Disease Mechanisms in Atopic Dermatitis: A Review of Aetiological Factors

Abstract

Atopic dermatitis is a prevalent inflammatory skin condition characterized by itch and dry skin, which affects 15-20% of children and 3-5% of adults. This article reviews epidemiological, clinical and experimental data to provide an overview of the most important disease mechanisms in atopic dermatitis. Genetic predisposition, environmental insults, atopic triggers, complex host immune response and skin barrier changes, and altered skin microbiota are discussed. Whilst our understanding of atopic dermatitis has improved dramatically in recent years, many basic aspects are still not understood. Further research is needed to fully understand this complex skin disease.

Keywords: aetiology; pathomechanism; pathophysiology; risk; atopic dermatitis.

Fig. 1

Theoretical outline of how genetic risk genes and environmental risk exposures interact and may impact the risk of atopic dermatitis (AD). If a child reaches the threshold bar for AD, the disease will manifest. Factors that increase the risk of AD are represented by yellow vertical lines, whereas factors that decrease the risk are represented by green vertical lines. Once AD has manifested, the lines are shown in red.

Fig. 2

Important skin barrier changes in atopic dermatitis (AD). Innate and acquired inflammation in AD leads to downregulation and degradation of filaggrin and tight junction proteins, in turn leading to a dry and leaky skin barrier with elevated pH, which allows bacteria to colonize and allergens, irritants and microorganisms to invade. Tight junction reduction further allows antigen presenting cells to move upwards and meet the antigens. Lipid synthesis is compromised at several levels, which acts in concert with protein dysfunction to allow increased loss of water from the skin surface. In an attempt to restore the skin barrier and prevent excessive water loss, acanthosis occurs, often in conjunction with mild spongiosis.