Biological therapy of psoriasis.

The treatment of psoriasis has undergone a revolution with the advent of biologic therapies, including infliximab, etanercept, adalimumab, efalizumab, and alefacept. These medications are designed to target specific components of the immune system and are a major technological advancement over traditional immunosuppressive medications. These usually being well tolerated are being found useful in a growing number of immune-mediated diseases, psoriasis being just one example. The newest biologic, ustekinumab, is directed against the p40 subunit of the IL-12 and IL-23 cytokines. It has provided a new avenue of therapy for an array of T-cell-mediated diseases. Biologics are generally safe; however, there has been concern over the risk of lymphoma with use of these agents. All anti-TNF-alpha agents have been associated with a variety of serious and "routine" opportunistic infections.

Light, including ultraviolet.

Ultraviolet (UV) light is intricately linked to the functional status of the cutaneous immune system. In susceptible individuals, UV radiation can ignite pathogenic inflammatory pathways leading to allergy or autoimmunity. In others, this same UV radiation can be used as a phototherapy to suppress pathogenic cutaneous immune responses. These vastly different properties are a direct result of UV light's ability to ionize molecules in the skin and thereby chemically alter them. Sometimes these UV-induced chemical reactions are essential, the formation of pre-vitamin D(3) from 7-dehydrocholesterol, for example. In other instances they can be potentially detrimental. UV radiation can ionize a cell's DNA causing adjacent pyrimidine bases to chemically bond to each other. To prevent malignant transformation, a cell may respond to this UV-induced DNA damage by undergoing apoptosis. Although this pathway prevents skin cancer it also has the potential of inducing or exacerbating autoreactive immune responses by exposing the cell's nuclear antigens. Ultraviolet-induced chemical reactions can activate the immune system by a variety of other mechanisms as well. In response to UV irradiation keratinocytes secrete cytokines and chemokines, which activate and recruit leukocytes to the skin. In some individuals UV-induced chemical reactions can synthesize novel antigens resulting in a photoallergy. Alternatively, photosensitizing molecules can damage cells by initiating sunburn-like phototoxic reactions. Herein we review all types of UV-induced skin reactions, especially those involving the immune system.