MOLECULAR-BIOLOGY OF PSORIASIS AND ITS FUTURE MANAGEMENT

Psoriasis is a chronic inflammatory multifactorial disease and the pre cise molecular defects causing psoriasis remain unclear; but a genetic predisposition and environmental factors are involved in the pathogen esis, A strong genetic component is found in certain individuals and t he inheritance of psoriasis can be classified as autosomal dominant wi th variable penetrance, Clinically, psoriasis represents a collection of similar disorders with a variable phenotype, making investigation a t the molecular level extremely complex, Lesions are characterized by hyperproliferation and abnormal epidermal differentiation, together wi th a strong inflammatory and immunological component, However, studies over the last 20 years have failed to find molecular alterations that are either specific to the psoriatic lesion or characteristic of unin volved skin, Trauma, stress and chemicals are all known to precipitate psoriasis in susceptible individuals, but the molecular mechanisms ar e not understood, The accumulation of inflammatory cells in the epider mis and altered dermal vessels are major characteristics, and these ch anges are driven by release of cytokines and growth factors, Many inve stigations have shown that the process of epidermal differentiation in the lesion is aberrant, Increased transit time of cells through the e pidermis combined with a shift to the 'hyperproliferative state' preve nts the keratinocyte from completing the preprogrammed molecular event s necessary for normal terminal differentiation, Calcium and its bindi ng proteins are important in terms of providing the driving force for epidermal differentiation, and vitamin D-3 analogues have proved to be useful therapeutic agents in psoriasis, However, while they do reduce proliferation and stimulate epidermal differentiation, the precise me chanisms by which these agents work is also unknown although they do a ffect T-helper cell populations and may moderate the lymphocyte drive associated with the lesion, Every psoriatic patient presents an indivi dual problem in terms of treatment as there is a wide variation in the type, extent, duration and history of the disease, However, while top ical therapy with a variety of regimens is preferred, difficult cases do require more aggressive systemic therapy, It is indisputable that a further understanding of the molecular pathogenesis of psoriasis, the identification of genes linked to the condition and an appreciation o f how uninvolved psoriatic skin differs from normal will have an impac t on both how we view and treat this disfiguring skin disorder, Only w hen we have a complete picture of the events that initiate and drive t he psoriatic lesion will we be able to develop effective regimens to c ontrol this condition.