Update on psoriasis therapy: a perspective from the USA. (1/54)

Because physicians from different nations frequently acquire the use of a new medication at different times, the international exchange of experiences with the new medication is valuable in maximizing its efficacy worldwide. In recent years, many new therapeutic agents have been approved for treating psoriasis in the United States. These include the topical agent calcipotriol and the systemic agents acitretin and cyclosporine. In addition to new agents, a new therapeutic paradigm, sequential therapy, has been introduced recently. It is the hope of the authors that by sharing this paradigm and experiences with these agents in the United States, dermatologists in Japan may gain further insight into optimizing the use of these agents in the treatment of psoriasis.  (+info)

Lichen planus. (2/54)

Lichen planus is an inflammatory mucocutaneous condition with characteristic violaceous polygonal flat-topped papules and plaques. Pruritus is often severe. Skin lesions may be disfiguring, and involvement of the oral mucosa or genital mucosa in severe cases may be debilitating. Oral lichen planus may predispose to the development of squamous cell carcinoma within lesions. Involvement of the scalp and the nails may also occur. While most cases of lichen planus are idiopathic, some may be caused by the ingestion of certain medications (e.g., gold, antimalarial agents, penicillamine, thiazide diuretics, beta blockers, nonsteroidal anti-inflammatory drugs, quinidine and angiotensin-converting enzyme inhibitors) or linked to hepatitis C virus infection. Patients with localized lichen planus are usually treated with potent topical steroids, while systemic steroids are used to treat patients with generalized lichen planus.  (+info)

Efficacy of acitretin in severe psoriasis. (3/54)

Acitretin (Soriatane, Roche Pharmaceuticals) is an aromatic retinoid, effective in the treatment of severe psoriasis. This study highlights data from two existing clinical trials to capture PASI 50 and PASI 75 responder rates which represent a common metric used in current psoriasis clinical trials. A review of pharmacokinetics, safety and a discussion of relapse rate establish acitretin as an efficacious, convenient, oral treatment for initial and maintenance therapy of severe psoriasis.  (+info)

Pityriasis rubra pilaris. (4/54)

Pityriasis rubra pilaris is a chronic, papulosquamous dermatosis of unclear etiology. The case of a 61-year-old man with pityriasis rubra pilaris is presented. The clinical forms, histopathologic features, and treatment options of pityriasis rubra pilaris are reviewed.  (+info)

The distribution of cis- and trans-acitretin in human epidermis. (5/54)

The concentrations of trans-acitretin and its principal metabolite, cis-acitretin, were measured by h.p.l.c. after single and multiple dosing (50 mg orally for 13 days) in plasma, blister fluid and epidermal samples from four healthy male volunteers. Within-day epidermal concentrations of trans-acitretin exceeded those of the cis-form which were at the limit of assay sensitivity. No accumulation of trans-acitretin was observed in plasma or blister fluid but AUC values for the drug in blister roof cells tended to be higher after multiple dosing.  (+info)

Increasing the intracellular availability of all-trans retinoic acid in neuroblastoma cells. (6/54)

Recent data indicate that isomerisation to all-trans retinoic acid (ATRA) is the key mechanism underlying the favourable clinical properties of 13-cis retinoic acid (13cisRA) in the treatment of neuroblastoma. Retinoic acid (RA) metabolism is thought to contribute to resistance, and strategies to modulate this may increase the clinical efficacy of 13cisRA. The aim of this study was to test the hypothesis that retinoids, such as acitretin, which bind preferentially to cellular retinoic acid binding proteins (CRABPs), or specific inhibitors of the RA hydroxylase CYP26, such as R116010, can increase the intracellular availability of ATRA. Incubation of SH-SY5Y cells with acitretin (50 microM) or R116010 (1 or 10 microM) in combination with either 10 microM ATRA or 13cisRA induced a selective increase in intracellular levels of ATRA, while 13cisRA levels were unaffected. CRABP was induced in SH-SY5Y cells in response to RA. In contrast, acitretin had no significant effect on intracellular retinoid concentrations in those neuroblastoma cell lines that showed little or no induction of CRABP after RA treatment. Both ATRA and 13cisRA dramatically induced the expression of CYP26A1 in SH-SY5Y cells, and treatment with R116010, but not acitretin, potentiated the RA-induced expression of a reporter gene and CYP26A1. The response of neuroblastoma cells to R116010 was consistent with inhibition of CYP26, indicating that inhibition of RA metabolism may further optimise retinoid treatment in neuroblastoma.  (+info)

