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.