Current concepts of the pathogenesis of acne: implications for drug treatment.
The pathogenesis of acne is complex, with strong evidence supporting the involvement of sebaceous hyperplasia, follicular hyperkeratinisation, bacterial hypercolonisation, as well as immune reactions and inflammation. High sebum concentrations and follicular hyperkeratinisation lead to a change of the follicular milieu with consecutive proliferation of bacteria, chiefly Propionibacterium acnes. This leads to further increased production of the pro-inflammatory cytokines interleukin-1alpha and tumour necrosis factor alpha by T cells and keratinocytes, leading to proliferation of both cell types. Follicular keratinocytes fail to differentiate by apoptosis and produce hypergranulosis similar to the impermeable skin outer layer, resulting in the formation of microcomedones. Further inflammatory responses lead to the development of increasing degrees of severity in inflammatory forms of acne. Retinoids aid the differentiation and reduce the hyperproliferation of keratinocytes, and can inhibit the migration of leucocytes. Combination therapy using retinoids plus benzoyl peroxide or antibacterials can treat existing acne lesions faster than the individual agents alone and can also prevent the development of new lesions. The new retinoids (e.g. adapalene) have not only the typical potent comedolytic activity but also anti-inflammatory effects. When added to antibacterial therapy, topical retinoids demonstrate faster and significantly greater reduction of inflammatory acne lesions and comedones than antibacterials alone.
Gollnick
Harald
H
University Clinic for Dermatology and Venereology, Otto-von-Guericke-University, Magdeburg, Germany. harald.gollnick@medizin.uni-magdeburg.de
D000152:Acne Vulgaris / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D000284:Administration, Oral; D000287:Administration, Topical; D000728:Androgens / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001585:Benzoyl Peroxide / Q000008:administration & dosage / Q000627:therapeutic use*; D003872:Dermatitis / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D004359:Drug Therapy, Combination; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy; D006801:Humans; D019787:Linoleic Acid / Q000172:deficiency; D011425:Propionibacterium acnes / Q000187:drug effects / Q000472:pathogenicity; D012176:Retinoids / Q000008:administration & dosage / Q000627:therapeutic use*; D012627:Sebaceous Glands / Q000378:metabolism / Q000473:pathology; D012629:Sebum / Q000378:metabolism
D000728:Androgens; D000900:Anti-Bacterial Agents; D012176:Retinoids; D019787:Linoleic Acid; D001585:Benzoyl Peroxide