Possible involvement of keratinocyte-derived microvesicle particles in human photosensitivity disorders

Background: Previous murine studies have implicated acid sphingomyelinase-(aSMase) generated subcellular microvesicle particles (MVP) in photosensitivity. Objective: The current double-blinded placebo-controlled studies examined if a single localized ultraviolet B radiation (UVB) treatment generated more MVP in human subjects with self-identified photosensitivity versus normal controls. A topical 4% formulation of the aSMase inhibitor imipramine applied immediately after UVB blocked the MVP release and erythema responses. Erythema responses at 24 and 72 h in response to multiple UVB fluences and minimal erythema doses (MED) at 24 h and effects of imipramine were also tested. Results: Small cohorts of 10 adult self-identified photosensitive subjects and 10 controls were enrolled in these pilot studies which revealed increased levels of skin MVP in UVB-treated photosensitive subjects over controls which correlated with MED values. Moreover, post-UVB application of imipramine blunted UVB-induced MVP responses as well as tended to diminish erythema levels at 4 h but not at 24- or 72 h in photosensitive patients. Conclusion: Though limited by low numbers of self-identified subjects, these pilot studies provide some support for the hypothesis that MVP could be involved in multiple types of human photosensitivity responses and suggest aSMase inhibition as a potential therapeutic strategy.