ROLES OF VEHICLES FOR SKIN TREATMENT 193 Exposure to tensides represents a common potential workplace irritant. Protection against tensides seems to be more effective with a lipid-enriched, lipid-external-phase emollient, such as w/o emulsions (27 ,28). In contrast, Held and colleagues showed that a four-week pretreatment of normal skin with some w/o cosmetic vehicles increases susceptibility to detergents (sodium lauryl sulfate) (29). Incorporation of high amounts of emulsifiers into the vehicle and subsequently emulsifying the intercorneocyte lipids could be the reason for the controversial results. Moreover, emulsifiers can act as carriers of aggressive substances, enhancing their penetration into the skin. Alternatively, the deposited lipids can function as traps (solvents) for tensioactive molecules. Thus the long-term application of barrier creams in working conditions where detergents are present should be carefully evaluated. Clinical observations have established the knowledge that skin irritants are more harm­ ful in dry skin conditions. Therefore, vehicles often are used to increase the water content of the stratum corneum as a preventive measure (30,31). Moisturizer-containing cos­ metic vehicles prevent irritant skin reactions induced by detergents, and may also accelerate the regeneration of permeability barrier function in irritated skin (32). Cos­ metic vehicles with moisturizing properties usually contain, either singly or in combi­ nation, humectants such as ammonia, lactic acid, citric acid, and pyrrolidone carboxylic acid and their salts, and urea, glycerol, sorbitol, and amino acids. Most of these agents belong to a group considered "natural moisturizing factors" (NMF), as it is similar to the blend of hydrosoluble ingredients found in the stratum corneum. Their common prop­ erties include the increase of hydration and the enhancement of water-binding capacity in the upper stratum corneum. Reduced NMF content in the stratum corneum can diminish water absorption capacity and may result in perturbation of corneodesmolysis, leading to hyperkeratosis (33). It has been shown that dry environmental conditions increase epidermal DNA synthesis and amplify the hyperproliferative response to barrier disruption (34-3 7). Furthermore, changes in environmental humidity contribute to the seasonal exacerbations/amelioration of cutaneous disorders such as atopic dermatitis and psoriasis, diseases that are characterized by a defective barrier, epidermal hyperplasia, and inflammation (3 5 ). Application of topical glycerol prevented the epidermal hyperplasia and dermal mast cell hypertrophy and degranulation induced by exposure to low hu­ midity (3 5 ). Cosmetic vehicles with barrier properties can also prevent certain types of epidermal damage. For example, Fartasch and colleagues have shown that alterations of the lower part of the stratum corneum and damage to the nucleated layers of the epidermis are induced by sodium lauryl sulfate (38). In this model, formation of lamellar lipid mem­ brane structures was disturbed in the lower stratum corneum. In contrast, the upper stratum corneum showed intact intercellular lipid bilayers. The barrier disruption effect of SLS was prevented by the application of a barrier cream ( discussed in more detail below), with diminished sodium lauryl sulfate penetration as the likely mechanism (38). DERMATOLOGICAL AND COSMETIC VEHICLES IN A TOPIC DERMATITIS The value of well-formulated vehicles in the treatment of atopic dermatitis is widely recognized. In atopic dermatitis, stratum corneum hydration and water binding capac­ ity are reduced (39-41), and impaired permeability barrier function is readily ob-

194 JOURNAL OF COSMETIC SCIENCE served in involved skin (40,42). These patients also are more prone to develop an irritant contact dermatitis (43). Furthermore, they show a less pronounced so-called "hardening effect," i.e., with repeated skin barrier disruption, the barrier deterioration stopped after a certain time, suggesting that the stratum corneum adapts to the repeated barrier insults ( 44). The content of barrier lipids is reduced most prominently that of ceramide 1 and ceramide 3 is reduced in the stratum corneum of atopic dermatitis patients (42,45). This reduction of ceramide levels may result from the increased activity of the enzyme sphingomyelin deacylase (46,47). However, sebaceous gland activity is also reduced in these patients, the role of which remains unknown (48). Moreover, in the stratum corneum of atopic dermatitis patients the membrane-coating granules or la­ mellar bodies are incompletely extruded and organized. This, along with the altered stratum corneum lipid content, may partly explain the impaired barrier function in these patients (49). Finally, patients with atopic dermatitis show an increase in Staphylococcus aureus coloni­ zation (50,51). A reduction of S. aureus colonization resulted in a significant clinical improvement (5 2). Clinical observation indicates that treating atopic skin with an effective moisturizer leads to a clinical improvement in some cases without the use of antibiotics. Thus, ideal cosmetic vehicles for patients with atopic dermatitis should: • Improve barrier function • Have protective properties • Improve stratum corneum hydration • Have an antibacterial active compound (e.g., reduce colonization of S. aureus) These demands can be met by cosmetic vehicles: • Showing w/o emulsion properties with a high water content (27) • Containing a moisturizer (e.g., glycerol, urea) (53,54) • Having a physiological lipid mixture (5 5-57) • Containing an antiseptically active compound (e.g., triclosan) (30,58-59) In this regard, urea-containing cosmetic vehicles were able to improve skin barrier function and to reduce skin susceptibility to irritants in patients suffering from atopic dermatitis (54). Evening primrose oil (20%) in a w/o emulsion also improved barrier function and stratum corneum hydration in atopic patients (60). Some examples of useful simple formulations for water-rich (with low water activity) w/o vehicles for patients with atopic dermatitis are given below (1). W/0 EMULSION I Urea Glycerol 85% Triclosan Eucerinum w/o vehicle 1 1 Beiersdorf, Hamburg, Germany. 5.0 10.0 3.0 ad 100.0