Decreased level of ceramides in stratum corneum of atopic dermatitis : an etiologic factor in atopic dry skin ?

Aged epidermis displays altered drug permeability, increased susceptibility to irritant contact dermatitis, and often severe xerosis, suggesting compromise of the aged epidermal barrier. To delineate the functional, structural, and lipid biochemical basis of epidermal aging, we compared barrier function in young (20-30 yr) vs aged (> 80 yr) human subjects, and in a murine model. Baseline transepidermal water loss in both aged humans and senescent mice was subnormal. However, the aged barrier was perturbed more readily with either acetone or tape stripping (18 +/- 2 strippings vs 31 +/- 5 strippings in aged vs young human subjects, respectively). Moreover, after either acetone treatment or tape stripping, the barrier recovered more slowly in aged than in young human subjects (50 and 80% recovery at 24 and 72 h, respectively, in young subjects vs 15% recovery at 24 h in aged subjects), followed by a further delay over the next 6 d. Similar differences in barrier recovery were seen in senescent vs young mice. Although the total lipid content was decreased in the stratum corneum of aged mice (approximately 30%), the distribution of ceramides (including ceramide 1), cholesterol, and free fatty acids was unchanged. Moreover, a normal complement of esterified, very long-chain fatty acids was present. Finally, stratum corneum lamellar bilayers displayed normal substructure and dimensions, but were focally decreased in number, with decreased secretion of lamellar body contents. Thus, assessment of barrier function in aged epidermis under basal conditions is misleading, since both barrier integrity and barrier repair are markedly abnormal. These functional changes can be attributed to a global deficiency in all key stratum corneum lipids, resulting in decreased lamellar bilayers in the stratum corneum interstices. This constellation of findings may explain the increased susceptibility of intrinsically aged skin to exogenous and environmental insults.

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The aged epidermal permeability barrier : structural, functional, and lipid biochemical abnormalities in humans and a senescent murine model

Stratum Corneum Moisturization at the Molecular Level

Emollients and moisturizing creams are used to break the dry skin cycle and to maintain the smoothness of the skin. The term ‘moisturizer’ is often used synonymously with emollient, but moisturizers often contain humectants in order to hydrate the stratum corneum. Dryness is frequently linked to an impaired barrier function observed, for example, in atopic skin, psoriasis, ichthyosis, and contact dermatitis. Dryness and skin barrier disorders are not a single entity, but are characterized by differences in chemistry and morphology in the epidermis. Large differences also exist between moisturizing creams. Moisturizers have multiple functions apart from moistening the skin. Similar to other actives, the efficacy is likely to depend on the dosage, where compliance is a great challenge faced in the management of skin diseases. Strong odor from ingredients and greasy compositions may be disagreeable to the patients. Furthermore, low pH and sensory reactions, from lactic acid and urea for example, may reduce patient acceptance. Once applied to the skin, the ingredients can stay on the surface, be absorbed into the skin, be metabolized, or disappear from the surface by evaporation, sloughing off, or by contact with other materials. In addition to substances considered as actives, e.g. fats and humectants, moisturizers contain substances conventionally considered as excipients (e.g. emulsifiers, antioxidants, preservatives). Recent findings indicate that actives and excipients may have more pronounced effects in the skin than previously considered. Some formulations may deteriorate the skin condition, whereas others improve the clinical appearance and skin barrier function. For example, emulsifiers may weaken the barrier. On the other hand, petrolatum has an immediate barrier-repairing effect in delipidized stratum corneum. Moreover, one ceramide-dominant lipid mixture improved atopic dermatitis and decreased transepidermal water loss (TEWL) in an open-label study in children. In double-blind studies moisturizers with urea have been shown to reduce TEWL in atopic and ichthyotic patients. Urea also makes normal and atopic skin less susceptible against irritation to sodium laurilsulfate. Treatments improving the barrier function may reduce the likelihood of further aggravation of the disease. In order to have optimum effect it is conceivable that moisturizers should be tailored with respect to the epidermal abnormality. New biochemical approaches and non-invasive instruments will increase our understanding of skin barrier disorders and facilitate optimum treatments. The chemistry and function of dry skin and moisturizers is a challenging subject for the practicing dermatologist, as well as for the chemist developing these agents in the pharmaceutical/cosmetic industry.

Role of topical emollients and moisturizers in the treatment of dry skin barrier disorders.

Stratum corneum lipids play a predominant role in maintaining the water barrier of the skin. In order to understand the biological variation in the levels and composition of ceramides, ceramide 1 subtypes, cholesterol and fatty acids, stratum corneum lipids collected from tape strippings from three body sites (face, hand, leg) of female Caucasians of different age groups were analysed. In addition, we studied the influence of seasonal variation on the lipid composition of stratum corneum from the same body sites. The main lipid species were quantified using high-performance thin-layer chromatography and individual fatty acids using gas chromatography. Our findings demonstrated significantly decreased levels of all major lipid species, in particular ceramides, with increasing age. Similarly, the stratum corneum lipid levels of all the body sites examined were dramatically depleted in winter compared with spring and summer. The relative levels of ceramide 1 linoleate were also depleted in winter and in aged skin whereas ceramide 1 oleate levels increased. The other fatty acid levels remained fairly constant with both season and age, apart from lignoceric and heptadecanoic acid which showed a decrease in winter compared with summer. The decrease in the mass levels of intercellular lipids and the altered ratios of fatty acids esterified to ceramide 1, are likely to contribute to the increased susceptibility of aged skin to perturbation of barrier function and xerosis, particularly during the winter months.

Stratum corneum lipids: the effect of ageing and the seasons.

Lipids of the stratum corneum are implicated in cohesion and desquamation of the stratum corneum as well as in the maintenance of normal barrier function. Evidence linking the intercellular lipids to such processes has mainly been derived from studies on acquired or inherited diseases of lipid metabolism manifesting abnormalities in the structure and the function of the stratum corneum. We have studied the composition of stratum corneum lipids in clinically normal individuals with typical xerosis or 'winter dry skin' in order to establish if the lipid composition differs from that of normal individuals, showing no signs of xerosis. The amount of total stratum corneum lipids was not related to xerosis (22.0 +/- 1.8 micrograms/cm2 for normal skin, and 26.3 +/- 2.9 micrograms/cm2 for severe xerosis), and no correlation was evident between polar lipids, cholesterol sulfate (2.8 +/- 0.5% for normal skin, and 1.6 +/- 0.2% for severe xerosis), or ceramides types I-VI, and dry skin. It therefore appears that dramatic changes in stratum corneum lipids are not detectable in normal 'winter dry' skin. However, a decreased proportion of neutral lipids (sterol esters, triglycerides), coupled to increased amounts of free fatty acids, were found associated to the severity of dry skin. Apart from a decline in the sebaceous function and in esterases activity, winter dry skin does not appear to be associated to dramatic changes in polar stratum corneum lipids.

Stratum corneum Lipids in Skin Xerosis

Stratum corneum lipids (SCL) were collected on the right and left legs of 50 subjects of varying ages and skin dryness. The level of dryness and composition of the lipid was the same on both sides. Wh

Age-associated changes in stratum corneum lipids and their relation to dryness.

Background: Studies comparing purported antiaging compounds are rare. Objective: To compare in a randomized, placebo-controlled double-blind study 10% glycolic ac

T. J. Stoudemayer

Papers

Stratum corneum Lipids in Skin Xerosis

Age-associated changes in stratum corneum lipids and their relation to dryness.

Comparative effects of retinoic acid, glycolic acid and a lipophilic derivative of salicylic acid on photodamaged epidermis.