Abstract
Despite the acknowledged contributions of a defective epidermal permeability barrier,
dryness of the skin, and the propensity to develop secondary infections to the etiology
and pathophysiology of atopic dermatitis (AD), these epidermal changes have, until
recently, been assumed to reflect downstream consequences that are secondary phenomena
of the primary immunologic abnormality—the historical “inside-outside” view that AD
is basically an intrinsic inflammatory disease.
In this review, we focused on the role of the epidermal barrier function in the pathophysiology
of AD. Specifically, we presented data in support of a barrier-initiated pathogenesis
of AD, ie, the “outside-inside” concept. First, we reviewed the evidence on the existence
of inherited barrier abnormalities in AD. Reported studies on the possible association
of mutations in the filaggrin gene (FLG) and data on human tissue kallikreins (KLKs) and AD have been addressed. We then
dealt with the question of the causal link between impaired epidermal barrier and
inflammation. Finally, the association between innate immune defense system and the
increased avidity of Staphylococcus aureus for atopic skin was examined.
Despite very convincing evidence to support the barrier-initiated pathogenesis of
AD, the view that AD reflects the downstream consequences of a primary immunologic
abnormality cannot be dismissed out of hand. Almost every line of evidence in support
of the role of the epidermal barrier as the “driver” of the disease activity can be
challenged and at least partially contradicted by opposing evidence.
Until more data are available and until all the dust settles around this issue, we
should take advantage of what we already know and use our knowledge for practical
purposes. Deployment of specific strategies to restore the barrier function in AD
means the use of moisturizers as first-line therapy.
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© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
