Aetiology and pathogenesis of psoriasis.
The hereditary transmission of psoriasis is suggested by epidemiological data and familial association, but remains incompletely defined, not appearing to follow simple autosomal dominant or recessive patterns. The confusion may be due to a multifactorial inheritance, or to inheritance of only a 'predisposition' to disease which requires an environmental stimuli for expression. Recent advances in genetic mapping indicate genetic heterogeneity, and suggest that definition of psoriasis at the level of the gene may soon be possible. Two of the three major pathogenic features of psoriasis--abnormal keratinocyte differentiation and hyperproliferation of keratinocytes--are secondary to altered growth and maturation kinetics related to the normal wound healing process. The third major pathogenic feature--infiltration of inflammatory components into the skin--can be explained by keratinocyte release of a wide variety of cytokines, immune and inflammatory modulators. Three theories have been proposed for the relationship between epidermal keratinocyte and immunocyte activation. The first theory proposes direct activation of epidermal keratinocytes by physical, chemical, or ultraviolet injury, increasing the synthesis and release of cytokines, which trigger T-lymphocyte activation in an antigen-independent fashion. The other two theories propose persistent T-lymphocyte stimulation as a result of either antigen/superantigen presentation by antigen-presenting cells, or as a result of autoreactivity. One or more of these mechanisms may be operative in different patients, at different times, or in response to different environmental stimuli. Also, the genetic heterogeneity of psoriasis suggests that different mechanisms could be linked to different genetic loci. Advances in understanding the aetiology and pathogenesis of psoriasis suggest the possibility of innovative, targeted therapies.
Ortonne
J P
JP
Service de Dermatologie, Hôpital Pasteur, Nice, France.
D000293:Adolescent; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D012867:Skin / Q000276:immunology / Q000473:pathology
D016207:Cytokines