ceramide-3 and Dermatitis--Atopic

Disturbances of skin barrier function occur in several skin diseases, e.g., atopic dermatitis (AD), irritant/allergic contact dermatitis (ICD, ACD). Skin barrier damage triggers the production of cytokines that stimulate lipogenesis which may also cause inflammatory processes. The aim of this study was to evaluate the efficacy of a topical skin lipid mixture in the treatment of ICD, ACD and AD. 580 consecutive patients suffering from ICD, ACD or AD were treated with a skin lipid mixture containing ceramide-3 and patented nanoparticles. Patients received the lipid mixture alone or in combination with topical corticosteroids until clearance or for 8 weeks. Both treatment groups statistically improved all parameters considered at week 4 and 8 as compared to baseline. Between the 2 treatment groups, there was a statistically significant difference in favour of combined therapy for (ICD, ACD, AD, respectively): erythema, pruritus and overall disease severity; erythema and pruritus; erythema, pruritus, fissuring and overall disease severity. No statistically significant difference was found for (ICD, ACD, AD, respectively): dryness, scaling and fissuring; scaling, fissuring and overall disease severity; dryness and scaling. Between the 2 ACD treatment groups, there was a statistically significant difference in favour of the skin lipid mixture for dryness. In conclusion, the study shows that balanced lipid mixtures are effective in improving barrier properties and the clinical condition of the skin in contact dermatitis.

Topics: Administration, Topical; Adolescent; Adult; Anti-Inflammatory Agents; Cholesterol; Data Interpretation, Statistical; Dermatitis; Dermatitis, Allergic Contact; Dermatitis, Atopic; Dermatitis, Irritant; Drug Therapy, Combination; Female; Glucocorticoids; Glycosphingolipids; Humans; Lipids; Male; Middle Aged; Oleic Acid; Palmitic Acid; Severity of Illness Index; Skin; Treatment Outcome

Atopic dermatitis is a common skin disease of unknown etiology with an impaired permeability barrier function. To learn more about the molecular pathology in lesional skin, we analyzed levels of free extractable as well as protein-bound barrier lipids in the epidermis of atopic dermatitis subjects. The amount of protein-bound omega-hydroxyceramides in healthy epidermis comprised 46-53 wt% of total protein-bound lipids, whereas this percentage was decreased to 23-28 wt% in nonlesional areas and even down to 10-25 wt% in affected atopic skin areas of the subjects. Furthermore, the partial amount of free extractable very long chain fatty acids with more than 24 carbon atoms was reduced in affected regions down to 25 wt% and in nonlesional regions of the atopic dermatitis subjects down to 40 wt% compared to healthy controls. This "hydrocarbon chain length deficiency" regarding the barrier lipids in atopic skin was supported by metabolic labeling studies with [14C]-serine in cultured epidermis. The biosynthesis of free glucosylceramides and free ceramides was remarkably decreased in affected skin areas of the atopic subjects compared to healthy control subjects. Especially affected were the de novo syntheses of ceramide 4 (i.e., ceramide EOH, consisting of a very long chain N-acyl omega-hydroxy fatty acid esterified with linoleic acid and 6-hydroxysphingosine as sphingoid base) and ceramide 3 (ceramide NP, consisting of a nonhydroxy N-acyl fatty acid and phytosphingosine). In conclusion, this study revealed that the lesional epidermis in atopic dermatitis has considerable deficiencies within main barrier lipid components, which may contribute to the severely damaged permeability barrier.

Topics: Adolescent; Adult; Biopsy; Dermatitis, Atopic; Epidermis; Fatty Acids, Nonesterified; Female; Glycosphingolipids; Humans; Hydroxylation; Male; Middle Aged; Proteins