Current Drug Targets - Inflammation & Allergy - Volume 3, Issue 2, 2004

Psoriasis is a chronic inflammatory skin disease affecting 1-3% of the general population worldwide. Although in many patients the disease is mild and can be easily controlled with topical treatments, in about one third of cases the disease is severe with a high impact on patients' quality of life. Complex genetic predisposition and a variety of trigger factors are both important elements in disease expression and are presented in Read More

The prevalence of psoriasis is relatively high in the general population, ranging between 0.6% and 4.8%, mainly as a result of chronicity and the absence of a cure. Although genetic-environmental interaction has been proposed as a model for the causation of psoriasis, the evidence for environmental factors is rather scarce. Risk factors, which have been documented in epidemiological studies include smoking, alcohol c Read More

Psoriasis [OMIM*177900] is a common, chronic and papulosquamous inflammatory skin disease affecting approximately 2% of Caucasian. However, this disorder is rare among Japanese, Eskimos, West Africans and North American blacks and very uncommon in North American and South American natives. The causes for these variations are likely to be both genetic and environmental. Population-based studies and t Read More

Psoriasis is characterized by sustained T cell activation by antigen-presenting cells (APCs) in the lesions, and by a deviation of T cell differentiation to type 1 helper T and type 1 cytotoxic T cells, although no specific antigens have yet been determined. These characteristics are at least promoted by decreased IL-10 expression and the increased IL-12 expression observed in both the skin and stimulated peripheral blood mononucle Read More

Psoriasis is a complex disease with a spectrum of clinical manifestations. Psoriasis may express as a few coin-sized erythemato-squamous plaques up to widespread disease covering the entire body surface (erythrodermic psoriasis). Psoriasis may present as a few stable plaques or unstable disease, rapidly relapsing after treatment. Some patients may respond excellently to topical treatments whereas other patients may be Read More

Psoriasis is now accepted as a T-cell-mediated disease and that targeting of T cell function and / or trafficking is a logical approach to therapy. As a consequence of recombinant DNA technologies biologic therapies are synthesisable in sufficient quantities for clinical use. The original proof of concept for T-celltargeted therapies in psoriasis came with the demonstration that anti-CD4 monoclonal antibodies were effective. Progr Read More

As leukocytes play a primary role in the immunopathogenesis of psoriasis, it is a reasonable assumption that preventing those cells from localizing to the sites of cutaneous inflammation can stop the disease process. Selectins, a family of three singlechain transmembrane adhesion molecules, which bind to carbohydrate moieties displayed on other cells, are pivotally involved in the initial steps of leukocyte recruitment, i.e. tethe Read More

Chemokines are members of a superfamily of small, cytokine-like, chemotactic proteins that have recently been shown to critically regulate leukocyte trafficking. Accumulating evidence indicates that the chronically relapsing inflammatory skin disease psoriasis represents a T cell-mediated disease. Thus, the understanding of the underlying mechanisms of memory T cell homing to the skin may provide promising t Read More

Tumor necrosis factor-α (TNF-α) plays a fundamental role in the initiation and persistence of skin inflammation in psoriasis. The best evidence of the essential activity of this cytokine in the pathogenesis of psoriasis came from the observation that selective TNF-α blockers are dramatically effective in the therapy of this disease. The TNF-α inhibitors, infliximab and etanercept, have been employed with success in moderate to severe Read More

Interleukin (IL)-10 is a pluripotent cytokine with effects on numerous cell populations, in particular circulating and resident immune cells as well as epithelial cells. With its potent immunoregulatory capacities its main biological function seems to be the limitation and termination of inflammatory responses. Thus its low level expression found in psoriasis may have pathophysiological relevance for this immune disease. Remarkably, Read More

The experience with biologicals in currently available animal models suggest that inflammatory autoimmune disease depend on IFN-γ-producing T helper (Th) cells. Deletion of T cells improves most of these autoimmune diseases but bears the risks of general immunosuppression. Alternatively, selective deviation of the inflammatory, disease-inducing Th cells into an anti-inflammatory Th cell phenotype may be a promising strate Read More

Psoriasis is a common inflammatory and hyperproleferative skin disease characterized by infiltrated plaques of the skin and may involve nails, scalp and intertreginous areas. Recent years of research has shown that psoriasis can be treated topically with analogs of vitamin-D3. Impaired differentiation and increased proliferation of epidermal keratinocytes are key features in psoriatic lesions together with a local activation Read More

While psoriasis is upon the age of biological treatments, additional researches have led to other new therapies for psoriasis, including targets aimed at nuclear receptors. PPARs are members of the nuclearhormone- receptor superfamily, including retinoid receptors and vitamin D receptors. Recent works have highlighted the role of PPARs, which transduce a wide variety of signals into a set of cellular responses at the level of Read More

Psoriasis is recognised as a multifactorial disease with inflammatory, proliferative, angiogenic and genetic components contributing to the pathology. The disease, which may vary in intensity, remains clinically unmet although there have been several recent advances that have had a substantial impact on suffering. Histone deacetylase inhibitors represent a new class of therapeutic agent, initially developed for oncolog Read More