Acne Pathophysiology
Acne vulgaris is the result of multifactorial processes in and around the pilosebaceous unit. Currently, the major pathogenic factors are thought to be:
- PDF / 153,314 Bytes
- 10 Pages / 439.37 x 666.14 pts Page_size
- 63 Downloads / 252 Views
Acne Pathophysiology Shinjita Das and Rachel Reynolds
1.1
Introduction
Acne vulgaris is the result of multifactorial processes in and around the pilosebaceous unit. Currently, the major pathogenic factors are thought to be: 1. 2. 3. 4. 5.
Androgens [1–3] Sebum [4] Abnormal keratinization [5] Propionibacterium acnes (P. acnes) [6] Innate immune system-mediated inflammation [6, 7]
The traditional notion that these factors contribute independently to acne development has been replaced by a more nuanced understanding of their complex interplay. Though the multifactorial nature of acne pathogenesis makes effective treatment challenging, research has shed light on both the mechanisms of action of current treatments and discovered new targets for acne therapy.
S. Das, M.D. Department of Dermatology, Harvard Combined Dermatology Residency Program, Boston, MA, USA e-mail: [email protected] R. Reynolds, M.D. (*) Department of Dermatology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Brookline, MA 02215, USA e-mail: [email protected] J.A. Zeichner (ed.), Acneiform Eruptions in Dermatology: A Differential Diagnosis, DOI 10.1007/978-1-4614-8344-1_1, © Springer Science+Business Media New York 2014
3
4
1.2
S. Das and R. Reynolds
Overview of the Innate Immune System
The immune system consists of both innate (rapid response but no memory to pathogens) and adaptive (delayed, antigen-specific response forming memory) mechanisms against pathogens [8]. The skin is a first-line agent of the innate immune system. As an anatomic barrier, skin physically prevents invasion of external toxins and maintains an acidic stratum corneum (from free fatty acids generated by P. acnes) that limits bacterial colonization [9–11]. It can also generate soluble immune factors (antimicrobial peptides, complement factors, chemokines, and cytokines) and express pattern recognition receptors (PRRs) to mediate responses against pathogen-associated molecular patterns (PAMPs) via effector cells, such as monocytes/macrophages, natural killer (NK) cells, neutrophils, and dendritic cells (DCs) [12–15].
1.2.1
Toll-Like Receptors
Toll-like receptors (TLRs), a subtype of PRRs found on immune cells (such as neutrophils, monocytes/macrophages, and DCs), serve as potent initiators of innate immune responses. While nearly a dozen TLRs have been identified, TLR2 and TLR4 seem to play the greatest roles in acne pathogenesis (via P. acnes activation) [16, 17]. Stimulation of TLRs by microbial ligands activates various pathways that converge at the level of transcriptional regulation of inflammatory genes via nuclear factor κB (NF-κB). This results in release of inflammatory molecules (such as IL-1, IL-6, IL-8, IL-10, IL-12, and TNFα) and destruction of pathogens by effector cells like neutrophils and NK cells [18, 19].
1.2.2
Inflammation via Innate Immune System
Innate immunity-mediated inflammation is both a precipitating and propagating factor in acne pathogenesis. The key player appears to be IL-1α. There are multiple hypoth
Data Loading...
