Since their introduction 15 years ago, retinoids have been increasingly used for topical and systemic treatment of psoriasis and other hyperkeratotic and parakeratotic skin disorders, keratotic genodermatoses, severe acne and acne-related dermatoses, and also for therapy and/or chemoprevention of skin cancer and other neoplasia. Oxidative metabolites of vitamin A (retinol) are natural retinoids present at low levels in the peripheral blood. Synthetic retinoids are classified into 3 generations including nonaromatic, monoaromatic and polyaromatic compounds. They are detectable in plasma 30-60 minutes after systemic administration, and reach maximum concentrations 2 to 4 hours later. Elimination half-life is 10 to 20 hours for isotretinoin, 80 to 175 days for etretinate and 2 to 4 days for, trans-acitretin; the latter, however, partially converts into etretinate. Retinoid concentrations in skin are rather low in contrast to subcutaneous fat tissue. Intracellularly, retinoids interact with cytosolic proteins and specific nuclear receptors. Two classes of nuclear receptors have been suggested to mediate retinoid activity at the molecular level, RARs and RXRs. The expression of retinoid receptors is tissue specific; skin mainly espresses RAR gamma and RXR alpha. Retinoids affect epidermal cell growth and differentiation as well as sebaceous gland activity and exhibit immunomodulatory and anti-inflammatory properties. Current retinoid research targets the development of receptor-selective retinoids for tailoring and/or improving their therapeutic profile. Currently, tretinoin is used systemically for acute promyelocytic leukaemia, etretinate and acitretin for psoriasis and related disorders, as well as other disorders of keratinisation and isotretinoin for seborrhoea, severe acne, rosacea and acneiform dermatoses. Systemic retinoids are also applied for chemoprevention of epithelial skin cancer and cutaneous T cell lymphoma. The major adverse effect of retinoids is teratogenicity; all other adverse effects are dose-dependent and controllable. Contraception is, therefore, essential during retinoid treatment in women of child-bearing age. Clinical monitoring requires physical examination for adverse effects every 3 to 4 weeks and proper laboratory investigations, also including analysis of retinoid bioavailability in selected cases. Topical retinoids are rapidly developing at present and seem promising for the future; their clinical application includes acne, aging, photodamage, precanceroses, skin cancer and disorders of skin pigmentation. The development of receptor-specific retinoids for topical treatment of psoriasis and/or acne may lead to interesting new compounds based on our current concepts of retinoid function.

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The dermal papilla of the mammalian hair follicle plays an important role in regulating and controlling the hair cycle. Distinct functional stages of dermal papilla cells (DPC) are involved in this process, thus suggesting that the dermal papilla is a highly specialized suborgan of the pilosebaceous unit. The aim of the present study was to investigate the functional properties of cultured DPC in various assays and to compare their functional properties with those of dermal fibroblasts (DFB). In monolayer cell cultures DPC showed an aggregative growth pattern, different to that of DFB, and lower proliferation rates, as compared to the controls. Adhesion assays performed using a 51[Cr]labeling method showed strong adhesion of both cell populations to collagen types I and IV, fibronectin and laminin, but DPC in vitro showed significantly higher adhesiveness to collagen type IV, a major component of the basement membrane of dermal papillae in vivo. The capacity of DPC to reorganize extracellular matrix components, as measured by gel contraction with three-dimensional collagen type I lattices, proved to be significantly lower than that of DFB and, moreover, DPC lysed the collagen lattices completely after 48 h in culture. The functional differences between DPC and DFB were paralleled by higher surface expression and synthesis levels of the beta 1, alpha 1, and alpha 5 chains of integrin adhesion receptors in DPC, as detected by fluorescence-activated cell-sorter analysis and radioimmunoprecipitation. These findings provide evidence that DPC are a highly specialized cell population, which clearly differs from another mesenchymal cell type, DFB. After their isolation and cultivation in vitro, DPC still preserve functional properties related to important steps of cell-matrix interaction involved in the hair cycle.

Background: Isotretinoin for oral therapy in severe acne conglobata and acne nodulocystica represents a significant achievement; however, the drug exerts several mucocutaneous and systemic adverse effects, besides its teratogenic potency. Objective: The aim of this study was to investigate the plasma levels of isotretinoin and of 4-oxo-isotretinoin over long-term treatment of severe acne and to assess any correlation with the given dose, the clinical improvement and the occurrence of side effects. Methods: Forty-one patients with severe acne and acne-related disorders were studied under long-term oral intake of isotretinoin. Therapeutic effects and side effects were evaluated prior, during and at the end of therapy. The plasma levels of isotretinoin and of its major metabolite 4-oxoisotretinoin were measured by reversed-phase HPLC and were correlated with the administered oral dose and the number and frequency of side effects. Results: Dose-dependent plasma levels of isotretinoin and its metabolite were observed. At a mean dosage of 0.75–1.0 mg/kg/day, 404 ± 142 ng/ml were measured, whereas the plasma levels of 4-oxo-isotretinoin were 1–2 × higher. The plasma levels correlated well with the orally administered dose of isotretinoin and the observed mucocutaneous side effects. Conclusion: The study demonstrates that measuring of the plasma levels may be a helpful tool to monitor the individual therapeutic dose regimen in patients with severe acne in order to minimize undesired side effects and to control oral intake.