Early intervention of atopic dermatitis as a preventive strategy for progression of food allergy

Abstract

Background: Atopic diseases, such as atopic dermatitis (AD) and food allergy (FA), have increased in prevalence in industrialized countries during the past few decades and pose a significant health burden. They appear to have a common underlying mechanism and a natural disease progression. AD is generally the first atopic disease to manifest followed by other atopic diseases, such as FA, allergic rhinitis, or allergic asthma suggesting that they are likely different manifestations of the same disease. BODY: Evidence suggests that allergic sensitization occurs through an impaired skin barrier, while consumption of these foods at an early age may actually result in tolerance. This has been termed the Dual-Allergen-Exposure hypothesis. Loss of barrier integrity has been hypothesized to enable penetration of allergens, pollutants, and microbes and initiation of an inflammatory immune cascade of events leading to sensitization. The immune dysfunction is thought to further exacerbate the impaired skin barrier to form a vicious cycle. There is much interest in preventing or protecting the skin barrier from developing a proinflammatory atopic state, which may potentially lead to the development of AD and subsequently, FA.

Conclusion: Research on preventing or treating skin barrier dysfunction is ongoing. A number of studies have evaluated the efficacy of emollients in preventing AD and FA with mixed results. Studies have differed in the study design, population characteristics, emollients type, and frequency, duration, and area of application. Emollient type has varied widely from oils, creams, petrolatum-based lotions, and trilipid creams. Current research is directed towards the use of trilipid emollients that are similar to the skin's natural lipid composition with a 3:1:1 ratio of ceramides, cholesterol and free fatty acids and a pH that is similar to that of skin to determine their effectiveness for skin barrier repair and prevention of AD and FA.

Keywords: Atopic dermatitis; Ceramides; Eczema; Emollients; Filaggrin; Food allergy; Prevention; Skin barrier; Stratum corneum; Trilipids.

Fig. 1

A dysfunctional skin barrier caused by exposure to pollutants, pathogenic microbes, and genetic mutations predisposes towards atopic sensitization, the first manifestation of which is atopic dermatitis. An impaired skin barrier releases proinflammatory epidermal cytokines, IL-25, IL-33, and TSLP. In this proinflammatory environment, resident antigen presenting cells further skew naïve T cells towards a Th2 proinflammatory state. ILC2 cells also play a key role in allergic sensitization. ILC2 cells are found near barrier surfaces and are activated by IL-33. Th2 and ILC2 cells produce a number of cytokines, key among them being IL-4, IL-5 and IL-13. In the presence of IL-4 and IL-13, B-cells undergo isotype class switching to IgE producing cells. IgE antibodies then bind to high-affinity FcεRI receptors on the surface of mast cells and basophils and prime these cells for future encounters with the allergen leading to a state of atopic sensitization. In sensitized individuals, subsequent encounters with an allergen leads to cross linking of IgE bound to FcεRI receptors and degranulation and release of proinflammatory mediators by basophils and mast cells leading to eosinophilic infiltration, smooth muscle contraction, vascular permeability, and mucous secretion