Efficacy and Safety Considerations in Topical Treatments for Atopic Dermatitis

Noreen Heer Nicol, MS, RN, FNP


Dermatology Nursing. 2010;22(3):2-11. 

In This Article

Skin Barrier Dysfunction in AD

The outermost epidermal layer (stratum corneum) plays a key role in the pathogenesis of AD. The stratum corneum is a dense protein-lipid matrix that prevents epidermal water loss and functions as a barrier to irritants, allergens, and infectious organisms. This barrier undergoes constant renewal, and its thickness is constant ( Jensen et al., 2004; Palmer et al., 2006).

In patients with AD, the stratum corneum is susceptible to environmental damage and allergen penetration through the skin ( Jakasa, Verberk, Esposito, Box, & Kezic, 2007; Proksch et al., 2006). Hydration is impaired in AD as well; transepidermal water loss, a marker of barrier function, is increased up to fourfold in lesional skin compared with healthy skin (Proksch et al., 2006).

Genetic linkage studies have highlighted the importance of the chromosome 1q21, which contains a collection of genes known as the epidermal differentiation complex. Mutations of the filaggrin gene, located in the epidermal differentiation complex, have been identified as a strong predisposing factor for AD (Howell et al., 2007; Palmer et al., 2006; Weidinger et al., 2008). Such mutations can cause loss or reduction of the filaggrin protein, which is essential for the formation and hydration of the skin barrier. Reduced expression of filaggrin is found in AD, especially in lesional skin (see Figure 1) (Cork et al., 2006; Proksch et al., 2006).

Figure 1.

Epidermal Skin Barrier Breakdown in Atopic Dermatitis (AD).
(a) In individuals with healthy skin, the stratum corneum is intact. (b/c) In individuals genetically predisposed to AD, breakdown of the stratum corneum is evident. (d) Skin barrier breakdown allows the penetration of environmental agents such as allergens and bacteria.
Source: Reprinted with permission from Cork et al., 2006. © American Academy of Allergy, Asthma and Immunology.

Atopic dermatitis skin is deficient in antimicrobial peptides needed to defend against bacteria, fungi, and viruses (Ong et al., 2002), which may explain increased susceptibility to skin infections. This vulnerability highlights the importance of skin care measures aimed at maintaining a healthy skin barrier. Most patients with AD are colonized by Staphylococcus aureus. More than half of these patients develop immunoglobulin E molecules directed against toxins known as superantigens produced by S. aureus strains (Ong & Leung, 2006). These super-antigens dysregulate normal immune responses in patients with AD compared with healthy individuals. Moreover, superantigens are implicated in the induction of corticosteroid insensitivity, which complicates treatment response to corticosteroid therapy in patients with AD (Hauk & Leung, 2001).