title: Abnormal epidermal barrier in the pathogenesis of atopic dermatitis.
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.
authors.affiliation: Dermatology Unit, Kaplan Medical Center, Rehovot 76100, Israel. wolf_r@netvision.net.il
authors.forename: Ronni
authors.initials: R
authors.lastname: Wolf
authors.forename: Danny
authors.initials: D
authors.lastname: Wolf
mesh_terms: D003876:Dermatitis, Atopic / Q000209:etiology*; D004643:Emollients / Q000627:therapeutic use*; D004817:Epidermis / Q000473:pathology*; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D010539:Permeability; D012307:Risk Factors; D012869:Skin Absorption; D013207:Staphylococcal Skin Infections / Q000150:complications; D013211:Staphylococcus aureus / Q000302:isolation & purification
chemical_list: D004643:Emollients; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins