Plaque psoriasis in children and adolescents – the role of etanercept

Federica Ricceri, Lara Tripo, Leonardo Pescitelli, Francesca PrignanoDivision of Clinical, Preventive and Oncology Dermatology, Department of Critical Care Medicine and Surgery, University of Florence, Florence, ItalyBackground: Childhood-onset psoriasis affects approximately one-third of the psoriatic population. Among many potential treatments of childhood psoriasis, biological agents are emerging as a valuable option in the management of this disease. In Europe, etanercept has recently been approved for children aged 6 years and over. Data from a well-designed clinical trial indicate that in children, etanercept effectively reduces psoriasis symptoms, with beneficial effects evident as early as 4 weeks after the onset of therapy. The treatment is generally well tolerated; mild injection site reactions are the most common adverse events reported in the literature. Published data of etanercept use in children show promising results, but further clinical studies are necessary to confirm its long-term efficacy and safety.Keywords: pediatric psoriasis, anti-TNF-α, etanercep

Erythrodermic psoriasis treated with ustekinumab: An Italian multicenter retrospective analysis

Erythrodermic psoriasis (EP) is one of the most severe cutaneous conditions which may lead to serious morbidity and even mortality. This condition is often difficult to manage and, due to its rarity (estimated prevalence 1–2.25% of psoriatic patients) there is a lack of high-quality medical literature examining treatment options [1]

Plaque psoriasis in children and adolescents – the role of etanercept

Federica Ricceri, Lara Tripo, Leonardo Pescitelli, Francesca PrignanoDivision of Clinical, Preventive and Oncology Dermatology, Department of Critical Care Medicine and Surgery, University of Florence, Florence, ItalyBackground: Childhood-onset psoriasis affects approximately one-third of the psoriatic population. Among many potential treatments of childhood psoriasis, biological agents are emerging as a valuable option in the management of this disease. In Europe, etanercept has recently been approved for children aged 6 years and over. Data from a well-designed clinical trial indicate that in children, etanercept effectively reduces psoriasis symptoms, with beneficial effects evident as early as 4 weeks after the onset of therapy. The treatment is generally well tolerated; mild injection site reactions are the most common adverse events reported in the literature. Published data of etanercept use in children show promising results, but further clinical studies are necessary to confirm its long-term efficacy and safety.Keywords: pediatric psoriasis, anti-TNF-α, etanercep

Anti-TNF-alpha molecules establish a more differentiated phenotype in psoriatic epidermis

Several cutaneous inflammatory diseases and their clinical phenotypes are recapitulated in animal models of skin disease. However, the identification of shared pathways for disease progression is limited by the ability to delineate the complex biochemical processes fundamental for development of the disease. Identifying common signaling pathways that contribute to cutaneous inflammation and immune function will facilitate better scientific and therapeutic strategies to span a variety of inflammatory skin diseases. Aberrant antimicrobial peptide (AMP) expression and activity is one mechanism behind the development and severity of several inflammatory skin diseases and directly influences the susceptibility of skin to microbial infections. Our studies have recently exposed a newly identified pathway for negative regulation of AMPs in the skin by the cholinergic anti-inflammatory pathway via acetylcholine (ACh). The role of ACh in AMP regulation of immune and permeability barrier function in keratinocytes is reviewed, and the importance for a better comprehension of cutaneous disease progression by cholinergic signaling is discussed

Anti-tumor necrosis factor-alfa and psoriasis : new insights on keratinocyte differentiation markers

Tumor necrosis factor-alfa (TNF-\u3b1) is a cytokine that plays a central role in the pathogenesis of psoriasis; the treatment with anti\u2013TNF-\u3b1 agents, as etanercept, has proved to be highly effective although its mechanism on the overall epidermal cytoarchitecture has still to be elucidated. The aim of the present study was to investigate if etanercept treatment of psoriatic patients could affect the expression of the main biomarkers of keratinocyte terminal differentiation (TD) along with epithelial cell proliferation

Morphological analysis of the effects of tumor necrosis factor-alpha and interleukin-17 in a three-dimensional organotipic model of normal human skin

