Anna Campanati

Effect of etanercept on insulin sensitivity in nine patients with psoriasis.

Metabolic syndrome is associated to chronic low grade inflammation, characterized by increased levels of inflammatory cytokines, such as Tumor Necrosis Factor-α (TNF-α) and Interleukin-6 (IL-6). In particular, TNF-α causes a decrease in the insulin-stimulated kinases related to the early phases of the insulin cascade, thereby leading to insulin resistance. Etanercept is a human fusion protein used in the treatment of psoriasis and inflammatory arthritis. It blocks inflammatory response by interfering in the binding of TNF-α to its receptors. The aim of this case report study is to verify the effect of Etanercept on insulin sensitivity, lipid profile and inflammatory status in psoriatic patients. Nine psoriatic patients with stable, active, plaque type psoriasis were enrolled and treated with Etanercept for 24 weeks. We found an improvement in the metabolic assessment with a significant reduction of insulin plasma levels. In particular, this treatment allows to maintain their euglycemic state with lower insulin plasma levels, as confirmed by the improved Homeostasis Model Assessment (HOMA) index. We conclude that Etanercept, probably acting on inflammation, improves insulin sensitivity in psoriatic subjects.

Immunogenicity of anti-TNFα therapy in psoriasis: a clinical issue?

Introduction: Immunogenicity of antitumor necrosis factor-alpha (TNFα) agents has been proven to play a significant role in the variability of clinical responses among patients with chronic inflammatory diseases. However, its clinical impact on the outcome of patients with psoriasis and psoriatic arthritis receiving anti-TNFα treatment is not yet fully clear. Despite the high rates of efficacy of anti-TNFα agents in psoriasis, a substantial proportion of patients remain who experience a primary or secondary failure or significant side effects, which are potentially ascribable to immunogenicity. Areas covered: Topics include immunologic response elicited by anti-TNFα agents, the impact of immunogenicity on treatment response to anti-TNFα and the role played by immunogenicity in the lack of efficacy of anti-TNFα agents (infliximab, adalimumab and etanercept) in psoriasis. Expert opinion: Based on data available in the literature and the clinical experience of the authors, this article suggests the optimal approach to drug monitoring and antidrug antibody assay and the most effective use of biologic immunotherapies in this setting. Immunogenicity should be taken into account in the adoption of therapeutic choices in psoriatic patients, such as anti-TNFα agent intensification, or switching to another anti-TNFα agent or a drug with a different mechanism of action.

Effect of biologic therapies targeting tumour necrosis factor-α on cutaneous mesenchymal stem cells in psoriasis

Summary Background  Psoriasis is a Th1 immune‐mediated, inflammatory disease, in which skin lesions appear many years before the related metabolic and cardiovascular comorbidities, according to the theory of the ‘psoriatic march’. Inducible nitric oxide synthetase (iNOS), tumour necrosis factor (TNF)‐α and vascular endothelial growth factor (VEGF) are directly implicated in determining both skin lesions and systemic involvement in psoriasis. Reactive oxygen species actively promote the secretion of inflammatory Th1 cytokines directly involved in the pathogenesis of psoriasis.

The mesenchymal stem cell profile in psoriasis.

Background  The expression of inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) and the level of total oxyradical scavenging capacity have been evaluated extensively in the cutaneous cells of patients with psoriasis. As yet, no indications are available about the undifferentiated cells, the mesenchymal stem cells (MSCs), isolated from skin.

Correlation between lipoprotein(a) and lipid peroxidation in psoriasis: role of the enzyme paraoxonase-1

Background  Psoriasis is a chronic, inflammatory skin disease associated with abnormal plasma lipid metabolism and with a high frequency of cardiovascular events. Modifications of plasma lipids and an increase in the levels of biochemical markers of lipid peroxidation have been reported in subjects with psoriasis, suggesting a relationship between psoriasis, lipoproteins and oxidative damage.

