Psoriasis Pathophysiology

Psoriasis is a common skin disorder affecting millions of people. It affects 2 to 3% of the Caucasian population, usually in individuals between 15 and 30 years old. (Liu, Krueger, & Bowcock, 2007). There are several different forms of the disease. The most common type is chronic plague psoriasis. It presents itself as silvery-scaled patches usually on the knees, elbows, lower back, and scalp. Outbreaks can be triggered by infection, such as strep throat, drug-use, psychological stress, hormonal changes and skin injury.

The exact cause is still unknown; however, research has provided some interesting insights into the pathophysiology of psoriasis. The most evident pathophysiological change leading to psoriasis is hyperproliferation and abnormal differentiation of keratinocytes. Keratinocytes are cells in the epidermis that produce keratin, a “protein that helps protect the skin and underlying tissues from heat, microbes, and chemicals. ” (Tortora & Derrickson, 2006). Patients with psoriasis shed and replace these cells every two to six days. This is quite a bit faster than normal which is 21 to 28 days so a buildup of dead and living cells is created.

(Reid, 2007). This is what causes the flaky, red patches seen in psoriasis patients. “The most common explanation for keratinocyte hyperproliferation is that it is mediated by pro-inflammatory cytokines (regulatory molecules) produced by T cells and dendritic cells that accumulate in diseased skin. ” (Jullien, 2006). Psoriasis can be classified as an auto-immune disease. An autoimmune disease is “produced by failure of the immune system to recognize and tolerate self-antigens. ” (Fox, 2008). Psoriasis is considered a T-cell mediated, Type-1 autoimmune disease.

T cells are activated by mistake and infiltrate the skin causing the hyperproliferation and differentiation of keratinocytes. Most of the T cells that are activated are memory T cells. Studies have shown that the more of these memory T cells in the epidermis, the more severe psoriasis is. Although not yet verified, natural killer T cells also seem to play a role in the development of psoriasis. T cells are not the only increased leukocytes in psoriasis patients. Neutrophils, mast cells, dendritic cells, and natural killer cells are also increased. Dendritic cells are the other important cell of study for psoriasis.

There are three subsets of cutaneous dendritic cells which include: immature dendritic cells (iDC), mature myeloid dendritic cells (mDC), and plasmacytoid dendritic cells (pDC). All three are increased in patients with psoriasis. These cells “overall could equal or exceed the number of T cells in lesions. ” (Jullien, 2006). Langerhans cells are one type of immature dendritic cell. There job is to “engulf protein antigens by pinocytosis, partially digest these proteins into shorter polypeptides, and move these polypeptides to the surface. ” (Fox, 2008).

Once they are at the surface, they are associated with histocompatibility antigen, which in turn activates the T lymphocytes. As mentioned before, this unnecessary activation of T cells will lead to the hyperproliferation and differentiation of keratinocytes. In order for these cells to be activated in a way that causes the inflammatory process associated with psoriasis, they must migrate to the skin. “Recruitment of leukocytes out of the blood stream into the different skin compartments is an active and selective process. ” (Jullien, 2006). Memory T cells “express the skin homing receptor CLA (cutaneous lymphocyte-associated antigen).

” This is an adhesion molecule that allows T cells to bind to the receptors. Memory T cells also have unique chemokine receptors that allow them to migrate to the skin. The genetics of psoriasis, like most scientific data, is a work in progress. Complex gene expression changes in psoriasis are well known, however, the relationship between genetic factors and the cellular components of immunity have yet to be understood. Studies have shown that genetics do attribute to the “predisposition of the disease and it is estimated that the heritability for psoriasis is between 60 and 90%.

” (Liu, Krueger, & Bowcock, 2007). Children have about a 15% chance of developing it if one of their parents has psoriasis and a 75% chance if both parents have it. New hypothesis and theories are being developed everyday in regards to psoriasis. The pathophysiology of psoriasis will be continually updated. At this point in time, the major pathophysiological changes are keratinocyte hyperproliferation and differentiation due to an increased number of leukocytes, mainly T cells and dendritic cells. It will be interesting to see what new research brings about in the coming years.

Words: 813 References Fox, S. (2008). Human Physiology. New York: McGraw Hill. Jullien, D. (2006). Psoriasis Pathophysiology. Journal of the European Academy of Dermatology & Venereology , 10-23. Liu, Y. , Krueger, J. G. , & Bowcock, A. M. (2007). Psoriasis: genetic associations and immune system changes. Genes & Immunity , 1-12. Reid, F. (2007). Psoriasis: treatment and management in primary care. Primary Health Care , 25-29. Tortora, G. , & Derrickson, B. (2006). Principles of Anatomy and Physiology. New Jersey: John Wiley & Sons Inc.