Epicutaneous sensitization in the development of food allergy: What is the evidence and how can this be prevented?

Abstract

There is increasing evidence regarding the importance of allergic sensitization through the skin. In this review, we provide an overview of the atopic march and immune mechanism underlying the sensitization and effector phase of food allergy. We present experimental models and human data that support the concept of epicutaneous sensitization and how this forms one half of the dual‐allergen exposure hypothesis. We discuss specific important elements in the skin (FLG and other skin barrier gene mutations, Langerhans cells, type 2 innate lymphoid cells, IL‐33, TSLP) that have important roles in the development of allergic responses as well as the body of evidence on environmental allergen exposure and how this can sensitize an individual. Given the link between skin barrier impairment, atopic dermatitis, food allergy, allergic asthma, and allergic rhinitis, it is logical that restoring the skin barrier and prevention or treating atopic dermatitis would have beneficial effects on prevention of related allergic diseases, particularly food allergy. We present the experimental and human studies that have evaluated this approach and discuss various factors which may influence the success of these approaches, such as the type of emollient chosen for the intervention, the role of managing skin inflammation, and differences between primary and secondary prevention of atopic dermatitis to achieve the desired outcome.

Particulate matter causes skin barrier dysfunction

“…It has been suggested that maintaining normal skin barrier function is critical for the prevention and control of allergic diseases such as AD and food allergy (FA) (14,16,(60)(61)(62). It is also well known that FLG deficiency and increased TEWL are associated with skin barrier dysfunction and increased allergen sensitization (20,35,(63)(64)(65).…”

“…The epidermis, the outermost part of the skin, provides a physical and functional barrier to prevent invasions of allergens, pathogens, and air pollutants such as PM into the human body (13)(14)(15). Recently, it has been suggested that a disrupted skin barrier promotes epicutaneous sensitization (14,16). Epithelial barrier dysfunction induces type 2 immune responses and is considered an initial step in developing atopic dermatitis (AD) and the atopic march (14,16,17).…”

Advances and novel developments in environmental influences on the development of atopic diseases

“…These are also increased interest in sensitive and specific biomarkers for diagnosis and for evaluation of disease severity and prognosis with therapy. With the understanding of the natural progression of the atopic diseases, studies are now in progress to determine whether by preventing skin sensitization and atopic dermatitis, we can prevent the subsequent manifestation of other atopic diseases, such as food allergy 118 . Some of the basic cellular and humoral factors involved in Th2‐mediated allergic diseases are well understood and have led to the development of biologics and other novel therapeutics, which are in various stages of development.…”

Recent advances in mechanisms of food allergy and anaphylaxis

“…However, the demonstration of a positive correlation between environmental non-oral peanut protein exposure levels and development of peanut allergy suggests non-oral environmental exposure as a potential route of sensitization 66 . The observed natural history of the “allergic march”, whereby individuals presenting with atopic dermatitis (AD) in infancy or early childhood proceed to develop concomitant sensitization to food and aeroallergens in later childhood and adult life, has led to the evolving concept of contribution from the skin as a route of food sensitization 67 – 71 . An archetypal example is AD, a common inflammatory skin disease in childhood affecting nearly 20–30% of the population and is associated with skin barrier disruption linked with mutations in human skin barrier genes filaggrin ( FLG ), serine peptidase inhibitor Kazal type 5 ( SPINK5 ), corneodesmosin ( CDSN ), and mattrin ( TMEM79 ) 72 – 74 .…”