Phase I clinical trial of O6-benzylguanine and topical carmustine in the treatment of cutaneous T-cell lymphoma, mycosis fungoides type.

Objectives: To evaluate the toxic effects and maximum tolerated dose of topical carmustine [1,3-bis(2-chloroethyl)-1-nitrosourea] following intravenous O6-benzylguanine in the treatment of cutaneous T-cell lymphoma (CTCL), and to determine pharmacodynamics of O6-alkylguanine DNA alkyltransferase activity in treated CTCL lesions.

Design: Open-label, dose-escalation, phase I trial.

Setting: Dermatology outpatient clinic and clinical research unit at a university teaching hospital.

A retrospective study to investigate racial and ethnic variations in the treatment of psoriasis with etanercept.

Objectives: Psoriasis is a chronic inflammatory condition that occurs worldwide; however, few studies have examined this condition in non-Caucasian populations. The purpose of this study was to investigate racial/ethnic differences in demographics, psoriasis severity, efficacy, safety, and health-related quality of life in patients treated with etanercept using data from the Etanercept Assessment of Safety and Effectiveness (EASE) in Psoriasis trial.

Patients And Methods: This is an investigator-initiated evaluation of data from the EASE study.

Preliminary clinical and pharmacologic investigation of photodynamic therapy with the silicon phthalocyanine photosensitizer pc 4 for primary or metastatic cutaneous cancers.

Photodynamic therapy (PDT) for cutaneous malignancies has been found to be an effective treatment with a range of photosensitizers. The phthalocyanine Pc 4 was developed initially for PDT of primary or metastatic cancers in the skin. A Phase I trial was initiated to evaluate the safety and pharmacokinetic profiles of systemically administered Pc 4 followed by red light (Pc 4-PDT) in cutaneous malignancies.

Topical application of green and white tea extracts provides protection from solar-simulated ultraviolet light in human skin.

Background: Tea polyphenols have been found to exert beneficial effects on the skin via their antioxidant properties.

Aims: We sought to determine whether topical application of green tea or white tea extracts would prevent simulated solar radiation-induced oxidative damages to DNA and Langerhans cells that may lead to immune suppression and carcinogenesis.

Methods: Skin samples were analysed from volunteers or skin explants treated with white tea or green tea after UV irradiation.

Differences in binding and effector functions between classes of TNF antagonists.

There are currently two Food and Drug Administration-approved classes of biologic agents that target tumor necrosis factor-alpha (TNF-alpha): anti-TNF monoclonal antibodies (mAbs) (adalimumab and infliximab), and soluble TNF receptors (etanercept). This study examined the ability of the TNF antagonists to: (1) bind various polymorphic variants of cell surface-expressed Fc receptors (FcgammaRs) and the complement component C1q, and (2) mediate Ab-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC) killing of cells expressing membrane-bound TNF (mTNF) in vitro. Both mAbs and the soluble TNF receptor demonstrated low-level binding to the activating receptors FcgammaRI, FcgammaRIIa, and FcgammaRIIIa, and the inhibitory receptor FcgammaRIIb, in the absence of exogenous TNF.

Patient-reported outcomes and health-care resource utilization in patients with psoriasis treated with etanercept: continuous versus interrupted treatment.

Objective: The 24-week Etanercept Assessment of Safety and Effectiveness (EASE) study evaluated the effectiveness and tolerability of continuous versus interrupted etanercept treatment in patients with moderate to severe plaque psoriasis. The objective of this analysis was to assess patient-reported outcomes (PROs) and health-care resource utilization (HRU) data from the EASE study.

Methods: Patients received open-label etanercept 50 mg twice weekly for 12 weeks and then received either continued or interrupted (single round of discontinuation and re-treatment with etanercept) etanercept 50 mg once weekly for the second 12 weeks.

Immune protective effect of a moisturizer with DNA repair ingredients.

Ultraviolet (UV) light damages DNA and impairs immune surveillance. The faulty repair of DNA after UV exposure is associated with immune suppression and facilitates photodamage that leads to photoaged skin and the growth of skin cancer. Sunscreens have been developed to filter UV light from entering the skin, but are not beneficial once DNA damage has occurred.

Determination of in vivo dose response and allergen-specific T cells in subjects contact-sensitized to squaric acid dibutyl ester.

Background: Squaric acid dibutyl ester (SADBE) is a known contact sensitizer, but dose-response data are not defined.

Objective: To determine the relationship between sensitization dose and contact hypersensitivity (CHS) response to SADBE in human volunteers. The study also aimed to investigate whether SADBE-reactive blood T cells could be detected using ex vivo mature dendritic cells (DCs) as antigen-presenting cells.

