Novel topically active antimicrobial/anti-inflammatory compounds for acne

INTRODUCTION Acne vulgaris (acne) is the most common skin disease encountered, affecting over 80% of the population at some point in their lifetime. Acne not only creates relatively short-term physical and psychological effects for the sufferer, but if recalcitrant to normal treatment or left unchecked, it can also cause more permanent physical effects such as facial scarring that may produce profound psychological consequences. Acne is caused by abnormal follicular hyperkeratosis (plugging) and abnormal sebum production within pilosebaceous units (composed of a hair follicle, sebaceous glands, and a follicular canal) in the skin. Normally, sebum is secreted from the follicular canal to aid in the removal of desquamated follicular epithelial cells via the infundibulum at the top of the follicle. In acne, the dilated orifice of affected follicles can be blocked with excess sebum and/or keratin from desquamated cells, promoting proliferation of bacteria that normally reside in the pilosebaceous unit. This combination of events can result in immune reactions, inflammation, and comedone formation in the pilosebaceous unit lasting for days or weeks. Excess sebum is caused by an increase in the level of androgens, and excess keratin results from an increase in ductal keratinocytes (e.g., from hyperplasia that may also result from high androgen levels), an inadequate separation of ductal corneocytes, or a combination of both (1,2).