New developments in our understanding of acne pathogenesis and treatment

Abstract

Interest in sebaceous gland physiology and its diseases is rapidly increasing. We provide a summarized update of the current knowledge of the pathobiology of acne vulgaris and new treatment concepts that have emerged in the last 3 years (2005)(2006)(2007)(2008). We have tried to answer questions arising from the exploration of sebaceous gland biology, hormonal factors, hyperkeratinization, role of bacteria, sebum, nutrition, cytokines and toll-like receptors (TLRs). Sebaceous glands play an important role as active participants in the innate immunity of the skin. They produce neuropeptides, excrete antimicrobial peptides and exhibit characteristics of stem cells. Androgens affect sebocytes and infundibular keratinocytes in a complex manner influencing cellular differentiation, proliferation, lipogenesis and comedogenesis. Retention hyperkeratosis in closed comedones and inflammatory papules is attributable to a disorder of terminal keratinocyte differentiation. Propionibacterium acnes, by acting on TLR-2, may stimulate the secretion of cytokines, such as interleukin (IL)-6 and IL-8 by follicular keratinocytes and IL-8 and -12 in macrophages, giving rise to inflammation. Certain P. acnes species may induce an immunological reaction by stimulating the production of sebocyte and keratinocyte antimicrobial peptides, which play an important role in the innate immunity of the follicle. Qualitative changes of sebum lipids induce alteration of keratinocyte differentiation and induce IL-1 secretion, contributing to the development of follicular hyperkeratosis. High glycemic load food and milk may induce increased tissue levels of 5a-dihydrotestosterone. These new aspects of acne pathogenesis lead to the considerations of possible customized therapeutic regimens. Current research is expected to lead to innovative treatments in the near future. Biology of sebaceous glandsThe sebaceous gland is a holocrine gland, and its secretion is formed by the complete disintegration of the glandular cells. Excreting sebum is the major function of sebaceous glands (1), and increased sebum excretion is a major concurrent event that parallels the development of acne lesions. With the development of human sebaceous gland experimental models for in vitro studies (2-5), considerable progress has been made in our understanding of many new

An update on the role of the sebaceous gland in the pathogenesis of acne

“…AA and calcium ionophore enhance the level of IL-6 and IL-8, but that of IL-1β and TNFα is not affected. 9,41 Psoriasin, a member of the S100 gene family, was shown to be highly expressed in the epidermis and the ductus seboglandularis of acne-involved skin in contrast to uninvolved control. 84 Psoriasin has been suggested to be involved in the pathogenesis of several inflammatory skin diseases, and its levels increase in response to inflammatory stress.…”

Studying the genetic predisposing factors in the pathogenesis of acne vulgaris

“…Androgens have long been known to play a key role in the development of acne [76,77], seborrhoea [75], hirsutism, and androgenic alopecia [78].…”

Retinoid plus antimicrobial combination treatments for acne

“…In addition to the pathogenic factors from the classical model, altered sebum lipid quality, regulation of steroidogenesis in the skin, interaction with neuropeptidases, androgen activity, nutrition, and the presence of any pro-and anti-inflammatory agents have also been implicated in acne development. 10 The sebaceous gland plays a more prominent role in acne development. Sebaceous glands express neuropeptide (NP) receptors such as corticotrophin-releasing hormone, Β-endorphin, melanocortins, NP Y, vasoactive intestinal polypeptide, and calcitonin gene-related peptide.…”