Utilization of narrow-band ultraviolet light B therapy and etanercept for the treatment of psoriasis (UNITE): efficacy, safety, and patient-reported outcomes.

Background: Moderate to severe psoriasis is a significant inflammatory disease that frequently requires systemic therapies to effectively treat the underlying disorder. Etanercept and narrow-band ultraviolet light B (NB-UVB) are widely used to treat this disease.

Objective: To evaluate the effectiveness, tolerability, and patient-reported outcomes of combination etanercept plus NB-UVB phototherapy in moderate to severe plaque psoriasis.

Psoriasis treatment patterns: results of a cross-sectional survey of dermatologists.

Objective: The study evaluated community physician prescribing patterns for patients with psoriasis.

Methods: US dermatologists actively practicing general dermatology and treating 10 or more patients with psoriasis/mo were interviewed (n = 90) in April and June 2006 and they recruited 8 to 10 consecutive patients for record review (n = 895, mean age = 46 years, 51% men). Proportion of patients treated with systemic, biologic, or topical therapy as reported by the dermatologist and recorded in the records was assessed by psoriasis severity.

Apoptosis mechanisms related to the increased sensitivity of Jurkat T-cells vs A431 epidermoid cells to photodynamic therapy with the phthalocyanine Pc 4.

To examine the clinical applicability of Pc 4, a promising second-generation photosensitizer, for the photodynamic treatment of lymphocyte-mediated skin diseases, we studied the A431 and Jurkat cell lines, commonly used as surrogates for human keratinocyte-derived carcinomas and lymphocytes, respectively. As revealed by ethyl acetate extraction and absorption spectrophotometry, uptake of Pc 4 into the two cell lines was linear with Pc 4 concentration and similar on a per cell basis but greater in Jurkat cells on a per mass basis. Flow cytometry showed that uptake was linear at low doses; variations in the dose-response for uptake measured by fluorescence supported differential aggregation of Pc 4 in the two cell types.

UV protective effects of DNA repair enzymes and RNA lotion.

Solar UV radiation is known to cause immune suppression, believed to be a critical factor in cutaneous carcinogenesis. Although the mechanism is not entirely understood, DNA damage is clearly involved. Sunscreens function by attenuating the UV radiation that reaches the epidermis.

Use of etanercept for psoriatic arthritis in the dermatology clinic: the Experience Diagnosing, Understanding Care, and Treatment with Etanercept (EDUCATE) study.

Objective: To assess the efficacy and tolerability of etanercept to treat psoriatic arthritis.

Materials And Methods: A total of 1,122 patients who had active psoriatic arthritis were enrolled in a Phase 4, non-randomized, open-label, single-arm, 24-week study. These patients had clinically stable, plaque psoriasis involving >or=10% body surface area and joint disease (either >or=two swollen and >or=two tender/painful joints for >or=3 months, or >or=one joint with sacroiliitis or spondylitis).

Binding characteristics of tumor necrosis factor receptor-Fc fusion proteins vs anti-tumor necrosis factor mAbs.

Tumor necrosis factor (TNF) antagonists are efficacious in the treatment of various autoimmune diseases. Two classes of TNF antagonists are currently commercially available: soluble TNF receptor-Fc fusion proteins (etanercept) and anti-TNF mAbs (adalimumab and infliximab). The classes differ in molecular structures and mechanisms of action.

Etanercept improves psoriatic arthritis patient-reported outcomes: results from EDUCATE.

Experience Diagnosing, Understanding Care, and Treatment With Etanercept (EDUCATE) is a multicenter, phase 4, 24-week, open-label study of the safety and efficacy of etanercept therapy in patients with psoriatic arthritis (PsA) in routine dermatologic practice. We present data on patient-reported outcomes (PROs) from EDUCATE, which demonstrate that subjects with PsA achieved clinically meaningful improvements in both skin- and joint-related PROs after 24 weeks of treatment.

Reductions in healthcare resource utilization in psoriatic arthritis patients receiving etanercept therapy: results from the educate trial.

The Experience Diagnosing, Understanding Care, and Treatment with Enbrel (EDUCATE) trial is a phase IV, 24-week, multicenter, open-label study of etanercept 50 mg weekly in the treatment of psoriatic arthritis (PsA) in community dermatology clinics. In this study, patients with active PsA and moderate to severe plaque psoriasis have measurable uses of healthcare resources at baseline, reflecting a burden of illness. Etanercept significantly reduced healthcare resource utilization, absenteeism, and caregiver assistance in PsA patients after 24 weeks of treatment.

