A model that explains how maintenance of normal homeostasis in human epidermis is achieved describes a heterogeneous cell population of stem cells (SC) and transit amplifying cells (TAC). There must be a tightly regulated balance between SC self-renewal and the generation of TAC that undergo a limited number of divisions before giving rise to postmitotic, terminally differentiated cells. To investigate whether this balance is disturbed in psoriatic epidermis, we have characterized flow sorted enriched SC and TAC using immunocytochemistry, flow cytometry, and real-time quantitative PCR. Our data demonstrate phenotypical and functional differences in SC (beta(1)-integrin bright) and TAC (beta(1)-integrin dim) enriched fractions between normal and psoriatic keratinocytes. Some of these were expected, such as mRNA levels of keratins 6 and 10 and of the Ki-67 antigen. Most remarkable were differences in phenotype of the psoriatic TAC compared with TAC from normal skin. These subpopulations also displayed striking differences following culture. Downregulation of markers associated with the regenerative phenotype (psoriasin, elafin, psoriasis-associated fatty acid binding protein) in cultured psoriatic dim cells in the absence of hyperproliferation suggests that proliferation and regenerative maturation are coupled. From these results, in combination with our earlier findings, we propose a model for epidermal growth control in which TAC play a crucial role.

Psoriasis of the scalp is a frequently occurring condition affecting approximately 2% of the Western population. The sharply demarcated erythematosquamous lesions with silver-white scaling characterize scalp psoriasis. Quality of life can be seriously reduced by this condition and therefore long term treatment is needed in most patients. Coal tar shampoos, containing 2 to 10% coal tar solution, are effective in scalp psoriasis. However, no double-blind studies are available to support such an assumption. Salicylic acid 5 to 10% has a pronounced keratolytic effect. Salicylic acid should be formulated in an ointment, which can be washed off easily. Crude coal tar is the most effective tar available for the treatment of psoriasis. An important feature of coal tar is its potent efficacy against pruritus. At the scalp, the application of crude coal tar is difficult. Therefore coal tar solution is the most frequently applied tar preparation in scalp psoriasis. Dithranol 0.1 to 3% is manufactured in various formulations. Treatment is initiated at a low concentration and the concentration is increased stepwise until a slight irritation, the feeling of warmth, is reached. In the treatment of scalp psoriasis, cream formulations are used. Imidazole antifungals have been used with success in scalp psoriasis. Overgrowth of the scalp with pityrosporon is a well-known feature of scalp psoriasis and seborrheic dermatitis. In case of resistance to other topical treatments use of a topical or systemic imidazole derivative might be helpful. So far, topical corticosteroids are the most frequently used treatments for psoriasis of the scalp. Corticosteroids inhibit epidermal proliferation, inhibit inflammation and modulate immune functions. Topical corticosteroids are fast acting: within 3 to 4 weeks maximal efficacy is reached. No data are available to support the efficacy and safety of topical corticosteroids during long term use. However, from epidemiologic surveys we know that these treatments are used by the majority of patients for more than 8 weeks. Since 1992 vitamin D3 formulations have been developed for the treatment of psoriasis. Calcipotriol is available in most countries. Tacalcitol is available in Japan and several other countries. Vitamin D3 analogues inhibit epidermal proliferation, enhance cornification and inhibit inflammation. Therefore, vitamin D3 analogues have a substantial antipsoriatic effect. Systemic treatments such as methotrexate, cyclosporine and acitretin are indicated in patients with recalcitrant disease. Management of scalp psoriasis requires long term strategies in order to reach an optimal improvement of the condition, while avoiding the adverse effects associated with the long term use of treatments.

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