitis, proctocolitis and enteropathy syndromes. The contemporary definitionof food allergy thus includes several clinical entities with differentpathophysiologies (see Table 1) resulting from exposureto different foods. Coeliac disease is an important non-IgE mediated condition butas it has distinct symptoms and prognosis different from atopic conditions it willbe excluded from this review [3].

Uncertainty in estimating the incidence and prevalence of food allergy is in part dueto changing definitions and imprecision in terminology, with investigators oftenfailing to make clear whether they are studying food hypersensitivity in general,IgE-mediated conditions, non-IgE mediated morbidities, or some combination or subsetof these reactions. Another major contributing factor to this uncertainty is thatrelatively few epidemiological studies have utilised the gold standard of diagnosis– the double-blind, placebo-controlled food challenge (DBPCFC) [4‐10]. Rather, many studies have based their estimates of the frequency of foodallergy on measurements of lay/patient perceptions of food allergy, which are knownto substantially overestimate the actual frequency [11‐21]. There is clearly a need for large, population-based, longitudinalstudies employing DBPCFCs to secure the diagnosis of food allergy, [22] but in the interim there is also a need to make better sense of theextant literature in order to, amongst other things, inform estimates on thefrequency of the disease, provide insights into disease aetiology, and enable riskstratification, which can be used to inform management decisions and deliberationson prognosis.

Epidemiological measures of particular interest for food allergy therefore includeestimates of incidence and prevalence, risk and prognostic factors, and risk ofrecurrence and death. The following epidemiological definitions proposed by Last,and adapted for food allergy will be employed in this review [23].

This systematic synthesis of studies published between January 2000 and September2012 will provide estimates of the frequency of food allergy across different agegroups and geographical regions in Europe. It will take into account the suitabilityof the study design for the research question, potential for selection bias, and themethods of exposure and outcome assessments. One strength of the review is that wewill be able to examine all the different methods that have been used to measurefood allergy (self-report, specific sensitization to food allergens, and foodchallenges, and their various combinations) as well as the different measures ofoccurrence of food allergy (point prevalence, life-time prevalence, and incidence),which will give us the opportunity to study different estimates of the frequency offood allergy according to these varied definitions.