Atopic barrier function

There are several genetic skin diseases with known defects in the lipid metabolism. Atopic dermatitis, lamellar ichthyosis, and psoriasis have been the most widely studied with respect to epidermal barrier function and alterations in the lipid profile. Deviations in the lipid profile have been linked with an impaired stratum corneum barrier function. Atopic dermatitis is characterized by inflammatory, dry and easily irritable skin, and overall reduced ceramide levels in the stratum corneum [58-60]. In particular a significant decrease in the ceramide 1 level is observed, whereas the levels of oleate that is esterified to ceramide 1 are elevated [59]. Both aberrations may be responsible for the reduced order of the lamellar phases as observed with freeze fracture electron microscopy [61]. It has further been established that, in comparison to healthy stratum corneum, the fraction of lipids forming a hexagonal packing is increased [61]. A recent study reveals that the level of free fatty acids... 

Proksch, E. Nissen, H-P. Bremgartner, M. Urquhart, C., Bathing in a magnesium-rich Dead Sea salt solution improves skin barrier function, enhances skin hydration, and reduces inflammation in atopic dry skin. Int. J. Dermatol. 44, 151-157, 2005. 

The characteristics of hydration level and barrier function of SC in various types of dry skin were reviewed and summarized in Table 9.3. They are senile xerosis, seasonal allergic rhinitis, ichthyosis valgaris, and experimentally induced dry skin including atopic xerosis and dry skin by hemodialysis. The water content decreased in every type of dry skin and the free amino acids content also decreased corresponding to the decrease of the water content. However, the TEWL or the ceramide levels showed no clear tendency throughout every type of dry skin, especially ceramides showed higher or lower value even though the water content in SC was consistently lower in every type of dry skin. 

Dry, scaly skin is characterized by a decrease in the water retention capacity of the stratum corneum (SC),1 with water content diminished to less than 10%. Barrier function of the SC is usually declined, and transepidermal water loss (TEWL) is increased because of an abnormality on barrier homeostasis.2 People feel tightness of their skin, and the skin surface becomes rough, scaly, and sensitive. Hyperkeratosis, abnormal scaling, and epidermal hyperplasia are usually observed in the dry skin.2 Keratinization also shows abnormal features.2 These phenomena are commonly observed in atopic dermatitis and psoriasis.3 Dermatitis induced by environmental factors such as exposure to chemicals, low humidity, and UV radiation also shows these features. Thus, many researchers have been investigating the cause and treatment of dry skin, and there is currently great interest in adequate model systems for dry skin studies. In this chapter, I will describe several model systems of dry skin for clinical research of dermatitis associated with skin surface dryness and also mention recent studies to improve the dry skin. 

As described previously, one can induce dry, scaly skin, which shows features very similar to dermatitis such as atopic dermatitis and psoriasis. Use of this experimentally induced dry skin should enable the discovery of a new clinical methodology to cure or care for skin problems. Recently, several excellent in vitro skin models have been reported. Although they are also very useful models for the study of cutaneous metabolism, their function and microstructure are still different from those of intact skin. On the other hand, the mechanisms underlying abnormal desquamation, that is, scaling in the dry skin such as atopic dermatitis, are not completely known. Sato et al. reported55 the inhibition of protease in the SC induced scale without affecting epidermal mitosis. This result seems to be no direct relationship between skin surface appearance and epidermal proliferation. However, decline of SC barrier function induced epidermal hyperplasia, as described earlier.30 The loss of water content from SC also induced epidermal DNA synthesis.30 Further mechanistic studies on each of the dry skin features are required. 

Chamlin, S.I., Kao, J., Frieden, I.J., Sheu, M.Y., Fowler, A.J., Fluhr, J.W., Williams, M.L., and Elias, P.M., Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis changes in barrier function provide a sensitive indicator of disease activity. J. Am. Acad. Dermatol., 47, 198— 208, 2002. 

Atopic dermatitis is the most common itchy dermatosis, with well-documented alteration in the stratum comeum function. Numerous studies have revealed an increase in the basal transepidermal water loss (TEWL) in the stratum corneum of patients with this condition. Of note, this increase in TEWL was also described in the clinically unaffected skin of atopies.2 There have been direct correlations shown between the degree of inflammation and severity of barrier impairment in atopic dermatitis. Despite these findings, to date there have been no definitive reports correlating degree of barrier function with itch variability. 

Importantly, not all moisturizers provide the same effect in restoration of the barrier function. Certain lipid mixtures or an inadequate concentration of physiologic lipids actually have been demonstrated to inhibit barrier restoration.42,43 Newer ceramide-dominant emollients have been developed in efforts to restore the intrinsic physiologic lipid concentration of the skin. One type of ceramide-dominant emollient was shown to significantly improve the overall severity of atopic dermatitis and demonstrated correction of transepidermal water losses in these patients.44 Unfortunately, studies using ceramide-dominant emollients for patients with atopic dermatitis did not use itch improvement as an endpoint. However, these types of moisturizers likely have a role in the improvement of itch associated with dry skin. 

Thune, P. et al., The water barrier function of the skin in relation to the water content of stratum corneum, pH and skin lipids. The effect of alkaline soap and syndet on dry skin in elderly, non-atopic patients, Acta Derm. Venereol., 68, 277, 1988. 

