Pathogenesis of Psoriasis
Psoriasis is an immune-mediated inflammatory disease characterized by keratinocyte hyperproliferation.11287
Psoriasis is a genetic disease, however patterns of hereditary transmission are complex and not completely understood. At least 8 susceptibility loci (designated PSORS I-VIII) have been identified to date through genetic mapping studies. Among these, HLA-Cw6, termed PSORS1, is a major susceptibility allele, yielding strong genetic linkage in early-onset psoriasis. In addition, genome wide association studies have identified polymorphisms in a number of genes, including components of IL12/23 pathways, that confer significant risk for psoriasis.12224 In addition, environmental factors such as skin trauma (known as Köbner’s phenomenon), infection, certain drugs, and stress may contribute to development of psoriasis.11287, 11923
Figure 3201 – Development of Psoriatic Skin Lesions
Figure1, page 966, Int J Biochem Cell Biol. 2009;41(5):963-968 is used with permission of Elsevier Inc. All rights reserved.
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“Various stimuli (such as physical trauma, infections, etc.) can all trigger an initial episode of psoriasis in those individuals who already have a genetic predisposition. After the initial trigger, one of the earliest events driving the inflammatory eruption are the secretion of IFN-α from plasmacytoid dendritic cells (pDCs) and the production of TNF-α by cells of the innate and adaptive immune system. Large amounts of IFN-α released by pDCs induce activation of the local immune effector cells enabling them to secrete cytokines that further promote the inflammatory cascade. TNF-α is a highly active cytokine of the inflammatory infiltrate and is mainly released by activated macrophages (MΦ), dermal DCs and in a lesser extent by keratinocytes andT cells. The high levels of TNF-α lead to the maturation of DCs into potent antigen presenting cells (APCs), and secondly, in conjunction with other cytokines, TNF-α up-regulates the expression of endothelial E-selectin and ICAM-1 attracting further CLA+T cells into the skin. In addition, the panel of cytokines released by T lymphocytes also contributes to the stimulation of epidermal keratinocytes and is at least partially responsible for typical changes seen in psoriasis. They induce the expression of ICAM-1, CD40 and MHC-II, the release of various cytokines, and trigger keratinocyte hyperproliferation leading to epidermal hyperplasia (acanthosis). Finally, α1β1 integrin is expressed only on epidermal but not dermalT cells defining key effectors in psoriasis as intraepidermal but not totalT cells correlate with onset of the disease.”11923
Resolution of psoriasis is associated with decreased
lesional infiltration of
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References:| 11287. | Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol . 2008;58(5):826-850. |
| 11923. | Tonel G, Conrad C. Interplay between keratinocytes and immune cells--recent insights into psoriasis pathogenesis. Int J Biochem Cell Biol . 2009;41(5):963-968. |
| 12224. | Nair RP, et al. Genomewide Scan Reveals Association of Psoriasis with IL-23 and NF-κB Pathways. Nat Genet. 2009; 41(2): 199–204. |
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