Psoriasis is an autoimmune chronic inflammatory disease in which epidermal keratinocytes and innate immunity effector cells play a pivotal role in the lesion formation in genetically predisposed subjects (Bonifati et al., 1999). Among the several cytokines involved in psoriasis pathogenesis, tumor necrosis factor (TNF)-alpha and interleukin (IL)-17 play a relevant role. TNF-alpha stimulates the production of many chemokines, induces cell proliferation, and is proapoptotic. IL-17 is involved in the recruitment/activation of neutrophils and induces keratin 17 (K17) expression in psoriatic lesions. The present study is focussed on the early effects of these proinflammatory cytokines on i) the molecular composition of intercellular junctions (desmocollin (DSC)1/desmoglein (DSG)1, E-cadherin, and occludin) ii) on K17 expression iii) on immunophenotype/number of epidermal Langerhans cells (LCs) after cytokines exposure. Ultrastructural analysis was performed in on all samples. Skin explants obtained from plastic surgery of healthy 20-40 year-old women (n = 7) after informed consent, were cultured overnight in Dulbecco's modified Eagle's medium and divided before adding 100 ng/ml TNF-alpha or 50 ng/ml IL-17 or a combination of both cytokines (Donetti et al., 2014). Samples were harvested 24, 48, and 72 hours after cytokine incubation. Occludin immunostaining was non homogeneous in cytokine treated samples, starting from 24 hours of culture. Interestingly, K17 expression was induced only in IL-17-treated samples only. No differences were observed in DSC1, DSG1 and E-cadherin expression by immunofluorescence. LC number was significantly higher in samples treated with both cytokines (216.71\ub115.10%) than in TNF-alpha (125.74\ub126.24%) or IL-17 (100.14\ub138.42%) alone. TEM analysis revealed that spaces were enlarged in the basal and spinous layer, especially upon TNF-alpha treatment, but desmosomes were uniformly distributed. Upon TNF-alpha stimulus LCs appeared with few organelles, mostly mitochondria, lysosomes, and scattered peripherical Birbeck granules. Upon IL-17 stimulus, LCs showed a cytoplasm with many mitochondria and numerous Birbeck granules close to the perinuclear space and Golgi apparatus, but also at the periphery, at the beginning of the dendrites. The addition of both cytokines did not modify LC ultrastructure. Altogether this study strongly suggests that this model is useful to study the early, direct, and specific effects of specific psoriatic cytokines on the different cell population

Metastatic vulvar carcinoma

We describe a case of metastatic vulvar carcinom

Tumour necrosis factor-alpha and interleukin-17 differently affects Langerhans cell distribution and activation in an innovative three-dimensional model of normal human skin

Among the several cytokines involved in the psoriasis pathogenesis, tumor necrosis factor (TNF)-alpha and interleukin (IL)-17 play a central role. Many biomolecular steps remain unknown due to difficulty to obtain psoriatic models. To investigate the effect of TNF-alpha and IL-17 on the ultrastructure, immunophenotype, and number of epidermal Langerhans cells (LCs), human skin explants (n=7) were cultured air-liquid interface in a Transwell system. Four different conditions were used: medium alone (control), medium added with 100 ng/ml TNF-alpha or 50 ng/ml IL-17 or a combination of both cytokines. Samples were harvested 24 and 48 h after cytokine addition and were frozen. Samples harvested at 24h were also processed for transmission electron microscopy (TEM). By immunofluorescence analysis with anti-human Langerin antibody (three experiments/sample) we calculated the percentage of LCs/mm(2) of living epidermis after 24 and 48 h of incubation (considering control as 100%). At 24h LC number was significantly higher in samples treated with both cytokines (216.71+15.10%; p<0.001) and in TNF-alpha (125.74+26.24%; p<0.05). No differences were observed in IL-17-treated samples (100.14+38.42%). After 48 h, the number of epidermal Langerin-positive cells in IL-17- and TNF-alpha treated samples slightly decreased (94.99+36.79% and 101.37+23% vs. their controls, respectively). With the combination of both cytokines epidermal LCs strongly decreased (120+13.36%). By TEM, upon TNF-alpha stimulus LCs appeared with few organelles, mostly mitochondria, lysosomes, and scattered peripherical BGs. Upon IL-17 stimulus, LCs showed a cytoplasm with many mitochondria and numerous BGs close to the perinuclear space and Golgi apparatus, but also at the periphery, at the beginning of the dendrites. The addition of both cytokines did not affect LC ultrastructure. Our study showed that IL-17 induced significant changes in LC ultrastructure, while the combination of both cytokines seems to have a strong chemo-attractant effect on epidermal LCs, supporting the relevance of investigating the interplay between LCs and pro-inflammatory cytokines in the ongoing of the disease

Tuscany consensus for the diagnosis, treatment and follow-up of moderate-to-severe psoriasis

Psoriasis is traditionally defined as an inflammatory chronic--relapsing disease of the skin. It is also -- as widely demonstrated -- a disease associated with multiple comorbidities: arthropathy, inflammatory bowel disease, metabolic, cardiovascular, ocular and psychological disorders. The disease also has a significant impact on patients' quality of life, whose work ability decreases considerably with clear consequences for the social costs. Therefore, if we consider that in Tuscany, more than 100,000 people out of 3,672,202 suffer from psoriasis, it is of paramount importance focusing the attention on a rational model of clinical and therapeutic management of the disease

Tuscan consensus for the diagnosis, treatment and follow-up of moderate-to-severe psoriasis

Psoriasis is traditionally defined as an inflammatory chronic--relapsing disease of the skin. It is also -- as widely demonstrated -- a disease associated with multiple comorbidities: arthropathy, inflammatory bowel disease, metabolic, cardiovascular, ocular and psychological disorders. The disease also has a significant impact on patients' quality of life, whose work ability decreases considerably with clear consequences for the social costs. Therefore, if we consider that in Tuscany, more than 100,000 people out of 3,672,202 suffer from psoriasis, it is of paramount importance focusing the attention on a rational model of clinical and therapeutic management of the disease