Effects of retinoid therapy on insulin sensitivity, lipid profile and circulating adipocytokines. (7/54)

OBJECTIVE: In vitro and in vivo models indicate that all-trans retinoic acids influence glucose and lipid metabolism. We aimed to evaluate the effects of chronic treatment with acitretin, an all-trans retinoic acid, on glucose metabolism, lipid profile and adiponectin and resistin levels. DESIGN: Ten normoglycemic, normolipemic patients affected with psoriasis vulgaris were studied before and after 1 and 3 months of oral treatment with 35 microg of acitretin. METHODS: Glucose metabolism, lipid profile, and adiponectin and resistin levels were evaluated in basal conditions and after acitretin treatment. Ten healthy subjects matched for age, body mass index (BMI) and insulin sensitivity were studied as controls. RESULTS: One-month acitretin treatment reduced psoriasis activity, insulin sensitivity, evaluated as QUICKI values (0.364 +/- 0.034 versus 0.329 +/- 0.051; P < 0.05) and HOMA-IR index (1.53 +/- 0.73 versus 2.59 +/- 1.41; P < 0.05), and high-density lipoprotein (HDL)-cholesterol levels (45.2 +/- 11.7 versus 39.4 +/- 10.4 mg/dl; P = 0.01). The impairment in glucose and lipid homeostasis was transient and not associated to BMI variations. Adiponectin levels did not change during the treatment, while resistin levels, which were higher in untreated patients than in controls (9.4 +/- 4.4 versus 6.2 +/- 2.1 ng/ml; P = 0.05), fell within the normal range after 1 and 3 months of therapy. The normalization of resistin levels occurred without significant changes in circulating tumor necrosis factor alpha (TNFalpha) levels, which persisted elevated throughout the treatment. CONCLUSIONS: Treatment with a low dose of acitretin induced a mild, transient reduction of insulin sensitivity and HDL-cholesterol levels that was not related to modifications of adiponectin, resistin and TNFalpha levels. Although the role of resistin in humans remains elusive, the levels of this adipocytokine seem to be affected, at least in part, by retinoids.  (+info)

Interaction between genetic control of vascular endothelial growth factor production and retinoid responsiveness in psoriasis. (8/54)

Vascular endothelial growth factor (VEGF) promotes angiogenesis, and elevated levels are found in plaques of psoriasis. Two VEGF polymorphisms, +405 and -460, are associated with early-onset psoriasis and are close to the functional activator protein-1 site (+419) through which retinoids, an established systemic therapy for psoriasis, can block production of VEGF. We report that peripheral blood mononuclear cells (PBMCs) and epidermal keratinocytes (KC) from patients with psoriasis demonstrate differential, genotype-dependent, regulation of VEGF. For PBMCs, VEGF genotype distinguishes two groups of patients with psoriasis - "high and low VEGF producers" (P < 0.001). In contrast, KC production of VEGF is not genotype dependent. However, the effects of all-trans retinoic acid (RA) on cellular expression of VEGF are determined by both cell type and genotype. RA inhibits KC production of VEGF in a genotype-dependent manner (P < 0.005) whereas RA stimulates PBMCs production irrespective of VEGF genotype (P < 0.001). We also report that the -460 VEGF polymorphism appears to have a clinical pharmacogenetic role in predicting response or non-response of psoriasis to acitretin (P = 0.01). In future, determination of VEGF gene polymorphisms and thus individual patient VEGF "signatures" may be used as a prognostic factor for psoriasis susceptibility/severity and as a means for optimizing treatment response.  (+info)

• 1
• 2
• 3
• 4
• 5
• 6
• 7