Introduction:
Atopic conditions, including atopic dermatitis (AD), food and environmental allergies and asthma, have become an important public health concern world-wide.1 This review will focus primarily on early interventions to prevent food allergy (FA).2-4 Recent studies reinforce the strong connection between early severe AD and the development of FA. Pediatric FA has become an epidemic in many countries, with increasing rates in the past few decades, although substantial variations from 1% to 10% exist by country. To date, some of the highest rates have been observed in high-income countries such as the United Kingdom, United States, and Australia, where population-based surveys and analyses of healthcare utilization data suggest the burden of disease has substantially increased.5-9 While there is consensus that prevalence has increased in many parts of the world, the magnitude is difficult to ascertain due to numerous factors, including a lack of systematic population-based surveillance efforts incorporating repeated, validated prevalence assessments, and high-quality estimates lacking from many countries. Figure 1 visualizes the most recently available population-based estimates of pediatric FA prevalence.10-12
It is also difficult to estimate FA prevalence globally or compare rates by country because of the limited international coordination of disease surveillance efforts, leading to heterogeneity in study design, FA case definitions, and study populations.10,13Even in studies with similar populations, direct comparisons of prevalence rates are challenging as there are variations in social, cultural, and economic factors. Despite the literature gaps, extensive research into paediatric FA epidemiology provides insight into possible FA aetiology and promising disease prevention avenues. For example, an epidemiologic finding of disparate rates of infant peanut allergy among genetically similar populations in the UK and Israel led to insights regarding the protective role of early life exposure to major food allergens.14 These insights have now been tested in randomized controlled trials (RCTs) and translated into clinical practice guidelines that advocate the early introduction of allergenic solids for primary prevention.15-17
The multifactorial aetiology of FA is well-recognised, with environmental and genetic factors contributing to FA development. However, strategies to manage FA remain limited in most cases to strict allergen avoidance and managing allergic reactions, including teaching patients/caregivers to administer epinephrine during suspected anaphylaxis, which can adversely impact patient/caregiver quality of life. 18 Food allergen immunotherapy appears to offer transient protection but is allergen-specific, time-intensive, and side effects limit tolerability.19 Even when gold standard treatments exist, prevention remains the ultimate goal since it can circumvent early morbidity from disease and ameliorate treatment burden.
AD often heralds the atopic march and frequently precedes the development of FA, allergic asthma and allergic rhinitis. Whether AD is the primary insult, or the earliest manifestation of other underlying factors is not yet fully established. However, AD is a significant risk factor for FA and may play a key role in FA prevention. Numerous studies suggest a causal role of cutaneous sensitization in FA’s development where both the skin barrier and immunology are thought to be key players.20
The true global prevalence for AD is also unclear, with previous studies indicating paediatric AD prevalence varying by country.21 Between 1999-2004 the International Study of Asthma and Allergies in Childhood incorporated a standardized school-based sampling methodology and symptom questionnaire to estimate current AD prevalence among 6-7-year-olds in 60 countries and estimates for 13-14-year-olds in 96 countries. Subsequent studies have independently verified the increase of increasing several countries. These landmark findings are visualized in Figures 2 and 3. However, they are nearly 20 years old, and no comparable effort to systematically assess longitudinal changes in the global prevalence of AD has since been undertaken.
The dietary impact of early life nutrition is another staple of FA prevention. It has been studied to varying degrees, including the impact of oral tolerance induction, breast and formula feeding, Vitamin D, dietary diversity, and the role of pre-, pro-and syn-biotics. The interaction of the skin and diet come together in the interplay between oral tolerance induction and epicutaneous allergen exposure. This forms the basis of the dual-allergen exposure hypothesis, which proposes that epicutaneous food allergen exposure in early life is associated with the development of FA, whilst early life oral exposure is protective.22-24
Finally, microbial factors may impact FA prevention with the mode of delivery at birth, pet exposure and bacterial (S. aureus ) colonisation. The roles of viruses and fungi are still unknown. This review will explore AD, the infant diet, microbial factors, and the complex interplay of all factors in FA development, focusing primarily on early intervention to prevent FA. We conclude our review with a discussion of future and ongoing research including key topics that must be addressed.