Effect of Allium Cepa-Allantoin-Pentaglycan Gel on Skin Hypertrophic Scars: Clinical and Video-Capillaroscopic Results of an Open-Label, Controlled, Nonrandomized Clinical Trial

BACKGROUND Hypertrophic scar formation is a process in which prolonged angiogenesis sustained by vascular endothelial growth factor cutaneous expression plays an important role. OBJECTIVE This in vivo study was conducted to evaluate the clinical effect of a topical gel containing onion extract, allantoin, and pentaglycan on hypertrophic scars and keloids. MATERIALS AND METHODS Thirty people with hypertrophic scars or keloids were examined. Fifteen patients received a topical application of a gel containing allium cepa, allantoin, and pentaglycan twice a day for 24 weeks, the remaining 15 patients received no topical treatments. A clinical evaluation and an intravital videocapillaroscopy were performed on every patient at baseline (T0) and 24 weeks (T24) after the treatment. RESULTS Only the patients who received the topical treatment showed a significant reduction in neoangiogenetic features, demonstrated through an improvement of erythema and all videocapillaroscopic markers of neoangiogenesis. These changes induced by therapy led to a general improvement of the lesions. CONCLUSION Topical applications of a gel containing allium cepa, pentaglycan, and allantoin twice a day for 24 weeks seems to be useful in reducing neoangiogenesis in hypertrophic scars and keloids, resulting in clinical improvement of skin lesions. The authors have indicated no significant interest with commercial supporters.

A Patient with Psoriasis and Vitiligo Treated with Etanercept

Psoriasis is a chronic, immune-mediated, inflammatory dermatosis whose aetiopathogenesis remains unclear, although tumour necrosis factor alpha (TNFα) appears to play a crucial role. The biological potential of TNFα inhibitors, such as etanercept, which reduce the inflammatory cascade, has radically changed the therapeutic management of patients with psoriasis and other immunomediated inflammatory diseases, associated with TNFα. The pathogenesis of the selective destruction of melanocytes in vitiligo is not fully understood, although there is growing evidence that several T helper type 1 cytokines, particularly TNFα, may be involved in the depigmentation process.A patient is described who presented with both psoriasis and vitiligo, and was treated with etanercept. After 24 weeks of therapy, the patient’s psoriasis had improved markedly and the patient noted a mild improvement of vitiligo, with a reduction in macules and repigmentation in the scapular region.

CTACK /CCL27 expression in psoriatic skin and its modification after administration of etanercept

Background  Tumour necrosis factor‐α upregulates the expression of a cutaneous T cell‐attracting chemokine (CTACK/CCL27), that promotes migration of cutaneous lymphocyte‐associated antigen‐positive lymphocytes into the skin. The role of CTACK/CCL27 in pathogenesis of psoriasis has recently been documented but no data are available at the present time on its modification in psoriatic cutaneous tissue after administration of etanercept.

Lichen striatus in adults and pimecrolimus: open, off‐label clinical study

Background  Lichen striatus is a well‐known, acquired, self‐healing, linear inflammatory dermatosis. Lichen striatus occurring in adults tends to be more extensive and itchy than in children, sometimes requiring symptomatic treatment. The therapeutic approach usually adopted is topical steroids, even though prolonged use may lead to several side‐effects, particularly cutaneous atrophy.

Characterization and profiling of immunomodulatory genes in resident mesenchymal stem cells reflect the Th1-Th17/Th2 imbalance of psoriasis.

The expression of genes encoding for Th1, Th2 and Th17 cytokines has been extensively evaluated in differentiated skin cells of psoriatic patients. The microenvironment exerts a control on the phenotype of resident mesenchymal stem cells (MSCs) into the skin of psoriasis patients. Aim of the study was to extensively evaluate the relative expression of 43 genes encoding for Th1, Th2 and Th17 cytokines in MSCs isolated from skin of psoriasis patients. MSCs resident into psoriatic skin were isolated, characterized and profiled by PCR array for the relative expression of genes encoding for cytokines involved in Th1, Th2 and Th17 pathways. MSCs isolated from the skin of healthy subjects were used as control. The MSCs isolated from skin of psoriasis patients showed a greater relative expression of the most part of the analyzed genes encoding for Th1 and Th17 cytokines: INF-γ, CCR5, CXCL9, CXCL10, IL6, IL8, TNF-α, IL23A, CCL2, CCL20, CXCL2, CXCL5, IL17C, IL17F, IL17RA, IL21, TLR2 than healthy subjects. On the contrary, the relative expression of genes encoding for Th2 cytokines: CCL1, CCL22, CXCL12, IL2, IL3, IL4, IL13B, IL 22, IL 27, TGF-β1, was similar between the MSCs isolated from psoriasis and healthy subjects. In conclusion, the MSCs isolated from psoriasis show an imbalance between the Th1-Th17 and Th2 pathways, which reflects the well-known abnormal balance observed in differentiated skin cells. This evidence could strengthen the hypothesis of an early involvement of resident MSCs in the pathogenesis of psoriasis.