A Look at Epidermal Barrier Function in Atopic Dermatitis

Physiologic Lipid Replacement and the Role of Ceramides

Dušan Sajić MD, PhD; Rachel Asiniwasis, MD; Sandy Skotnicki-Grant, MD, FRCPC

Disclosures

Skin Therapy Letter. 2012;17(7) 

In This Article

Epidermal Barrier Dysfunction

Traditionally, it was thought that the primary pathogenic mechanism of atopic dermatitis was initiated by immune dysfunction leading to a Th2 cytokine imbalance, increased inflammation, and secondary disruption of the epidermal barrier.[1,3] However, accumulating evidence suggests that rather than merely having a bystander effect, a primary defect in the stratum corneum plays a major role in driving the pathogenesis of atopic dermatitis that leads to sustained cytokine release, recruitment of pro-inflammatory molecules, and stimulation of a Th2 response.[3,4] Moreover, further barrier disruption in the chronic stages of AD, through mechanical scratching, not only perpetuates but alters the response to a mostly Th1 type.[5] In addition, while several other cytokines and T cell subsets like IL-31 and Th2,[6] respectively, have recently been identified within the skin of patients with AD, the role of the skin barrier influencing their expression remains unclear.[7]

AD has been separated into two different subtypes, i.e., intrinsic and extrinsic, which were derived on the basis of the extrinsic subtype stemming from allergic sensitization to an external antigen with subsequent allergen specific IgE production, and the intrinsic variant describes patients with all clinical features of AD, but no detectable allergen specific IgE. However, these subtypes may actually represent different stages of evolution based on the relative degree of sensitization. Under this view, AD in infancy is thought to begin as "intrinsic" or non-atopic dermatitis, and over time it progresses to "true" atopy in the majority of cases via allergen exposure through what is now being more widely recognized as a primarily defective epidermal barrier function.[1,2]

It is well established that the first line of defense within the epidermal barrier is the stratum corneum, which serves several fundamental roles in maintaining protection from the environment as well as preventing water loss. This "outside-in" theory views a primary defect in the stratum corneum as a key condition that drives the inflammatory cascade of AD, predisposing to increased transepidermal water loss (TEWL), penetration of irritants, allergens, secondary infection, and increased inflammation.[8] Several lines of evidence demonstrate the capacity of the cutaneous barrier to initiate and perpetuate AD including observations that: the defects in the barrier result in elevated pH that activates proteases capable of directly inducing a Th2 inflammatory response,[9] the severity of the barrier defect parallels AD severity,[10,11] the barrier defect persists longer than both the clinical lesions and the underlying inflammation,[11] several genetic disorders with skin lesions similar to AD implicate abnormal gene coding that affect the epidermal barrier, and lastly,[12] therapeutic strategies aimed at repairing the epidermal barrier, as further discussed below, also ameliorates both the inflammation and the clinically involved skin.[13]

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