PSORIASIS - IMMUNE INDICATORS AND TREATMENT

Psoriasis is a common, economically important, skin disorder that caus es considerable patient morbidity. Histologically, it is characterised by hyperproliferation of keratinocytes and inflammatory cell infiltra tion. Immunogenetic studies have subdivided psoriasis into sporadic an d familial subtypes, with distinct genetic linkages. The skin contains all the elements of an intrinsic immune system, including T cells, an tigen-presenting cells and endothelial cells. In addition, keratinocyt es secrete immunoregulatory cytokines. Immune dysregulation is now tho ught to be central to the pathogenesis of psoriasis. A variety of alte rations in the skin immune system have been reported. These include: ( i) upregulation of adhesion molecules on vascular endothelium; (ii) in flux of T cells, predominantly CD4+, some of which appear to be autore active; (iii) increased number and function of antigen-presenting cell s; and (iv) increased production of pro-inflammatory or growth-stimula ting cytokines such as interleukin-6, interleukin-8 and transforming g rowth factor-alpha. The standard treatments for psoriasis include topi cal corticosteroids, dithranol, calcipotriol, ultraviolet B photothera py, psoralen plus ultraviolet A (PUVA) therapy, retinoids, methotrexat e and hydroxycarbamide (hydroxyurea). These may be effective at least in part because they inhibit keratinisation or keratinocyte proliferat ion. However, all, and in particular steroids, ultraviolet B photother apy and PUVA therapy, may have additional immunosuppressive effects th at contribute to their antipsoriatic action. The clinical efficacy of cyclosporin, and of anti-CD4 monoclonal antibodies, provides the best evidence that psoriasis is an immunologically-mediated disorder.