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SATURDAYNovember 8SESSION 43:40 – 4:00 |
Brigette Dreno Acne is more an inflammatory disease of the pilo sebaceous follicle than an infectious disease. In recent years, research has led to a greater understanding of the pathogenesis of acne. The pilo sebaceous follicle is the target organ in acne, explaining the distribution of acne primarily on the face, chest, and back, areas with the greatest concentration of pilo sebaceous glands. The most notable pathophysiologic factors that influence the development of acne are: Sebaceous glands: In patients with acne, the overall size of the sebaceous gland increases and the number of lobules per gland increases. The sebaceous glands start to enlarge with androgenic stimulus at approximately 7 to 8 years of age (adrenarche), with a resultant increase in sebum excretion. Recent studies have demonstrated evidence that sebocytes have the cellular mechanisms needed to metabolize androgens, in particular 5-alpha-reductase (type 1) and 3_ and 17_ hyydroxysteroid déhydrogénase (6). In acne patients, excess sebum production is mainly due to an hyper-responsiveness of some sebaceous gland to androgens since not all sebaceous glands are affected (mainly face and trunk) and that more often a constant level of androgen is noted in the blood. New recent data have also shown that receptors to neuro mediators were present on sebaceous glands (substance P and alpha MSH). Substance P affects the individual size of the gland contributing to abnormalities in differentiation and proliferation as well as lipid synthesis (7). Thus the role of the stress in acne could be related to the liberation of neuro mediators as substance P which stimulates sebum production. Ductal hypercornification of pilosebaceous follicle: Abnormal desquamation occurs early in the formation of retentional acne lesions (figure 2) and is linked to keratinocyte hyperproliferation and abnormal differentiation (8). The mechanisms that control this process have not yet been fully elucidated; however, lipid composition, androgens, and local cytokines are all thought to have an important role. Indeed, recent data firstly show that irritation of infundibular (by example, changes in sebum composition or secretion), results in release of a cytokine IL-1a by these cells and initiation of comedogenesis. Moreover, it has also been demonstrated that keratinocytes have the cellular mechanisms needed to metabolize androgens as sebaceous follicle. Abnormalities of intra cellular (keratinocyte) metabolism of androgens could play a role in the hypercornification of pilosebaceous follicle. Inflammation of pilosebaceous follicle: Propionibacterium acnes is the main bacterial agent of acne. It is not thought to be infectious in acne but more probably to produce different inflammatory substances (lipase, chemotactic factor, …) which induce the development of inflammatory lesions (figure 4). There is a correlation between the reduction P acnes and the clinical improvement of acne. This reduction in P acnes is associated with a reduction in pro-inflammatory mediators. The intensity of host response to inflammatory stimuli most likely explains the variations in the intensity of inflammatory acne. Certain cytokines as TNF alpha, interferon gamma may be inflammatory triggers, and whether neuro inflammatory mediators play an additional role is currently under debate. Moreover, very recently it has been shown that immediate immunity (9) might be implicated in inflammatory reaction in acne through Toll Like Receptors (TLR 2, TLR 4) which are receptors expressed by keratinocytes and which may be activated directly by bacterial antigens as propionibacterium acnes inducing an immediate production of inflammatory cytokines by the activated keratinocytes. |