Rippke, F. etal., Stratum corneum pH in atopic dermatitis impact on skin barrier function and colonization with Staphylococcus aureus, Am. J. Clin. Dermatol., 5, 217, 2004. 

Loden, M., Andersson, A.-C., and Lindberg, M., Improvement in skin barrier function in patients with atopic dermatitis after treatment with a moisturizing cream (Canoderm ), Br J. Dermatol., 140, 264, 1999. 

Burr and Burr reported in 1929 a new deficiency disease produced by the rigid exclusion of fat from the diet. 1 Rodents fed a fat-free diet showed reduced growth and reproductive failure, accompanied by two prominent changes in the skin, that is, increased scaliness and impaired barrier function.1,2 Reversal of the features of deficiency by administration of linoleic acid (LA), led to the concept of essential fatty acids (EFA) that cannot be synthesized by the higher animals.2 Similarities between the clinical features of EFA deficiency and atopic dermatitis led Hansen in 1937 to discover low blood levels of unsaturated fat in atopic children,3 and he later reported that EFA-deficient infants developed an eczematous rash, which responded to LA supplements.4 Several studies had previously examined a range of dietary oil supplements in atopic dermatitis,5-8 with generally reported benefit. 

Atopic eczema is a chronic, relapsing, inflammatory skin condition. Typically it is characterised by an itchy red rash (often associated with the skin flexures). It is associated with a family history of other atopic diseases such as asthma and hay fever. Due to the reduced barrier function of the dry skin, eczematous skin can be particularly sensitive to irritants. 

Skin diseases including essential fatty acid deficiency and ichthyosis may also affect the transdermal delivery of a compound. Studies have shown that the epidermal barrier function is altered by abnormal lipid composition in noneczematous atopic dry skin. Numerous other dermatologic conditions affect the anatomical structure and function of skin, which may impact on the nature of the toxic responses seen. 

Fartasch, M., and T. L. Diepgen. 1992. The barrier function in atopic dry skin. Acta Derm. Venereol. 176 (Suppl.) 26-31. 

As shown in Fig. 5, the prevalence of skin burning decreased after the first few days of treatment, ostensibly as the skin healed and the therapeutic barrier function was restored. Of particular note, no increase was observed in the rate of infections during the 1 -year study. Improvement in the patient s atopic dermatitis was seen early in the study and was sustained throughout the remainder of the study [124]. 

Barrier Function and Skin Reactivity in Non-atopic Eaema... 

At eczematous skin sites, barrier impairment is well demonstrated by an increase in TEWL values. In non-atopic eczematous patients, basal barrier function and skin reactivity at healthy skin sites vary according to the activity of eczema. When skin lesions are present, barrier impairment is also evident at healthy skin sites. 

Barrier Function and Skin Hyper-Reactivity in Atopic Eczema... 

Abe T, Ohkido M, Yamamoto K (1978) Studies on skin surface barrier functions, skin surface lipids and transepidermal water loss in atopic skin during childhood. J Dermatol 5 223-229... 

Rajka G (1974) Transepidermal water loss on the hands in atopic dermatitis. Arch Dermatol Forsch 251 111-115 Reed JT, Ghadially R, Elias PM (1995) Skin type but neither race nor gender, influence epidermal permeability barrier function. Arch Dermatol 131 1134-1138 Reed WB, Kierland RR, Code CF (1958) Vascular reactions in chronically inflamed skin. Ill Action of histamine, the histamine releaser 48-80 and monoethanolamine nicotinate (Nicamin). Arch Dermatol 77 263-268 Reinertson R, Wheatley V (1959) Studies on the chemical composition of human epidermal lipids. J Invest Dermatol 32 49-58 Rietschel RL (1995) Physiologic response of chronically inflamed and accommodated human skin. Curr Probl Dermatol 23 104-107... 

Tupker RA, Pinnagoda J, Coenraads PJ, Nater JP (1990) Susceptibility to irritants role of barrier function, skin dryness and history of atopic dermatitis. Br J Dermatol 123 199-202... 

Exposure to low-dose UVR may benefit other types of dry skin, beyond atopic dry skin and atopic eczema, as it increases ceramides and all other SC lipids (Lehmann et al. 1991 Rawlings et al. 1995 Rawlings et al. 1996). However, even without sun exposure, during summer, barrier function improves due to the increased lipid production (Rogers et al. 1996). 

Schwarz T (1988) Die Bedeutung epidermaler Zytokine in der UV-induzierten Immunsuppression. Hautarzt 39 642-646 Tupker RA, Pinnagoda J, Coenraads PJ, Nater P (1990) Susceptibility to irritants role of barrier function, skin dryness and history of atopic dermatitis. Br J Dermatol 123 199-205 Widmer J, Eisner P, Burg G (1994) Skin irritant reactivity following experimental cumulative irritant contact dermatitis. Contact Dermatitis 30 35-39... 

In the first part the biosynthesis of fatty acids in skin with its role in barrier function as well as the role of dietary fatty acids on skin cell function and in the treatment of inflammatory skin diseases is presented. The second part deals with skin as a source of proinflammatory eicosanoids, especially with the keratinocyte as a major cellular source. Metabolism of eicosanoids in skin, its role in psoriasis and atopic dermatitis as well as pharmacological inhibition of eicosanoid biosynthesis is reviewed. 

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