Acne's emerging 'fifth' factor

The scientific basis for its action has always been stated to be its binding properties and selective affinities for retinoic acid receptors on the nuclear membrane of cells, thereby modulating gene transactivation and gene expression in human keratinocytes. Nevertheless, the common explanation for its efficacy is that retinoids are unplugging agents, thereby addressing one of the four factors producing acne, namely the microcomedone.

However, the cells composing the microcomedone are non-viable cells that have been programmed for keratinization and are without functional nuclear membranes. These agents may act solely on the basal cells of the epidermis, but this needs to be better substantiated. Of note, other acids have been shown to be comedolytic without necessarily affecting nuclear membrane receptors in basal cells.

The second point of retinoid action is on the P. acnes biofilm.

In short, P. acnes reside within the pilosebaceous unit in a biofilm, living in a community of bacteria that encase themselves within an extracellular polysaccharide lining, which the organisms secrete after adherence to the surface. This gylcocalyx polymer acts as a protective exoskeleton and serves as a physical barrier, limiting effective antimicrobial concentrations within the biofilm microenvironment. The gylcocalyx polymer secreted by P. acnes as a biofilm may explain the immunogenicity of the organism as well as the clinical course of the disease. Retinoids may act by altering the P. acnes biofilm in favor of clinical improvement.

The pathogenesis of acne is stated to be multifactorial with four main mechanisms: abnormal proliferation and differentiation of follicular keratinocytes (microcomedone theory), increased production of sebum, colonization of the pilosebaceous unit by P. acnes, and initiation of inflammatory reactions by bacterial antigens and pro-inflammatory factors. However the microbiological principle of biofilms as applied to acne may be the most significant mechanism in disease pathogenesis and in developing new pathways of assessment, exploration and treatment. With future publications elucidating that P. acnes is endowed with the ability to produce the enzymes required of biofilm development, this 'fifth' mechanism of acne pathogenesis may well become the predominant focus of attention in acne therapeutics.

Craig G. Burkhart, M.P.H., M.D. Clinical Professor, Medical University of Ohio at Toledo Clinical Assistant Professor, Ohio University College of Osteopathic Medicine.