TOPICAL RETINOID

All acne lesions begin as non-inflammatory lesions, either open or closed codemos. Topical retinoids are a mainstay of acne treatment due to their ability to hamper the primary acne lesion, the microcodemo. Additionally, retinoids have fairly potent anti-inflammatory effects. Retinoids are structural and functional analogs of vitamin A that exist in both topical and systemic forms. They act by binding to two nuclear receptor families within keratinocytes: the retinoic acid receptors (RAR), and the retinoid X receptors (RXR). Each of the receptor families contains three receptor isotypes: alpha, beta, and gamma. In the human epidermis RXR receptors are by and large the alpha isotype and RAR are generally the gamma isotype (35). Both families of receptors act as ligand-activated transcription factors. The RAR receptors function as a heterodimer by binding to RXR. The RXR receptors may act as homodimers or may bind to other nuclear receptors such as: vitamin D3, thyroid hormone, and peroxisome proliferator-activated receptors. The retinoid receptors bind to specific regulatory DNA sequences called retinoid hormone response elements (HREs) where transcription is activated. The retinoid HREs activate the transcription of genes that normalize follicular keratinization, and decrease cohesiveness of keratinocytes. This prevents the formation of microcodemos. The retinoid-receptor complex also antagonizes genes that do not contain retinoid HRE. AP-1 and NF-IL6 are key transcription factors in inflammatory responses. The retinoids suppress these transcription factors by competing for the co-activator proteins needed to activate AP-1 and NF-IL6 (36). These combined anti-comedogenic and anti-inflammatory properties make retinoids beneficial for patients with either non-inflammatory or inflammatory acne.