Prevention of atopic dermatitis

Abstract

Atopic dermatitis now affects one in five children, and may progress to asthma and hay fever. In the absence of effective treatments that influence disease progression, prevention is a highly desirable goal. The evidence for most existing disease prevention strategies, such as avoidance of allergens and dietary interventions, has been unconvincing and inconsistent. Fresh approaches to prevention include trying to induce tolerance to allergens in early life, and enhancing the defective skin barrier to reduce skin inflammation, sensitisation and subsequent allergic disease. Early and aggressive treatment of atopic dermatitis represents another possible secondary prevention strategy that could interrupt the development of autoimmunity, which may account for atopic dermatitis persistence. Large scale and long term randomized controlled trials are needed to demonstrate that these ideas result in clinical benefit.

Figure 1a and 1b.. World maps from the International Study of Asthma and Allergies in Childhood

World maps depicting flexural eczema symptoms in the last year showing changes in the prevalence of eczema symptoms for 13-14 year olds and 6-7 year olds in consecutive prevalence surveys conducted 5-10 years apart. Whilst some levelling off or even a decrease in eczema symptoms are noted in some developed countries in the 13-14 year old group, the trend is for eczema to be increasing throughout the world for the 6-7 year old groups.

Figure 2.. Mechanisms of IgE sensitization to epidermal self-proteins in patients with atopic dermatitis

Inflammation induces pruritus through IL-31 production. Scratching results in cellular damage and release of membranous and intracellular compounds from keratinocytes (KC) and possibly other skin cells. The local dendritic cells (DC) subjected to thymic stromal lymphopoietin (TSLP) will induce a T_H2 response and the generation of specific IgE directed against these self-proteins. IgE will bind to Fc ε RI on dendritic cells in the skin and thereby amplify the immune response and inflammatory reaction in the skin. (Reproduced with permission from Tang TS, Bieber T, Williams HC. Does “autoreactivity” play a role in atopic dermatitis? J Allergy Clin Immunol. 2012;129:1209-1215)

Figure 3.. The brick wall analogy of the stratum corneum of the epidermal barrier

In healthy skin the corneodesmosomes (iron rods) are intact throughout the stratum corneum. At the surface, the corneodesmosomes start to break down as part of the normal desquamation process, analogous to iron rods rusting (A). In an individual genetically predisposed to atopic dermatitis, premature breakdown of the corneodesmosomes leads to enhanced desquamation, analogous to having rusty iron rods all the way down through the brick wall (B). If the iron rods are already weakened, an environmental agent, such as soap, can corrode them much more easily. The brick wall starts falling apart (C) and allows the penetration of allergens (D). (Reproduced with permission from Cork MJ, Robinson DA, Vasilopoulos Y, Ferguson A, Moustafa M, MacGowan A, Duff GW, Ward SJ, Tazi-Ahnini R. New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions. J Allergy Clin Immunol. 2006;118:3-21)