Published online Feb 2, 2015. doi: 10.5314/wjd.v4.i1.16
Peer-review started: September 22, 2014
First decision: November 1, 2014
Revised: November 29, 2014
Accepted: December 16, 2014
Article in press: December 17, 2014
Published online: February 2, 2015
Atopic dermatitis (AD) is a chronic inflammatory skin disorder which can precede asthma and allergic rhinitis in a disease trajectory known as the atopic march. The pathophysiology of AD includes cutaneous inflammation, disrupted epidermal barrier function, xerosis and propensity to secondary infections. AD had previously been thought to arise from the systemic atopic immune response and therapies are therefore directed towards ameliorating Th2-mediated inflammation. However in recent years the focus has shifted towards primary defects in the skin barrier as an initiating event in AD. Links between loss-of-function variants in the gene encoding filaggrin and disrupted activity of epidermal serine proteases and AD have been reported. Based on these observations, a mechanism has been described by which epidermal barrier dysfunction may lead to inflammation and allergic sensitization. Exogenous and endogenous stressors can further exacerbate inherited barrier abnormalities to promote disease activity. Pathways underlying progression of the atopic march remain unclear, but recent findings implicate thymic stromal lymphopoietin as a factor linking AD to subsequent airway inflammation in asthma. This new appreciation of the epidermis in the development of AD should lead to deployment of more specific strategies to restore barrier function in atopic patients and potentially halt the atopic march.
Core tip: Atopic diseases [including atopic dermatitis (AD), allergic rhinitis and asthma] are characterised by Th2-type inflammation. Research over the past decade has highlighted a crucial role for primary skin barrier impairment in the pathogenesis of AD and associated atopic phenotypes. Notably, the epidermal protein, filaggrin, epidermal serine proteases, and the pro-Th2 cytokine thymic stromal lymphopoietin, have been implicated in disease development. We review the evidence upholding a role for epidermal defects in the initiation of skin inflammation in AD, allergic sensitization and pathogenesis of the “atopic march”, and discuss the clinical implications of these findings.