Ceramide Plays a Major Role in the Pathogenesis of Atopic Dermatitis.

Little is known about the pathophysiological linkages between altered ceramide profiles in the stratum corneum (SC) of patients with atopic dermatitis (AD) and their impaired skin barrier and water-holding functions. We studied that pathophysiological linkage by microanalysis of ceramides using NPLC-ESI Mass Spectrometry comparing before and after topical application of a designed synthetic pseudo-ceramide (pCer). Four weeks of treatment with pCer significantly reduced skin symptoms, accompanied by significant decreases in trans-epidermal water loss (TEWL) and increases in water content. In the SC ceramide profiles, Cer[NH/NP] increased and Cer[NS/AS] decreased with larger alkyl chain lengths in Cer[NS], distinctly representing a switch from an AD to a healthy skin phenotype. The levels of pCer that penetrated into the SC were significantly correlated with the SC water content but not with TEWL. The levels of Cer[NS] and the average carbon chain length of Cer[NS] were closely correlated with the pCer level in the SC. These findings indicate that the penetrated pCer contributes to shift the ceramide profile from an AD to a healthy skin phenotype. Taken together, the observed clinical efficacy of treatment with pCer provides a deep insight into the pathogenesis of AD as a ceramide-deficient disease.