Psoriasis is a chronic inflammatory multifactorial disease and the precise molecular defects causing psoriasis remain unclear; but a genetic predisposition and environmental factors are involved in the pathogenesis, A strong genetic component is found in certain individuals and the inheritance of psoriasis can be classified as autosomal dominant with variable penetrance, Clinically, psoriasis represents a collection of similar disorders with a variable phenotype, making investigation at the molecular level extremely complex, Lesions are characterized by hyperproliferation and abnormal epidermal differentiation, together with 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 uninvolved skin, Trauma, stress and chemicals are all known to precipitate psoriasis in susceptible individuals, but the molecular mechanisms are not understood, The accumulation of inflammatory cells in the epidermis and altered dermal vessels are major characteristics, and these changes are driven by release of cytokines and growth factors, Many investigations have shown that the process of epidermal differentiation in the lesion is aberrant, Increased transit time of cells through the epidermis combined with a shift to the 'hyperproliferative state' prevents the keratinocyte from completing the preprogrammed molecular events necessary for normal terminal differentiation, Calcium and its binding 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 mechanisms by which these agents work is also unknown although they do affect T-helper cell populations and may moderate the lymphocyte drive associated with the lesion, Every psoriatic patient presents an individual problem in terms of treatment as there is a wide variation in the type, extent, duration and history of the disease, However, while topical 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 of how uninvolved psoriatic skin differs from normal will have an impact on both how we view and treat this disfiguring skin disorder, Only when we have a complete picture of the events that initiate and drive the psoriatic lesion will we be able to develop effective regimens to control this condition.
