Their role in dermatology practice

Journal of Drugs in Dermatology, Oct, 2003 by Neil S Sadick

Introduction

Cosmeceutical skin care products, which fall somewhere between cosmetics and pharmaceuticals, are playing an increasing role in the dermatologist's daily practice (19). These agents contain active ingredients with known and documented biologic effects on the skin. Cosmeceutical sales represent the greatest growth segment of the skin-care market (10-11). Although many of these agents have previously been marketed in drug stores, department stores, and pharmacies, these agents are now commonly being dispensed by dermatologists in their office settings. There is therefore a growing strategic alliance between the dermatology community and the cosmetic industry, which is in a process of evolution (1-4).

The major challenge facing the practicing dermatologist is how to employ this ever-growing array of products to improve patient care. Many questions are still unanswered, and the ultimate recommendation of which are optional products for the aging patient should be based upon peer-reviewed, scientifically based clinical research studies which prove the agent's therapeutic efficacy.

Photoaging Classification

The goals of any photoaging program can be summarized by aiming to improve the photoaging triad (Figure 1). This consists of attempting to decrease wrinkling, even skin pigmentation, and improve skin surface characteristics (12-14).

[FIGURE 1 OMITTED]

Photoaging may be classified into three types (Table 1). The first deals with epidermal and superficial dermal changes involving vascular, pigmentary, and pilosebaceous alterations. Type II involves full dermal alterations, which manifests clinically as rhytid formation. Type III rejuvenation involves subcutaneous senescence, and is manifested by lipodystrophy and contour irregularities. Most of the cosmeceuticals utilized to date help improve Type I changes, including the correction of fine rhytids, pigmentary, vascular, and pilosebaceous alterations (14).

Structural Changes Associated with Photoaging

Changes associated with aging involve all layers of the epidermis and dermal matrix. Decreased cell adhesions, migration, and differentiation occur at the epidermal level, while decreased fibroblast number, loss of collagen and glycosaminoglycans, and increased elastic tissue breakdown round out the clinical changes occurring in the dermis (13-14) (Table 2).

At a molecular level it has been shown that in both intrinsic as well as extrinsic photoaging, cells produce excessive amounts of free radicals, which under physiologic conditions are removed by both enzymatic as well as non-enzymatic antioxidants. The combined antioxidant system scavenges free radicals and protects cells from damage.

In both intrinsically and photoaged skin, there is a shortage of both types of antioxidant antibodies. Thus, the challenged free radicals attack cell membranes, proteins, and DNA, resulting in direct cell damage and/or deregulation and leading to an increased incidence of carcinogenesis (15-25).

Free radicals also activate cell surface receptors on keratinocytes and fibroblasts causing upregulation of transcription factors such as activator protein-1 (AP-1) and nuclear factor kappa beta (NF-kb). The activation of AP-1 stimulates collagen-degrading enzymes including collagenase, gelatinase, and stromelysin. AP-1 also blocks collagen gene expression in dermal fibroblasts, impairing collagen synthesis. These changes lead to increased dermal matrix degradation eventuating in rhytid formation (23-25).

NF-kb is also upregulated by circulating free radicals. NF-kb induces release of proinflammatory cytokines such as tumor necrosis factor (TNF-a) and interleukin 1 (IL-1), IL-6, and IL-8. Acting through cell surface receptors, these cytokines amplify AP-1 and NF-kb release, leading to further actinic damages (20).

With this background in mind, antioxidants which typically have been shown to have photoprotective effects on skin when used in appropriate concentrations to allow epidermal penetration, as well as epidermal and dermal stimulatory agents such as retinoids and polyhydroxy acids, are being incorporated into multiple skin care products by manufacturers in an attempt to slow down the aging process. These products are often components of ongoing, non-invasive, non-ablative programs which are being incorporated by some dermatologists into patients' at-home treatment programs (26-27).

Cosmeceutical Agents Presently in Use Hydroxy Acids

Hydroxy acid (AHA) rejuvenation increases type I collagen mRNA and hyaluronic acid content of the epidermis and dermis. In addition, these agents have been shown to increase epidermal maturation characteristics. These agents may also have kera tolytic properties, although not as significant as with the b hydroxy acids (BHAs), e.g., salicylic acid (28). Glycolic acid, lactic acid, and malic acid are the most commonly utilized AHAs.

At home, AHA usage may vary from 10-40% applied nightly. These agents may be compounded with 34% hydroquinone to treat photoaged skin associated with significant pigment dyschromia.