Dynamic stratum corneum ceramide alterations reflect barrier dysfunction and clinical response to topical chlormethine treatment in early-stage mycosis fungoides.

Abstract

Early-stage mycosis fungoides (MF), a cutaneous T-cell lymphoma, presents as patches and/or plaques with an impaired skin barrier. The stratum corneum (SC) lipid matrix is important for skin barrier function. Alterations in the SC ceramide profile have been linked to a reduced barrier function in benign inflammatory skin diseases and might also be an underlying factor in the impaired barrier function in MF. Therefore, we characterized barrier function and SC ceramide profiles in lesional and non-lesional skin of 21 patients with early-stage MF and 10 healthy controls, and assessed how these barrier and ceramide characteristics evolve during chlormethine gel treatment in patients. Barrier function was measured by transepidermal water loss. SC ceramides were collected by tape stripping and analyzed by liquid chromatography-mass spectrometry. Local inflammatory markers were measured in suction blister fluid. At baseline, MF lesions showed impaired barrier function accompanied by distinct changes in the SC ceramide profile, including altered ceramide subclass composition and reduced ceramide chain length. These abnormalities occurred in the context of a predominantly type 1-skewed inflammatory milieu. Importantly, both barrier dysfunction and ceramide alterations were dynamic and improved in patients with a clinical response to chlormethine gel treatment, alongside reduced lesion severity and local inflammation. Longitudinal associations of ceramide characteristics with barrier function, clinical lesion severity, and inflammatory markers support SC ceramide alterations as dynamic correlates of MF disease activity. Together, these findings suggest that SC ceramide alterations may reflect a downstream consequence of inflammation that is shared across inflammatory dermatoses.

Keywords: Ceramides; Chlormethine; Cutaneous T-cell lymphoma; Mycosis fungoides; Skin barrier; Stratum corneum; Transepidermal water loss.