Immunohistochemical staining for CD45R isoforms in paraffin sections to diagnose mycosis fungoides-type cutaneous T-cell lymphoma.

The definitive diagnosis of mycosis fungoides (MF)-type cutaneous T-cell lymphoma (CTCL) is difficult because a cumulative set of information is typically required: clinical features, histopathology, and special diagnostic tests (typically immunophenotyping and T-cell receptor gamma [TCRgamma] gene rearrangement). Fresh tissue is not always available for the special tests. We report a simple and readily available procedure evaluating the staining pattern on formalin-fixed, paraffin-embedded skin that can help with the diagnosis of patch/plaque stage MF.

A randomized, open-label trial of continuous versus interrupted etanercept therapy in the treatment of psoriasis.

Background: Although etanercept is used as a continuous therapy for moderate to severe plaque psoriasis, intermittent use may be necessary in some instances.

Objective: In this randomized, open-label study, we evaluated the effectiveness and safety of continuous versus interrupted etanercept therapy.

Methods: All patients received uninterrupted etanercept 50 mg twice weekly during the first 12 weeks, followed by either continuous (n = 1272) or interrupted (n = 1274) etanercept 50 mg once weekly in the next 12 weeks.

Clinical characteristics of psoriatic arthritis and psoriasis in dermatologists' offices.

Objective: To describe the skin and joint disease of patients with psoriatic arthritis being treated in dermatology clinics.

Methods: A total of 1122 patients who had active psoriatic arthritis were enrolled in a Phase 4, non-randomized, open-label, single-arm, 24-week study. They were treated at 108 community and 17 academic dermatology centers.

Etanercept for the treatment of psoriasis in the elderly.

This study's objective was to analyze the effect of etanercept on Psoriasis Area and Severity Index (PASI) 50, PASI 75, and Dermatology Life Quality Index in geriatric and nongeriatric populations. We conducted a post hoc analysis of two large phase III randomized placebo trials of etanercept. There were no statistically significant differences between the elderly and young with regard to the number of patients reaching a PASI 50 or PASI 75 at any of the 3 dosing regimens.

Peritransplant use of ultraviolet-B irradiation (UV-B) therapy is detrimental to allogeneic stem cell transplantation outcome.

Whole-body UV-B phototherapy has been used for the treatment of graft-versus-host disease (GVHD) of the skin and has systemic immunosuppressive and tolerogenic effects. We hypothesized that whole-body UV-B therapy would improve donor engraftment and decrease the incidence and severity of GVHD that is associated with decreased intensity allogeneic hematopoietic stem cell transplantation. This study tested the feasibility of using UV-B phototherapy that was initiated before grafting and continued until engraftment to determine its effect on transplantation outcome.

What have we learned in dermatology from the biologic therapies?

Recent advances in our basic understanding of immunology, specifically the roles of various cell types involved in immune response and the action of cytokines they produce, has radically changed our understanding of the origin of inflammatory dermatoses, and other autoimmune diseases. Broadened comprehension of the immune response on a molecular level has facilitated the development of biologic therapeutics for the treatment of psoriasis, atopic dermatosis, and other inflammatory conditions. However, despite major advances in development and use of targeted biologics for controlling autoimmune disease, effective cures for these conditions remain to be developed and genetic determinants of predisposition to such diseases remain to be identified.

Defining early mycosis fungoides.

This editorial review summarizes the results of 5 meetings sponsored by the International Society for Cutaneous Lymphoma at which the clinicopathologic and ancillary features of early mycosis fungoides were critically examined. Based on this analysis, an algorithm was developed for the diagnosis of early mycosis fungoides involving a holistic integration of clinical, histopathologic, immunopathologic, and molecular biological characteristics. A novel aspect of this algorithm is that it relies on multiple types of criteria rather than just one, for example, histopathology.

Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation.

The balance between regulatory and effector functions is important for maintaining efficient immune responses, while avoiding autoimmunity. The inflammatory skin disease psoriasis is sustained by the ongoing activation of pathogenic effector T cells. We found that a CD4(+) T lymphocyte subpopulation in peripheral blood, phenotypically CD25(high), CTLA-4(+), Foxp3(high) (regulatory T (Treg) cells), is deficient in its suppressor activity in psoriasis.

Implementation of dermato-epidemiology curriculum at Case Western Reserve University dermatology program.

Dermato-epidemiology curriculum has been identified by the American Academy of Dermatology (AAD) as an important foundation for dermatology residency training. However, no one has yet reported implementation of dermato-epidemiology curriculum. To evaluate and relate our experience carrying out a dermato-epidemiology resident education initiative, based on recommendations by the AAD Epidemiology Committee.