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Background For more than 50 years, proteolytic enzymes have been extensively used in laboratory settings for the purposes of in vitro epidermal separation and keratinocyte isolation. However, the topical, in vivo pharmacologic properties of these enzymes are virtually unknown. Previous therapeutic applications for topically applied proteases have been limited to wound débridement.

Objective To characterize the clinical and histologic effects of topically applied proteases as a method of therapeutic epidermal ablation.

Materials and methods SKH-1 hairless mouse and human skin samples were exposed both in vitro and in vivo to varying concentrations of the proteases subtilisin, trypsin, and dispase for different exposure durations. The effects of protease exposure were then assessed by both clinical and histologic examination.

Results Exposure of both human and mouse skin samples to topical protease solutions resulted in reproducible, differential patterns of epidermal ablation: subcorneal, intraepidermal, and subepidermal. In a limited study, topical application of trypsin solution resulted in the scar-free ablation of lesions of seborrheic keratosis located on the lower extremity.

Conclusion Topically applied proteases represent an alternative method of epidermal ablation with several potential advantages over existing techniques. Further studies are needed to delineate ideal enzyme formulations, vehicles, and applications.

HOWARD FEIN, MD, HAS A PENDING US PATENT APPLICATION CONCERNING THE DERMATOLOGIC APPLICATIONS OF TOPICAL PROTEASE THERAPY.