Atopic Dermatitis Knowledge Centre
Pathophysiology
Skin barrier function
The skin of atopic dermatitis patients displays an impaired barrier function, characterised by increased transepidermal water loss (TEWL). Both lesional and non-lesional skin of atopic dermatitis sufferers exhibits a reduced capacity for water retention.34 Disrupted skin barrier functions in atopic dermatitis patients involve several factors including: changes in lipid composition of the stratum corneum, the outermost viable layer of the epidermis; alterations in keratinocyte proliferation and differentiation profiles; and increased microbial colonisation of the skin.35
Increased basal TEWL results in the dry, scaly skin characteristic of atopic dermatitis, and occurs in response to decreased levels of specific ceramides (lipid molecules composed of sphingosine and a fatty acid, in the stratum corneum).36 As illustrated in the figure below, reductions in these lipid molecules affect the organisational structure of the outer epidermal layer, permitting more water to escape and allowing increased subcutaneous access to allergens, irritants and microbes. Reductions in ceramide 1 in both lesional and non-lesional skin are associated with increased TEWL and an increased susceptibility to irritants. Decreased levels of ceramide 3 in the stratum corneum have no effect on water retention, but are strongly linked to an increased susceptibility to allergens and irritants.37, 38
Skin Barrier Function In Normal And Atopic Skin
Keratinocyte proliferation and differentiation are also important factors in atopic dermatitis-associated skin barrier dysfunction. In lesional and non-lesional atopic dermatitis skin, rates of keratinocyte proliferation, compared to normal, healthy skin are increased.39 Accelerated rates of cellular proliferation are often associated with disturbances in differentiation and this appears to be a crucial factor in the pathogenesis of atopic dermatitis. In patients with atopic dermatitis, corneocytes – the outermost layer of epidermal cells formed in the final stage of keratinocyte differentiation – are significantly smaller than those observed in skin from healthy individuals. This reduction in cell size affects the organisational structure of the stratum corneum (as demonstrated in the figure above), even in clinically asymptomatic skin, permitting increased TEWL and exacerbating the risk of antigen penetration.39
References:
34. Choi SJ, Song MG, Sung WT, et al. Comparison of transepidermal water loss, capacitance and pH values in the skin between intrinsic and extrinsic atopic dermatitis patients. J Korean Med Sci 2003; 18: 93-6.
35. Lee SH, Jeong SK, Ahn SK. An update of the defensive barrier function of skin. Yonsei Med J 2006; 47: 293-306.
36. Imokawa G, Abe A, Jin K, et al. Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin? J Invest Dermatol 1991; 96: 523-6.
37. Jensen JM, Folster-Holst R, Baranowsky A, et al. Impaired sphingomyelinase activity and epidermal differentiation in atopic dermatitis. J Invest Dermatol 2004; 122: 1423-31.
38. Di Nardo A, Wertz P, Giannetti A, et al. Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Derm Venereol 1998; 78: 27-30.
39. Proksch E, Folster-Holst R, Jensen JM. Skin barrier function, epidermal proliferation and differentiation in eczema. J Dermatol Sci 2006; 43: 159-69.
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